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DEPO-MEDRONE WITH LIDOCAINE INJECTION

Active substance(s): LIDOCAINE HYDROCHLORIDE / METHYLPREDNISOLONE ACETATE

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date:09-Oct-17 08:22:27

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Package leaflet: Information for the patient

Depo-Medrone®
with Lidocaine
methylprednisolone acetate and
lidocaine hydrochloride

PAA069703
47

Process Black

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

code

PAA069703

guidelines

TSE-I091C

dimensions

866x214/27

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).

date

22-jun-17 EA

country

ENGLAND

• 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 8.7 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’.

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 - 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.
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.
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 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.

Continued overleaf...

PHYSICIAN LEAFLET

Depo-Medrone
with Lidocaine

®

methylprednisolone acetate and
lidocaine hydrochloride
The following information is intended for healthcare professionals only.
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 DepoMedrone 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
Undesirable Effects
System Organ
Class
Infections and Common
Infection (including increased
infestations
susceptibility and severity of
infections with suppression of
clinical symptoms and signs)
Not Known
Opportunistic infection; Injection
site infection; Peritonitis;
Recurrence of dormant
tuberculosis
Immune system Not Known
Drug hypersensitivity,
disorders
Anaphylactic reaction
Blood and
Not Known
Leukocytosis
lymphatic
system disorders
Cushingoid
Endocrine
Common
disorders
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.
Metabolism and Common
Glucose tolerance impaired;
nutrition disorders
Sodium retention; Fluid retention;
Increased requirements for
insulin (or oral hypoglycemic
agents in diabetics).
Not Known
Alkalosis hypokalaemic;
Dyslipidaemia, Increased
appetite (which may result in
Weight increased); Epidural
lipomatosis

MedDRA
System Organ
Class
Psychiatric
disorders

Undesirable Effects

Common

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

VERSO

Not Known

Nervous system Not Known
disorders

Eye disorders

Common
Not Known

Ear and labyrinth Not Known
disorders
Cardiac
Not Known
disorders
Vascular
Common
disorders
Not Known
Respiratory,
Not Known
thoracic and
mediastinal
disorders
Gastrointestinal Common
disorders
Not Known

Hepatobiliary
Not known
disorders
Skin and
Common
subcutaneous
Not Known
tissue disorders

Musculoskeletal Common
and connective
tissue disorders Not Known

Process Black

Reproductive
Not Known
system and
breast disorders
General disorders Common
and administration
site conditions
Not Known

code

PAA069703

guidelines

TSE-I091C

Vertigo
Cardiac failure congestive (in
susceptible patients)
Hypertension
Hypotension; Embolism arterial,
Thrombotic events
Pulmonary embolism, Hiccups

Peptic ulcer (with possible
Peptic ulcer perforation and
Peptic ulcer haemorrhage)
Gastric haemorrhage; Intestinal
perforation; Pancreatitis;
Oesophagitis ulcerative;
Oesophagitis; Oesophageal
candidiasis; Abdominal pain;
Abdominal distension;
Diarrhoea; Dyspepsia; Nausea
Hepatitis, Increase of liver
enzymes
Ecchymosis; Acne
Angioedema; Petechiae;
Skin atrophy; Skin striae; Skin
hyperpigmentation; Skin
hypopigmentation; Hirsutism;
Rash; Erythema; Pruritus;
Urticaria; Hyperhidrosis
Growth retardation;
Osteoporosis; Muscular weakness
Osteonecrosis; Pathological
fracture; Muscle atrophy;
Myopathy; Neuropathic
arthropathy; Arthralgia; Myalgia
Menstruation irregular
Impaired healing;
Oedema peripheral; Irritability
Injection site reaction; Abscess
sterile; Fatigue; Malaise

dimensions

866x214/27

MedDRA
System Organ
Class
Investigations

Frequency

Common
Not Known

Undesirable Effects

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)
Injury, poisoning Not Known
Tendon rupture (particularly
and procedural
of the Achilles tendon);
complications
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
Frequency
Undesirable Effects
System Organ
Class
Immune system Not known
Anaphylactic reaction
Psychiatric
Common
Confusional state; Euphoric
disorders
mood; Nervousness; Anxiety
Nervous System Common
Loss of consciousness;
disorders
Convulsion; Hypoaesthesia;
Tremor; Somnolence; Dizziness
Eye disorders
Common
Diplopia; Vision blurred ;
Ear and labyrinth Common
Tinnitus
disorders
Cardiac disorders Common
Bradycardia
Vascular
Common
Hypotension
disorders
Not known
Circulatory collapse; Cardiac
arrest
Respiratory,
Common
Respiratory arrest;
thoracic and
Respiratory depression
mediastinal
disorders
Gastrointestinal Common
Vomiting
disorders
Skin lesion; Urticaria
Skin and
Not known
subcutaneous
disorders
Musculoskeletal Common
Muscle twitching
and connective
tissue disorders
Oedema; Feeling cold;
General disorders Common
and
Feeling hot
administration site
conditions
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.

