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DEPO-MEDROL WITH LIDOCAINE

Active substance(s): LIDOCAINE / METHYLPREDNISOLONE

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Immune system
common
• Increased susceptibility to infections which can hide or change normal
reactions to skin tests, such as that for tuberculosis.
Metabolism and nutrition disorders
• Accumulation of fat tissue on localized parts of the body.
Muscles, bones and joints
common
• Muscle weakness.
• Muscle twitching.
• Brittle bones (bones that break easily).
not known
• Broken bones or fractures.
• Muscle wasting.
• Breakdown of bone due to poor circulation of blood, this causes pain in the
hip.
• Joint pain.
• Torn muscle tendons causing pain and/or swelling.
• Muscle cramps or spasms.
• Swollen or painful joints due to infection.
Nerves and mood issues
common
Steroids including methylprednisolone can cause serious mental health
problems. These are common in both adults and children. They can affect
about 5 in every 100 people taking medicines like methylprednisolone.
• Feeling depressed, including thinking about suicide.
• Feeling high (mania) or moods that go up and down.
• Feeling anxious, having problems sleeping, difficulty in thinking or being
confused and losing your memory.
• Feeling, seeing or hearing things which do not exist. Having strange and
frightening thoughts, changing how you act or having feelings of being
alone.
• Other nervous system side effects may include convulsions (seizures),
amnesia (loss of memory), cognitive disorder (mental changes), tremor,
dizziness and headache, drowsiness, difficulty breathing, sensation of cold,
heat or numbness, tinnitus or unconsciousness.
• Back pain or weakness (due to Epidural Lipomatosis, a rare disorder in
which an abnormal amount of fat is deposited on or outside the lining of
the spine).
Skin
common
• Acne.
• Bruising.
not known
• Abscess, especially near injection sites.
• Thinning of skin, stretch marks.
• Small purple/red patches on the skin.
• Pale or darker patches on your skin, or raised patches which are an
unusual colour.
• Increased hair on the body and face (hirsutism).
• Rash, skin redness, itching, hives.
• Increased sweating.
If you experience any of the side effects listed above tell your doctor
immediately.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes
any possible side effects not listed on this leaflet. You can also report side
effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
or search for MHRA Yellow Card in the Google Play or Apple App Store. By
reporting side effects, you can help provide more information on the
safety of this medicine.

5

Expiry Date
Do not use this medicine after the expiry date shown on the carton label or
vial label. Each vial is for single use only. After use your doctor should take
the container and syringe away. If anything is left over, take it to your
pharmacist (chemist) for safe disposal. If your medicine become
discoloured or shows any other signs of deterioration, consult your
pharmacist (chemist) who will tell you what to do.
Storing your Medication
• KEEP OUT OF THE SIGHT AND REACH OF CHILDREN.
• Store below 25°C.
• Protect from freezing.
Important
Remember this medicine is for you. Only a doctor can prescribe it. Never
give your medicine to anyone, it may harm them, even if their symptoms are
the same as yours. This leaflet does not tell you everything about this
medicine, If you have any questions or are not sure about anything then ask
your doctor or pharmacist

6

Depo-Medrone® with Lidocaine

How to store Depo-Medrone with Lidocaine

Contents of the pack and other information

What Depo-Medrone with Lidocaine contains
Each 1ml vial contains 40mg methylprednisolone acetate and 10mg
Lidocaine hydrochloride. Each vial also contains sodium chloride,
myristyl-gamma-picolinium chloride, benzyl alcohol as 8.7mg per ml,
macrogol, sodium hydroxide, hydrochloric acid and water for injections.
What a Depo-Medrone with Lidocaine looks like
Depo-Medrone with Lidocaine is a white, sterile aqueous suspension for
injection. Depo-Medrone with Lidocaine is available in cartons of 1 x 1ml vial
or 3 x 1ml vial’s.
Manufacturer and Licence Holder
Depo-Medrone is manufactured by Pfizer Manufacturing Belgium NV.,
Rijksweg 12, B-2870, Puurs Belgium and is procured from within the EU and
repackaged by the Product Licence Holder: Lexon (UK) Limited, Unit 18,
Oxleasow Road, East Moons Moat, Redditch, Worcestershire, B98 0RE.

POM

Depo-Medrone with Lidocaine PL:15184/0926

Depo-Medrone witth lidocaine is a registered trademark of Pharmacia &
Upjohn Limited.
Leaflet revision date: 23/11/17

Blind or partially sighted?
Is this leaflet hard to see or read?
Phone Lexon (UK) Limited,
Tel: 01527 505414 to obtain the leaflet
in a format suitable for you

Ref:0926/231117/1/F

(methylprednisolone acetate and lidocaine hydrochloride)

Patient Information Leaflet
Read all of this leaflet carefully before you start taking this medicine
because it contains important information for you.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This
includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:
1 What Depo-Medrone with Lidocaine is and what it is used for
2 What you need to know before you use Depo-Medrone with
Lidocaine
3 How to use Depo-Medrone with Lidocaine
4 Possible side effects
5 How to store Depo-Medrone with Lidocaine
6 Contents of the pack and other information

1

What Depo-Medrone with Lidocaine is and what it is used
for

Depo-Medrone with Lidocaine contains methylprednisolone acetate and
lidocaine hydrochloride.
Methylprednisolone belongs to a group of medicines called corticosteroids or
steroids. Corticosteroids are produced naturally in your body and are
important for many body functions. When injected into the body, such as in or
near a joint, corticosteroids help reduce symptoms caused by inflammatory
or rheumatic conditions.
This medicine also contains lidocaine which is a local anaesthetic. Lidocaine
helps to reduce any local pain caused by injecting this medicine.
This medicine will be injected by a doctor or nurse to help treat the
symptoms caused by the following conditions:
• Bursitis: inflammation in the fluid containing spaces around the shoulder,
knee and/or elbow joints. For this condition this medicine will be injected
directly into one or more of these spaces.
• Osteoarthritis and rheumatoid arthritis: inflammation located in between
the joints. For these conditions this medicine will be injected directly into
one or more joint spaces.
• Epicondylitis, tendonitis and tenosynovitis: Tennis elbow (epicondylitis),
inflammation in a tendon (tendonitis), or a tendon’s covering sheath
(tenosynovitis). For these conditions this medicine will be injected into the
tendon or its tendon sheath.
Your doctor may use this medicine to treat conditions other than those listed
above. You must talk to your doctor, if you do not feel better or if you feel
worse.

2

What you need to know before you use Depo-Medrone with
Lidocaine

Do not use Depo-Medrone with Lidocaine:
• If you think you have ever suffered an allergic reaction, or any other type
of reaction after being given Depo-Medrone with Lidocaine, or any other
medicine containing a corticosteroid or local anaesthetic or any of the other
ingredients of this medicine (listed in section 6). An allergic reaction may
cause a skin rash or reddening, swollen face or lips or shortness of breath.
• If you get a rash, or another symptom of an infection.
• If you have recently had, or are about to have any vaccination.
• In premature babies or neonates.
See your doctor immediately if any of the above applies to you.
Do not inject this medicine:
• into the Achilles tendon (which is located behind the ankle joint)
• directly into a vein (intravenous), the spinal cord (intrathecal), into the
nostrils (intranasal), in the eye (intraocular).

Warnings and precautions
Talk to your doctor or nurse before taking Depo-Medrone with Lidocaine if
you have any of the following conditions.
Your doctor may also have to monitor your treatment more closely, alter your
dose or give you another medicine.
• Acute adrenal insufficiency (when your body cannot produce enough
corticosteroid due to problems with your adrenal glands).
• Acute pancreatitis (inflammation of the pancreas).
• Chickenpox, measles, shingles or a herpes eye infection. If you think
you have been in contact with someone with chickenpox, measles or
shingles and you have not already had these illnesses, or if you are unsure
if you have had them.
• Severe depression or manic depression (bipolar disorder). This includes
having had depression before while taking steroid medicines like
Depo-Medrone with Lidocaine, or having a family history of these illnesses.
• Cushing’s disease (condition caused by an excess of cortisol hormone in
your body).
• Diabetes (or if there is a family history of diabetes).
• Epilepsy, fits or seizures.
• Glaucoma (increased pressure in the eye) or if there is a family history of
glaucoma.
• You have recently suffered a heart attack.
• Heart problems, including heart failure or infections.
• Hypertension (high blood pressure).
• Hypotension (low blood pressure).
• Hypothyroidism (an under-active thyroid).
• Joint infection – which is active and so requires treatment.
• Kidney or liver disease.
• Muscle problems (pain or weakness) have happened while taking steroid
medicines in the past.
• Myasthenia gravis (a condition causing tired and weak muscles).
• If you have recently had an operation.
• Osteoporosis (brittle bones).
• Pheochromocytoma (a rare tumour of adrenal gland tissue. The adrenal
glands are located above the kidneys).
• Skin abscess or other disorders of the skin.
• Stomach ulcer or other serious stomach or intestinal problems (ulcerative
colitis).
• Unusual stress.
• Thrombophlebitis - vein problems due to thrombosis (clots in the veins)
resulting in phlebitis (red, swollen and tender veins).
• Tuberculosis (TB) or if you have suffered tuberculosis in the past.
• Traumatic brain injury
You must tell your doctor before you take this medicine if you have any of
the conditions listed above.
Other medicines and Depo-Medrone with Lidocaine
Tell your doctor or pharmacist if you are taking, have recently taken or might
take any other medicines.
You should tell your doctor if you are taking any of the following medicines
which can affect the way Depo-Medrone with Lidocaine or the other medicine
works:
• Acetazolamide - used to treat glaucoma and epilepsy.
• Aminoglutethimide and cyclophosphamide– used for treating cancer.
• Antibacterials (such as isoniazid, erythromycin, clarithromycin and
troleandomycin).
• Anticoagulants - used to ‘thin’ the blood such as acenocoumarol,
phenindione and warfarin.
• Anticholinesterases - used to treat myasthenia gravis (a muscle
condition) such as distigmine and neostigmine.
• Antidiabetics – medicines used to treat high blood sugar.
• Antiemetics (such as aprepitant and fosaprepitant).
• Aspirin and non-steroidal anti-inflammatory medicines (also called
NSAIDs) such as ibuprofen used to treat mild to moderate pain.
• Barbiturates, carbamazepine, phenytoin and primidone – used to treat
epilepsy.
• Carbenoxolone - used for heartburn and acid indigestion.
Page 1

• Ciclosporin - used to treat conditions such as severe rheumatoid arthritis,










severe psoriasis or following an organ or bone marrow transplant.
Digoxin - used for heart failure and/or an irregular heart beat.
Diltiazem – used for heart problems or high blood pressure.
Ethinylestradiol and norethindrone – oral contraceptives.
Indinavir and ritonavir – used to treat HIV infections.
Ketoconazole or itraconazole – used to treat fungal infections.
Pancuronium and vecuronium – or other medicines called
neuromuscular blocking agents which are used in some surgical
procedures.
Potassium depleting agents – such as diuretics (sometimes called water
tablets), amphotericin B, xanthenes or beta2 agonists (e.g. medicines
used to treat asthma).
Rifampicin and rifabutin – antibiotics used to treat tuberculosis (TB)
Tacrolimus – used following an organ transplant to prevent rejection of the
organ.
Vaccines - tell your doctor or nurse if you have recently had, or are about
to have any vaccination. You must not have ‘live’ vaccines while using this
medicine. Other vaccines may be less effective.

3

How to use Depo-Medrone with Lidocaine

Steroid Cards
Remember to always carry a Steroid Treatment Card. Make sure your
doctor or pharmacist has filled out the details of your medicine,
including the dose and how long you will require steroid treatment.
You should show your steroid card to anyone who gives you treatment (such
as a doctor, nurse or dentist) while you are taking this medicine, and for 3
months after your last injection.
If you are admitted to hospital for any reason always tell your doctor or nurse
that you are taking this medicine. You can also wear a medic-alert bracelet or
pendant to let medical staff know that you are taking a steroid if you have an
accident or become unconscious.

If you are taking long term medication(s)

Dosage information
Your doctor will decide on the site of injection, how much of the medicine and
how many injections you will receive depending on the condition being
treated and its severity. Your doctor will inject you with the lowest dose for
the shortest possible time to get effective relief of your symptoms.

If you are being treated for diabetes, high blood pressure or water retention
(oedema) tell your doctor as he/she may need to adjust the dose of the
medicines used to treat these conditions.

Adults
Your doctor/nurse will tell you how many injections you will require for the
condition you are being treated for, and when you will get them.

Before you have any operation, tell your doctor, dentist or anaesthetist that
you are taking this medicine.

Joints - the normal dose for the injections into joint will depend on the size of
the joint. Large joints (e.g. knee, ankle and shoulder) may require 20 - 80 mg
(0.5 – 2 ml), medium sized joints (e.g. elbow or wrist) 10 - 40 mg (0.25 – 1
ml) and small joints (e.g. finger or toe joints) may require a 4 - 10 mg (0.1 0.25 ml) dose.
Joint injections may be given weekly over a period of several weeks,
depending on how quickly you respond to treatment.



If you require a test to be carried out by your doctor or in hospital it is
important that you tell the doctor or nurse that you are taking Depo-Medrone
with Lidocaine. This medicine can affect the results of some tests.
Depo-Medrone with Lidocaine with drink
Do not drink grapefruit juice while taking this medicine.
Pregnancy and breast-feeding
If you are pregnant, think you may be pregnant or are planning to have a
baby, ask your doctor or pharmacist for advice before taking this medicine,
as this medicine could slow the baby’s growth.

Bursitis, epicondylitis (tennis elbow) and tendonitis – the usual dose is
between 4-30 mg (0.1 - 0.75 ml). In most cases repeat injections will not be
needed for bursitis and epicondylitis. Repeat injections may be necessary to
treat long standing tendonitis.

Cataracts have been observed in infants born to mothers treated with
long-term corticosteroids during pregnancy.

Elderly
Treatment will normally be the same as for younger adults. However your
doctor may want to see you more regularly to check how you are getting on
with this medicine.

If you are breast-feeding, ask your doctor or pharmacist for advice before
taking this medicine, as small amounts of corticosteroid medicines may get
into breast milk.

Children
Corticosteroids can affect growth in children so your doctor will prescribe the
lowest dose that will be effective for your child.

If you continue breast-feeding while you are having treatment, your baby will
need extra checks to make sure he or she is not being affected by your
medicine.

If you are given more Depo-Medrone with Lidocaine than you should
If you think you have been given too many injections of this medicine please
speak to your doctor immediately.

Driving and using machines
Undesirable effects, such as dizziness, vertigo, visual disturbances and
fatigue are possible after treatment with corticosteroids. If you are affected do
not drive or operate machinery.

Stopping/reducing the dose of your Depo-Medrone with Lidocaine

Depo-Medrone with Lidocaine contains benzyl alcohol and sodium.
This medicine contains benzyl alcohol. The amount of benzoyl alcohol per ml
is 8.7 mg. It may cause toxic and allergic reactions. This medicine should not
be used in pre-term or full-term neonates unless strictly necessary because
of the risk of severe toxicity including abnormal respiration (“gasping
syndrome”).
Talk to your doctor or pharmacist if you have liver or kidney problems or if
you are pregnant or breast-feeding as high volumes may lead to toxicity
(metabolic perturbation).
This medicinal product contains less than 1 mmol sodium (23 mg) per vial,
i.e. essentially ‘sodium-free’.

Page 2

Your doctor will decide when it is time to stop your treatment.
You will need to come off this treatment slowly if you:
• have been given more than 6 mg (0.15 ml) Depo-Medrone with Lidocaine
for more than 3 weeks;
• have been given high doses of Depo-Medrone with Lidocaine, over 32 mg
(0.8 ml) daily, even if it was only for 3 weeks or less;
• have already had a course of corticosteroid tablets or injections in the last
year;
• already have problems with your adrenal glands (adrenocortical
insufficiency) before you started this treatment.
You will need to come off this medicine slowly to avoid withdrawal
symptoms. These symptoms may include itchy skin, fever, muscle and joint
pains, runny nose, sticky eyes, sweating and weight loss.
If your symptoms seem to return or get worse as your dose of this medicine
is reduced tell your doctor immediately.
Mental problems while taking Depo-Medrone with Lidocaine
Mental health problems can happen while taking steroids like Depo-Medrone
with Lidocaine (see also section 4, Possible Side Effects).
• These illnesses can be serious.
• Usually they start within a few days or weeks of starting the medicine.

• They are more likely to happen at high doses.
• Most of these problems go away if the dose is lowered or the medicine is
stopped. However if the problems do happen they might need treatment.

Talk to a doctor if you (or someone using this medicine) show any signs of
mental problems. This is particularly important if you are depressed, or might
be thinking about suicide. In a few cases mental problems have happened
when doses are being lowered or stopped.
If you have any further questions on the use of this medicine, ask your
doctor,pharmacist or nurse.

