1. Name of the medicinal product

Methylprednisolone Acetate Injectable suspension USP 40mg/1ml Taj Pharma.
Methylprednisolone Acetate Injectable suspension USP 80mg/1ml Taj Pharma.
Methylprednisolone Acetate Injectable suspension USP 400mg/10ml Taj Pharma.
Methylprednisolone Acetate Injectable suspension USP 400mg/5ml Taj Pharma.

  1. Qualitative and quantitative composition

a) Methylprednisolone Acetate Injectable suspension USP 40mg/1ml
Each ml contains:
Methylprednisolone acetate USP                 40mg
Polyethylene glycol                                       29mg
Myristyl-gamma-picolinium Chloride        0.195mg

b) Methylprednisolone Acetate Injectable suspension USP 80mg/1ml
Each ml contains:
Methylprednisolone acetate USP                 80mg
Polyethylene glycol                                      29mg
Myristyl-gamma-picolinium Chloride       0.195mg

c) Methylprednisolone Acetate Injectable suspension USP 400mg/10ml
Each ml contains:
Methylprednisolone acetate USP                 40mg
Polyethylene glycol                                      29mg
Myristyl-gamma-picolinium Chloride       0.195mg

d) Methylprednisolone Acetate Injectable suspension USP 400mg/5ml
Each ml contains:
Methylprednisolone acetate USP                80mg
Polyethylene glycol                                     29mg
Myristyl-gamma-picolinium Chloride      0.195mg

For the full list of excipients, see section 6.1.

  1. Pharmaceutical form

Suspension for Injection.

White, sterile, white aqueous suspension.

  1. Clinical particulars

4.1 Therapeutic indications

Depo-Medrone may be used locally or systemically, particularly where oral therapy is not feasible.

Depo-Medrone may be used by any of the following routes: intramuscular, intra-articular, periarticular, intrabursal, intralesional or into the tendon sheath. It must not be used by the intrathecal or intravenous routes (see section 4.3 and section 4.8).

Intramuscular administration:

  1. Rheumatic disorders

Rheumatoid arthritis

  1. Collagen diseases/arteritis

Systemic lupus erythematosus

  1. Dermatological diseases

Severe erythema multiforme (Stevens-Johnson syndrome)

  1. Allergic states

Bronchial asthma

Drug hypersensitivity reactions

Angioneurotic oedema

  1. Gastro-intestinal diseases

Ulcerative colitis

Crohn’s disease

  1. Respiratory diseases

Fulminating or disseminated tuberculosis (with appropriate antituberculous chemotherapy)

Aspiration of gastric contents

  1. Miscellaneous

TB meningitis (with appropriate antituberculous chemotherapy)

Intra-articular administration:

Rheumatoid arthritis

Osteo-arthritis with an inflammatory component

Soft tissue administration (intrabursal, periarticular, into tendon sheath):

Synovitis not associated with infection

Epicondylitis

Tenosynovitis

Plantar fasciitis

Bursitis

Intralesional:

Keloids

Localized lichen planus

Localized lichen simplex

Granuloma annulare

Discoid lupus erythematosus

Alopecia areata

4.2 Posology and method of administration

Depo-Medrone should not be mixed with any other suspending agent or solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever suspension and container permit. Depo-Medrone may be used by any of the following routes: intramuscular, intra-articular, periarticular, intrabursal, intralesional and into the tendon sheath. It must not be used by the intrathecal or intravenous routes (see sections 4.3 and 4.8).

Undesirable effects may be minimised by using the lowest effective dose for the minimum period (see section 4.4).

Depo-Medrone vials are intended for single dose use only.

Intramuscular – for sustained systemic effect:

Allergic conditions (asthma, drug reactions), 80 – 120 mg (2 – 3 ml).

Dermatological conditions, 40 – 120 mg (1 – 3 ml).

Rheumatic disorders and collagen diseases (rheumatoid arthritis, SLE), 40 – 120 mg (1 – 3 ml) per week.

Dosage must be individualized and depends on the condition being treated and its severity.

The frequency of intramuscular injections should be determined by the duration of clinical response.