date

22-jun-17 EA

country

ENGLAND

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.
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
Wwater 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.
7. MARKETING AUTHORISATION HOLDER
Pfizer Limited,
Ramsgate Road,
Sandwich,
Kent CT13 9NJ
UK
8. MARKETING AUTHORISATION NUMBER
PL 00057/0964
9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION
Date of first authorisation:
03 March 1981
Date of latest renewal:
25 November 1991
This leaflet was last revised in: 10/2016.
Ref: DML 14_1

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.
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 in this leaflet. You can also
report side effects directly via the Yellow Card
Scheme at: www.mhra.gov.uk/yellowcard
By reporting side effects you can help provide
more information on the safety of this medicine.

What Depo-Medrone with Lidocaine looks
like and contents of the pack
Depo-Medrone with Lidocaine is a white, sterile
suspension for injection contained in a glass vial
fitted with a rubber cap.
Depo-Medrone with Lidocaine is available in
packs containing 1 or 10 vials, containing 1 ml or
2 ml of suspension. Not all packs may be
marketed.
Marketing Authorisation Holder
Pfizer Limited, Ramsgate Road, Sandwich,
Kent CT13 9NJ, UK.
Manufacturer
Pfizer Manufacturing Belgium NV, Rijksweg 12,
B-2870 Puurs, Belgium.
Company contact address
For further information on your medicine contact
Medical Information at the following address:
Pfizer Limited, Walton Oaks,
Dorking Road Tadworth, Surrey, KT20 7NS.
Tel: 01304 616161.
This leaflet was last revised in: 10/2016.
Ref: DML 14_1

Text Free area

Frequency

5. How to store
Depo-Medrone with
Lidocaine

Keep this medicine out of the sight and reach of
children.
Do not use this medicine after the expiry date
which is stated on the label and carton after EXP.
The expiry date refers to the last day of that
month.
Do not store above 25°C.Do not freeze.
Do not throw away any medicines via wastewater
or household waste. Ask your pharmacist how to
throw away medicines you no longer use. 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 are methylprednisolone
acetate and lidocaine hydrochloride. Each millilitre
of this medicine contains 40 mg of
methylprednisolone acetate and 10 mg of
lidocaine hydrochloride.
The other ingredients are sodium chloride,
myristyl-gamma-picolinium chloride, benzyl
alcohol, macrogol, sodium hydroxide,
hydrochloric acid and water for injections.

PAA069703

methylprednisolone acetate and lidocaine hydrochloride
The following information is intended for healthcare professionals only

4. CLINICAL PARTICULARS

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.

4.1 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

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

1. NAME OF THE MEDICINAL PRODUCT
Depo-Medrone with Lidocaine

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

date:20-okt-17 09:51:34

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

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.

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

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.

country

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

ENGLAND

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

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Depo-Medrone® with Lidocaine

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

01-Aug-17 GL

PHYSICIAN LEAFLET

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.

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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.

3. How to use Depo-Medrone with Lidocaine

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

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).

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 - 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.
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.
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 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.

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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

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

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 8.7 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’.

TSE-I013H

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.

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.









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methylprednisolone acetate and lidocaine hydrochloride

• 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:

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Depo-Medrone® with Lidocaine

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.

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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

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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.
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.

MedDRA System Organ Class
Infections and infestations
Immune system disorders
Blood and lymphatic
system disorders
Endocrine disorders

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:

Frequency
Common
Not Known
Not Known
Not Known

Undesirable Effects
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
Drug hypersensitivity, Anaphylactic reaction
Leukocytosis

Common
Not Known

Cushingoid
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

• 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).

