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DEPO-MEDRONE WITH LIDOCAINE (40MG + 10MG)/ML

Active substance(s): LIDOCAINE HYDROCHLORIDE / METHYLPREDNISOLONE ACETATE

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Package leaflet: Information for the patient

Depo-Medrone® with Lidocaine
(40mg + 10mg)/ml
(methylprednisolone acetate and lidocaine
hydrochloride)
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.
The name of your medicine is Depo-Medrone with
Lidocaine (40mg + 10mg)/ml but will be referred to
as Depo-Medrone with Lidocaine throughout this
leaflet.
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.
 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.

If you are taking long term medication(s)
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.
Before you have any operation, tell your doctor,
dentist or anaesthetist that you are taking this
medicine.
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.
Cataracts have been observed in infants born to
mothers treated with long-term corticosteroids
during pregnancy.
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.
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.
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.
Depo-Medrone with Lidocaine contains benzyl
alcohol and sodium.
This medicine contains benzyl alcohol. The amount
of benzoyl alcohol per ml is 8.7mg. 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 1mmol
sodium (23mg) per vial, i.e. essentially
'sodium-free'.

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.
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.
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.
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 – 80mg (0.5 – 2ml), medium sized joints
(e.g. elbow or wrist) 10 – 40mg (0.25 – 1ml) and
small joints (e.g. finger or toe joints) may require a
4 - 10mg (0.1 - 0.25ml) dose.
Joint injections may be given weekly over a period of
several weeks, depending on how quickly you
respond to treatment.
Bursitis, epicondylitis (tennis elbow) and
tendonitis – the usual dose is between
4-30mg (0.1 - 0.75ml). In most cases repeat
injections will not be needed for bursitis and
epicondylitis. Repeat injections may be necessary to
treat long standing tendonitis.
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.
Children
Corticosteroids can affect growth in children so your
doctor will prescribe the lowest dose that will be
effective for your child.
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.
Stopping/reducing the dose of your
Depo-Medrone with Lidocaine
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 6mg (0.15ml)
Depo-Medrone with Lidocaine for more than 3
weeks;






have been given high doses of Depo-Medrone
with Lidocaine, over 32mg (0.8ml) 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 blood
stained 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.

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. How to store Depo-Medrone with
Lidocaine
Keep out of the sight and reach of children.
Do not store above 25°C. Avoid freezing.
Do not mix with other agents.
Do not use this medicine after the expiry date which
is stated on the carton and vial label after 'Exp'. The
expiry date refers to the last day of that month.
Each vial is for single use only. After use, your
doctor should take the container and syringe away. If
anything is left behind, return it to your pharmacy for
safe disposal.
This medicine should not be used if the product is
any colour other than white, or if particles can be
seen in it.
Remember if your doctor tells you to stop using this
medicine, return any unused medicine to your
pharmacist for safe disposal. Only keep this
medicine if your doctor tells you to.
Medicines should not be disposed of via wastewater
or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These
measures will help to protect the environment.
6. Contents of the pack and other
information
What Depo-Medrone with Lidocaine contains
The active substances in Depo-Medrone with
lidocaine are methylprednisolone acetate and
lidocaine hydrochloride.
Each millilitre of the suspension contains 40mg of
methylprednisolone acetate and 10mg lidocaine
hydrochloride. The other ingredients are macrogol
3350, sodium chloride (salt), myristyl-gammapicolinium chloride, benzyl alcohol and water.
What Depo-Medrone with Lidocaine looks like
Depo-Medrone with Lidocaine is a sterile, white
suspension (liquid) for injection comes in a glass
container (vial) of 1ml.
Manufacturer: Pfizer Manufacturing Belgium NV,
Rijksweg 12, B-2870 Puurs, Belgium.
Procured from within the EU and repackaged by
the Product Licence holder: B&S Healthcare, Unit
4, Bradfield Road, Ruislip, Middlesex, HA4 0NU, UK.
Depo-Medrone® with Lidocaine
(40mg + 10mg)/ml; PL 18799/2750
Leaflet date:24.10.2017

POM

Depo-Medrone with Lidocaine is a registered
trademark of Pharmacia Limited

Blind or partially sighted?
Is this leaflet hard to see or read?
Call 0208 515 3763 to obtain the
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The following information is intended for healthcare
professionals only.
®

Depo-Medrone with Lidocaine
(40mg + 10mg)/ml

(methylprednisolone acetate and lidocaine hydrochloride)

1. NAME OF THE MEDICINAL PRODUCT
Depo-Medrone with Lidocaine (40mg + 10mg)/ml

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 - 2ml
(20 - 80mg of steroid); medium joint (elbow, wrist), 0.25 - 1ml
(10 - 40 mg of steroid); small joint (metacarpophalangeal,
interphalangeal, sternoclavicular, acromioclavicular), 0.1 - 0.25ml
(4 - 10mg of steroid).
Periarticular: Epicondylitis. Infiltrate 0.1 - 0.75ml (4 - 30mg of steroid)
into the affected area.
Intrabursal: Subdeltoid bursitis, prepatellar bursitis, olecranon
bursitis. For administration directly into bursae, 0.1 - 0.75ml
(4 - 30mg 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 - 0.75ml
(4 - 30mg 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 antiinfective 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 32mg
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 antiinflammatory 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.