On average the effect of a single 2 ml (80 mg) injection may be expected to last approximately two weeks.

Intra-articular: Rheumatoid arthritis, osteo-arthritis. The dose of Depo-Medrone depends upon 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), 20 – 80 mg (0.5 – 2 ml); medium joint (elbow, wrist), 10 – 40 mg (0.25 – 1 ml); small joint (metacarpophalangeal, interphalangeal, sternoclavicular, acromioclavicular), 4 – 10 mg (0.1 – 0.25 ml).

Intrabursal: Subdeltoid bursitis, prepatellar bursitis, olecranon bursitis. For administration directly into bursae, 4 – 30 mg (0.1 – 0.75 ml). In most cases, repeat injections are not needed.

Intralesional: Keloids, localised lichen planus, localized lichen simplex, granuloma annulare, alopecia areata, and discoid lupus erythematosus. For administration directly into the lesion for local effect in dermatological conditions, 20 – 60 mg (0.5 – 1.5 ml). For large lesions, the dose may be distributed by repeated local injections of 20 – 40 mg (0.5 – 1 ml). One to four injections are usually employed. Care should be taken to avoid injection of sufficient material to cause blanching, since this may be followed by a small slough.

Peri-articular: Epicondylitis. Infiltrate 4 – 30 mg (0.1 – 0.75 ml) into the affected area.

Into the tendon sheath: Tenosynovitis, epicondylitis. For administration directly into the tendon sheath, 4 – 30 mg (0.1 – 0.75 ml). In recurrent or chronic conditions, repeat injections may be necessary.

Special precautions should be observed when administering Depo-Medrone. Intramuscular injections should be made deeply into the gluteal muscles. The usual technique of aspirating prior to injection should be employed to avoid intravascular administration. Doses recommended for intramuscular injection must not be administered superficially or subcutaneously.

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. 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 per cent procaine hydrochloride solution. A 20-24 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 care should be taken to inject Depo-Medrone 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.

The usual sterile precautions should be observed, with each injection.

Paediatric population:

Dosage may be reduced for infants and children but should be governed more by the severity of the condition and response of the patient, than by age or size.

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 Special warnings and special precautions for use).

4.3 Contraindications

Depo-Medrone is contraindicated:

  • in patients with known hypersensitivity to the active substance or to any of the excipients listed in section 6.1
  • 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, see section 4.8)
  • for use by the intravenous route

Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.

4.4 Special warnings and precautions for use

Warnings and Precautions:

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 vials are intended for single dose use only. Any multidose use of the product may lead to contamination.

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.

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. 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 and intramuscular injection should include precautions against injection or leakage into the dermis. Injection into the deltoid muscle should be avoided because of a high incidence of subcutaneous atrophy.

Intralesional doses should not be placed too superficially, particularly in easily visible sites in patients with deeply pigmented skins, since there have been rare reports of subcutaneous atrophy and depigmentation.

Systemic absorption of methylprednisolone occurs following intra-articular injection of Depo-Medrone. 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.

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.

The slower rate of absorption by intramuscular administration should be recognised.

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.

Do not use intra-synovially, intrabursally or intratendinous administration for local effect in the presence of acute infection.

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.

The use of Depo-Medrone in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen. 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. This effect may be minimized by use of alternate-day therapy.

In addition, acute adrenal insufficiency leading to a fatal outcome may occur if glucocorticoids are withdrawn abruptly. Drug-induced secondary adrenocortical insufficiency may therefore be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Salt and/or a mineralocorticoid are only needed if mineralocorticoid secretion is impaired.

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.

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.

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

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids. Central serous chorioretinopathy, may lead to retinal detachment.

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.

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

High doses of corticosteroids may produce acute pancreatitis.

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. Glucocorticoid therapy may mask peritonitis or other signs or symptoms associated with gastrointestinal disorders such as perforation, obstruction or pancreatitis. 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.

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

Caution is required in patients with systemic sclerosis because an increased incidence of scleroderma renal crisis has been observed with corticosteroids, including methylprednisolone. Blood pressure and renal function (s-creatinine) should therefore be routinely checked. When renal crisis is suspected, blood pressure should be carefully controlled.