4

Possible side effects

Like all medicines, this medicine can cause side effects, although not
everybody gets them. Your doctor will have given you this medicine for a
condition which if not treated properly could become serious.
In certain medical conditions medicines like Depo-Medrone with
Lidocaine (steroids) should not be stopped abruptly. If you suffer from
any of the following symptoms seek IMMEDIATE medical attention. Your
doctor will then decide whether you should continue taking your
medicine:
• Allergic reactions, such as skin rash, swelling of the face or wheezing and
difficulty breathing. This type of side effect is rare, but can be serious.
• Pancreatitis, stomach pain which may spread through to your back,
possibly accompanied by vomiting, shock and loss of consciousness.
• Burst or bleeding ulcers, symptoms of which are severe stomach pain
which may go through to the back and could be associated with bleeding
from the back passage, black or bloodstained stools and/or vomiting blood.
• Infections. This medicine can hide or change the signs and symptoms of
some infections, or reduce your resistance to the infection, so that they are
hard to diagnose at an early stage. Symptoms might include a raised
temperature and feeling unwell. Symptoms of a flare up of a previous TB
infection could be coughing blood or pain in the chest. This medicine may
also make you more likely to develop a severe infection.
• Peritonitis, an inflammation (irritation) of the peritoneum, the thin tissue
that lines the inner wall of the abdomen and covers most of the abdominal
organs. Symptoms are, the stomach (abdomen) being very painful or
tender, the pain may become worse when the stomach is touched or when
you move.
• Pulmonary embolus (blood clot in the lung) symptoms include sudden
sharp chest pain, breathlessness and coughing up blood.
• Raised pressure within the skull of children (pseudotumour cerebri)
symptoms of which are headaches with vomiting, lack of energy and
drowsiness. This side effect usually occurs after treatment is stopped.
• Thrombophlebitis (blood clots or thrombosis in a leg vein), symptoms of
which include painful swollen, red and tender veins.
If you experience any of the following side effects, or notice any other
unusual effects not mentioned in this leaflet, tell your doctor
immediately.
The side effects may occur with certain frequencies, which are defined as
follows:
• common: may affect up to 1 in 10 people.
• not known: frequency cannot be estimated from the available data.
Blood, heart and circulation
common
• High blood pressure, symptoms of which are headaches, or generally
feeling unwell.
• Slowing heart rate (bradycardia).
not known
• Problems with the pumping of your heart (heart failure) symptoms of which
are swollen ankles, difficulty in breathing and palpitations (awareness of
heart beat) or irregular beating of the heart, irregular or very fast or slow
pulse, cardiac arrest.
• Low blood pressure, symptoms may include dizziness, fainting,
lightheadedness, blurred vision, a rapid or irregular heartbeat (palpitations).
• Increase of white blood cells (leukocytosis).
• Increased clotting of the blood.

Body water and salts
common
• Swelling and high blood pressure, caused by increased levels of water and
salt content.
• Cramps and spasms, due to the loss of potassium from your body. In rare
cases this can lead to congestive heart failure (when the heart cannot
pump properly).
Digestive system
common
• Ulcers.
• Vomiting (being sick).
not known
• Nausea (feeling sick).
• Thrush in the gullet (discomfort on swallowing).
• Indigestion.
• Diarrhoea.
• Bloated stomach.
• Abdominal pain.
• Hiccups.
Ears
not known
• A feeling of dizziness or spinning (vertigo).
Eyes
common
• Glaucoma (raised pressure within the eye, causing pain in the eyes and
headaches).
• Cataracts (indicated by failing eyesight).
not known
• Swollen optic nerve (causing a condition called papilloedema, and which
may cause sight disturbance).
• Increased intra-ocular pressure, with possible damage to the optic nerve
(indicated by failing eyesight).
• Thinning of the clear part at the front of the eye (cornea) or of the white
part of the eye (sclera).
• Worsening of viral or fungal eye infections.
• Protruding of the eyeballs (exophthalmos).
• Blindness, blurred or double vision.
• Blurred or distorted vision (due to disease of the retina and choroid
membrane).
Hepatobiliary disorders
• Methylprednisolone can damage your liver, hepatitis and increase of liver
enzymes have been reported.
General disorders
common
• Poor wound healing.
• Irritability.
not known
• Feeling tired or unwell.
• Skin reactions at the site of injection.
Hormones and metabolic system
common
• Slowing of normal growth in infants, children and adolescents which may
be permanent.
• Round or moon-shaped face (Cushingoid facies).
• Diabetes or worsening of existing diabetes.
not known
• Irregular or no periods in women.
• Increased appetite and weight gain.
• Abnormal localized or tumour-like accumulations of fat in the tissues.
• Prolonged therapy can lead to lower levels of some hormones which in turn
can cause low blood pressure and dizziness. This effect may persist for
months.
• The amount of certain chemicals (enzymes) called alanine transaminase,
aspartate transaminase and alkaline phosphatase that help the body digest
drugs and other substances in your body may be raised after treatment
with a corticosteroid. The change is usually small and the enzyme levels
return to normal after your medicine has cleared naturally from your
system. You will not notice any symptoms if this happens, but it will show
up if you have a blood test.
Ref:0926/231117/1/B

Page 3

Immune system
common
• Increased susceptibility to infections which can hide or change normal
reactions to skin tests, such as that for tuberculosis.
Metabolism and nutrition disorders
• Accumulation of fat tissue on localized parts of the body.
Muscles, bones and joints
common
• Muscle weakness.
• Muscle twitching.
• Brittle bones (bones that break easily).
not known
• Broken bones or fractures.
• Muscle wasting.
• Breakdown of bone due to poor circulation of blood, this causes pain in the
hip.
• Joint pain.
• Torn muscle tendons causing pain and/or swelling.
• Muscle cramps or spasms.
• Swollen or painful joints due to infection.
Nerves and mood issues
common
Steroids including methylprednisolone can cause serious mental health
problems. These are common in both adults and children. They can affect
about 5 in every 100 people taking medicines like methylprednisolone.
• Feeling depressed, including thinking about suicide.
• Feeling high (mania) or moods that go up and down.
• Feeling anxious, having problems sleeping, difficulty in thinking or being
confused and losing your memory.
• Feeling, seeing or hearing things which do not exist. Having strange and
frightening thoughts, changing how you act or having feelings of being
alone.
• Other nervous system side effects may include convulsions (seizures),
amnesia (loss of memory), cognitive disorder (mental changes), tremor,
dizziness and headache, drowsiness, difficulty breathing, sensation of cold,
heat or numbness, tinnitus or unconsciousness.
• Back pain or weakness (due to Epidural Lipomatosis, a rare disorder in
which an abnormal amount of fat is deposited on or outside the lining of
the spine).
Skin
common
• Acne.
• Bruising.
not known
• Abscess, especially near injection sites.
• Thinning of skin, stretch marks.
• Small purple/red patches on the skin.
• Pale or darker patches on your skin, or raised patches which are an
unusual colour.
• Increased hair on the body and face (hirsutism).
• Rash, skin redness, itching, hives.
• Increased sweating.
If you experience any of the side effects listed above tell your doctor
immediately.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes
any possible side effects not listed on this leaflet. You can also report side
effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
or search for MHRA Yellow Card in the Google Play or Apple App Store. By
reporting side effects, you can help provide more information on the
safety of this medicine.

5

Expiry Date
Do not use this medicine after the expiry date shown on the carton label or
vial label. Each vial is for single use only. After use your doctor should take
the container and syringe away. If anything is left over, take it to your
pharmacist (chemist) for safe disposal. If your medicine become
discoloured or shows any other signs of deterioration, consult your
pharmacist (chemist) who will tell you what to do.
Storing your Medication
• KEEP OUT OF THE SIGHT AND REACH OF CHILDREN.
• Store below 25°C.
• Protect from freezing.
Important
Remember this medicine is for you. Only a doctor can prescribe it. Never
give your medicine to anyone, it may harm them, even if their symptoms are
the same as yours. This leaflet does not tell you everything about this
medicine, If you have any questions or are not sure about anything then ask
your doctor or pharmacist

6

Depo-Medrol® with Lidocaine

How to store Depo-Medrol with Lidocaine

Contents of the pack and other information

What Depo-Medrol with Lidocaine contains
Each 1ml vial contains 40mg methylprednisolone acetate and 10mg
Lidocaine hydrochloride. Each vial also contains sodium chloride,
myristyl-gamma-picolinium chloride, benzyl alcohol as 8.7mg per ml,
macrogol, sodium hydroxide, hydrochloric acid and water for injections.
What a Depo-Medrol with Lidocaine looks like
Depo-Medrol with Lidocaine is a white, sterile aqueous suspension for injection. Depo-Medrol with Lidocaine is available in cartons of 1 x 1ml vial or 3 x
1ml vial’s.
Manufacturer and Licence Holder
Depo-Medrol is manufactured by Pfizer Manufacturing Belgium NV., Rijksweg
12, B-2870, Puurs Belgium and is procured from within the EU and repackaged by the Product Licence Holder: Lexon (UK) Limited, Unit 18, Oxleasow
Road, East Moons Moat, Redditch, Worcestershire, B98 0RE.

POM

Depo-Medrol with Lidocaine PL:15184/0926

Depo-Medrol witth lidocaine is a registered trademark of Pharmacia & Upjohn
Limited.
Leaflet revision date: 23/11/17

Blind or partially sighted?
Is this leaflet hard to see or read?
Phone Lexon (UK) Limited,
Tel: 01527 505414 to obtain the leaflet
in a format suitable for you

Ref:0926/231117/2/F

(methylprednisolone acetate and lidocaine hydrochloride)

Patient Information Leaflet
Read all of this leaflet carefully before you start taking this medicine
because it contains important information for you.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This
includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:
1 What Depo-Medrol with Lidocaine is and what it is used for
2 What you need to know before you use Depo-Medrol with
Lidocaine
3 How to use Depo-Medrol with Lidocaine
4 Possible side effects
5 How to store Depo-Medrol with Lidocaine
6 Contents of the pack and other information

1

What Depo-Medrol with Lidocaine is and what it is used
for

Depo-Medrol with Lidocaine contains methylprednisolone acetate and
lidocaine hydrochloride.
Methylprednisolone belongs to a group of medicines called corticosteroids or
steroids. Corticosteroids are produced naturally in your body and are
important for many body functions. When injected into the body, such as in or
near a joint, corticosteroids help reduce symptoms caused by inflammatory
or rheumatic conditions.
This medicine also contains lidocaine which is a local anaesthetic. Lidocaine
helps to reduce any local pain caused by injecting this medicine.
This medicine will be injected by a doctor or nurse to help treat the
symptoms caused by the following conditions:
• Bursitis: inflammation in the fluid containing spaces around the shoulder,
knee and/or elbow joints. For this condition this medicine will be injected
directly into one or more of these spaces.
• Osteoarthritis and rheumatoid arthritis: inflammation located in between
the joints. For these conditions this medicine will be injected directly into
one or more joint spaces.
• Epicondylitis, tendonitis and tenosynovitis: Tennis elbow (epicondylitis),
inflammation in a tendon (tendonitis), or a tendon’s covering sheath
(tenosynovitis). For these conditions this medicine will be injected into the
tendon or its tendon sheath.
Your doctor may use this medicine to treat conditions other than those listed
above. You must talk to your doctor, if you do not feel better or if you feel
worse.

2

What you need to know before you use Depo-Medrol
with Lidocaine

Do not use Depo-Medrol with Lidocaine:
• If you think you have ever suffered an allergic reaction, or any other type
of reaction after being given Depo-Medrol with Lidocaine, or any other
medicine containing a corticosteroid or local anaesthetic or any of the other
ingredients of this medicine (listed in section 6). An allergic reaction may
cause a skin rash or reddening, swollen face or lips or shortness of breath.
• If you get a rash, or another symptom of an infection.
• If you have recently had, or are about to have any vaccination.
• In premature babies or neonates.
See your doctor immediately if any of the above applies to you.
Do not inject this medicine:
• into the Achilles tendon (which is located behind the ankle joint)
• directly into a vein (intravenous), the spinal cord (intrathecal), into the
nostrils (intranasal), in the eye (intraocular).

Warnings and precautions
Talk to your doctor or nurse before taking Depo-Medrol with Lidocaine if you
have any of the following conditions.
Your doctor may also have to monitor your treatment more closely, alter your
dose or give you another medicine.
• Acute adrenal insufficiency (when your body cannot produce enough
corticosteroid due to problems with your adrenal glands).
• Acute pancreatitis (inflammation of the pancreas).
• Chickenpox, measles, shingles or a herpes eye infection. If you think
you have been in contact with someone with chickenpox, measles or
shingles and you have not already had these illnesses, or if you are unsure
if you have had them.
• Severe depression or manic depression (bipolar disorder). This includes
having had depression before while taking steroid medicines like
Depo-Medrol with Lidocaine, or having a family history of these illnesses.
• Cushing’s disease (condition caused by an excess of cortisol hormone in
your body).
• Diabetes (or if there is a family history of diabetes).
• Epilepsy, fits or seizures.
• Glaucoma (increased pressure in the eye) or if there is a family history of
glaucoma.
• You have recently suffered a heart attack.
• Heart problems, including heart failure or infections.
• Hypertension (high blood pressure).
• Hypotension (low blood pressure).
• Hypothyroidism (an under-active thyroid).
• Joint infection – which is active and so requires treatment.
• Kidney or liver disease.
• Muscle problems (pain or weakness) have happened while taking steroid
medicines in the past.
• Myasthenia gravis (a condition causing tired and weak muscles).
• If you have recently had an operation.
• Osteoporosis (brittle bones).
• Pheochromocytoma (a rare tumour of adrenal gland tissue. The adrenal
glands are located above the kidneys).
• Skin abscess or other disorders of the skin.
• Stomach ulcer or other serious stomach or intestinal problems (ulcerative
colitis).
• Unusual stress.
• Thrombophlebitis - vein problems due to thrombosis (clots in the veins)
resulting in phlebitis (red, swollen and tender veins).
• Tuberculosis (TB) or if you have suffered tuberculosis in the past.
• Traumatic brain injury
You must tell your doctor before you take this medicine if you have any of
the conditions listed above.
Other medicines and Depo-Medrol with Lidocaine
Tell your doctor or pharmacist if you are taking, have recently taken or might
take any other medicines.
You should tell your doctor if you are taking any of the following medicines
which can affect the way Depo-Medrol with Lidocaine or the other medicine
works:
• Acetazolamide - used to treat glaucoma and epilepsy.
• Aminoglutethimide and cyclophosphamide– used for treating cancer.
• Antibacterials (such as isoniazid, erythromycin, clarithromycin and
troleandomycin).
• Anticoagulants - used to ‘thin’ the blood such as acenocoumarol,
phenindione and warfarin.
• Anticholinesterases - used to treat myasthenia gravis (a muscle
condition) such as distigmine and neostigmine.
• Antidiabetics – medicines used to treat high blood sugar.
• Antiemetics (such as aprepitant and fosaprepitant).
• Aspirin and non-steroidal anti-inflammatory medicines (also called
NSAIDs) such as ibuprofen used to treat mild to moderate pain.
• Barbiturates, carbamazepine, phenytoin and primidone – used to treat
epilepsy.
• Carbenoxolone - used for heartburn and acid indigestion.
Page 1

• Ciclosporin - used to treat conditions such as severe rheumatoid arthritis,










severe psoriasis or following an organ or bone marrow transplant.
Digoxin - used for heart failure and/or an irregular heart beat.
Diltiazem – used for heart problems or high blood pressure.
Ethinylestradiol and norethindrone – oral contraceptives.
Indinavir and ritonavir – used to treat HIV infections.
Ketoconazole or itraconazole – used to treat fungal infections.
Pancuronium and vecuronium – or other medicines called
neuromuscular blocking agents which are used in some surgical
procedures.
Potassium depleting agents – such as diuretics (sometimes called water
tablets), amphotericin B, xanthenes or beta2 agonists (e.g. medicines
used to treat asthma).
Rifampicin and rifabutin – antibiotics used to treat tuberculosis (TB)
Tacrolimus – used following an organ transplant to prevent rejection of the
organ.
Vaccines - tell your doctor or nurse if you have recently had, or are about
to have any vaccination. You must not have ‘live’ vaccines while using this
medicine. Other vaccines may be less effective.

3

How to use Depo-Medrol with Lidocaine

Steroid Cards
Remember to always carry a Steroid Treatment Card. Make sure your
doctor or pharmacist has filled out the details of your medicine,
including the dose and how long you will require steroid treatment.
You should show your steroid card to anyone who gives you treatment (such
as a doctor, nurse or dentist) while you are taking this medicine, and for 3
months after your last injection.
If you are admitted to hospital for any reason always tell your doctor or nurse
that you are taking this medicine. You can also wear a medic-alert bracelet or
pendant to let medical staff know that you are taking a steroid if you have an
accident or become unconscious.

If you are taking long term medication(s)

Dosage information
Your doctor will decide on the site of injection, how much of the medicine and
how many injections you will receive depending on the condition being
treated and its severity. Your doctor will inject you with the lowest dose for
the shortest possible time to get effective relief of your symptoms.

If you are being treated for diabetes, high blood pressure or water retention
(oedema) tell your doctor as he/she may need to adjust the dose of the medicines used to treat these conditions.

Adults
Your doctor/nurse will tell you how many injections you will require for the
condition you are being treated for, and when you will get them.

Before you have any operation, tell your doctor, dentist or anaesthetist that
you are taking this medicine.

