Boxed Warning

PELIOSIS HEPATIS, A CONDITION IN WHICH LIVER AND SOMETIMES SPLENIC TISSUE IS REPLACED WITH BLOOD-FILLED CYSTS, HAS BEEN REPORTED IN PATIENTS RECEIVING ANDROGENIC ANABOLIC STEROID THERAPY. THESE CYSTS ARE SOMETIMES PRESENT WITH MINIMAL HEPATIC DYSFUNCTION, BUT AT OTHER TIMES THEY HAVE BEEN ASSOCIATED WITH LIVER FAILURE. THEY ARE OFTEN NOT RECOGNIZED UNTIL LIFE-THREATENING LIVER FAILURE OR INTRA-ABDOMINAL HEMORRHAGE DEVELOPS. WITHDRAWAL OF DRUG USUALLY RESULTS IN COMPLETE DISAPPEARANCE OF LESIONS. LIVER CELL TUMORS ARE ALSO REPORTED. MOST OFTEN THESE TUMORS ARE BENIGN AND ANDROGEN-DEPENDENT, BUT FATAL MALIGNANT TUMORS HAVE BEEN REPORTED. WITHDRAWAL OF DRUG OFTEN RESULTS IN REGRESSION OR CESSATION OF PROGRESSION OF THE TUMOR. HOWEVER, HEPATIC TUMORS ASSOCIATED WITH ANDROGENS OR ANABOLIC STEROIDS ARE MUCH MORE VASCULAR THAN OTHER HEPATIC TUMORS AND MAY BE SILENT UNTIL LIFE-THREATENING INTRA-ABDOMINAL HEMORRHAGE DEVELOPS. BLOOD LIPID CHANGES THAT ARE KNOWN TO BE ASSOCIATED WITH INCREASED RISK OF ATHEROSCLEROSIS ARE SEEN IN PATIENTS TREATED WITH ANDROGENS OR ANABOLIC STEROIDS. THESE CHANGES INCLUDE DECREASED HIGH-DENSITY LIPOPROTEINS AND SOMETIMES INCREASED LOW-DENSITY LIPOPROTEINS. THE CHANGES MAY BE VERY MARKED AND COULD HAVE A SERIOUS IMPACT ON THE RISK OF ATHEROSCLEROSIS AND CORONARY ARTERY DISEASE.

Indications and Usage

Oxandrolone is indicated as adjunctive therapy to offset the protein catabolism associated with prolonged administration of corticosteroids, and for the relief of the bone pain frequently accompanying osteoporosis (see DOSAGE AND ADMINISTRATION ).

Dosage and Administration

Therapy with anabolic steroids is adjunctive to and not a replacement for conventional therapy. The duration of therapy with oxandrolone will depend on the response of the patient and the possible appearance of adverse reactions. Therapy should be intermittent.

Adults

The response of individuals to anabolic steroids varies. The daily adult dosage is 2.5 mg to 20 mg given in 2 to 4 divided doses. The desired response may be achieved with as little as 2.5 mg or as much as 20 mg daily. A course of therapy of 2 to 4 weeks is usually adequate. This may be repeated intermittently as indicated.

Children

For children the total daily dosage of oxandrolone is <0.1 mg per kilogram body weight or <0.045 mg per pound of body weight. This may be repeated intermittently as indicated.

Contraindications

Known or suspected carcinoma of the prostate or the male breast.
Carcinoma of the breast in females with hypercalcemia (androgenic anabolic steroids may stimulate osteolytic bone resorption).
Pregnancy, because of possible masculinization of the fetus. Oxandrolone has been shown to cause embryotoxicity, fetotoxicity, infertility, and masculinization of female animal offspring when given in doses 9 times the human dose.
Nephrosis, the nephrotic phase of nephritis.
Hypercalcemia.

Adverse Reactions

Patients with moderate to severe COPD or COPD patients who are unresponsive to bronchodilators should be monitored closely for COPD exacerbation and fluid retention.

The following adverse reactions have been associated with use of anabolic steroids:

Hepatic

Cholestatic jaundice with, rarely, hepatic necrosis and death. Hepatocellular neoplasms and peliosis hepatis with long-term therapy (see WARNINGS ). Reversible changes in liver function tests also occur including increased bromsulfophthalein (BSP) retention, changes in alkaline phosphatase and increases in serum bilirubin, aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (ALT, SGPT).

In Males

Prepubertal:

Phallic enlargement and increased frequency or persistence of erections.

Postpubertal:

Inhibition of testicular function, testicular atrophy and oligospermia, impotence, chronic priapism, epididymitis, and bladder irritability.

