METHYLPREDNISOLONE ACETATE- methylprednisolone acetate_injection, suspension

Glucocorticoids, naturally occurring and synthetic, are adrenocortical steroids. Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt retaining properties, are used in replacement therapy in adrenocortical deficiency states. Their synthetic analogs are used primarily for their anti- inflammatory effects in disorders of many organ systems. Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body’s immune response to diverse stimuli.

A. FOR INTRAMUSCULAR ADMINISTRATION Allergic States: Dermatologic Diseases: Endocrine Disorders: Gastrointestinal Diseases Hematologic Disorders: Miscellaneous: Neoplastic Diseases: Nervous System: Ophthalmic Diseases: Sympathetic ophthalmia, temporal arteritis, uveitis and ocular inflammatory conditions unresponsive to topical corticosteroids. Renal Diseases: Respiratory Diseases: Rheumatic Disorders B. FOR INTRA-ARTICULAR OR SOFT TISSUE ADMINISTRATION (See WARNINGS C. FOR INTRALESIONAL ADMINISTRATION

NOTE: CONTAINS BENZYL ALCOHOL (see WARNINGS PRECAUTIONS: Pediatric Use Because of possible physical incompatibilities, Methylprednisolone acetate Sterile Aqueous Suspension should not be diluted or mixed with other solutions. The initial dosage of parenterally administered Methylprednisolone acetate injectable suspension will vary from 4 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. A. Administration for Local Effect 1. Rheumatoid Arthritis and Osteoarthritis Size of Joint Examples Range of Dosage Large Knees 20 to 80 mg Medium Elbows 10 to 40 mg Small Metacarpophalangeal 4 to 10 mg Procedure: Suitable sites for intra-articular injection are the knee, ankle, wrist, elbow, shoulder, phalangeal, and hip joints. Since difficulty is not infrequently encountered in entering the hip joint, precautions should be taken to avoid any large blood vessels in the area. Joints not suitable for injection are those that are anatomically inaccessible such as the spinal joints and those like the sacroiliac joints that are devoid of synovial space. Treatment failures are most frequently the result of failure to enter the joint space. Little or no benefit follows injection into surrounding tissue. If failures occur when injections into the synovial spaces are certain, as determined by aspiration of fluid, repeated injections are usually futile. 2. Bursitis. 3. Miscellaneous: Ganglion, Tendinitis, Epicondylitis. 4. Injections for Local Effect in Dermatologic Conditions. When multidose vials are used, special care to prevent contamination of the contents is essential. (See WARNINGS B. Administration for Systemic Effect adrenogenital syndrome rheumatoid arthritis dermatologic lesions Cortisone, 25 Triamcinolone, 4 Hydrocortisone, 20 Paramethasone, 2 Prednisolone, 5 Betamethasone, 0.75 Prednisone, 5 Dexamethasone, 0.75 Methylprednisolone, 4 These dose relationships apply only to oral or intravenous administration of these compounds. When these substances or their derivatives are injected intramuscularly or into joint spaces, their relative properties may be greatly altered.

The following adverse reactions have been reported with Methylprednisolone acetate injectable suspension or other corticosteroids: Allergic reactions Blood and lymphatic system disorders Cardiovascular WARNINGS Dermatologic Endocrine Fluid and electrolyte disturbances Gastrointestinal Metabolic Musculoskeletal Neurologic/Psychiatric Ophthalmic Other WARNINGS The following adverse reactions have been reported with the following routes of administration: Intrathecal/Epidural Intranasal Ophthalmic Miscellaneous injection sites scalp, tonsillar fauces, sphenopalatine ganglion To report SUSPECTED ADVERSE REACTIONS, contact Slayback Pharma at 1-844-566-2505 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