Joints - the normal dose for the injections into joint will depend on the size of
the joint. Large joints (e.g. knee, ankle and shoulder) may require 20 - 80 mg
(0.5 – 2 ml), medium sized joints (e.g. elbow or wrist) 10 - 40 mg (0.25 – 1
ml) and small joints (e.g. finger or toe joints) may require a 4 - 10 mg (0.1 0.25 ml) dose.
Joint injections may be given weekly over a period of several weeks,
depending on how quickly you respond to treatment.



If you require a test to be carried out by your doctor or in hospital it is
important that you tell the doctor or nurse that you are taking Depo-Medrol
with Lidocaine. This medicine can affect the results of some tests.
Depo-Medrol with Lidocaine with drink
Do not drink grapefruit juice while taking this medicine.
Pregnancy and breast-feeding
If you are pregnant, think you may be pregnant or are planning to have a
baby, ask your doctor or pharmacist for advice before taking this medicine,
as this medicine could slow the baby’s growth.

Bursitis, epicondylitis (tennis elbow) and tendonitis – the usual dose is
between 4-30 mg (0.1 - 0.75 ml). In most cases repeat injections will not be
needed for bursitis and epicondylitis. Repeat injections may be necessary to
treat long standing tendonitis.

Cataracts have been observed in infants born to mothers treated with
long-term corticosteroids during pregnancy.

Elderly
Treatment will normally be the same as for younger adults. However your
doctor may want to see you more regularly to check how you are getting on
with this medicine.

If you are breast-feeding, ask your doctor or pharmacist for advice before
taking this medicine, as small amounts of corticosteroid medicines may get
into breast milk.

Children
Corticosteroids can affect growth in children so your doctor will prescribe the
lowest dose that will be effective for your child.

If you continue breast-feeding while you are having treatment, your baby will
need extra checks to make sure he or she is not being affected by your
medicine.

If you are given more Depo-Medrol with Lidocaine than you should
If you think you have been given too many injections of this medicine please
speak to your doctor immediately.

Driving and using machines
Undesirable effects, such as dizziness, vertigo, visual disturbances and
fatigue are possible after treatment with corticosteroids. If you are affected do
not drive or operate machinery.

Stopping/reducing the dose of your Depo-Medrol with Lidocaine

Depo-Medrol with Lidocaine contains benzyl alcohol and sodium.
This medicine contains benzyl alcohol. The amount of benzoyl alcohol per ml
is 8.7 mg. It may cause toxic and allergic reactions. This medicine should not
be used in pre-term or full-term neonates unless strictly necessary because
of the risk of severe toxicity including abnormal respiration (“gasping
syndrome”).
Talk to your doctor or pharmacist if you have liver or kidney problems or if
you are pregnant or breast-feeding as high volumes may lead to toxicity
(metabolic perturbation).
This medicinal product contains less than 1 mmol sodium (23 mg) per vial,
i.e. essentially ‘sodium-free’.

Page 2

Your doctor will decide when it is time to stop your treatment.
You will need to come off this treatment slowly if you:
• have been given more than 6 mg (0.15 ml) Depo-Medrol with Lidocaine
for more than 3 weeks;
• have been given high doses of Depo-Medrol with Lidocaine, over 32 mg
(0.8 ml) daily, even if it was only for 3 weeks or less;
• have already had a course of corticosteroid tablets or injections in the last
year;
• already have problems with your adrenal glands (adrenocortical
insufficiency) before you started this treatment.
You will need to come off this medicine slowly to avoid withdrawal
symptoms. These symptoms may include itchy skin, fever, muscle and joint
pains, runny nose, sticky eyes, sweating and weight loss.
If your symptoms seem to return or get worse as your dose of this medicine
is reduced tell your doctor immediately.
Mental problems while taking Depo-Medrol with Lidocaine
Mental health problems can happen while taking steroids like Depo-Medrol
with Lidocaine (see also section 4, Possible Side Effects).
• These illnesses can be serious.
• Usually they start within a few days or weeks of starting the medicine.

• They are more likely to happen at high doses.
• Most of these problems go away if the dose is lowered or the medicine is
stopped. However if the problems do happen they might need treatment.

Talk to a doctor if you (or someone using this medicine) show any signs of
mental problems. This is particularly important if you are depressed, or might
be thinking about suicide. In a few cases mental problems have happened
when doses are being lowered or stopped.
If you have any further questions on the use of this medicine, ask your
doctor,pharmacist or nurse.

4

Possible side effects

Like all medicines, this medicine can cause side effects, although not
everybody gets them. Your doctor will have given you this medicine for a
condition which if not treated properly could become serious.
In certain medical conditions medicines like Depo-Medrol with
Lidocaine (steroids) should not be stopped abruptly. If you suffer from
any of the following symptoms seek IMMEDIATE medical attention. Your
doctor will then decide whether you should continue taking your
medicine:
• Allergic reactions, such as skin rash, swelling of the face or wheezing and
difficulty breathing. This type of side effect is rare, but can be serious.
• Pancreatitis, stomach pain which may spread through to your back,
possibly accompanied by vomiting, shock and loss of consciousness.
• Burst or bleeding ulcers, symptoms of which are severe stomach pain
which may go through to the back and could be associated with bleeding
from the back passage, black or bloodstained stools and/or vomiting blood.
• Infections. This medicine can hide or change the signs and symptoms of
some infections, or reduce your resistance to the infection, so that they are
hard to diagnose at an early stage. Symptoms might include a raised
temperature and feeling unwell. Symptoms of a flare up of a previous TB
infection could be coughing blood or pain in the chest. This medicine may
also make you more likely to develop a severe infection.
• Peritonitis, an inflammation (irritation) of the peritoneum, the thin tissue
that lines the inner wall of the abdomen and covers most of the abdominal
organs. Symptoms are, the stomach (abdomen) being very painful or
tender, the pain may become worse when the stomach is touched or when
you move.
• Pulmonary embolus (blood clot in the lung) symptoms include sudden
sharp chest pain, breathlessness and coughing up blood.
• Raised pressure within the skull of children (pseudotumour cerebri)
symptoms of which are headaches with vomiting, lack of energy and
drowsiness. This side effect usually occurs after treatment is stopped.
• Thrombophlebitis (blood clots or thrombosis in a leg vein), symptoms of
which include painful swollen, red and tender veins.
If you experience any of the following side effects, or notice any other
unusual effects not mentioned in this leaflet, tell your doctor
immediately.
The side effects may occur with certain frequencies, which are defined as
follows:
• common: may affect up to 1 in 10 people.
• not known: frequency cannot be estimated from the available data.
Blood, heart and circulation
common
• High blood pressure, symptoms of which are headaches, or generally
feeling unwell.
• Slowing heart rate (bradycardia).
not known
• Problems with the pumping of your heart (heart failure) symptoms of which
are swollen ankles, difficulty in breathing and palpitations (awareness of
heart beat) or irregular beating of the heart, irregular or very fast or slow
pulse, cardiac arrest.
• Low blood pressure, symptoms may include dizziness, fainting,
lightheadedness, blurred vision, a rapid or irregular heartbeat (palpitations).
• Increase of white blood cells (leukocytosis).
• Increased clotting of the blood.

Body water and salts
common
• Swelling and high blood pressure, caused by increased levels of water and
salt content.
• Cramps and spasms, due to the loss of potassium from your body. In rare
cases this can lead to congestive heart failure (when the heart cannot
pump properly).
Digestive system
common
• Ulcers.
• Vomiting (being sick).
not known
• Nausea (feeling sick).
• Thrush in the gullet (discomfort on swallowing).
• Indigestion.
• Diarrhoea.
• Bloated stomach.
• Abdominal pain.
• Hiccups.
Ears
not known
• A feeling of dizziness or spinning (vertigo).
Eyes
common
• Glaucoma (raised pressure within the eye, causing pain in the eyes and
headaches).
• Cataracts (indicated by failing eyesight).
not known
• Swollen optic nerve (causing a condition called papilloedema, and which
may cause sight disturbance).
• Increased intra-ocular pressure, with possible damage to the optic nerve
(indicated by failing eyesight).
• Thinning of the clear part at the front of the eye (cornea) or of the white
part of the eye (sclera).
• Worsening of viral or fungal eye infections.
• Protruding of the eyeballs (exophthalmos).
• Blindness, blurred or double vision.
• Blurred or distorted vision (due to disease of the retina and choroid
membrane).
Hepatobiliary disorders
• Methylprednisolone can damage your liver, hepatitis and increase of liver
enzymes have been reported.
General disorders
common
• Poor wound healing.
• Irritability.
not known
• Feeling tired or unwell.
• Skin reactions at the site of injection.
Hormones and metabolic system
common
• Slowing of normal growth in infants, children and adolescents which may
be permanent.
• Round or moon-shaped face (Cushingoid facies).
• Diabetes or worsening of existing diabetes.
not known
• Irregular or no periods in women.
• Increased appetite and weight gain.
• Abnormal localized or tumour-like accumulations of fat in the tissues.
• Prolonged therapy can lead to lower levels of some hormones which in turn
can cause low blood pressure and dizziness. This effect may persist for
months.
• The amount of certain chemicals (enzymes) called alanine transaminase,
aspartate transaminase and alkaline phosphatase that help the body digest
drugs and other substances in your body may be raised after treatment
with a corticosteroid. The change is usually small and the enzyme levels
return to normal after your medicine has cleared naturally from your
system. You will not notice any symptoms if this happens, but it will show
up if you have a blood test.
Ref:0926/231117/1/B

Page 3

Distribution:
Methylprednisolone:
Methylprednisolone is widely distributed into the tissues, crosses the blood-brain
barrier, and is secreted in breast milk. Its apparent volume of distribution is
approximately 1.4 L/kg. The plasma protein binding of methylprednisolone in
humans is approximately 77%.
Lidocaine:
The plasma protein binding of lidocaine is concentration-dependent, and
binding decreases as concentration increases. At concentrations of 1 to 5 µg/mL,
60%-80% lidocaine is protein bound. Binding is also dependent on the plasma
concentration of the α1-acid glycoprotein.
Lidocaine has a volume of distribution at steady state of 91 L.
Lidocaine readily crosses the placenta, and equilibrium of unbound drug
concentration is rapidly reached. The degree of plasma protein binding in the
foetus is less than in the mother, which results in lower total plasma
concentrations in the foetus.
Metabolism:
Methylprednisolone:
In humans, methylprednisolone is metabolized in the liver to inactive metabolites;
the major ones are 20α-hydroxymethylprednisolone and
20β-hydroxymethylprednisolone. Metabolism in the liver occurs primarily via the
CYP3A4. (For a list of drug interactions based on CYP3A4-mediated
metabolism, see section 4.5.)
Methylprednisolone, like many CYP3A4 substrates, may also be a substrate for
the ATP-binding cassette (ABC) transport protein p-glycoprotein, influencing
tissue distribution and interactions with other medicines modulated by P-gp.
Lidocaine:
Lidocaine is mainly metabolized by the liver. The main metabolites of lidocaine
are monoethylglycine xylidide, glycinexylidide, 2,6-dimethylaniline, and
4-hydroxy-2,6-dimethylaniline. The lidocaine N-dealkylation to monoethylglycine
xylidide is considered to be mediated by both CYP1A2 and CYP3A4. The
metabolite 2,6-dimethylaniline is converted to 4-hydroxy-2,6-dimethylaniline by
CYP2A6 and CYP2E1.
Elimination:
Methylprednisolone:
The mean elimination half-life for total methylprednisolone is in the range of 1.8
to 5.2 hours. Total clearance is approximately 5 to 6 mL/min/kg.
Lidocaine:
The clearance of lidocaine in plasma following intravenous bolus administration
is 9 to 10 mL/min/kg.
The elimination half life of lidocaine following intravenous bolus injection is
typically 1.5 to 2 hours.
The pharmacological actions of monoethylglycine xylidide and glycinexylidide are
similar to but less potent than those of lidocaine. Monoethylglycine xylidide has a
half life of approximately 2.3 hours and glycinexylidide has a half life of about 10
hours and may accumulate after long-term administration.
Only 3% of lidocaine is excreted unchanged by the kidneys. About 73% of
lidocaine appears in the urine as 4-hydroxy-2,6-dimethylaniline metabolite.
Special Population
Methylprednisolone:
No pharmacokinetic studies have been performed for methylprednisolone in
special populations.
Special Population
Lidocaine:
Hepatic impairment
Following intravenous administration, the half life of lidocaine has approximately
3-fold increase in patients with liver impairment. Pharmacokinetic data of
lidocaine after intra-articular, intra-bursa and intra-cyst administrations for local
effect are not available in hepatic impairment.
Renal impairment
Mild to moderate renal impairment (CLcr 30-60 mL/min) does not affect lidocaine
pharmacokinetics but may increase the accumulation of glycinexylidide
metabolite following intravenous administration. However, lidocaine clearance
decreases about half and its half life is approximately doubled with increased
accumulation of glycinexylidide metabolite in patients with severe renal
impairment (Clcr <30 mL/min).
The pharmacokinetics of lidocaine and its main metabolite of monoethylglycine
xylidide are not altered significantly in haemodialysis patients who receive an
intravenous dose of lidocaine.
Pharmacokinetic data of lidocaine after intra-articular, intra-bursa and intra-cyst
administrations for local effect are not available in renal impairment.
No dosing adjustments are necessary in renal failure. Methylprednisolone is
haemodialysable.
5.3 Preclinical safety data
Methylprednisolone
Based on conventional studies of safety pharmacology and repeated dose
toxicity, no unexpected hazards were identified. The toxicities seen in the
repeated-dose studies were those expected to occur with continued exposure to
exogenous adrenocortical steroids.
Mutagenic potential:
There was no evidence of a potential for genetic and chromosome mutations
when tested in limited studies performed in bacteria and mammalian cells.
Carcinogenic potential:
Long-term studies in animals have not been performed to evaluate carcinogenic
potential, as the drug is indicated for short-term treatment only. There were no
signs indicative of carcinogenic activity in studies conducted to date.
Reproductive toxicity:
Reproductive fertility studies in animals have not been performed to evaluate
specifically the potential of impairment of fertility. There is no evidence that
corticosteroids impair fertility.
An increased frequency of cleft palate was observed among the offspring of mice
treated during pregnancy with methylprednisolone in doses similar to those
typically used for oral therapy in humans.
An increased frequency of cardiovascular defects and decreased body weight
were observed among the offspring of pregnant rats treated with
methylprednisolone in a dose that was similar to that used for oral therapy in
humans but was toxic to the mothers. In contrast, no teratogenic effect was
noted in rats with doses <1-18 times
those typically used for oral therapy in humans in another study. High
frequencies of foetal death and a variety of central nervous system and skeletal
anomalies were reported in the offspring of pregnant rabbits treated with
methylprednisolone in doses less than those used in humans. The relevance of
these findings to the risk of malformations in human infants born to mothers
treated with methylprednisolone in pregnancy is unknown. Safety margins for the
reported teratogenic effects are unknown.
Lidocaine
Carcinogenic potential:
Long-term studies in animals have not been performed to evaluate carcinogenic
potential.
Mutagenic potential:
Genotoxicity studies were carried out with lidocaine and its metabolites. The
Salmonella microsomal assay (Salmonella typhimurium strains TA100, TA98,
and TA1538 with 1, 10, 100 and 500 mg/plate), with or without metabolic
activation, with lidocaine and its metabolites monoethylglycinexylidine,
N-hydroxylidocaine, N-hydroxy-monoethylglycinexylidine, 2,6-xylidine,
2,6-dimethylphenylhydroxylamine, did not reveal any mutagenic activity.
However, metabolite 2,6-dimethylaniline, has been shown to have mutagenic
and carcinogenic potential.
Reproductive toxicity:
Lidocaine has not been shown to affect male or female fertility.
Methylprednisolone plus Lidocaine
Carcinogenic potential:
Long-term studies in animals have not been performed to evaluate carcinogenic
potential.
The toxicity of lidocaine was not significantly altered in rats that were treated with
the combination of lidocaine and methylprednisolone.
Mutagenic potential:
Genotoxicity studies have not been conducted with the combination of
methylprednisolone and lidocaine (see above for genotoxicity as it pertains to the
individual drugs).