Side effects for the Depo-Medrone component may be observed
including:
MedDRA
Frequency
System
Organ Class
Infections and Common
infestations

Not Known

Immune
system
disorders
Blood and
lymphatic
system
disorders
Endocrine
disorders

Drug hypersensitivity, Anaphylactic
reaction

Not Known

Leukocytosis

Common

Cushingoid

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.

Lidocaine
Adequate human reproductive studies have not been done with
Lidocaine.

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.

Metabolism
Common
and nutrition
disorders
Not Known

Psychiatric
disorders

Common

Not Known

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).

Nervous
system
disorders

Not Known

Eye disorders Common
Not Known

Ear and
labyrinth
disorders

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

Not Known

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

The use of local anaesthetics such as lidocaine during labour and
delivery may be associated with adverse effects on mother and
foetus.

Undesirable Effects

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
Cataract; Glaucoma
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
Vertigo

MedDRA
System
Organ Class
Cardiac
disorders

Frequency

Undesirable Effects

Vascular
disorders

Common
Hypertension
Not Known Hypotension; Embolism arterial,
Thrombotic events

Not Known Cardiac failure congestive (in
susceptible patients)

Respiratory,
Not Known Pulmonary embolism, Hiccups
thoracic
and mediastinal
disorders
Gastrointestinal Common
Peptic ulcer (with possible Peptic
ulcer perforation and Peptic ulcer
disorders
haemorrhage)
Not Known Gastric haemorrhage; Intestinal
perforation; Pancreatitis;
Oesophagitis ulcerative;
Oesophagitis; Oesophageal candidiasis; Abdominal pain; Abdominal distension; Diarrhoea;
Dyspepsia; Nausea
Hepatobiliary
disorders

Not Known Hepatitis, Increase of liver
enzymes

Skin and
Common
Ecchymosis; Acne
subcutaneous
Not Known Angioedema; Petechiae;
tissue disorders
Skin atrophy; Skin striae;
Skin hyperpigmentation;
Skin hypopigmentation;
Hirsutism; Rash;
Erythema; Pruritus;
Urticaria; Hyperhidrosis
Musculoskeletal Common
Growth retardation;
Osteoporosis;
and connective
tissue
Muscular weakness
disorders
Not Known Osteonecrosis; Pathological fracture; Muscle atrophy;
Myopathy; Neuropathic
arthropathy; Arthralgia; Myalgia
Reproductive
Not Known
system and
breast disorders
General disorCommon
ders and
administration
site conditions Not Known
Investigations

Menstruation irregular
Impaired healing; Oedema
peripheral; Irritability
Injection site reaction; Abscess
sterile; Fatigue; Malaise

Common
Blood potassium decreased
Not Known 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)

Injury, poisoning Not Known
and
procedural
complications

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.

† 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
System
Organ Class

Frequency

Undesirable Effects

Immune
system
Psychiatric
disorders

Not Known

Anaphylactic reaction

Common

Confusional state; Euphoric
mood; Nervousness; Anxiety

Nervous System
disorders

Common

Loss of consciousness;
Convulsion; Hypoaesthesia;
Tremor; Somnolence;
Dizziness
Diplopia; Vision blurred;
Tinnitus

Eye disorders
Common
Ear and labyrinth Common
disorders
Cardiac disorders Common

Bradycardia

Vascular
disorders

Common

Hypotension

Not Known

Respiratory,
thoracic and
mediastinal
disorders
Gastrointestinal
disorders
Skin and
subcutaneous
disorders
Musculoskeletal
and connective
tissue disorders

Common

Circulatory collapse;
Cardiac arrest
Respiratory arrest;
Respiratory depression

Common

Vomiting

Not Known

Skin lesion;
Urticaria

Common

Muscle twitching

General disorders Common
and
administration
site conditions

Oedema;
Feeling cold;
Feeling hot

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.

CERTAIN SIDE EFFECTS REPORTED WITH SOME NON
RECOMMENDED ROUTES OF ADMINISTRATION:

Pharmacokinetic data of lidocaine after intra-bursa and intra-cyst
administrations for local effect are not available.

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.

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%.

Extradural: Wound dehiscence, loss of sphincter control.

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.

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.

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-2,6dimethylaniline 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, 2,6dimethylphenylhydroxylamine, 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
macrogol 3350
sodium chloride (salt)
myristyl-gamma-picolinium chloride
benzyl alcohol
water.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
See expiry date on packaging.
6.4 Special precautions for storage
Do not store above 25°C.
Avoid freezing. Do not mix with other agents.
6.5 Nature and contents of container
Sterile, white suspension (liquid) for injection and comes in glass
containers (vials) of 1ml.
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.
Procured from within the EU and repackaged by the Product
Licence holder: B&S Healthcare, Unit 4, Bradfield Road, Ruislip,
Middlesex, HA4 0NU, UK.
POM
Leaflet Date: 24.10.2017
Depo-Medrone® with Lidocaine (40mg + 10mg)/ml;
PL 18799/2750

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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