Corticosteroids should be used with caution in patients with renal insufficiency.

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).

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.

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.

Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects (see section 4.5).

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

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. Co-administration 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 co-administration.

  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.

The acetylation rate and clearance of isoniazid (CYP3A4 inhibitor), an antibacterial drug, can be increased by methylprednisolone.

  1. 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.

  1. Steroids may reduce the effects of anticholinesterases in myasthenia gravis. 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.

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.

  1. 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.

  1. 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.

  1. Antidiabetics- Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.
  2. Antiemetics – Aprepitant and fosaprepitant (CYP3A4 inhibitors and substrates)
  3. Antivirals – HIV protease inhibitors:

1) Indinavir, ritonavir and pharmacokinetic enhancers (cobicistat) (CYP3A4 inhibitors and substrates) may increase plasma concentrations of corticosteroids.

2) Corticosteroids may induce the metabolism of HIV-protease inhibitors resulting in reduced plasma concentrations.

  1. Calcium channel blocker – Diltiazem (CYP3A4 inhibitor and substrate).
  2. Contraceptives (oral) – Ethinylestradiol/norethindrone (CYP3A4 inhibitors and substrate).
  3. Other immunosuppressants like cyclophosphamide and tacrolimus are substrates of CYP3A4.
  4. Potassium-depleting agents -When corticosteroids are administered concomitantly with potassium-depleting agents (e.g. 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.
  5. Grapefruit juice – CYP3A4 inhibitor.

4.6 Fertility, pregnancy and lactation

Fertility

Corticosteroids have been shown to impair fertility in animal studies (see section 5.3).

Pregnancy

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. In humans, the risk of low birth weight appears to be dose related and may be minimized by administering lower corticosteroid doses.

Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate, intra-uterine growth retardation and effects 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. However, corticosteroids do not appear to cause congenital anomalies when given to pregnant women.

Since adequate human reproductive studies have not been done with methylprednisolone acetate, this medicinal product should be used during pregnancy only after a careful assessment of the benefit-risk ratio to the mother and fetus.

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

Breast-feeding

Corticosteroids are excreted in small amounts in breast milk, 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, but the benefits of breast-feeding are likely to outweigh any theoretical risk.

Corticosteroids distributed into breast milk may interfere with endogenous glucocorticoid production in nursing infants. This medicinal product should be used during breast feeding only after a careful assessment of the benefit-risk ratio to the mother and infant.

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).