Reproductive toxicity:
Reproductive toxicity studies have not been conducted with the combination of
methylprednisolone and lidocaine (see above for reproductive toxicity as it
pertains to the individual drugs).
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium chloride
Myristyl-gamma-picolinium chloride
Benzyl alcohol
Macrogol
Sodium hydroxide
Hydrochloric acid
Water for injections.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years.
6.4 Special precautions for storage
Do not store above 25°C.
Do not freeze.
6.5 Nature and contents of container
Glass vials with rubber cap containing 1 or 2 ml of suspension.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
No special requirements.
Any unused medicinal product or waste material should be disposed off in
accordance with local requirements.
Pharmaceutical precautions
Depo-Medrone with Lidocaine should not be stored above 25°C and
protected from freezing.
Depo-Medrone with Lidocaine should not be mixed with any other fluid.
Discard any remaining suspension after use.
Legal Category:
POM
Package quantities:
1 x 1ml vial pack or 3 x 1ml packs.
Manufacturer and Licence Holder
This medicine is manufactured by Pfizer manufacturing Belgium NV, Rijksweg
12, 2870 Puurs, Belgium and is procured from within the EU and repackaged
by the Product Licence Holder: Lexon (UK) Limited, Unit 18, Oxleasow Road,
East Moons Moat, Redditch, Worcestershire, B98 0RE.
PL:15184/0926 - Depo-Medrone with Lidocaine
Depo-Medrone is a registered trademark of Pharmacia & Upjohn Limited.
Leaflet revision date: 23/11/17

Depo-Medrone® with Lidocaine

Ref:0926/231117/1P-F

(methylprednisolone acetate and lidocaine hydrochloride)

PHYSICIAN LEAFLET
1. NAME OF THE MEDICINAL PRODUCT
Depo-Medrone with Lidocaine
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Methyprednisolone 4%, Lidocaine Hydrochloride 1%
Excipients with known effect:
Also contains 8.7 mg/ml benzyl alcohol
For the full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
Suspension for Injection.
White, sterile aqueous suspension
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Corticosteroid (glucocorticoid). Depo-Medrone with Lidocaine is indicated in
conditions requiring a glucocorticoid effect: e.g. anti-inflammatory or
anti-rheumatic. It is recommended for local use where the added anaesthetic
effect would be considered advantageous.
Depo-Medrone with Lidocaine may be used as follows:
Intra-articular administration
Rheumatoid arthritis
Osteo-arthritis with an inflammatory component
Periarticular administration
Epicondylitis
Intrabursal administration
Subacromial bursitis
Prepatellar bursitis
Olecranon bursitis
Tendon sheath administration
Tendinitis
Tenosynovitis
Epicondylitis
Therapy with Depo-Medrone with Lidocaine does not obviate the need for the
conventional measures usually employed. Although this method of treatment will
ameliorate symptoms, it is in no sense a cure and the hormone has no
effect on the cause of the inflammation.
4.2 Posology and method of administration
Depo-Medrone with Lidocaine should not be mixed with any other
preparation as flocculation of the product may occur. Parenteral drug products
should be inspected visually for particulate matter and discoloration prior to
administration whenever suspension and container permit. Depo-Medrone with
Lidocaine may be used by any of the following routes: intra-articular,
periarticular, intrabursal, and into the tendon sheath. It must not be used by the
intrathecal, or intravenous routes (see sections 4.3 and 4.8).
Adults
Intra-articular: Rheumatoid arthritis, osteo-arthritis. The dose of
Depo-Medrone with Lidocaine depends on the size of the joint and the
severity of the condition. Repeated injections, if needed, may be given at
intervals of one to five or more weeks depending upon the degree of relief
obtained from the initial injection. A suggested dosage guide is: large joint (knee,
ankle, shoulder), 0.5 - 2 ml (20 - 80 mg of steroid); medium joint (elbow, wrist),
0.25 - 1 ml (10 - 40 mg of steroid); small joint
(metacarpophalangeal, interphalangeal, sternoclavicular, acromioclavicular), 0.1
- 0.25 ml (4 - 10 mg of steroid).
Periarticular: Epicondylitis. Infiltrate 0.1 - 0.75 ml (4 - 30 mg of steroid) into the
affected area.
Intrabursal: Subdeltoid bursitis, prepatellar bursitis, olecranon bursitis.
For administration directly into bursae, 0.1 - 0.75 ml (4 - 30 mg of steroid). In
most acute cases, repeat injections are not needed.
Into the tendon sheath: Tendinitis, tenosynovitis, epicondylitis.
For administration directly into the tendon sheath, 0.1 - 0.75 ml (4 - 30 mg of
steroid). In recurrent or chronic conditions, repeat injections may be
necessary.
Paediatric population
For infants and children, the recommended dosage should be reduced, but
dosage should be governed by the severity of the condition rather than by strict
adherence to the ratio indicated by age or body weight.
Elderly:
When used according to instructions, there is no information to suggest that a
change in dosage is warranted in the elderly. However, treatment of elderly
patients, particularly if long-term, should be planned bearing in mind the more
serious consequences of the common side-effects of corticosteroids in old age
and close clinical supervision is required (see section 4.4).
Special precautions should be observed when administering Depo-Medrone with
Lidocaine:
Intra-articular injections should be made using precise, anatomical
localisation into the synovial space of the joint involved. The injection site for
each joint is determined by that location where the synovial cavity is most
superficial and most free of large vessels and nerves. Suitable sites for
intra-articular injection are the knee, ankle, wrist, elbow, shoulder, phalangeal
and hip joints. The spinal joints, unstable joints and those devoid of synovial
space are not suitable. Treatment failures are most frequently the result of failure
to enter the joint space. Intra-articular injections should be made with care as
follows: ensure correct positioning of the needle into the synovial space and
aspirate a few drops of joint fluid. The aspirating syringe should then be replaced
by another containing Depo-Medrone with Lidocaine. To ensure position of the
needle synovial fluid should be aspirated and the injection made.
After injection the joint is moved slightly to aid mixing of the synovial fluid and the
suspension. Subsequent to therapy care should be taken for the patient not to
overuse the joint in which benefit has been obtained. Negligence in this matter
may permit an increase in joint deterioration that will more than offset the
beneficial effects of the steroid.
Intrabursal injections should be made as follows: the area around the
injection site is prepared in a sterile way and a wheal at the site made with 1
percent procaine hydrochloride solution. A 20 to 24 gauge needle attached to a
dry syringe is inserted into the bursa and the fluid aspirated. The needle is left in
place and the aspirating syringe changed for a small syringe containing the
desired dose. After injection, the needle is withdrawn and a small
dressing applied. In the treatment of tenosynovitis and tendinitis, care should be
taken to inject Depo-Medrone with Lidocaine into the tendon sheath rather than
into the substance of the tendon. Due to the absence of a true tendon sheath,
the Achilles tendon should not be injected with Depo-Medrone with
Lidocaine.
The usual sterile precautions should be observed with each injection.
4.3 Contraindications
Depo-Medrone with Lidocaine is contraindicated:
• in patients with known hypersensitivity to the active substances or to any of
the excipients listed in section 6.1
• in patients with known hypersensitivity to other local anaesthetics of the
amide type
• in patients who have systemic infection unless specific anti-infective
therapy is employed
• for use by the intrathecal route (due to its potential for neurotoxicity)
• for use by the intravenous route (see section 4.8)
Administration of live or live, attenuated vaccines is contraindicated in patients
receiving immunosuppressive doses of corticosteroids.
4.4 Special warnings and precautions for use
Undesirable effects may be minimised by using the lowest effective dose for the
minimum period. Frequent patient review is required to appropriately titrate the
dose against disease activity (see section 4.2).
Depo-Medrone with Lidocaine vials are intended for single dose use only.
Any multidose use of the product may lead to contamination.
Depo-Medrone with Lidocaine is not recommended for intranasal, intra-ocular, or
any other unapproved route of administration.
Severe medical events have been reported in association with the
intrathecal/epidural routes of administration (see section 4.8). Appropriate
measures must be taken to avoid intravascular injection.
Due to the absence of a true tendon sheath, the Achilles tendon should not be
injected with Depo-Medrone with Lidocaine.

While crystals of adrenal steroids in the dermis suppress inflammatory
reactions, their presence may cause disintegration of the cellular elements and
physiochemical changes in the ground substance of the connective
tissue. The resultant infrequently occurring dermal and/or subdermal changes
may form depressions in the skin at the injection site and the possibility of
depigmentation. The degree to which this reaction occurs will vary with the
amount of adrenal steroid injected. Regeneration is usually complete within a few
months or after all crystals of the adrenal steroid have been absorbed. In order to
minimize the incidence of dermal and subdermal atrophy, care must be exercised
not to exceed recommended doses in injections. Multiple small injections into the
area of the lesion should be made whenever possible. The technique of
intra-articular injection should include precautions against injection or leakage
into the dermis.
Systemic absorption of methylprednisolone occurs following intra-articular
injection of Depo-Medrone with Lidocaine. Systemic as well as local effects can
therefore be expected.
Adrenal cortical atrophy develops during prolonged therapy and may persist for
months after stopping treatment. In patients who have received more than
physiological doses of systemic corticosteroids (approximately 6 mg
methylprednisolone) for greater than 3 weeks, withdrawal should not be abrupt.
How dose reduction should be carried out depends largely on whether the
disease is likely to relapse as the dose of systemic corticosteroids is
reduced. Clinical assessment of disease activity may be needed during
withdrawal. If the disease is unlikely to relapse on withdrawal of systemic
corticosteroids, but there is uncertainty about HPA suppression, the dose of
systemic corticosteroid may be reduced rapidly to physiological doses. Once a
daily dose of 6 mg methylprednisolone is reached, dose reduction should be
slower to allow the HPA-axis to recover.
The following precautions apply for parenteral corticosteroids:
Following intra-articular injection, the occurrence of a marked increase in pain
accompanied by local swelling, further restriction of joint motion, fever, and
malaise are suggestive of septic arthritis. If this complication occurs and the
diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should be
instituted.
No additional benefit derives from the intramuscular administration of
Depo-Medrone with Lidocaine. Where parenteral corticosteroid therapy for
sustained systemic effect is desired, plain Depo-Medrone should be used.
Local injection of a steroid into a previously infected joint is to be avoided.
Intra-articular corticosteroids are associated with a substantially increased risk of
inflammatory response in the joint, particularly bacterial infection
introduced with the injection. Charcot-like arthropathies have been reported
particularly after repeated injections. Appropriate examination of any joint fluid
present is necessary to exclude any bacterial infection, prior to injection.
Corticosteroids should not be injected into unstable joints.
Sterile technique is necessary to prevent infections or contamination.
Immunosuppressant Effects/Increased Susceptibility to Infections
Corticosteroids may increase susceptibility to infection, may mask some signs of
infection, and new infections may appear during their use. Suppression of the
inflammatory response and immune function increases the susceptibility to
fungal, viral and bacterial infections and their severity. The clinical
presentation may often be atypical and may reach an advanced stage before
being recognised.
With increasing doses of corticosteroids, the rate of occurrence of infectious
complications increases. Persons who are on drugs which suppress the
immune system are more susceptible to infections than healthy individuals.
Chickenpox and measles, for example, can have a more serious or even fatal
course in non-immune children or adults on corticosteroids.
Chickenpox is of serious concern since this normally minor illness may be fatal in
immunosuppressed patients. Patients (or parents of children) without a definite
history of chickenpox should be advised to avoid close personal
contact with chickenpox or herpes zoster and if exposed they should seek
urgent medical attention. Passive immunization with varicella/zoster
immunoglobin (VZIG) is needed by exposed non-immune patients who are
receiving systemic corticosteroids or who have used them within the previous 3
months; this should be given within 10 days of exposure to chickenpox. If a
diagnosis of chickenpox is confirmed, the illness warrants specialist care and
urgent treatment. Corticosteroids should not be stopped and the dose may need
to be increased.
Live vaccines should not be given to individuals with impaired immune
responsiveness. The antibody response to other vaccines may be
diminished.
If corticosteroids are indicated in patients with latent tuberculosis or
tuberculin reactivity, close observation is necessary as reactivation of the
disease may occur. During prolonged corticosteroid therapy, these patients
should receive chemoprophylaxis. The role of corticosteroids in septic shock has
been controversial, with early studies reporting both beneficial and detrimental
effects. More recently, supplemental corticosteroids have been suggested to be
beneficial in patients with established septic shock who exhibit adrenal
insufficiency. However, their routine use in septic shock is not recommended. A
systematic review of short-course, high-dose corticosteroids did not support their
use. However, meta-analyses, and a review suggest that longer courses (5-11
days) of low-dose corticosteroids might reduce mortality, especially in patients
with vasopressor-dependent septic shock.
Immune System Effects
Allergic reactions may occur. Because rare instances of skin reactions and
anaphylactic/anaphylactoid reactions have occurred in patients receiving
corticosteroid therapy, appropriate precautionary measures should be taken
prior to administration, especially when the patient has a history of drug
allergy.
Endocrine Effects
Pharmacologic doses of corticosteroids administered for prolonged periods may
result in hypothalamic-pituitary-adrenal (HPA) suppression (secondary
adrenocortical insufficiency). The degree and duration of adrenocortical
insufficiency produced is variable among patients and depends on the dose,
frequency, time of administration, and duration of glucocorticoid therapy.
Abrupt withdrawal of systemic corticosteroid treatment, which has continued up
to 3 weeks is appropriate if it considered that the disease is unlikely to relapse.
Abrupt withdrawal of doses up to 32 mg daily of methylprednisolone for 3 weeks
is unlikely to lead to clinically relevant HPA-axis suppression, in the majority of
patients. In the following patient groups, gradual withdrawal of systemic
corticosteroid therapy should be considered even after courses
lasting 3 weeks or less:
• Patients who have had repeated courses of systemic corticosteroids,
particularly if taken for greater than 3 weeks.
• When a short course has been prescribed within one year of cessation of
long-term therapy (months or years).
• Patients who may have reasons for adrenocortical insufficiency other than
exogenous corticosteroid therapy.
• Patients receiving doses of systemic corticosteroid greater than 32 mg daily of
methylprednisolone.
• Patients repeatedly taking doses in the evening.
Since mineralocorticoid secretion may be impaired, salt and/or a
mineralocorticoid should be administered concurrently.
A steroid “withdrawal syndrome,” seemingly unrelated to adrenocortical
insufficiency, may also occur following abrupt discontinuance of
glucocorticoids. This syndrome includes symptoms such as: anorexia,
nausea, vomiting, lethargy, headache, fever, joint pain, desquamation,
myalgia, weight loss, and/or hypotension. These effects are thought to be due to
the sudden change in glucocorticoid concentration rather than to low
corticosteroid levels. Because glucocorticoids can produce or aggravate
Cushing’s syndrome, glucocorticoids should be avoided in patients with
Cushing’s disease. There is an enhanced effect of corticosteroids on patients
with hypothyroidism.
Metabolism and Nutrition
Corticosteroids, including methylprednisolone, can increase blood glucose,
worsen pre-existing diabetes, and predispose those on long-term
corticosteroid therapy to diabetes mellitus.

