Methylprednisolone Acetate

Description

DESCRIPTION Methylprednisolone acetate injectable suspension, USP is an anti-inflammatory glucocorticoid for intramuscular, intra-articular, soft tissue or intralesional injection. It is available as single-dose vials in 40 mg/mL. Each mL of these preparations contains: ## 40 mg/mL Methylprednisolone Acetate, USP 40 mg Polyethylene glycol 3350 29 mg Myristyl-gamma-picolinium chloride 0.195 mg Sodium chloride was added to adjust tonicity. When necessary, pH was adjusted with sodium hydroxide and/or hydrochloric acid. The pH of the finished product remains within the USP specified range (e.g., 3.0 to 7.0). The chemical name for methylprednisolone acetate is pregna-1,4-diene-3,20-dione, 21-(acetyloxy)-11,17-dihydroxy-6-methyl-,(6α,11β)- and the molecular weight is 416.51. The structural formula is represented below: Methylprednisolone acetate injectable suspension, USP contains methylprednisolone acetate, USP which is the 6-methyl derivative of prednisolone. Methylprednisolone acetate, USP is a white or almost white crystalline powder which melts at about 213° with some decomposition. It is soluble in dioxane, sparingly soluble in acetone, alcohol, chloroform, and methanol, and slightly soluble in ether. It is practically insoluble in water. 1

What Is Methylprednisolone Acetate Used For?

INDICATIONS AND USAGE A. For Intramuscular Administration When oral therapy is not feasible and the strength, dosage form, and route of administration of the drug reasonably lend the preparation to the treatment of the condition, the intramuscular use of methylprednisolone acetate injectable suspension is indicated as follows: Allergic States : Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in asthma, atopic dermatitis, contact dermatitis, drug hypersensitivity reactions, serum sickness, transfusion reactions. Dermatologic Diseases : Bullous dermatitis herpetiformis, exfoliative dermatitis, mycosis fungoides, pemphigus, severe erythema multiforme (Stevens-Johnson syndrome). Endocrine Disorders : Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance), congenital adrenal hyperplasia, hypercalcemia associated with cancer, nonsupportive thyroiditis. Gastrointestinal Diseases : To tide the patient over a critical period of the disease in regional enteritis (systemic therapy) and ulcerative colitis. Hematologic Disorders : Acquired (autoimmune) hemolytic anemia, congenital (erythroid) hypoplastic anemia (Diamond Blackfan anemia), pure red cell aplasia, select cases of secondary thrombocytopenia. Miscellaneous : Trichinosis with neurologic or myocardial involvement, tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy. Neoplastic Diseases : For palliative management of: leukemias and lymphomas. Nervous System : Cerebral edema associated with primary or metastatic brain tumor or craniotomy. Ophthalmic Diseases : Sympathetic ophthalmia, temporal arteritis, uveitis, ocular inflammatory conditions unresponsive to topical corticosteroids. Renal Diseases : To induce diuresis or remission of proteinuria in idiopathic nephrotic syndrome, or that due to lupus erythematosus. Respiratory Diseases : Berylliosis, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy, idiopathic eosinophilic pneumonias, symptomatic sarcoidosis. Rheumatic Disorders : As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in acute gouty arthritis; acute rheumatic carditis; ankylosing spondylitis; psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy). For the treatment of dermatomyositis, polymyositis, and systemic lupus erythematosus. B. For Intra-articular Or Soft Tissue Administration ( See WARNINGS ) Methylprednisolone acetate injectable suspension is indicated as adjunctive therapy for short-term administration (to tide the...

Dosage and Administration

DOSAGE AND ADMINISTRATION Because of possible physical incompatibilities, methylprednisolone acetate injectable suspension should not be diluted or mixed with other solutions. The initial dosage of parenterally administered methylprednisolone acetate injectable suspension will vary from 4 mg to 120 mg, depending on the specific disease entity being treated. However, in certain overwhelming, acute, life-threatening situations, administration in dosages exceeding the usual dosages may be justified and may be in multiples of the oral dosages. It Should Be Emphasized that Dosage Requirements Are Variable and Must Be Individualized on the Basis of the Disease Under Treatment and the Response of the Patient. After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. Situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient’s individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment. In this latter situation, it may be necessary to increase the dosage of the corticosteroid for a period of time consistent with the patient’s condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly. A. Administration for Local Effect Therapy with methylprednisolone acetate injectable suspension 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. 1. Rheumatoid Arthritis and Osteoarthritis. The dose for intra-articular administration depends upon the size of the joint and varies with the severity of the condition in the individual patient. In chronic cases, injections may be repeated at intervals ranging from one to five or more weeks, depending upon the degree of relief obtained from the initial injection. The doses in the following table are given as a general guide: Size of Joint Examples Range of Dosage Large Knees Ankles Shoulders 20 mg to 80 mg Medium Elbows Wrists 10 mg to 40 mg Small Metacarpophalangeal Interphalangeal Sternoclavicular Acromioclavicular 4 mg to 10 mg Procedure: It is recommended that the anatomy of the joint involved be reviewed before attempting intra-articular injection. In order to obtain the full anti-inflammatory effect, it is important that the injection be made into the synovial space. Employing the same sterile technique as for a lumbar puncture, a sterile 20 to 24 gauge needle (on a dry syringe) is quickly inserted into the synovial cavity. Procaine infiltration is elective. The aspiration of only a few...