MedDRA

System Organ Class

Frequency Undesirable Effects
Infections and infestations Not Known Infection (including increased susceptibility and severity of infections with suppression of clinical symptoms and signs); Opportunistic infection; Injection site infection; Peritonitis; Recurrence of dormant tuberculosis
Blood and lymphatic system disorders Not Known Leukocytosis
Immune system disorders Not Known Drug hypersensitivity, Anaphylactic reaction, Anaphylactoid reaction
Endocrine disorders 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 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 nutrition disorders Not Known Metabolic acidosis; Glucose tolerance impaired; Sodium retention; Fluid retention; Increased requirements for insulin (or oral hypoglycaemic agents in diabetics)[not a MedDRA PT]; Alkalosis hypokalaemic; Dyslipidaemia, Increased appetite (which may result in Weight increased); Lipomatosis
Psychiatric disorders Not Known Affective disorder (including Depressed mood, Euphoric mood, Affect lability, Drug dependence, Suicidal ideation). The following events were most common in children: Mood swings; Abnormal behaviour; Insomnia; Psychotic disorder (including Mania, Delusion, Hallucination, and Schizophrenia [aggravation of]); Confusional state; Mental disorder; Anxiety; Personality change; Mood swings; Abnormal behaviour; Insomnia; Irritability (children and adults)
Nervous system disorders Not Known Intracranial pressure increased (with Papilloedema [Benign intracranial hypertension]); Seizure; Amnesia; Cognitive disorder; Dizziness; Headache
Eye disorders Not Known Cataract; Glaucoma; Exophthalmos; Vision blurred (see also section 4.4); Chorioretinopathy; rare instances of blindness associated with intralesional therapy around the face and head [not a MedDRA PT]; Increased intra-ocular pressure, with possible damage to the optic nerve; Corneal or scleral thinning; Exacerbation of ophthalmic viral or fungal disease
Ear and labyrinth disorders Not Known Vertigo
Cardiac disorders Not Known Cardiac failure congestive (in susceptible patients)
Vascular disorders Not Known Hypertension; Hypotension; Embolism arterial, Thrombotic events
Respiratory, thoracic and mediastinal disorders Not Known Pulmonary embolism, Hiccups
Gastrointestinal disorders Not Known Peptic ulcer (with possible Peptic ulcer perforation and Peptic ulcer haemorrhage); Gastric haemorrhage; Intestinal perforation; Pancreatitis; Oesophagitis ulcerative; Oesophagitis; Abdominal pain; Abdominal distension; Diarrhoea; Dyspepsia; Nausea
Hepatobiliary disorders Not known Hepatitis, Increase of liver enzymes
Skin and subcutaneous tissue disorders Not Known Angioedema; Hirsutism; Petechiae; Ecchymosis; Skin atrophy; Erythema; Hyperhidrosis; Skin striae; Skin hyperpigmentation; Rash; Pruritus; Urticaria; Acne; Skin hypopigmentation
Musculoskeletal and connective tissue disorders Not Known Growth retardation; Osteoporosis; Muscular weakness; Osteonecrosis; Pathological fracture; Muscle atrophy; Myopathy; Neuropathic arthropathy; Arthralgia; Myalgia
Reproductive system and breast disorders Not Known Menstruation irregular
General disorders and administration site conditions Not Known Abscess sterile; Impaired healing; Oedema peripheral; Fatigue; Malaise; Injection site reaction
Investigations 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
Injury, poisoning and procedural complications Not Known 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)

#Peritonitis may be the primary presenting sign or symptom of a gastrointestinal disorder such as perforation, obstruction or pancreatitis (see section 4.4).

CERTAIN SIDE EFFECTS REPORTED WITH SOME CONTRAINDICATED AND 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, seizure, sensory disturbance.

Extradural: Wound dehiscence, loss of sphincter control.

Intranasal: Permanent/temporary blindness, rhinitis.

Ophthalmic: (Subconjunctival) – Redness and itching, abscess, slough at injection site, residue at injection site, increased intra-ocular pressure, decreased vision – blindness, infection.

Miscellaneous injection sites: Scalp, tonsillar fauces, sphenopalatine ganglion: blindness.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important.

4.9 Overdose

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.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Glucocorticoids.

Methylprednisolone acetate is a synthetic glucocorticoid. It has greater anti-inflammatory potency than prednisolone and less tendency than prednisolone to induce sodium and water retention. An aqueous suspension may be injected directly into joints and soft tissues in the treatment of rheumatoid arthritis, osteoarthritis, bursitis and similar inflammatory conditions. For prolonged systemic effect it may be administered intramuscularly.

5.2 Pharmacokinetic properties

Absorption:

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 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).

Distribution:

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%.

Metabolism:

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.

Elimination:

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.

No dosing adjustments are necessary in renal failure. Methylprednisolone is haemodialysable.

Methylprednisolone acetate is less soluble than methylprednisolone.

5.3 Preclinical safety data

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.

Mutagenesis:

Methylprednisolone has not been formally evaluated for genotoxicity. Studies using structurally related analogues of methylprednisolone showed no evidence of a potential for genetic and chromosome mutations in limited studies in bacteria and mammalian cells.

Carcinogenesis:

Methylprednisolone has not been formally evaluated in rodent carcinogenicity studies. Variable results have been obtained with other glucocorticoids tested for carcinogenicity in mice and rats. However, published data indicate that several related glucocorticoids including budesonide, prednisolone, and triamcinolone acetonide can increase the incidence of hepatocellular adenomas and carcinomas after oral administration in drinking water to male rats. These tumorigenic effects occurred at doses which were less than the typical clinical doses on a mg/m2 basis. The clinical relevance of these findings is unknown.