Psychiatric Effects
Patients and/or carers should be warned that potentially severe psychiatric
adverse reactions may occur with systemic steroids (see section 4.8).
Symptoms typically emerge within a few days or weeks of starting treatment.
Risks may be higher with high doses/systemic exposure (see section 4.5),
although dose levels do not allow prediction of the onset, type, severity or
duration of reactions. Most reactions recover after either dose reduction or
withdrawal, although specific treatment may be necessary. Patients/carers
should be encouraged to seek medical advice if worrying psychological
symptoms develop, especially if depressed mood or suicidal ideation is
suspected. Patients/carers should be alert to possible psychiatric
disturbances that may occur either during or immediately after dose
tapering/withdrawal of systemic steroids, although such reactions have been
reported infrequently.
Particular care is required when considering the use of systemic
corticosteroids in patients with existing or previous history of severe affective
disorders in themselves or in their first degree relatives. These would include
depressive or manic-depressive illness and previous steroid psychosis.
Nervous System Effects
Corticosteroids should be used with caution in patients with seizure
disorders.
Corticosteroids should be used with caution in patients with myasthenia gravis
(also see myopathy statement in Musculoskeletal Effects section).
There have been reports of epidural lipomatosis in patients taking
corticosteroids, typically with long-term use at high doses.
Ocular Effects
Prolonged use of corticosteroids may produce posterior subcapsular cataracts
and nuclear cataracts (particularly in children), exophthalmos, or increased
intraocular pressure, which may result in glaucoma with possible damage to the
optic nerves, and may enhance the establishment of
secondary ocular infections due to fungi or viruses.
Corticosteroids should be used cautiously in patients with ocular herpes
simplex, because of possible corneal perforation.
Corticosteroid therapy has been associated with central serous
chorioretinopathy, which may lead to retinal detachment.
Cardiac Effects
Adverse effects of glucocorticoids on the cardiovascular system, such as
dyslipidaemia and hypertension, may predispose treated patients with existing
cardiovascular risk factors to additional cardiovascular effects, if high doses and
prolonged courses are used. Accordingly, corticosteroids should be
employed judiciously in such patients and attention should be paid to risk
modification and additional cardiac monitoring if needed.
Systemic corticosteroids should be used with caution, and only if strictly
necessary, in cases of congestive heart failure.
Vascular Effects
Corticosteroids should be used with caution in patients with hypertension.
Thrombosis including venous thromboembolism has been reported to occur with
corticosteroids. As a result corticosteroids should be used with caution in patients
who have or may be predisposed to thromboembolic disorders.
Gastrointestinal Effects
There is no universal agreement on whether corticosteroids per se are
responsible for peptic ulcers encountered during therapy; however,
glucocorticoid therapy may mask the symptoms of peptic ulcer so that
perforation or haemorrhage may occur without significant pain. In combination
with NSAIDs, the risk of developing gastrointestinal ulcers is increased.
Corticosteroids should be used with caution in nonspecific ulcerative colitis, if
there is a probability of impending perforation, abscess or other pyogenic
infection. Caution must also be used in diverticulitis, fresh intestinal
anastomoses, active or latent peptic ulcer, when steroids are used as direct or
adjunctive therapy.
Hepatobiliary Effects
Drug induced liver injury including acute hepatitis or liver enzyme increase can
result from cyclical pulsed IV methylprednisolone (usually at initial dose > 1 g /
day). Rare cases of hepatotoxicity have been reported. The time to onset can be
several weeks or longer. In the majority of case reports resolution of the adverse
events has been observed after treatment was discontinued. Therefore,
appropriate monitoring is required.
High doses of corticosteroids may produce acute pancreatitis.
Corticosteroids should be used with caution in patients with liver failure or
cirrhosis.
Musculoskeletal Effects
An acute myopathy has been reported with the use of high doses of
corticosteroids, most often occurring in patients with disorders of
neuromuscular transmission (e.g. myasthenia gravis), or in patients receiving
concomitant therapy with anticholinergics, such as neuromuscular blocking drugs
(e.g. pancuronium). This acute myopathy is generalized, may involve ocular and
respiratory muscles, and may result in quadriparesis. Elevations of creatine
kinase may occur. Clinical improvement or recovery after stopping
corticosteroids may require weeks to years.
Osteoporosis is a common but infrequently recognized adverse effect
associated with a long-term use of large doses of glucocorticoid.
Renal and Urinary Disorders
Corticosteroids should be used with caution in patients with renal insufficiency.
Injury, Poisoning and Procedural Complications
Systemic corticosteroids are not indicated for, and therefore should not be used
to treat, traumatic brain injury, a multicenter study revealed an increased
mortality at 2 weeks and 6 months after injury in patients administered
methylprednisolone sodium succinate compared to placebo. A causal association
with methylprednisolone sodium succinate treatment has not been established.
Investigations
Average and large doses of hydrocortisone or cortisone can cause elevation of
blood pressure, salt and water retention, and increased excretion of
potassium. These effects are less likely to occur with the synthetic derivatives
except when used in large doses. Dietary salt restriction and potassium
supplementation may be necessary. All corticosteroids increase calcium
excretion.
Care should be taken for patients receiving cardioactive drugs such as digoxin
because of steroid induced electrolyte disturbance/potassium loss (see section
4.8).
Other
Patients should carry 'Steroid Treatment' cards which give clear guidance on the
precautions to be taken to minimise risk and which provide details of
prescriber, drug, dosage and the duration of treatment.
Corticosteroids should be used with caution in patients with a predisposition to
thrombophlebitis. Aspirin and nonsteroidal anti-inflammatory agents should be
used cautiously in conjunction with corticosteroids.
Pheochromocytoma crisis, which can be fatal, has been reported after
administration of systemic corticosteroids. Corticosteroids should only be
administered to patients with suspected or identified pheochromocytoma after an
appropriate risk/benefit evaluation.
Paediatric population
Intravenous administration of the preservative benzyl alcohol has been
associated with serious adverse event, and death in paediatric patients
including neonates characterized by central nervous system depression,
metabolic acidosis, gasping respirations, cardio-vascular failure and
haematological anomalies (“gasping syndrome”). The minimum amount of benzyl
alcohol at which toxicity may occur is not known. Use only if it is
necessary and if there are no alternatives possible. If given in high volumes,
should be used with caution and preferably for short term treatment in
subjects with liver or kidney impairment because of the risk of accumulation and
toxicity (metabolic acidosis)
Premature and low-birth weight infants may be more likely to develop toxicity.
Benzyl Alcohol containing products should not be used in pre-term or full-term
neonates unless strictly necessary
Corticosteroids cause growth retardation in infancy, childhood and
adolescence which may be irreversible. Growth and development of infants and
children on prolonged corticosteroid therapy should be carefully
observed. Treatment should be limited to the minimum dosage for the
shortest possible time. The use of such a regimen should be restricted to those
most serious indications. Infants and children on prolonged corticosteroid therapy are at special risk from raised intracranial pressure.
High doses of corticosteroids may produce pancreatitis in children.

4.5 Interaction with other medicinal products and other forms of
interaction
Methylprednisolone is a cytochrome P450 enzyme (CYP) substrate and is mainly
metabolized by the CYP3A enzyme. CYP3A4 is the dominant enzyme of the
most abundant CYP subfamily in the liver of adult humans. It catalyzes
6β-hydroxylation of steroids, the essential Phase I metabolic step for both
endogenous and synthetic corticosteroids. Many other compounds are also
substrates of CYP3A4, some of which (as well as other drugs) have been shown
to alter glucocorticoid metabolism by induction (upregulation) or inhibition of the
CYP3A4 enzyme.
CYP3A4 INHIBITORS – Drugs that inhibit CYP3A4 activity generally
decrease hepatic clearance and increase the plasma concentration of CYP3A4
substrate medications, such as methylprednisolone. In the presence of a
CYP3A4 inhibitor, the dose of methylprednisolone may need to be titrated to
avoid steroid toxicity.
CYP3A4 INDUCERS – Drugs that induce CYP3A4 activity generally increase
hepatic clearance, resulting in decreased plasma concentration of medications
that are substrates for CYP3A4. Coadministration may require an increase in
methylprednisolone dosage to achieve the desired result.
CYP3A4 SUBSTRATES – In the presence of another CYP3A4 substrate, the
hepatic clearance of methylprednisolone may be affected, with corresponding
dosage adjustments required. It is possible that adverse events associated with
the use of either drug alone may be more likely to occur with coadministration.
1. Convulsions have been reported with concurrent use of methylprednisolone
and ciclosporin (CYP3A4 inhibitor and substrate). Since concurrent
administration of these agents results in a mutual inhibition of metabolism (which
may increase the plasma concentrations of either or both drugs), it is possible
that convulsions and other adverse effects associated with the
individual use of either drug may be more apt to occur.
2. Drugs that induce hepatic enzymes, such as rifampicin (antibiotic CYP3A4
inducer), rifabutin, carbamazepine (anticonvulsant CYP3A4 inducer and
substrate), phenobarbitone and phenytoin (anticonvulsants CYP3A4
inducers), primidone, and aminoglutethimide (aromatase inhibitor) enhance the
metabolism of corticosteroids and its therapeutic effects may be reduced.
Aminoglutethimide- induced adrenal suppression may exacerbate endocrine
changes caused by prolonged glucocorticoid treatment.
3. Antibiotics/Antimycotics - Drugs such as erythromycin (macrolide
antibacterial CYP3A4 inhibitor and substrate), itraconazole and ketoconazole
antifungal CYP3A4 inhibitors and substrates) may inhibit the metabolism of
corticosteroids and thus decrease their clearance.
Troleandomycin (CYP3A4 inhibitor), as well as clarithromycin, erythromycin,
itraconazole and ketoconazole (CYP3A4 inhibitors and substrates) increase the
effects and the side effects of methylprednisolone.
The acetylation rate and clearance of isoniazid (CYP3A4 inhibitor), an
antibacterial drug, can be increased by methylprednisolone.
4. Steroids may reduce the effects of anticholinesterases in myasthenia gravis.
An acute myopathy has been reported with the concomitant use of high doses of
corticosteroids and anticholinergics, such as neuromuscular blocking drugs (see
section 4.4).
Antagonism of the neuromuscular blocking effects of pancuronium and
vecuronium has been reported in patients taking corticosteroids. This
interaction may be expected with all competitive neuromuscular blockers.
The desired effects of hypoglycaemic agents (including insulin),
anti-hypertensives and diuretics are antagonised by corticosteroids, and the
hypokalaemic effects of acetazolamide, loop diuretics, thiazide diuretics and
carbenoxolone are enhanced.
5. The effect of methylprednisolone on oral anticoagulants is variable.
The efficacy of coumarin anticoagulants may be enhanced by concurrent
corticosteroid therapy and close monitoring of the INR or prothrombin time is
required to avoid spontaneous bleeding and to maintain the desired
anticoagulant effects.
There are also reports of diminished effects of anticoagulants when given
concurrently with corticosteroids.
6. There may be increased incidence of gastrointestinal bleeding and
ulceration when corticosteroids are given with NSAIDs. Methylprednisolone may
increase the clearance of high-dose aspirin, which can lead to decreased
salicylate serum levels. Discontinuation of methylprednisolone treatment can
lead to raised salicylate serum levels, which could lead to an increased risk of
salicylate toxicity. Salicylates and non-steroidal anti-inflammatory agents should
be used cautiously in conjunction with corticosteroids in hypothrombinaemia.
7. Antidiabetics - Because corticosteroids may increase blood glucose
concentrations, dosage adjustments of antidiabetic agents may be required.
8. Antiemetics - Aprepitant and fosaprepitant (CYP3A4 inhibitors and substrates).
9. Antivirals - HIV protease inhibitors: Indinavir and ritonavir (CYP3A4 inhibitors
and substrates) may increase plasma concentrations of corticosteroids.
Corticosteroids may induce the metabolism of HIV-protease inhibitors resulting in
reduced plasma concentrations.
10. Calcium channel blocker - Diltiazem (CYP3A4 inhibitor and substrate).
11. Contraceptives (oral) - Ethinylestradiol/norethindrone (CYP3A4 inhibitors and
substrate).
12. Other immunosuppressants like cyclophosphamide and tacrolimus are
substrates of CYP3A4.
13. Potassium-depleting agents - When corticosteroids are administered
concomitantly with potassium-depleting agents (i.e. diuretics), patients should be
observed closely for development of hypokalaemia. There is also an increased
risk of hypokalaemia with concurrent use of corticosteroids with amphotericin B,
xanthenes, or beta2 agonists.
14. Grapefruit juice - CYP3A4 inhibitor.
4.6 Fertility, pregnancy and lactation
Fertility
There is no evidence showing that corticosteroids impair fertility (see section
5.3).
Pregnancy
Methylprednisolone
The ability of corticosteroids to cross the placenta varies between individual
drugs, however, methylprednisolone does cross the placenta. One retrospective
study found an increased incidence of low birth weights in infants born of
mothers receiving corticosteroids.
Administration of corticosteroids to pregnant animals can cause abnormalities of
foetal development including cleft palate, intra-uterine growth retardation and
affects on brain growth and development. There is no evidence that
corticosteroids result in an increased incidence of congenital abnormalities, such
as cleft palate in man, however, when administered for long periods or
repeatedly during pregnancy, corticosteroids may increase the risk of
intra-uterine growth retardation. Hypoadrenalism may, in theory, occur in the
neonate following prenatal exposure to corticosteroids but usually resolves
spontaneously following birth and is rarely clinically important. Although neonatal
adrenal insufficiency appears to be rare in infants who were exposed in utero to
corticosteroids, those exposed to substantial doses of corticosteroids must be
carefully observed and evaluated for signs of adrenal insufficiency. As with all
drugs, corticosteroids should only be prescribed when the benefits to the mother
and child outweigh the risks. When corticosteroids are essential, however,
patients with normal pregnancies may be treated as though they were in the
non-gravid state. Cataracts have been observed in infants born to mothers
treated with long-term corticosteroids during pregnancy.
Lidocaine
Adequate human reproductive studies have not been done with Lidocaine.
The use of local anaesthetics such as lidocaine during labour and delivery may
be associated with adverse effects on mother and foetus.
Lidocaine readily crosses the placenta. Benzyl alcohol can cross the placenta
Breast-feeding
Methylprednisolone
Corticosteroids are distributed in small amounts in breast milk and may
suppress growth and interfere with endogenous glucocorticoid production in
nursing infants. However, doses of up to 40 mg daily of methylprednisolone are
unlikely to cause systemic effects in the infant. Infants of mothers taking higher
doses than this may have a degree of adrenal suppression. Since
adequate reproductive studies have not been performed in humans with
glucocorticoids, these drugs should be administered to nursing mothers only if
the benefits of therapy are judged to outweigh the potential risks to the infant.
Lidocaine It is not known whether lidocaine is excreted in human breast milk.

4.7 Effects on ability to drive and use machines
The effect of corticosteroids on the ability to drive or use machinery has not been
systematically evaluated. Undesirable effects, such as dizziness,
vertigo, visual disturbances, and fatigue are possible after treatment with
corticosteroids. If affected, patients should not drive or operate machinery.
4.8 Undesirable effects
The incidence of predictable undesirable side effects associated with the use of
corticosteroids, including hypothalamic-pituitary-adrenal suppression
correlates with the relative potency of the drug, dosage, timing of
administration and duration of treatment (See section 4.4).
Side effects for the Depo-Medrone component may be observed including:
MedDRA

Frequency

Common

Not Known
Immune system
disorders

Not Known

Blood and lymphatic
system disorders

Not Known

Endocrine
disorders

Metabolism and
nutrition disorders

Nervous system
disorders

Eye disorders

Not Known

Glucose tolerance impaired; Sodium retention;
Fluid retention; Increased requirements for insulin
(or oral hypoglycemic agents in diabetics).
Alkalosis hypokalaemic; Dyslipidaemia, Increased
appetite (which may result in Weight increased);
Epidural lipomatosis
Affective disorder (including Depressed mood,
Euphoric mood). Mood swings; Abnormal
behaviour; Insomnia
Affective disorder (including Affect lability,
psychological dependence [not a MedDRA PT],
Suicidal ideation), Psychotic disorder (including
Mania, Delusion, Hallucination, and Schizophrenia
[aggravation of]); Confusional state; Mental disorder;
Anxiety; Personality change
Intracranial pressure increased
(with Papilloedema [Benign intracranial
hypertension]); Convulsion; Amnesia; Cognitive
disorder; Dizziness; Headache; Epidural
lipomatosis

Common

Cataract; Glaucoma

Not Known

Exophthalmos; chorioretinopathy; Rare instances of
blindness associated with intralesional therapy
around the face and head [not a MedDRA PT];
Increased intra-ocular pressure, with possible
damage to the optic nerve; Corneal or scleral
thinning; Exacerbation of ophthalmic viral or
fungal disease

Ear and labyrinth
disorders

Not Known

Vertigo

Cardiac disorders

Not Known

Cardiac failure congestive (in susceptible
patients)

Vascular disorders

Common

Not Known

Hypertension

Hypotension; Embolism arterial, Thrombotic
events

Respiratory, thoracic
and mediastinal
disorders

Not Known

Pulmonary embolism, Hiccups

Gastrointestinal
disorders

Common

Peptic ulcer (with possible Peptic ulcer
perforation and Peptic ulcer haemorrhage)

Not Known

Hepatobiliary disorders Not Known

Skin and subcutaneous Common
tissue disorders

Musculoskeletal and
connective tissue
disorders

Reproductive system
and breast disorders

General disorders and
administration site
conditions

Ecchymosis; Acne

Common

Growth retardation; Osteoporosis;
Muscular weakness
Osteonecrosis; Pathological fracture; Muscle
atrophy; Myopathy; Neuropathic arthropathy;
Arthralgia; Myalgia

Not Known

Menstruation irregular

Common

Impaired healing; Oedema peripheral; Irritability

Common

Not Known

Injury, poisoning and
procedural
complications

Hepatitis, Increase of liver enzymes

Angioedema; Petechiae; Skin atrophy; Skin
striae; Skin hyperpigmentation; Skin
hypopigmentation; Hirsutism; Rash; Erythema;
Pruritus; Urticaria; Hyperhidrosis

Not Known

Investigations

Gastric haemorrhage; Intestinal perforation;
Pancreatitis; Oesophagitis ulcerative;
Oesophagitis; Oesophageal candidiasis;
Abdominal pain; Abdominal distension;
Diarrhoea; Dyspepsia; Nausea

Not Known

Not Known

Not Known

Frequency

Anaphylactic reaction

Psychiatric disorders

Common

Confusional state;
Euphoric mood;
Nervousness; Anxiety

Nervous System
disorders

Common

Loss of consciousness;
Convulsion;
Hypoaesthesia;
Tremor; Somnolence;
Dizziness

Eye disorders

Common

Diplopia; Vision
blurred ;

Common

Tinnitus

Common

Bradycardia

Common

Hypotension

Not known

Circulatory collapse;
Cardiac arrest

Respiratory, thoracic
and mediastinal
disorders

Common

Respiratory arrest;
Respiratory depression

Gastrointestinal
disorders

Common

Skin and
subcutaneous
disorders

Not known

Immune system

Leukocytosis

Hypopituitarism; Withdrawal symptoms - Too rapid
a reduction of corticosteroid dosage following
prolonged treatment can lead to acute adrenal
insufficiency, hypotension and death. However,
this is more applicable to corticosteroids with an
indication where continuous therapy is given (see
section 4.4). A 'withdrawal syndrome' may also
occur including, fever, myalgia, arthralgia, rhinitis,
conjunctivitis, painful itchy skin nodules and
loss of weight

Not Known

Undesirable Effects

Drug hypersensitivity, Anaphylactic reaction

Not Known

Common

Not known

System Organ Class

Opportunistic infection; Injection site infection;
Peritonitis; Recurrence of dormant tuberculosis

Cushingoid

Not Known

Psychiatric
disorders

Infection (including increased susceptibility and
severity of infections with suppression of clinical
symptoms and signs)

Common

Common

MedDRA

Undesirable Effects

System Organ Class

Infections and
infestations

† Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare
(≥1/10,000 to <1/1,000); Not known (frequency cannot be estimated from the
available data) Side effects for the Lidocaine component include:

Injection site reaction; Abscess sterile; Fatigue;
Malaise
Blood potassium decreased

Alanine aminotransferase increased; Aspartate
aminotransferase increased; Blood alkaline
phosphatase increased; Carbohydrate
tolerance decreased; Urine calcium increased;
suppression of reactions to skin tests [not a
MedDRA PT]; Blood urea increased;
Nitrogen balance negative (due to protein
catabolism)
Tendon rupture (particularly of the Achilles tendon);
Spinal compression fracture. Systemic
corticosteroids are not indicated for, and
therefore should not be used to treat, traumatic
brain injury.