Side Effects (Adverse Reactions)

ADVERSE REACTIONS The following adverse reactions have been reported with methylprednisolone acetate or other corticosteroids: Allergic reactions : Allergic or hypersensitivity reactions, anaphylactoid reaction, anaphylaxis, angioedema. Blood and lymphatic system disorders: Leukocytosis. Cardiovascular : Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction (see WARNINGS ), pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis. Dermatologic : Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scaly skin, ecchymoses and petechiae, edema, erythema, hyperpigmentation, hypopigmentation, impaired wound healing, increased sweating, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria. Endocrine : Decreased carbohydrate and glucose tolerance, development of cushingoid state, glycosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestations of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients. Fluid and electrolyte disturbances : Congestive heart failure in susceptible patients, fluid retention, hypokalemic alkalosis, potassium loss, sodium retention. Gastrointestinal : Abdominal distention, bowel/bladder dysfunction (after intrathecal administration), elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible subsequent perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis. Metabolic : Negative nitrogen balance due to protein catabolism. Musculoskeletal : Aseptic necrosis of femoral and humeral heads, calcinosis (following intra-articular or intra-lesional use), Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, postinjection flare (following intra-articular use), steroid myopathy, tendon rupture, vertebral compression fractures. Neurologic/Psychiatric : Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychic disorders, vertigo. Ophthalmic : Exophthalmoses, glaucoma, increased intraocular pressure, posterior subcapsular cataracts. Other : Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, injection site infections following non-sterile administration (see WARNINGS ), malaise, moon face, weight gain. The following adverse reactions have been reported with the following routes of administration: Intrathecal/Epidural : Arachnoiditis, bowel/bladder dysfunction, headache, meningitis, parapareisis/paraplegia, seizures, sensory disturbances. Intranasal : Allergic reactions, rhinitis, temporary/permanent visual impairment including blindness. Ophthalmic : Increased intraocular pressure, infection, ocular and periocular inflammation including allergic reactions, residue or slough at injection site, temporary/permanent visual impairment including blindness. Miscellaneous injection sites (scalp, tonsillar fauces, sphenopalatine ganglion): Blindness. To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

Drug Interactions Aminoglutethimide : Aminoglutethimide may lead to a loss of corticosteroid-induced adrenal suppression. Amphotericin B injection and potassium-depleting agents: When corticosteroids are administered concomitantly with potassium depleting agents (e.g., amphotericin B, diuretics), patients should be observed closely for development of hypokalemia. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure. Antibiotics : Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance (see PRECAUTIONS : Drug Interactions , Hepatic Enzyme Inhibitors ). Anticholinesterases: Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy. Anticoagulants , oral : Co-administration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect. Antidiabetics: Because corticosteroids may increase blood glucose concentration, dosage adjustments of antidiabetic agents may be required. Antitubercular drugs: Serum concentrations of isoniazid may be decreased. Cholestyramine: Cholestyramine may increase the clearance of oral corticosteroids. Cyclosporine: Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use. Digitalis glycosides: Patients on digitalis glycosides may be at risk of arrhythmias due to hypokalemia. Estrogens, including oral contraceptives: Estrogens may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect. Hepatic Enzyme Inducers (e.g., barbiturates, phenytoin, carbamazepine, rifampin): Drugs which induce cytochrome P450 3A4 enzyme activity may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased. Hepatic Enzyme Inhibitors (e.g., ketoconazole, macrolide antibiotics such as erythromycin and troleandomycin): Drugs which inhibit cytochrome P450 3A4 have the potential to result in increased plasma concentrations of corticosteroids. Ketoconazole : Ketoconazole has been reported to significantly decrease the metabolism of certain corticosteroids by up to 60%, leading to an increased risk of corticosteroid side effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) : Concomitant use of aspirin (or other nonsteroidal anti-inflammatory agents) and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be...

Contraindications

CONTRAINDICATIONS Methylprednisolone acetate injectable suspension is contraindicated in patients with known hypersensitivity to the product and its constituents. Intramuscular corticosteroid preparations are contraindicated for idiopathic thrombocytopenic purpura. Methylprednisolone acetate injectable suspension is contraindicated for intrathecal administration. This formulation of methylprednisolone acetate has been associated with reports of severe medical events when administered by this route. Methylprednisolone acetate injectable suspension is contraindicated in systemic fungal infections, except when administered as an intra-articular injection for localized joint conditions (see WARNINGS : Infections, Fungal Infections ).

Pregnancy and Breastfeeding

Pregnancy: Teratogenic Effects Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. Animal studies in which corticosteroids have been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring. There are no adequate and well-controlled studies in pregnant women. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who have received corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Nursing Mothers Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Because of the potential for serious adverse reactions in nursing infants from corticosteroids, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Overdosage

OVERDOSAGE Treatment of acute overdosage is by supportive and symptomatic therapy. For chronic overdosage in the face of severe disease requiring continuous steroid therapy, the dosage of the corticosteroid may be reduced only temporarily, or alternate day treatment may be introduced.

How Supplied

HOW SUPPLIED Methylprednisolone Acetate Injectable Suspension, USP is supplied as a white to off-white homogenous suspension in single-dose vial available in the following strengths and package sizes: 40 mg/mL (1 mL) Single vial in a carton: NDC 70121-1573-1 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. This product’s label may have been updated. For current full prescribing information, please visit www.amneal.com. Manufactured by: Amneal Pharmaceuticals Pvt. Ltd. Parenteral Unit Ahmedabad 382213, INDIA Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807 Rev. 07-2022-06