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 Sterile Aqueous Suspension is contraindicated for intrathecal administration. Reports of severe medical events have been associated with this route of administration. Methylprednisolone acetate injectable suspension is contraindicated for use in premature infants because the formulation contains benzyl alcohol. (See WARNINGS PRECAUTIONS: Pediatric Use 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
Teratogenic Effects This product contains benzyl alcohol as a preservative. PRECAUTIONS: Pediatric use
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 continue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
This product contains benzyl alcohol as a preservative. Benzyl alcohol, a component of this product, has been associated with serious adverse events and death, particularly in pediatric patients. The “gasping syndrome” (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth-weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although normal therapeutic doses of this product ordinarily delivers amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. The risk of benzyl alcohol toxicity depends on the quantity administered and the hepatic capacity to detoxify the chemical. Premature and low-birth-weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources. The adverse effects of corticosteroids in pediatric patients are similar to those in adults (see ADVERSE REACTIONS
Geriatric Use
Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Aminoglutethimide: Amphotericin B injection and potassium-depleting agents: Antibiotics: PRECAUTIONS: Drug Interactions Anticholinesterases: Anticoagulants, oral Antidiabetics Antitubercular drugs Cholestyramine Cyclosporine Digitalis glycosides Estrogens, including oral contraceptives Hepatic Enzyme Inducers (e.g., barbiturates, phenytoin, carbamazepine, rifampin): Hepatic Enzyme Inhibitors e.g., ketoconazole, macrolide antibiotics such as erythromycin and troleandomycin Ketoconazole Nonsteroidal anti-inflammatory drugs (NSAIDs): Skin Tests Vaccines WARNINGS: Infections, Vaccinations

SPL UNCLASSIFIED SECTION
NOT FOR USE IN NEONATES CONTAINS BENZYL ALCOHOL
WARNINGS
Serious Neurologic Adverse Reactions with Epidural Administration General PRECAUTIONS: Pediatric Use Multidose use of Methylprednisolone acetate Sterile Aqueous Suspension from a single vial requires special care to avoid contamination. Although initially sterile, any multidose use of vials may lead to contamination unless strict aseptic technique is observed. Particular care, such as use of disposable sterile syringes and needles, is necessary. Injection of Methylprednisolone acetate injectable suspension may result in dermal and/or subdermal changes, forming depressions in the skin at the injection site. It is critical that, during administration of Methylprednisolone acetate injectable suspension, appropriate technique be used and care taken to ensure proper placement of drug. Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy. Increased dosage of rapidly acting corticosteroids is indicated in patients on corticosteroid therapy subjected to any unusual stress before, during, or after the stressful situation (see ADVERSE REACTIONS Results from one multicenter, randomized, placebo-controlled study with methylprednisolone hemisuccinate, an IV corticosteroid, showed an increase in early (at 2 weeks) and late (at 6 months) mortality in patients with cranial trauma who were determined not to have other clear indications for corticosteroid treatment. High doses of systemic corticosteroids, including Methylprednisolone acetate injectable suspension, should not be used for the treatment of traumatic brain injury. Cardio-renal Literature reports suggest an apparent association between the use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with great caution in these patients. Endocrine Corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Drug induced secondary adrenocortical insufficiency may 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. Infections General These infections may be mild, but can be severe and at times fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. Corticosteroids may mask some signs of current infection. Do not use intra-articularly, intrabursally, or for intratendinous administration for local effect in the presence of acute local infection. Fungal Infections CONTRAINDICATIONS PRECAUTIONS: Drug Interactions Amphotericin B injection and potassium-depleting agents Special Pathogens Amoeba, Candida, Cryptococcus, Mycobacterium, Nocardia, Pneumocystis, and Toxoplasma. It is recommended that latent amebiasis or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or in any patient with unexplained diarrhea. Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides Strongyloides Corticosteroids should not be used in cerebral malaria. There is currently no evidence of benefit from steroids in this condition. Tuberculosis 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. Vaccinations Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered. However, the response to such vaccines cannot be predicted. Viral Infections Ophthalmic
Carcinogenesis,Mutagenesis, Impairment of Fertility
No adequate studies have been conducted in animals to determine whether corticosteroids have a potential for carcinogenesis or mutagenesis. Steroids may increase or decrease motility and number of spermatozoa in some patients. Corticosteroids have been shown to impair fertility in male rats.
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.

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METHYLPREDNISOLONE ACETATE- methylprednisolone acetate_injection, suspension Product manual source documgent