Ear and labyrinth
disorders

Cardiac disorders

Vascular disorders

Musculoskeletal and
connective tissue
disorders
General disorders and
administration
site conditions

Vomiting

Skin lesion; Urticaria

Common

Muscle twitching

Common

Oedema; Feeling cold; Feeling
hot

CERTAIN SIDE EFFECTS REPORTED WITH SOME NON RECOMMENDED
ROUTES OF ADMINISTRATION:
Intrathecal/Epidural: Usual systemic corticoid adverse reactions, headache,
meningismus, meningitis, paraparesis/paraplegia, spinal fluid abnormalities,
nausea, vomiting, sweating, arachnoiditis, functional gastrointestinal
disorder/bladder dysfunction, convulsions, sensory disturbances. The frequency
of these adverse reactions is not known.
Extradural: Wound dehiscence, loss of sphincter control.
Intranasal: Permanent/temporary blindness, allergic reactions, rhinitis.
Ophthalmic (Subconjunctival): Redness and itching, abscess, slough at injection
site, residue at injection site, increased intra-ocular pressure, decreased
vision - blindness, infection.
Miscellaneous: Scalp, tonsillar fauces, sphenopalatine ganglion: blindness.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/risk balance of
the medicinal product. Healthcare professionals are asked to report any
suspected adverse reactions via the Yellow Card Scheme. Website:
www.mhra.gov.uk/yellowcard
4.9 Overdose
Methylprednisolone
Following overdosage the possibility of adrenal suppression should be guarded
against by gradual diminution of dose levels over a period of time. In such event
the patient may require to be supported during any further traumatic episode.
Reports of acute toxicity and/or death following overdosage of corticosteroids are
rare. In the event of overdosage, no specific antidote is available; treatment is
supportive and symptomatic.
Methylprednisolone is dialysable.
Lidocaine
Overdose with lidocaine can manifest itself in a transient stimulation of the
central nervous system with early symptoms: yawning, restlessness, dizziness,
nausea, vomiting, dysarthria, ataxia, hearing and visual disturbances. With
moderate intoxication also twitching and convulsions can occur. This can be
followed by unconsciousness, respiratory depression and coma. In very severe
intoxication due to decreased myocardial contractility and delayed impulse
conduction, hypotension and cardiovascular collapse can be expected to be
followed by a complete heart block and cardiac arrest. Convulsions, hypotension
and respiratory depression and cardiac events should be treated as necessary.
Continual optimal oxygenation and ventilation and circulatory support as well as
treatment of acidosis are of vital importance.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Glucocorticoids, ATC Code: H02AB04
Pharmacotherapeutic group: Anaesthetics, ATC Code: N01BB02
Methylprednisolone
Methylprednisolone acetate is a synthetic glucocorticoid with the actions and use
of natural corticosteroids. However the slower metabolism of the synthetic
corticosteroid with their lower protein-binding affinity may account for their
increased potency compared with the natural corticosteroids.
Lidocaine
Lidocaine has the actions of a local anaesthetic.
5.2 Pharmacokinetic properties
No pharmacokinetic studies have been performed with the combination product
of methylprednisolone and lidocaine, however, data are provided from
pharmacokinetic studies performed with the individual product components
methylprednisolone and lidocaine.
Absorption:
Methylprednisolone:
One in-house study of eight volunteers determined the pharmacokinetics of a
single 40 mg intramuscular dose of Depo-Medrone. The average of the individual
peak plasma concentrations was 14.8 ± 8.6 ng/mL, the average of the individual
peak times (tmax) was 7.25 ± 1.04 hours, and the average area under the curve
(AUC) was 1354.2 ± 424.1 ng/mL x hrs (Day 1-21).
Lidocaine:
Pharmacokinetics of lidocaine after synovial absorption following intra-articular
bolus injection in patients with knee joint arthroscopy was studied with different
maximum concentration (Cmax) values reported. The Cmax values are 2.18
µg/mL at 1 hour (serum) and 0.63 µg/mL at 0.5 hour (plasma) following
administration of lidocaine doses of 7 mg/kg and 400 mg, respectively. Other
reported serum Cmax values are 0.69 µg/mL at 5 minutes and 0.278 µg/mL at 2
hours following administration of lidocaine doses of 25 mL of 1% and 20 mL of
1.5%, respectively.
Pharmacokinetic data of lidocaine after intra-bursa and intra-cyst administrations
for local effect are not available.
Ref:0926/231117/1P-B

Distribution:
Methylprednisolone:
Methylprednisolone is widely distributed into the tissues, crosses the blood-brain
barrier, and is secreted in breast milk. Its apparent volume of distribution is
approximately 1.4 L/kg. The plasma protein binding of methylprednisolone in
humans is approximately 77%.
Lidocaine:
The plasma protein binding of lidocaine is concentration-dependent, and
binding decreases as concentration increases. At concentrations of 1 to 5 µg/mL,
60%-80% lidocaine is protein bound. Binding is also dependent on the plasma
concentration of the α1-acid glycoprotein.
Lidocaine has a volume of distribution at steady state of 91 L.
Lidocaine readily crosses the placenta, and equilibrium of unbound drug
concentration is rapidly reached. The degree of plasma protein binding in the
foetus is less than in the mother, which results in lower total plasma
concentrations in the foetus.
Metabolism:
Methylprednisolone:
In humans, methylprednisolone is metabolized in the liver to inactive metabolites;
the major ones are 20α-hydroxymethylprednisolone and
20β-hydroxymethylprednisolone. Metabolism in the liver occurs primarily via the
CYP3A4. (For a list of drug interactions based on CYP3A4-mediated
metabolism, see section 4.5.)
Methylprednisolone, like many CYP3A4 substrates, may also be a substrate for
the ATP-binding cassette (ABC) transport protein p-glycoprotein, influencing
tissue distribution and interactions with other medicines modulated by P-gp.
Lidocaine:
Lidocaine is mainly metabolized by the liver. The main metabolites of lidocaine
are monoethylglycine xylidide, glycinexylidide, 2,6-dimethylaniline, and
4-hydroxy-2,6-dimethylaniline. The lidocaine N-dealkylation to monoethylglycine
xylidide is considered to be mediated by both CYP1A2 and CYP3A4. The
metabolite 2,6-dimethylaniline is converted to 4-hydroxy-2,6-dimethylaniline by
CYP2A6 and CYP2E1.
Elimination:
Methylprednisolone:
The mean elimination half-life for total methylprednisolone is in the range of 1.8
to 5.2 hours. Total clearance is approximately 5 to 6 mL/min/kg.
Lidocaine:
The clearance of lidocaine in plasma following intravenous bolus administration
is 9 to 10 mL/min/kg.
The elimination half life of lidocaine following intravenous bolus injection is
typically 1.5 to 2 hours.
The pharmacological actions of monoethylglycine xylidide and glycinexylidide are
similar to but less potent than those of lidocaine. Monoethylglycine xylidide has a
half life of approximately 2.3 hours and glycinexylidide has a half life of about 10
hours and may accumulate after long-term administration.
Only 3% of lidocaine is excreted unchanged by the kidneys. About 73% of
lidocaine appears in the urine as 4-hydroxy-2,6-dimethylaniline metabolite.
Special Population
Methylprednisolone:
No pharmacokinetic studies have been performed for methylprednisolone in
special populations.
Special Population
Lidocaine:
Hepatic impairment
Following intravenous administration, the half life of lidocaine has approximately
3-fold increase in patients with liver impairment. Pharmacokinetic data of
lidocaine after intra-articular, intra-bursa and intra-cyst administrations for local
effect are not available in hepatic impairment.
Renal impairment
Mild to moderate renal impairment (CLcr 30-60 mL/min) does not affect lidocaine
pharmacokinetics but may increase the accumulation of glycinexylidide
metabolite following intravenous administration. However, lidocaine clearance
decreases about half and its half life is approximately doubled with increased
accumulation of glycinexylidide metabolite in patients with severe renal
impairment (Clcr <30 mL/min).
The pharmacokinetics of lidocaine and its main metabolite of monoethylglycine
xylidide are not altered significantly in haemodialysis patients who receive an
intravenous dose of lidocaine.
Pharmacokinetic data of lidocaine after intra-articular, intra-bursa and
intra-cyst administrations for local effect are not available in renal impairment.
No dosing adjustments are necessary in renal failure. Methylprednisolone is
haemodialysable.
5.3 Preclinical safety data
Methylprednisolone
Based on conventional studies of safety pharmacology and repeated dose
toxicity, no unexpected hazards were identified. The toxicities seen in the
repeated-dose studies were those expected to occur with continued exposure to
exogenous adrenocortical steroids.
Mutagenic potential:
There was no evidence of a potential for genetic and chromosome mutations
when tested in limited studies performed in bacteria and mammalian cells.
Carcinogenic potential:
Long-term studies in animals have not been performed to evaluate carcinogenic
potential, as the drug is indicated for short-term treatment only. There were no
signs indicative of carcinogenic activity in studies conducted to date.
Reproductive toxicity:
Reproductive fertility studies in animals have not been performed to evaluate
specifically the potential of impairment of fertility. There is no evidence that
corticosteroids impair fertility.
An increased frequency of cleft palate was observed among the offspring of mice
treated during pregnancy with methylprednisolone in doses similar to those
typically used for oral therapy in humans.
An increased frequency of cardiovascular defects and decreased body weight
were observed among the offspring of pregnant rats treated with
methylprednisolone in a dose that was similar to that used for oral therapy in
humans but was toxic to the mothers. In contrast, no teratogenic effect was
noted in rats with doses <1-18 times
those typically used for oral therapy in humans in another study. High
frequencies of foetal death and a variety of central nervous system and skeletal
anomalies were reported in the offspring of pregnant rabbits treated with
methylprednisolone in doses less than those used in humans. The relevance of
these findings to the risk of malformations in human infants born to mothers
treated with methylprednisolone in pregnancy is unknown. Safety margins for the
reported teratogenic effects are unknown.
Lidocaine
Carcinogenic potential:
Long-term studies in animals have not been performed to evaluate carcinogenic
potential.
Mutagenic potential:
Genotoxicity studies were carried out with lidocaine and its metabolites. The
Salmonella microsomal assay (Salmonella typhimurium strains TA100, TA98,
and TA1538 with 1, 10, 100 and 500 mg/plate), with or without metabolic
activation, with lidocaine and its metabolites monoethylglycinexylidine,
N-hydroxylidocaine, N-hydroxy-monoethylglycinexylidine, 2,6-xylidine,
2,6-dimethylphenylhydroxylamine, did not reveal any mutagenic activity.
However, metabolite 2,6-dimethylaniline, has been shown to have mutagenic
and carcinogenic potential.
Reproductive toxicity:
Lidocaine has not been shown to affect male or female fertility.
Methylprednisolone plus Lidocaine
Carcinogenic potential:
Long-term studies in animals have not been performed to evaluate carcinogenic
potential.
The toxicity of lidocaine was not significantly altered in rats that were treated with
the combination of lidocaine and methylprednisolone.
Mutagenic potential:
Genotoxicity studies have not been conducted with the combination of
methylprednisolone and lidocaine (see above for genotoxicity as it pertains to the
individual drugs).

Reproductive toxicity:
Reproductive toxicity studies have not been conducted with the combination of
methylprednisolone and lidocaine (see above for reproductive toxicity as it
pertains to the individual drugs).
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium chloride
Myristyl-gamma-picolinium chloride
Benzyl alcohol
Macrogol
Sodium hydroxide
Hydrochloric acid
Water for injections.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years.
6.4 Special precautions for storage
Do not store above 25°C.
Do not freeze.
6.5 Nature and contents of container
Glass vials with rubber cap containing 1 or 2 ml of suspension.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
No special requirements.
Any unused medicinal product or waste material should be disposed off in
accordance with local requirements.
Pharmaceutical precautions
Depo-Medrol with Lidocaine should not be stored above 25°C and
protected from freezing.
Depo-Medrol with Lidocaine should not be mixed with any other fluid.
Discard any remaining suspension after use.
Legal Category:
POM
Package quantities:
1 x 1ml vial pack or 3 x 1ml packs.
Manufacturer and Licence Holder
This medicine is manufactured by Pfizer manufacturing Belgium NV, Rijksweg
12, 2870 Puurs, Belgium and is procured from within the EU and repackaged
by the Product Licence Holder: Lexon (UK) Limited, Unit 18, Oxleasow Road,
East Moons Moat, Redditch, Worcestershire, B98 0RE.
PL:15184/0926 - Depo-Medrol with Lidocaine
Depo-Medrol is a registered trademark of Pharmacia & Upjohn Limited.
Leaflet revision date: 23/11/17

Depo-Medrol ® with Lidocaine

Ref:0926/231117/12-F

(methylprednisolone acetate and lidocaine hydrochloride)

PHYSICIAN LEAFLET
1. NAME OF THE MEDICINAL PRODUCT
Depo-Medrol with Lidocaine
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Methyprednisolone 4%, Lidocaine Hydrochloride 1%
Excipients with known effect:
Also contains 8.7 mg/ml benzyl alcohol
For the full list of excipients, see section 6.1
3. PHARMACEUTICAL FORM
Suspension for Injection.
White, sterile aqueous suspension
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Corticosteroid (glucocorticoid). Depo-Medrol with Lidocaine is indicated in
conditions requiring a glucocorticoid effect: e.g. anti-inflammatory or
anti-rheumatic. It is recommended for local use where the added anaesthetic
effect would be considered advantageous.
Depo-Medrol with Lidocaine may be used as follows:
Intra-articular administration
Rheumatoid arthritis
Osteo-arthritis with an inflammatory component
Periarticular administration
Epicondylitis
Intrabursal administration
Subacromial bursitis
Prepatellar bursitis
Olecranon bursitis
Tendon sheath administration
Tendinitis
Tenosynovitis
Epicondylitis
Therapy with Depo-Medrol with Lidocaine does not obviate the need for the conventional measures usually employed. Although this method of treatment will
ameliorate symptoms, it is in no sense a cure and the hormone has no
effect on the cause of the inflammation.
4.2 Posology and method of administration
Depo-Medrol with Lidocaine should not be mixed with any other
preparation as flocculation of the product may occur. Parenteral drug products
should be inspected visually for particulate matter and discoloration prior to
administration whenever suspension and container permit. Depo-Medrol with Lidocaine may be used by any of the following routes: intra-articular,
periarticular, intrabursal, and into the tendon sheath. It must not be used by the
intrathecal, or intravenous routes (see sections 4.3 and 4.8).
Adults
Intra-articular: Rheumatoid arthritis, osteo-arthritis. The dose of
Depo-Medrol with Lidocaine depends on the size of the joint and the
severity of the condition. Repeated injections, if needed, may be given at
intervals of one to five or more weeks depending upon the degree of relief
obtained from the initial injection. A suggested dosage guide is: large joint (knee,
ankle, shoulder), 0.5 - 2 ml (20 - 80 mg of steroid); medium joint (elbow, wrist),
0.25 - 1 ml (10 - 40 mg of steroid); small joint
(metacarpophalangeal, interphalangeal, sternoclavicular, acromioclavicular), 0.1
- 0.25 ml (4 - 10 mg of steroid).
Periarticular: Epicondylitis. Infiltrate 0.1 - 0.75 ml (4 - 30 mg of steroid) into the
affected area.
Intrabursal: Subdeltoid bursitis, prepatellar bursitis, olecranon bursitis.
For administration directly into bursae, 0.1 - 0.75 ml (4 - 30 mg of steroid). In
most acute cases, repeat injections are not needed.
Into the tendon sheath: Tendinitis, tenosynovitis, epicondylitis.
For administration directly into the tendon sheath, 0.1 - 0.75 ml (4 - 30 mg of
steroid). In recurrent or chronic conditions, repeat injections may be
necessary.
Paediatric population
For infants and children, the recommended dosage should be reduced, but
dosage should be governed by the severity of the condition rather than by strict
adherence to the ratio indicated by age or body weight.
Elderly:
When used according to instructions, there is no information to suggest that a
change in dosage is warranted in the elderly. However, treatment of elderly
patients, particularly if long-term, should be planned bearing in mind the more
serious consequences of the common side-effects of corticosteroids in old age
and close clinical supervision is required (see section 4.4).
Special precautions should be observed when administering Depo-Medrol with
Lidocaine:
Intra-articular injections should be made using precise, anatomical
localisation into the synovial space of the joint involved. The injection site for
each joint is determined by that location where the synovial cavity is most
superficial and most free of large vessels and nerves. Suitable sites for
intra-articular injection are the knee, ankle, wrist, elbow, shoulder, phalangeal
and hip joints. The spinal joints, unstable joints and those devoid of synovial
space are not suitable. Treatment failures are most frequently the result of failure
to enter the joint space. Intra-articular injections should be made with care as
follows: ensure correct positioning of the needle into the synovial space and
aspirate a few drops of joint fluid. The aspirating syringe should then be replaced
by another containing Depo-Medrol with Lidocaine. To ensure position of the
needle synovial fluid should be aspirated and the injection made.
After injection the joint is moved slightly to aid mixing of the synovial fluid and the
suspension. Subsequent to therapy care should be taken for the patient not to
overuse the joint in which benefit has been obtained. Negligence in this matter
may permit an increase in joint deterioration that will more than offset the
beneficial effects of the steroid.
Intrabursal injections should be made as follows: the area around the
injection site is prepared in a sterile way and a wheal at the site made with 1
percent procaine hydrochloride solution. A 20 to 24 gauge needle attached to a
dry syringe is inserted into the bursa and the fluid aspirated. The needle is left in
place and the aspirating syringe changed for a small syringe containing the
desired dose. After injection, the needle is withdrawn and a small
dressing applied. In the treatment of tenosynovitis and tendinitis, care should be
taken to inject Depo-Medrol with Lidocaine into the tendon sheath rather than
into the substance of the tendon. Due to the absence of a true tendon sheath,
the Achilles tendon should not be injected with Depo-Medrol with
Lidocaine.
The usual sterile precautions should be observed with each injection.
4.3 Contraindications
Depo-Medrol with Lidocaine is contraindicated:
• in patients with known hypersensitivity to the active substances or to any of
the excipients listed in section 6.1
• in patients with known hypersensitivity to other local anaesthetics of the
amide type
• in patients who have systemic infection unless specific anti-infective
therapy is employed
• for use by the intrathecal route (due to its potential for neurotoxicity)
• for use by the intravenous route (see section 4.8)
Administration of live or live, attenuated vaccines is contraindicated in patients
receiving immunosuppressive doses of corticosteroids.
4.4 Special warnings and precautions for use
Undesirable effects may be minimised by using the lowest effective dose for the
minimum period. Frequent patient review is required to appropriately titrate the
dose against disease activity (see section 4.2).
Depo-Medrol with Lidocaine vials are intended for single dose use only.
Any multidose use of the product may lead to contamination.
Depo-Medrol with Lidocaine is not recommended for intranasal, intra-ocular, or
any other unapproved route of administration.
Severe medical events have been reported in association with the
intrathecal/epidural routes of administration (see section 4.8). Appropriate
measures must be taken to avoid intravascular injection.
Due to the absence of a true tendon sheath, the Achilles tendon should not be
injected with Depo-Medrol with Lidocaine.