In Females

Clitoral enlargement, menstrual irregularities.

CNS

Habituation, excitation, insomnia, depression, and changes in libido.

Hematologic

Bleeding in patients on concomitant anticoagulant therapy.

Breast

Gynecomastia.

Larynx

Deepening of the voice in females.

Hair

Hirsutism and male pattern baldness in females.

Skin

Acne (especially in females and prepubertal males).

Skeletal

Premature closure of epiphyses in children (see PRECAUTIONS, Pediatric Use ).

Fluid and Electrolytes

Edema, retention of serum electrolytes (sodium chloride, potassium, phosphate, calcium).

Metabolic/Endocrine

Decreased glucose tolerance (see PRECAUTIONS, Laboratory Tests ), increased creatinine excretion, increased serum levels of creatinine phosphokinase (CPK). Masculinization of the fetus. Inhibition of gonadotropin secretion.

Drug Interactions

Anticoagulants:

Anabolic steroids may increase sensitivity to oral anticoagulants. Dosage of the anticoagulant may have to be decreased in order to maintain desired prothrombin time. Patients receiving oral anticoagulant therapy require close monitoring, especially when anabolic steroids are started or stopped.

Warfarin:

A multidose study of oxandrolone, given as 5 or 10 mg BID in 15 healthy subjects concurrently treated with warfarin, resulted in a mean increase in S-warfarin half-life from 26 to 48 hours and AUC from 4.55 to 12.08 ng•hr/mL; similar increases in R-warfarin half-life and AUC were also detected. Microscopic hematuria (9/15) and gingival bleeding (1/15) were also observed. A 5.5-fold decrease in the mean warfarin dose from 6.13 mg/day to 1.13 mg/day (approximately 80-85% reduction of warfarin dose), was necessary to maintain a target INR of 1.5. When oxandrolone therapy is initiated in a patient already receiving treatment with warfarin, the INR or prothrombin time (PT) should be monitored closely and the dose of warfarin adjusted as necessary until a stable target INR or PT has been achieved.

Furthermore, in patients receiving both drugs, careful monitoring of the INR or PT, and adjustment of the warfarin dosage if indicated are recommended when the oxandrolone dose is changed or discontinued. Patients should be closely monitored for signs and symptoms of occult bleeding.

Oral Hypoglycemic Agents:

Oxandrolone may inhibit the metabolism of oral hypoglycemic agents.

Adrenal Steroids or ACTH:

In patients with edema, concomitant administration with adrenal cortical steroids or ACTH may increase the edema.

Drug Abuse and Dependence

Oxandrolone is classified as a controlled substance under the Anabolic Steroids Control Act of 1990 and has been assigned to Schedule III (non-narcotic).

Overdosage

No symptoms or signs associated with overdosage have been reported. It is possible that sodium and water retention may occur.

The oral LD₅₀ of oxandrolone in mice and dogs is greater than 5,000 mg/kg. No specific antidote is known, but gastric lavage may be used.

Description

Oxandrolone oral tablets contain 2.5 mg or 10 mg of the anabolic steroid oxandrolone. Oxandrolone is 17β-hydroxy-17α-methyl-2-oxa-5α-androstan-3-one with the following structural formula:

Molecular Formula: C₁₉H₃₀O₃

Molecular Weight: 306.44

Inactive ingredients include: corn starch, lactose monohydrate, magnesium stearate, and hypromellose.

Meets USP Dissolution Test 2.

Clinical Pharmacology

Anabolic steroids are synthetic derivatives of testosterone. Certain clinical effects and adverse reactions demonstrate the androgenic properties of this class of drugs. Complete dissociation of anabolic and androgenic effects has not been achieved. The actions of anabolic steroids are therefore similar to those of male sex hormones with the possibility of causing serious disturbances of growth and sexual development if given to young children. Anabolic steroids suppress the gonadotropic functions of the pituitary and may exert a direct effect upon the testes.

During exogenous administration of anabolic androgens, endogenous testosterone release is inhibited through inhibition of pituitary luteinizing hormone (LH). At large doses, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH).

Anabolic steroids have been reported to increase low-density lipoproteins and decrease high-density lipoproteins. These levels revert to normal on discontinuation of treatment.

How Supplied / Storage and Handling

NDC: 63629-7603-1: 30 Tablets in a BOTTLE

NDC: 63629-7603-2: 100 Tablets in a BOTTLE

NDC: 63629-7603-3: 90 Tablets in a BOTTLE

Professional Information — Oxandrin