Reproductive toxicity:

Methylprednisolone has not been evaluated in animal fertility studies. Corticosteroids have been shown to reduce fertility when administered to rats. Adverse effects on fertility in male rats administered corticosterone were observed and were reversible. Decreased weights and microscopic changes in prostate and seminal vesicles were observed. The numbers of implantations and live foetuses were reduced and these effects were not present following mating at the end of the recovery period.

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.

  1. Pharmaceutical particulars

6.1 List of excipients

Polyethylene glycol

Sodium chloride

Myristyl-gamma-picolinium chloride

Water for injections.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

5 years.

6.4 Special precautions for storage

Do not store above 25°C.

Do not freeze.

6.5 Nature and contents of container

Type I flint glass vial with a butyl rubber plug and metal seal. Each vial contains 1 ml, 2 ml, or 3 ml of Depo-Medrone 40 mg/ml.

6.6 Special precautions for disposal and other handling

Depo-Medrone should not be mixed with any other fluid. Discard any remaining suspension after use.

 

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Methylprednisolone Acetate Injectable suspension USP 40mg/1ml Taj Pharma.
Methylprednisolone Acetate Injectable suspension USP 80mg/1ml Taj Pharma.
Methylprednisolone Acetate Injectable suspension USP 400mg/5ml Taj Pharma.
Methylprednisolone Acetate Injectable suspension USP 400mg/10ml Taj Pharma.

Package leaflet: Information for the patient

methylprednisolone acetate

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
  • If you have any further questions, ask your doctor, pharmacist or
  • 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
What is in this leaflet
  1. What Methylprednisolone Acetate is and what it is used for
  2. What you need to know before you are given Methylprednisolone Acetate
  3. How Methylprednisolone Acetate is given to you
  4. Possible side effects
  5. How to store Methylprednisolone Acetate
  6. Contents of the pack and other information

 

  1. What Methylprednisolone Acetate is and what it is used for

Methylprednisolone Acetate contains methylprednisolone acetate.

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.

Boosting your body with extra corticosteroid such as Methylprednisolone Acetate can help when injected into the body by a doctor or nurse, such as in or near a joint, to treat local symptoms caused by inflammatory or rheumatic conditions such as:

  • 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
  • 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.
  • Plantar fasciitis: inflammation of the tissues of the sole of the
  • Skin problems: such as alopecia areata (patchy baldness), keloids (scar tissue), lichen planus or simplex (small, purplish raised patches of skin or spots), discoid lupus (round-shaped patches, often on the face) or granuloma annulare (circular warty growths).
  • Epicondylitis (tennis elbow) and tenosynovitis: For these conditions this medicine will be injected into the tendon

Alternatively this medicine may be injected into a muscle to help treat more general (systemic) problems affecting the whole body (e.g. symptoms caused by a hypersensitivity to a medicine), or allergic, inflammatory or rheumatic problems affecting the:

  • brain g. meningitis caused by tuberculosis

bowel and gut e.g. Crohn’s disease (inflammation of the gut) or ulcerative colitis (inflammation of the lower bowel)

  • joints g. rheumatoid arthritis
  • lungs g. asthma, tuberculosis or inflammation caused by breathing in (aspirating) vomit or stomach contents
  • skin g. Stevens-Johnson syndrome (an autoimmune disorder in which an immune system causes the skin to blister and peel) or systemic lupus erythematosus (lupus).

Your doctor may use this medicine to treat conditions other than those listed above. Ask your doctor if you are unsure why you have been given this medicine.

2.  What you need to know before you are given Methylprednisolone Acetate
Do not use Methylprednisolone Acetate if:
  • You think you have ever suffered an allergic reaction, or any other type of reaction after being given Methylprednisolone Acetate, or any other medicine containing a corticosteroid or any of the ingredients in this medicine (listed in section 6).An allergic reaction may cause a skin rash or reddening, swollen face or lips or shortness of
  • You get a rash, or another symptom of an
  • You have recently had, or are about to have any vaccination. See your doctor immediately if any of the above applies to
Do not inject this medicine:
  • into the Achilles tendon (which is located behind the ankle joint), or
  • directly into a vein (intravenous), the spinal cord (intrathecal), the outer covering of the brain (extradural), into the nostrils (intranasal) or in the eye (intraocular).
Warnings and precautions

Talk to your doctor or nurse before taking Methylprednisolone Acetate if you have any of the following conditions.