While crystals of adrenal steroids in the dermis suppress inflammatory
reactions, their presence may cause disintegration of the cellular elements and
physiochemical changes in the ground substance of the connective
tissue. The resultant infrequently occurring dermal and/or subdermal changes
may form depressions in the skin at the injection site and the possibility of
depigmentation. The degree to which this reaction occurs will vary with the
amount of adrenal steroid injected. Regeneration is usually complete within a few
months or after all crystals of the adrenal steroid have been absorbed. In order to
minimize the incidence of dermal and subdermal atrophy, care must be exercised
not to exceed recommended doses in injections. Multiple small injections into the
area of the lesion should be made whenever possible. The technique of
intra-articular injection should include precautions against injection or leakage
into the dermis.
Systemic absorption of methylprednisolone occurs following intra-articular
injection of Depo-Medrol with Lidocaine. Systemic as well as local effects can
therefore be expected.
Adrenal cortical atrophy develops during prolonged therapy and may persist for
months after stopping treatment. In patients who have received more than
physiological doses of systemic corticosteroids (approximately 6 mg
methylprednisolone) for greater than 3 weeks, withdrawal should not be abrupt.
How dose reduction should be carried out depends largely on whether the
disease is likely to relapse as the dose of systemic corticosteroids is
reduced. Clinical assessment of disease activity may be needed during
withdrawal. If the disease is unlikely to relapse on withdrawal of systemic
corticosteroids, but there is uncertainty about HPA suppression, the dose of
systemic corticosteroid may be reduced rapidly to physiological doses. Once a
daily dose of 6 mg methylprednisolone is reached, dose reduction should be
slower to allow the HPA-axis to recover.
The following precautions apply for parenteral corticosteroids:
Following intra-articular injection, the occurrence of a marked increase in pain
accompanied by local swelling, further restriction of joint motion, fever, and
malaise are suggestive of septic arthritis. If this complication occurs and the
diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should be
instituted.
No additional benefit derives from the intramuscular administration of
Depo-Medrone with Lidocaine. Where parenteral corticosteroid therapy for
sustained systemic effect is desired, plain Depo-Medrol should be used.
Local injection of a steroid into a previously infected joint is to be avoided.
Intra-articular corticosteroids are associated with a substantially increased risk of
inflammatory response in the joint, particularly bacterial infection
introduced with the injection. Charcot-like arthropathies have been reported
particularly after repeated injections. Appropriate examination of any joint fluid
present is necessary to exclude any bacterial infection, prior to injection.
Corticosteroids should not be injected into unstable joints.
Sterile technique is necessary to prevent infections or contamination.
Immunosuppressant Effects/Increased Susceptibility to Infections
Corticosteroids may increase susceptibility to infection, may mask some signs of
infection, and new infections may appear during their use. Suppression of the
inflammatory response and immune function increases the susceptibility to
fungal, viral and bacterial infections and their severity. The clinical
presentation may often be atypical and may reach an advanced stage before
being recognised.
With increasing doses of corticosteroids, the rate of occurrence of infectious
complications increases. Persons who are on drugs which suppress the
immune system are more susceptible to infections than healthy individuals.
Chickenpox and measles, for example, can have a more serious or even fatal
course in non-immune children or adults on corticosteroids.
Chickenpox is of serious concern since this normally minor illness may be fatal in
immunosuppressed patients. Patients (or parents of children) without a definite
history of chickenpox should be advised to avoid close personal
contact with chickenpox or herpes zoster and if exposed they should seek
urgent medical attention. Passive immunization with varicella/zoster
immunoglobin (VZIG) is needed by exposed non-immune patients who are
receiving systemic corticosteroids or who have used them within the previous 3
months; this should be given within 10 days of exposure to chickenpox. If a
diagnosis of chickenpox is confirmed, the illness warrants specialist care and
urgent treatment. Corticosteroids should not be stopped and the dose may need
to be increased.
Live vaccines should not be given to individuals with impaired immune
responsiveness. The antibody response to other vaccines may be
diminished.
If corticosteroids are indicated in patients with latent tuberculosis or
tuberculin reactivity, close observation is necessary as reactivation of the
disease may occur. During prolonged corticosteroid therapy, these patients
should receive chemoprophylaxis. The role of corticosteroids in septic shock has
been controversial, with early studies reporting both beneficial and detrimental
effects. More recently, supplemental corticosteroids have been suggested to be
beneficial in patients with established septic shock who exhibit adrenal
insufficiency. However, their routine use in septic shock is not recommended. A
systematic review of short-course, high-dose corticosteroids did not support their
use. However, meta-analyses, and a review suggest that longer courses (5-11
days) of low-dose corticosteroids might reduce mortality, especially in patients
with vasopressor-dependent septic shock.
Immune System Effects
Allergic reactions may occur. Because rare instances of skin reactions and
anaphylactic/anaphylactoid reactions have occurred in patients receiving
corticosteroid therapy, appropriate precautionary measures should be taken
prior to administration, especially when the patient has a history of drug
allergy.
Endocrine Effects
Pharmacologic doses of corticosteroids administered for prolonged periods may
result in hypothalamic-pituitary-adrenal (HPA) suppression (secondary
adrenocortical insufficiency). The degree and duration of adrenocortical
insufficiency produced is variable among patients and depends on the dose,
frequency, time of administration, and duration of glucocorticoid therapy.
Abrupt withdrawal of systemic corticosteroid treatment, which has continued up
to 3 weeks is appropriate if it considered that the disease is unlikely to relapse.
Abrupt withdrawal of doses up to 32 mg daily of methylprednisolone for 3 weeks
is unlikely to lead to clinically relevant HPA-axis suppression, in the majority of
patients. In the following patient groups, gradual withdrawal of systemic
corticosteroid therapy should be considered even after courses
lasting 3 weeks or less:
• Patients who have had repeated courses of systemic corticosteroids,
particularly if taken for greater than 3 weeks.
• When a short course has been prescribed within one year of cessation of
long-term therapy (months or years).
• Patients who may have reasons for adrenocortical insufficiency other than
exogenous corticosteroid therapy.
• Patients receiving doses of systemic corticosteroid greater than 32 mg daily of
methylprednisolone.
• Patients repeatedly taking doses in the evening.
Since mineralocorticoid secretion may be impaired, salt and/or a
mineralocorticoid should be administered concurrently.
A steroid “withdrawal syndrome,” seemingly unrelated to adrenocortical
insufficiency, may also occur following abrupt discontinuance of
glucocorticoids. This syndrome includes symptoms such as: anorexia,
nausea, vomiting, lethargy, headache, fever, joint pain, desquamation,
myalgia, weight loss, and/or hypotension. These effects are thought to be due to
the sudden change in glucocorticoid concentration rather than to low
corticosteroid levels. Because glucocorticoids can produce or aggravate
Cushing’s syndrome, glucocorticoids should be avoided in patients with
Cushing’s disease. There is an enhanced effect of corticosteroids on patients
with hypothyroidism.
Metabolism and Nutrition
Corticosteroids, including methylprednisolone, can increase blood glucose,
worsen pre-existing diabetes, and predispose those on long-term
corticosteroid therapy to diabetes mellitus.

Psychiatric Effects
Patients and/or carers should be warned that potentially severe psychiatric
adverse reactions may occur with systemic steroids (see section 4.8).
Symptoms typically emerge within a few days or weeks of starting treatment.
Risks may be higher with high doses/systemic exposure (see section 4.5),
although dose levels do not allow prediction of the onset, type, severity or
duration of reactions. Most reactions recover after either dose reduction or
withdrawal, although specific treatment may be necessary. Patients/carers
should be encouraged to seek medical advice if worrying psychological
symptoms develop, especially if depressed mood or suicidal ideation is
suspected. Patients/carers should be alert to possible psychiatric
disturbances that may occur either during or immediately after dose
tapering/withdrawal of systemic steroids, although such reactions have been
reported infrequently.
Particular care is required when considering the use of systemic
corticosteroids in patients with existing or previous history of severe affective
disorders in themselves or in their first degree relatives. These would include
depressive or manic-depressive illness and previous steroid psychosis.
Nervous System Effects
Corticosteroids should be used with caution in patients with seizure
disorders.
Corticosteroids should be used with caution in patients with myasthenia gravis
(also see myopathy statement in Musculoskeletal Effects section).
There have been reports of epidural lipomatosis in patients taking
corticosteroids, typically with long-term use at high doses.
Ocular Effects
Prolonged use of corticosteroids may produce posterior subcapsular cataracts
and nuclear cataracts (particularly in children), exophthalmos, or increased
intraocular pressure, which may result in glaucoma with possible damage to the
optic nerves, and may enhance the establishment of
secondary ocular infections due to fungi or viruses.
Corticosteroids should be used cautiously in patients with ocular herpes
simplex, because of possible corneal perforation.
Corticosteroid therapy has been associated with central serous
chorioretinopathy, which may lead to retinal detachment.
Cardiac Effects
Adverse effects of glucocorticoids on the cardiovascular system, such as
dyslipidaemia and hypertension, may predispose treated patients with existing
cardiovascular risk factors to additional cardiovascular effects, if high doses and
prolonged courses are used. Accordingly, corticosteroids should be
employed judiciously in such patients and attention should be paid to risk
modification and additional cardiac monitoring if needed.
Systemic corticosteroids should be used with caution, and only if strictly
necessary, in cases of congestive heart failure.
Vascular Effects
Corticosteroids should be used with caution in patients with hypertension.
Thrombosis including venous thromboembolism has been reported to occur with
corticosteroids. As a result corticosteroids should be used with caution in patients
who have or may be predisposed to thromboembolic disorders.
Gastrointestinal Effects
There is no universal agreement on whether corticosteroids per se are
responsible for peptic ulcers encountered during therapy; however,
glucocorticoid therapy may mask the symptoms of peptic ulcer so that
perforation or haemorrhage may occur without significant pain. In combination
with NSAIDs, the risk of developing gastrointestinal ulcers is increased.
Corticosteroids should be used with caution in nonspecific ulcerative colitis, if
there is a probability of impending perforation, abscess or other pyogenic
infection. Caution must also be used in diverticulitis, fresh intestinal
anastomoses, active or latent peptic ulcer, when steroids are used as direct or
adjunctive therapy.
Hepatobiliary Effects
Drug induced liver injury including acute hepatitis or liver enzyme increase can
result from cyclical pulsed IV methylprednisolone (usually at initial dose > 1 g /
day). Rare cases of hepatotoxicity have been reported. The time to onset can be
several weeks or longer. In the majority of case reports resolution of the adverse
events has been observed after treatment was discontinued. Therefore,
appropriate monitoring is required.
High doses of corticosteroids may produce acute pancreatitis.
Corticosteroids should be used with caution in patients with liver failure or
cirrhosis.
Musculoskeletal Effects
An acute myopathy has been reported with the use of high doses of
corticosteroids, most often occurring in patients with disorders of
neuromuscular transmission (e.g. myasthenia gravis), or in patients receiving
concomitant therapy with anticholinergics, such as neuromuscular blocking drugs
(e.g. pancuronium). This acute myopathy is generalized, may involve ocular and
respiratory muscles, and may result in quadriparesis. Elevations of creatine
kinase may occur. Clinical improvement or recovery after stopping
corticosteroids may require weeks to years.
Osteoporosis is a common but infrequently recognized adverse effect
associated with a long-term use of large doses of glucocorticoid.
Renal and Urinary Disorders
Corticosteroids should be used with caution in patients with renal insufficiency.
Injury, Poisoning and Procedural Complications
Systemic corticosteroids are not indicated for, and therefore should not be used
to treat, traumatic brain injury, a multicenter study revealed an increased
mortality at 2 weeks and 6 months after injury in patients administered
methylprednisolone sodium succinate compared to placebo. A causal association
with methylprednisolone sodium succinate treatment has not been established.
Investigations
Average and large doses of hydrocortisone or cortisone can cause elevation of
blood pressure, salt and water retention, and increased excretion of
potassium. These effects are less likely to occur with the synthetic derivatives
except when used in large doses. Dietary salt restriction and potassium
supplementation may be necessary. All corticosteroids increase calcium
excretion.
Care should be taken for patients receiving cardioactive drugs such as digoxin
because of steroid induced electrolyte disturbance/potassium loss (see section
4.8).
Other
Patients should carry 'Steroid Treatment' cards which give clear guidance on the
precautions to be taken to minimise risk and which provide details of
prescriber, drug, dosage and the duration of treatment.
Corticosteroids should be used with caution in patients with a predisposition to
thrombophlebitis. Aspirin and nonsteroidal anti-inflammatory agents should be
used cautiously in conjunction with corticosteroids.
Pheochromocytoma crisis, which can be fatal, has been reported after
administration of systemic corticosteroids. Corticosteroids should only be
administered to patients with suspected or identified pheochromocytoma after an
appropriate risk/benefit evaluation.
Paediatric population
Intravenous administration of the preservative benzyl alcohol has been
associated with serious adverse event, and death in paediatric patients
including neonates characterized by central nervous system depression,
metabolic acidosis, gasping respirations, cardio-vascular failure and
haematological anomalies (“gasping syndrome”). The minimum amount of benzyl
alcohol at which toxicity may occur is not known. Use only if it is
necessary and if there are no alternatives possible. If given in high volumes,
should be used with caution and preferably for short term treatment in
subjects with liver or kidney impairment because of the risk of accumulation and
toxicity (metabolic acidosis)
Premature and low-birth weight infants may be more likely to develop toxicity.
Benzyl Alcohol containing products should not be used in pre-term or full-term
neonates unless strictly necessary
Corticosteroids cause growth retardation in infancy, childhood and
adolescence which may be irreversible. Growth and development of infants and
children on prolonged corticosteroid therapy should be carefully
observed. Treatment should be limited to the minimum dosage for the
shortest possible time. The use of such a regimen should be restricted to those
most serious indications. Infants and children on prolonged corticosteroid
therapy are at special risk from raised intracranial pressure.
High doses of corticosteroids may produce pancreatitis in children.