MedDRA System Organ Class

Frequency

Metabolism and
nutrition disorders

Common

Psychiatric disorders

Not Known
Common
Not Known

Nervous system disorders

Not Known

Eye disorders

Common
Not Known

Ear and labyrinth disorders
Cardiac disorders
Vascular disorders

Not Known
Not Known
Common
Not Known
Not Known

Respiratory, thoracic and
mediastinal disorders
Gastrointestinal disorders

Common
Not Known

Hepatobiliary disorders
Skin and subcutaneous
tissue disorders

Not known
Common
Not Known

Musculoskeletal and
connective tissue disorders

Common
Not Known

Undesirable Effects
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.
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
Cardiac failure congestive (in susceptible patients)
Hypertension
Hypotension; Embolism arterial, Thrombotic events
Pulmonary embolism, Hiccups
Peptic ulcer (with possible Peptic ulcer perforation and Peptic ulcer haemorrhage)
Gastric haemorrhage; Intestinal perforation; Pancreatitis; Oesophagitis ulcerative; Oesophagitis; Oesophageal candidiasis;
Abdominal pain; Abdominal distension; Diarrhoea; Dyspepsia; Nausea
Hepatitis, Increase of liver enzymes
Ecchymosis; Acne
Angioedema; Petechiae; Skin atrophy; Skin striae; Skin hyperpigmentation; Skin hypopigmentation; Hirsutism; Rash; Erythema;
Pruritus; Urticaria; Hyperhidrosis
Growth retardation; Osteoporosis; Muscular weakness
Osteonecrosis; Pathological fracture; Muscle atrophy; Myopathy; Neuropathic arthropathy; Arthralgia; Myalgia

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.

MedDRA System Organ Class
Reproductive system
and breast disorders
General disorders
and administration
site conditions
Investigations

Frequency
Not Known

Undesirable Effects
Menstruation irregular

Common
Not Known

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

Common
Not Known

Injury, poisoning and
procedural complications

Not Known

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.

† 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
Not known
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 ;
Ear and labyrinth disorders
Common
Tinnitus
Cardiac disorders
Common
Bradycardia
Vascular disorders
Common
Hypotension
Not known
Circulatory collapse; Cardiac arrest
Respiratory, thoracic and
Common
Respiratory arrest; Respiratory depression
mediastinal disorders
Gastrointestinal disorders
Common
Vomiting
Skin and subcutaneous
Not known
Skin lesion; Urticaria
disorders
Muscle twitching
Musculoskeletal and
Common
connective tissue disorders
Oedema; Feeling cold; Feeling hot
General disorders and
Common
administration site conditions

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.
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.
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%.

• 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 in this
leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

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

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 this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date refers
to the last day of that month. Do not store above 25°C. Do not freeze.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away
medicines you no longer use. 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 are methylprednisolone acetate and lidocaine hydrochloride. Each millilitre of this medicine
contains 40 mg of methylprednisolone acetate and 10 mg of lidocaine hydrochloride.
The other ingredients are sodium chloride, myristyl-gamma-picolinium chloride, benzyl alcohol, macrogol, sodium
hydroxide, hydrochloric acid and water for injections.
What Depo-Medrone with Lidocaine looks like and contents of the pack
Depo-Medrone with Lidocaine is a white, sterile suspension for injection contained in a glass vial fitted with a rubber
cap.
Depo-Medrone with Lidocaine is available in packs containing 1 or 10 vials, containing 1 ml or 2 ml of suspension.
Not all packs may be marketed.
Marketing Authorisation Holder
Pfizer Limited, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.
Manufacturer
Pfizer Manufacturing Belgium NV, Rijksweg 12, B-2870 Puurs, Belgium.
Company contact address
For further information on your medicine contact Medical Information at the following address:
Pfizer Limited, Walton Oaks, Dorking Road Tadworth, Surrey, KT20 7NS. Tel: 01304 616161.
This leaflet was last revised in: 10/2016.
Ref: DML 14_1

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
Wwater 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.

7. MARKETING AUTHORISATION HOLDER

Pfizer Limited, Ramsgate Road, Sandwich, Kent CT13 9NJ UK

8. MARKETING AUTHORISATION NUMBER
PL 00057/0964

9. DATE OF FIRST AUTHORISATION/RENEWAL OF
AUTHORISATION
Date of first authorisation:
03 March 1981
Date of latest renewal:
25 November 1991
This leaflet was last revised in: 10/2016.
Ref: DML 14_1

PAA091191

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