Oxandrin®(oxandrolone tablets, USP)CIII

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.

Oxandrin^® 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:

Inactive ingredients include cornstarch, lactose, magnesium stearate, and hydroxypropyl methylcellulose.

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.

In a single dose pharmacokinetic study of Oxandrin in elderly subjects, the mean elimination half-life was 13.3 hours. In a previous single dose pharmacokinetic study in younger volunteers, the mean elimination half-life was 10.4 hours. No significant differences between younger and elderly volunteers were found for time to peak, peak plasma concentration or AUC after a single dose of Oxandrin. The correlation between plasma level and therapeutic effect has not been defined.

Oxandrin is indicated as adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who without definite pathophysiologic reasons fail to gain or to maintain normal weight, 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).

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

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

Cholestatic hepatitis and jaundice may occur with 17-alpha-alkylated androgens at a relatively low dose. If cholestatic hepatitis with jaundice appears or if liver function tests become abnormal, oxandrolone should be discontinued and the etiology should be determined. Drug-induced jaundice is reversible when the medication is discontinued.

In patients with breast cancer, anabolic steroid therapy may cause hypercalcemia by stimulating osteolysis. Oxandrolone therapy should be discontinued if hypercalcemia occurs.

Edema with or without congestive heart failure may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease. Concomitant administration of adrenal cortical steroid or ACTH may increase the edema.

In children, androgen therapy may accelerate bone maturation without producing compensatory gain in linear growth. This adverse effect results in compromised adult height.   The younger the child, the greater the risk of compromising final mature height. The effect on bone maturation should be monitored by assessing bone age of the left wrist and hand every 6 months (See PRECAUTIONS: Laboratory Tests).

Geriatric patients treated with androgenic anabolic steroids may be at an increased risk for the development of prostatic hypertrophy and prostatic carcinoma.

ANABOLIC STEROIDS HAVE NOT BEEN SHOWN TO ENHANCE ATHLETIC ABILITY.

Concurrent dosing of oxandrolone with warfarin may result in unexpectedly large increases in the INR or prothrombin time (PT). When oxandrolone is prescribed to patients being treated with warfarin, doses of warfarin may need to be decreased significantly to maintain the desirable INR level and diminish the risk of potentially serious bleeding (See PRECAUTIONS: Drug Interactions).

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 oral 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.

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.

Therapy with anabolic steroids is adjunctive to and not a replacement for conventional therapy. The duration of therapy with Oxandrin (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 Oxandrin is ≤0.1 mg per kilogram body weight or ≤0.045 mg per pound of body weight. This may be repeated intermittently as indicated.

Geriatric Use: Recommended dose for geriatric patients is 5 mg bid.

Oxandrin 2.5 mg tablets are oval, white, and scored with BTG on one side and “11” on each side of the scoreline on the other side; bottles of 100 (NDC 54396-111-11).

Oxandrin 10 mg tablets are capsule shaped, white, with BTG on one side and “10” on the other side; bottles of 60 (NDC 54396-110-60).

R_x only                      Issued: January, 2006

Manufactured for
Savient Pharmaceuticals, Inc. by:

DSM Pharmaceuticals, Inc.
Greenville, NC 27834

Pfizer Co.
New York, NY 10017

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Savient Pharmaceuticals, Inc.
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866-692-6374

©2005, Savient Pharmaceuticals, Inc.
Printed in USA