4.5 Interaction with other medicinal products and other forms of
interaction
Methylprednisolone is a cytochrome P450 enzyme (CYP) substrate and is mainly
metabolized by the CYP3A enzyme. CYP3A4 is the dominant enzyme of the
most abundant CYP subfamily in the liver of adult humans. It catalyzes
6β-hydroxylation of steroids, the essential Phase I metabolic step for both
endogenous and synthetic corticosteroids. Many other compounds are also
substrates of CYP3A4, some of which (as well as other drugs) have been shown
to alter glucocorticoid metabolism by induction (upregulation) or inhibition of the
CYP3A4 enzyme.
CYP3A4 INHIBITORS – Drugs that inhibit CYP3A4 activity generally
decrease hepatic clearance and increase the plasma concentration of CYP3A4
substrate medications, such as methylprednisolone. In the presence of a
CYP3A4 inhibitor, the dose of methylprednisolone may need to be titrated to
avoid steroid toxicity.
CYP3A4 INDUCERS – Drugs that induce CYP3A4 activity generally increase
hepatic clearance, resulting in decreased plasma concentration of medications
that are substrates for CYP3A4. Coadministration may require an increase in
methylprednisolone dosage to achieve the desired result.
CYP3A4 SUBSTRATES – In the presence of another CYP3A4 substrate, the
hepatic clearance of methylprednisolone may be affected, with corresponding
dosage adjustments required. It is possible that adverse events associated with
the use of either drug alone may be more likely to occur with coadministration.
1. Convulsions have been reported with concurrent use of methylprednisolone
and ciclosporin (CYP3A4 inhibitor and substrate). Since concurrent
administration of these agents results in a mutual inhibition of metabolism (which
may increase the plasma concentrations of either or both drugs), it is possible
that convulsions and other adverse effects associated with the
individual use of either drug may be more apt to occur.
2. Drugs that induce hepatic enzymes, such as rifampicin (antibiotic CYP3A4
inducer), rifabutin, carbamazepine (anticonvulsant CYP3A4 inducer and
substrate), phenobarbitone and phenytoin (anticonvulsants CYP3A4
inducers), primidone, and aminoglutethimide (aromatase inhibitor) enhance the
metabolism of corticosteroids and its therapeutic effects may be reduced.
Aminoglutethimide- induced adrenal suppression may exacerbate endocrine
changes caused by prolonged glucocorticoid treatment.
3. Antibiotics/Antimycotics - Drugs such as erythromycin (macrolide
antibacterial CYP3A4 inhibitor and substrate), itraconazole and ketoconazole
antifungal CYP3A4 inhibitors and substrates) may inhibit the metabolism of
corticosteroids and thus decrease their clearance.
Troleandomycin (CYP3A4 inhibitor), as well as clarithromycin, erythromycin,
itraconazole and ketoconazole (CYP3A4 inhibitors and substrates) increase the
effects and the side effects of methylprednisolone.
The acetylation rate and clearance of isoniazid (CYP3A4 inhibitor), an
antibacterial drug, can be increased by methylprednisolone.
4. Steroids may reduce the effects of anticholinesterases in myasthenia gravis.
An acute myopathy has been reported with the concomitant use of high doses of
corticosteroids and anticholinergics, such as neuromuscular blocking drugs (see
section 4.4).
Antagonism of the neuromuscular blocking effects of pancuronium and
vecuronium has been reported in patients taking corticosteroids. This
interaction may be expected with all competitive neuromuscular blockers.
The desired effects of hypoglycaemic agents (including insulin),
anti-hypertensives and diuretics are antagonised by corticosteroids, and the
hypokalaemic effects of acetazolamide, loop diuretics, thiazide diuretics and
carbenoxolone are enhanced.
5. The effect of methylprednisolone on oral anticoagulants is variable.
The efficacy of coumarin anticoagulants may be enhanced by concurrent
corticosteroid therapy and close monitoring of the INR or prothrombin time is
required to avoid spontaneous bleeding and to maintain the desired
anticoagulant effects.
There are also reports of diminished effects of anticoagulants when given
concurrently with corticosteroids.
6. There may be increased incidence of gastrointestinal bleeding and
ulceration when corticosteroids are given with NSAIDs. Methylprednisolone may
increase the clearance of high-dose aspirin, which can lead to decreased
salicylate serum levels. Discontinuation of methylprednisolone treatment can
lead to raised salicylate serum levels, which could lead to an increased risk of
salicylate toxicity. Salicylates and non-steroidal anti-inflammatory agents should
be used cautiously in conjunction with corticosteroids in hypothrombinaemia.
7. Antidiabetics - Because corticosteroids may increase blood glucose
concentrations, dosage adjustments of antidiabetic agents may be required.
8. Antiemetics - Aprepitant and fosaprepitant (CYP3A4 inhibitors and substrates).
9. Antivirals - HIV protease inhibitors: Indinavir and ritonavir (CYP3A4 inhibitors
and substrates) may increase plasma concentrations of corticosteroids.
Corticosteroids may induce the metabolism of HIV-protease inhibitors resulting in
reduced plasma concentrations.
10. Calcium channel blocker - Diltiazem (CYP3A4 inhibitor and substrate).
11. Contraceptives (oral) - Ethinylestradiol/norethindrone (CYP3A4 inhibitors and
substrate).
12. Other immunosuppressants like cyclophosphamide and tacrolimus are
substrates of CYP3A4.
13. Potassium-depleting agents - When corticosteroids are administered
concomitantly with potassium-depleting agents (i.e. diuretics), patients should be
observed closely for development of hypokalaemia. There is also an increased
risk of hypokalaemia with concurrent use of corticosteroids with amphotericin B,
xanthenes, or beta2 agonists.
14. Grapefruit juice - CYP3A4 inhibitor.
4.6 Fertility, pregnancy and lactation
Fertility
There is no evidence showing that corticosteroids impair fertility (see section
5.3).
Pregnancy
Methylprednisolone
The ability of corticosteroids to cross the placenta varies between individual
drugs, however, methylprednisolone does cross the placenta. One retrospective
study found an increased incidence of low birth weights in infants born of
mothers receiving corticosteroids.
Administration of corticosteroids to pregnant animals can cause abnormalities of
foetal development including cleft palate, intra-uterine growth retardation and
affects on brain growth and development. There is no evidence that
corticosteroids result in an increased incidence of congenital abnormalities, such
as cleft palate in man, however, when administered for long periods or
repeatedly during pregnancy, corticosteroids may increase the risk of
intra-uterine growth retardation. Hypoadrenalism may, in theory, occur in the
neonate following prenatal exposure to corticosteroids but usually resolves
spontaneously following birth and is rarely clinically important. Although neonatal
adrenal insufficiency appears to be rare in infants who were exposed in utero to
corticosteroids, those exposed to substantial doses of corticosteroids must be
carefully observed and evaluated for signs of adrenal insufficiency. As with all
drugs, corticosteroids should only be prescribed when the benefits to the mother
and child outweigh the risks. When corticosteroids are essential, however,
patients with normal pregnancies may be treated as though they were in the
non-gravid state. Cataracts have been observed in infants born to mothers
treated with long-term corticosteroids during pregnancy.
Lidocaine
Adequate human reproductive studies have not been done with Lidocaine.
The use of local anaesthetics such as lidocaine during labour and delivery may
be associated with adverse effects on mother and foetus.
Lidocaine readily crosses the placenta. Benzyl alcohol can cross the placenta
Breast-feeding
Methylprednisolone
Corticosteroids are distributed in small amounts in breast milk and may
suppress growth and interfere with endogenous glucocorticoid production in
nursing infants. However, doses of up to 40 mg daily of methylprednisolone are
unlikely to cause systemic effects in the infant. Infants of mothers taking higher
doses than this may have a degree of adrenal suppression. Since
adequate reproductive studies have not been performed in humans with
glucocorticoids, these drugs should be administered to nursing mothers only if
the benefits of therapy are judged to outweigh the potential risks to the infant.
Lidocaine It is not known whether lidocaine is excreted in human breast milk.

4.7 Effects on ability to drive and use machines
The effect of corticosteroids on the ability to drive or use machinery has not been
systematically evaluated. Undesirable effects, such as dizziness,
vertigo, visual disturbances, and fatigue are possible after treatment with
corticosteroids. If affected, patients should not drive or operate machinery.
4.8 Undesirable effects
The incidence of predictable undesirable side effects associated with the use of
corticosteroids, including hypothalamic-pituitary-adrenal suppression
correlates with the relative potency of the drug, dosage, timing of
administration and duration of treatment (See section 4.4).
Side effects for the Depo-Medrol component may be observed including:
MedDRA

Frequency

† Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare
(≥1/10,000 to <1/1,000); Not known (frequency cannot be estimated from the
available data) Side effects for the Lidocaine component include:
MedDRA

Frequency

Undesirable Effects

Immune system

Not known

Anaphylactic reaction

Psychiatric disorders

Common

Confusional state;
Euphoric mood;
Nervousness; Anxiety

Nervous System
disorders

Common

Eye disorders

Common

Diplopia; Vision
blurred ;

System Organ Class

Undesirable Effects

System Organ Class

Infections and
infestations

Common

Not Known

Infection (including increased susceptibility and
severity of infections with suppression of clinical
symptoms and signs)
Opportunistic infection; Injection site infection;
Peritonitis; Recurrence of dormant tuberculosis

Loss of consciousness;
Convulsion;
Hypoaesthesia;
Tremor; Somnolence;
Dizziness

Immune system
disorders

Not Known

Drug hypersensitivity, Anaphylactic reaction

Blood and lymphatic
system disorders

Not Known

Leukocytosis

Ear and labyrinth
disorders

Common

Tinnitus

Common

Cushingoid

Cardiac disorders

Common

Bradycardia

Not Known

Hypopituitarism; Withdrawal symptoms - Too rapid
a reduction of corticosteroid dosage following
prolonged treatment can lead to acute adrenal
insufficiency, hypotension and death. However,
this is more applicable to corticosteroids with an
indication where continuous therapy is given (see
section 4.4). A 'withdrawal syndrome' may also
occur including, fever, myalgia, arthralgia, rhinitis,
conjunctivitis, painful itchy skin nodules and
loss of weight

Not known

Hypotension

Common

Circulatory collapse;
Cardiac arrest

Endocrine
disorders

Metabolism and
nutrition disorders

Common

Not Known

Psychiatric
disorders

Common

Not Known

Nervous system
disorders

Eye disorders

Not Known

General disorders and
administration
site conditions

Alkalosis hypokalaemic; Dyslipidaemia, Increased
appetite (which may result in Weight increased);
Epidural lipomatosis

Skin and
subcutaneous
disorders

Affective disorder (including Depressed mood,
Euphoric mood). Mood swings; Abnormal
behaviour; Insomnia
Affective disorder (including Affect lability,
psychological dependence [not a MedDRA PT],
Suicidal ideation), Psychotic disorder (including
Mania, Delusion, Hallucination, and Schizophrenia
[aggravation of]); Confusional state; Mental disorder;
Anxiety; Personality change
Intracranial pressure increased
(with Papilloedema [Benign intracranial
hypertension]); Convulsion; Amnesia; Cognitive
disorder; Dizziness; Headache; Epidural
lipomatosis
Cataract; Glaucoma

Not Known

Exophthalmos; chorioretinopathy; Rare instances of
blindness associated with intralesional therapy
around the face and head [not a MedDRA PT];
Increased intra-ocular pressure, with possible
damage to the optic nerve; Corneal or scleral
thinning; Exacerbation of ophthalmic viral or
fungal disease

Ear and labyrinth
disorders

Not Known

Vertigo

Cardiac disorders

Not Known

Cardiac failure congestive (in susceptible
patients)

Vascular disorders

Common

Hypertension

Hypotension; Embolism arterial, Thrombotic
events

Respiratory, thoracic
and mediastinal
disorders

Not Known

Pulmonary embolism, Hiccups

Gastrointestinal
disorders

Common

Peptic ulcer (with possible Peptic ulcer
perforation and Peptic ulcer haemorrhage)

Not Known

Hepatobiliary disorders Not Known

Skin and subcutaneous Common
tissue disorders

Musculoskeletal and
connective tissue
disorders

Reproductive system
and breast disorders

General disorders and
administration site
conditions

Investigations

Hepatitis, Increase of liver enzymes

Ecchymosis; Acne

Angioedema; Petechiae; Skin atrophy; Skin
striae; Skin hyperpigmentation; Skin
hypopigmentation; Hirsutism; Rash; Erythema;
Pruritus; Urticaria; Hyperhidrosis

Common

Growth retardation; Osteoporosis;
Muscular weakness

Not Known

Osteonecrosis; Pathological fracture; Muscle
atrophy; Myopathy; Neuropathic arthropathy;
Arthralgia; Myalgia

Not Known

Menstruation irregular

Common

Impaired healing; Oedema peripheral; Irritability

Common

Not Known

Injury, poisoning and
procedural
complications

Gastric haemorrhage; Intestinal perforation;
Pancreatitis; Oesophagitis ulcerative;
Oesophagitis; Oesophageal candidiasis;
Abdominal pain; Abdominal distension;
Diarrhoea; Dyspepsia; Nausea

Not Known

Not Known

Not Known

Respiratory, thoracic
and mediastinal
disorders

Glucose tolerance impaired; Sodium retention;
Fluid retention; Increased requirements for insulin
(or oral hypoglycemic agents in diabetics).

Common

Not Known

Vascular disorders

Injection site reaction; Abscess sterile; Fatigue;
Malaise
Blood potassium decreased

Alanine aminotransferase increased; Aspartate
aminotransferase increased; Blood alkaline
phosphatase increased; Carbohydrate
tolerance decreased; Urine calcium increased;
suppression of reactions to skin tests [not a
MedDRA PT]; Blood urea increased;
Nitrogen balance negative (due to protein
catabolism)
Tendon rupture (particularly of the Achilles tendon);
Spinal compression fracture. Systemic
corticosteroids are not indicated for, and
therefore should not be used to treat, traumatic
brain injury.

Musculoskeletal and
connective tissue
disorders

Gastrointestinal
disorders

Common

Respiratory arrest;
Respiratory depression

Common

Vomiting

Not known

Skin lesion; Urticaria

Common

Muscle twitching

Common

Oedema; Feeling cold; Feeling
hot

CERTAIN SIDE EFFECTS REPORTED WITH SOME NON RECOMMENDED
ROUTES OF ADMINISTRATION:
Intrathecal/Epidural: Usual systemic corticoid adverse reactions, headache,
meningismus, meningitis, paraparesis/paraplegia, spinal fluid abnormalities,
nausea, vomiting, sweating, arachnoiditis, functional gastrointestinal
disorder/bladder dysfunction, convulsions, sensory disturbances. The frequency
of these adverse reactions is not known.
Extradural: Wound dehiscence, loss of sphincter control.
Intranasal: Permanent/temporary blindness, allergic reactions, rhinitis.
Ophthalmic (Subconjunctival): Redness and itching, abscess, slough at injection
site, residue at injection site, increased intra-ocular pressure, decreased
vision - blindness, infection.
Miscellaneous: Scalp, tonsillar fauces, sphenopalatine ganglion: blindness.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/risk balance of
the medicinal product. Healthcare professionals are asked to report any
suspected adverse reactions via the Yellow Card Scheme. Website:
www.mhra.gov.uk/yellowcard
4.9 Overdose
Methylprednisolone
Following overdosage the possibility of adrenal suppression should be guarded
against by gradual diminution of dose levels over a period of time. In such event
the patient may require to be supported during any further traumatic episode.
Reports of acute toxicity and/or death following overdosage of corticosteroids are
rare. In the event of overdosage, no specific antidote is available; treatment is
supportive and symptomatic.
Methylprednisolone is dialysable.
Lidocaine
Overdose with lidocaine can manifest itself in a transient stimulation of the
central nervous system with early symptoms: yawning, restlessness, dizziness,
nausea, vomiting, dysarthria, ataxia, hearing and visual disturbances. With
moderate intoxication also twitching and convulsions can occur. This can be
followed by unconsciousness, respiratory depression and coma. In very severe
intoxication due to decreased myocardial contractility and delayed impulse
conduction, hypotension and cardiovascular collapse can be expected to be
followed by a complete heart block and cardiac arrest. Convulsions, hypotension
and respiratory depression and cardiac events should be treated as necessary.
Continual optimal oxygenation and ventilation and circulatory support as well as
treatment of acidosis are of vital importance.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Glucocorticoids, ATC Code: H02AB04
Pharmacotherapeutic group: Anaesthetics, ATC Code: N01BB02
Methylprednisolone
Methylprednisolone acetate is a synthetic glucocorticoid with the actions and use
of natural corticosteroids. However the slower metabolism of the synthetic
corticosteroid with their lower protein-binding affinity may account for their
increased potency compared with the natural corticosteroids.
Lidocaine
Lidocaine has the actions of a local anaesthetic.
5.2 Pharmacokinetic properties
No pharmacokinetic studies have been performed with the combination product
of methylprednisolone and lidocaine, however, data are provided from
pharmacokinetic studies performed with the individual product components
methylprednisolone and lidocaine.
Absorption:
Methylprednisolone:
One in-house study of eight volunteers determined the pharmacokinetics of a
single 40 mg intramuscular dose of Depo-Medrol. The average of the individual
peak plasma concentrations was 14.8 ± 8.6 ng/mL, the average of the individual
peak times (tmax) was 7.25 ± 1.04 hours, and the average area under the curve
(AUC) was 1354.2 ± 424.1 ng/mL x hrs (Day 1-21).
Lidocaine:
Pharmacokinetics of lidocaine after synovial absorption following intra-articular
bolus injection in patients with knee joint arthroscopy was studied with different
maximum concentration (Cmax) values reported. The Cmax values are 2.18
µg/mL at 1 hour (serum) and 0.63 µg/mL at 0.5 hour (plasma) following
administration of lidocaine doses of 7 mg/kg and 400 mg, respectively. Other
reported serum Cmax values are 0.69 µg/mL at 5 minutes and 0.278 µg/mL at 2
hours following administration of lidocaine doses of 25 mL of 1% and 20 mL of
1.5%, respectively.
Pharmacokinetic data of lidocaine after intra-bursa and intra-cyst administrations
for local effect are not available.

Ref:0926/231117/12-B

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