Your doctor may also have to monitor your treatment more closely, alter your dose or give you another medicine.

  • Acute adrenal insufficiency (when your body cannot produce enough corticosteroid due to problems with your adrenal glands).
  • Acute pancreatitis (inflammation of the pancreas).
  • Chickenpox, measles, shingles or a herpes eye infection. If you think you have been in contact with someone with chickenpox, measles or shingles and you have not already had these illnesses, or if you are unsure if you have had
  • Severe depression or manic depression (bipolar disorder). This includes having had depression before while taking steroid medicines like Methylprednisolone Acetate, or having a family history of these
  • 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
  • Contact your doctor if you experience blurred vision or other visual disturbances.
  • You have recently suffered a heart attack.
  • Heart problems, including heart failure or
  • Hypertension (high blood pressure).
  • Hypotension (low blood pressure).
  • Hypothyroidism (an under-active thyroid).
  • Joint
  • Kidney or liver
  • Muscle problems (pain or weakness) have happened while taking steroid medicines in the
  • Myasthenia gravis (a condition causing tired and weak muscles).
  • Osteoporosis (brittle bones).
  • Pancreatitis (Inflammation of the pancreas which causes severe pain in the abdomen and back).
  • Peritonitis (Inflammation of the thin lining (peritoneum) around the gut and stomach).
  • Pheochromocytoma (a rare tumour of adrenal gland tissue. The adrenal glands are located above the kidneys).
  • Scleroderma (also known as systemic sclerosis, an autoimmune disorder), because the risk of a serious complication called scleroderma renal crisis may be increased. Signs of scleroderma renal crisis include raised blood pressure and decreased urine production.
  • Skin abscess.
  • Stomach ulcer or other serious stomach or intestinal
  • 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

· 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 Methylprednisolone Acetate

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 Methylprednisolone Acetate or the other medicine works:

  • Acetazolamide – used to treat glaucoma and
  • Aminoglutethimide and cyclophosphamide – used for treating
  • 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
  • Antidiabetics – medicines used to treat high blood
  • Antiemetics (such as aprepitant and fosaprepitant).
  • Antivirals (such as ritonavir, indinavir) and pharmacokinetic enhancers (such as cobicistat) used to treat HIV
  • Aspirin and non-steroidal anti-inflammatory medicines (also called NSAIDs) such as ibuprofen used to treat mild to moderate
  • Barbiturates, carbamazepine, phenytoin and primidone – used to treat
  • Carbenoxolone – used for heartburn and acid
  • Ciclosporin – used to treat conditions such as severe rheumatoid arthritis, severe psoriasis or following an organ or bone marrow
  • Digoxin – used for heart failure and/or an irregular
  • Diltiazem – used for heart problems or high blood
  • Ethinylestradiol and norethindrone – oral
  • Ketoconazole or itraconazole – used to treat fungal
  • Pancuronium and vecuronium – or other medicines called neuromuscular blocking agents which are used in some surgical
  • 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
  • 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
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 Methylprednisolone Acetate. This medicine can affect the results of some tests.

Methylprednisolone Acetate 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. There is a risk associated with low birth weight of the baby; this risk can be reduced by administering a lower dose of the medicine.

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.

Methylprednisolone Acetate contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially ‘sodium-free’.

3.  How Methylprednisolone Acetate is given to you 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 and epicondylitis (tennis elbow) – the usual dose is between 4 – 30 mg (0.1 –

ml). In most cases repeat injections will not needed for bursitis and epicondylitis. Repeat injections may be necessary to treat long standing conditions.

Skin conditions – the usual dose is between 20 – 60 mg (0.5 – 1.5 ml) injected into the affected part or parts of the skin.

For other more general conditions 40 – 120 mg (1 – 3 ml) of this medicine may be injected into a large muscle.

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 Methylprednisolone Acetate 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 Methylprednisolone Acetate

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 Methylprednisolone Acetate for more than 3 weeks
  • have been given high doses of Methylprednisolone Acetate, 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

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 Methylprednisolone Acetate

Mental health problems can happen while taking steroids like Methylprednisolone Acetate (see also section 4, Possible Side Effects).

  • These illnesses can be
  • Usually they start within a few days or weeks of starting the
  • They are more likely to happen at high
  • 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

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

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4.  Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Your doctor will have given you this medicine for a condition which if not treated properly could become serious.

In certain medical conditions medicines like Methylprednisolone Acetate (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 or dizziness. This type of side effect is rare, but can be
  • Pancreatitis, stomach pain spreading to your back, possibly accompanied by vomiting, shock and loss of
  • Ulcers 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
  • 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
  • Pulmonary embolus (blood clot in the lung) symptoms include sudden sharp chest pain, breathlessness and coughing up
  • 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
  • Thrombophlebitis (blood clots or thrombosis in a leg vein), symptoms of which include painful swollen, red and tender

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:

  • not known: frequency cannot be estimated from the available data
Blood, heart and circulation

not known

  • High blood pressure, symptoms of which are headaches, or generally feeling
  • 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
  • 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
Body water and salts

not known

  • 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

not known

  • Nausea (feeling sick) or vomiting (being sick).
  • Thrush in the gullet (discomfort on swallowing).
  • Bloated
  • Abdominal pain.
  • Persistent hiccups, especially when high doses are
Ears

not known

  • A feeling of dizziness or spinning (vertigo).
Eyes

not known

  • Cataracts (indicated by failing eyesight).
  • Glaucoma (raised pressure within the eye, causing pain in the eyes and headaches).
  • 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
  • Protruding of the eyeballs (exophthalmos).
  • Blurred or distorted vision (due to disease of the retina and choroid membrane).
General disorders

not known

  • Poor wound
  • Irritability in
  • Feeling tired or
  • Skin reactions at the site of
  • Irritability in
Hepatobiliary disorders

not known

  • Methylprednisolone can damage your liver, hepatitis and increase of liver enzymes have been
Hormones and metabolic system

not known

  • 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
  • Irregular or no periods in
  • Increased appetite and weight
  • Abnormal localized or tumour-like accumulations of fat in the
  • 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
  • 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
Immune system

not known

  • Increased susceptibility to infections which can hide or change normal reactions to skin tests, such as that for
Metabolism and nutrition disorders

not known

  • Accumulation of fat tissue on localized parts of the
  • 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).
Muscles, bones and joints

not known

  • Muscle
  • Brittle bones (bones that break easily).
  • Muscle
  • Broken bones or
  • Breakdown of bone due to poor circulation of blood, this causes pain in the
  • Joint pain.
  • Torn muscle tendons causing pain and/or
  • Muscle cramps or
  • Swollen or painful joints due to
Nerves and mood issues

not known

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
  • Feeling high (mania) or moods that go up and
  • Feeling anxious, having problems sleeping, difficulty in thinking or being confused and losing your
  • Feeling, seeing or hearing things which do not exist. Having strange and frightening thoughts, changing how you act or having feelings of being
  • Other nervous system side effects may include convulsions (seizures), amnesia (loss of memory), cognitive disorder (mental changes, dizziness and
Skin

not known

  • Abscess, especially near injection
  • Thinning of skin, stretch
  • Small purple/red patches on the
  • Pale or darker patches on your skin, or raised patches which are an unusual
  • Increased hair on the body and face (hirsutism).
  • Rash, itching,
  • Increased
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

5.  How to store Methylprednisolone Acetate

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 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 Methylprednisolone Acetate contains

The active substance is methylprednisolone acetate. Each millilitre contains 40 mg of methylprednisolone acetate.

The other ingredients are sodium chloride, polyethylene glycol, myristyl-gamma-picolinium chloride and water for injections.

What Methylprednisolone Acetate looks like and contents of the pack

Methylprednisolone Acetate is a sterile white suspension for injection contained in a glass vial fitted with a rubber cap and metal seal.

Methylprednisolone Acetate is available in packs containing 1 or 10 vials, containing 1 ml, 2 ml or 3 ml of suspension.

Not all pack sizes may be marketed.

7.Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com