Rx only life was 10.4 hours. No significant differences SOMETIMES PRESENT WITH MINIMAL In patients with breast cancer, anabolic SAVIENT PHARMACEUTICALS, INC. between younger and elderly volunteers were HEPATIC DYSFUNCTION, BUT AT steroid therapy may cause hypercalcemia by C III found for time to peak, peak plasma OTHER TIMES THEY HAVE BEEN stimulating osteolysis. Oxandrolone therapy concentration or AUC after a single dose of ASSOCIATED WITH LIVER FAILURE. should be discontinued if hypercalcemia Oxandrin®(oxandrolone tablets, USP) Oxandrin. The correlation between plasma level THEY ARE OFTEN NOT RECOGNIZED occurs. DESCRIPTION and therapeutic effect has not been defined. UNTIL LIFE-THREATENING LIVER Oxandrin® oral tablets contain 2.5 mg or 10 mg FAILURE OR INTRA-ABDOMINAL Edema with or without congestive heart of the anabolic steroid oxandrolone. INDICATIONS AND USAGE HEMORRHAGE DEVELOPS. failure may be a serious complication in Oxandrolone is 17β-hydroxy-17α-methyl-2- Oxandrin is indicated as adjunctive therapy to WITHDRAWAL OF DRUG USUALLY patients with pre-existing cardiac, renal, or oxa-5α-androstan-3-one with the following promote weight gain after weight loss following RESULTS IN COMPLETE hepatic disease. Concomitant administration structural formula extensive surgery, chronic infections, or severe DISAPPEARANCE OF LESIONS. of adrenal cortical steroid or ACTH may trauma, and in some patients who without LIVER CELL TUMORS ARE ALSO increase the edema. definite pathophysiologic reasons fail to gain or REPORTED. MOST OFTEN THESE to maintain normal weight, to offset the protein TUMORS ARE BENIGN AND In children, androgen therapy may accelerate catabolism associated with prolonged ANDROGEN-DEPENDENT, BUT FATAL bone maturation without producing administration of corticosteroids, and for the MALIGNANT TUMORS HAVE BEEN compensatory gain in linear growth. This relief of the bone pain frequently accompanying REPORTED. WITHDRAWAL OF DRUG adverse effect results in compromised adult Inactive ingredients include cornstarch, lactose, osteoporosis (See DOSAGE AND OFTEN RESULTS IN REGRESSION OR height. The younger the child, the greater magnesium stearate, and hydroxypropyl ADMINISTRATION). CESSATION OF PROGRESSION OF THE the risk of compromising final mature height. methylcellulose. TUMOR. HOWEVER, HEPATIC The effect on bone maturation should be DRUG ABUSE AND DEPENDENCE TUMORS ASSOCIATED WITH monitored by assessing bone age of the left CLINICAL PHARMACOLOGY Oxandrolone is classified as a controlled ANDROGENS OR ANABOLIC STEROIDS wrist and hand every 6 months (See Anabolic steroids are synthetic derivatives of substance under the Anabolic Steroids Control ARE MUCH MORE VASCULAR THAN PRECAUTIONS: Laboratory Tests). testosterone. Certain clinical effects and adverse Act of 1990 and has been assigned to Schedule OTHER HEPATIC TUMORS AND MAY reactions demonstrate the androgenic properties III (non-narcotic). BE SILENT UNTIL LIFE-THREATENING Geriatric patients treated with androgenic of this class of drugs. Complete dissociation of INTRA-ABDOMINAL HEMORRHAGE anabolic steroids may be at an increased risk anabolic and androgenic effects has not been CONTRAINDICATIONS DEVELOPS. BLOOD LIPID CHANGES for the development of prostatic hypertrophy achieved. The actions of anabolic steroids are 1. Known or suspected carcinoma of the THAT ARE KNOWN TO BE and prostatic carcinoma. therefore similar to those of male sex hormones prostate or the male breast. ASSOCIATED WITH INCREASED RISK with the possibility of causing serious 2. Carcinoma of the breast in females with OF ATHEROSCLEROSIS ARE SEEN IN ANABOLIC STEROIDS HAVE NOT BEEN disturbances of growth and sexual development if hypercalcemia (androgenic anabolic PATIENTS TREATED WITH SHOWN TO ENHANCE ATHLETIC given to young children. Anabolic steroids steroids may stimulate osteolytic bone ANDROGENS OR ANABOLIC ABILITY. suppress the gonadotropic functions of the resorption). STEROIDS. THESE CHANGES INCLUDE pituitary and may exert a direct effect upon the 3. Pregnancy, because of possible DECREASED HIGH-DENSITY PRECAUTIONS testes. masculinization of the fetus. Oxandrin LIPOPROTEINS AND SOMETIMES Concurrent dosing of oxandrolone and has been shown to cause embryotoxicity, INCREASED LOW-DENSITY warfarin may result in unexpectedly large During exogenous administration of anabolic fetotoxicity, infertility, and LIPOPROTEINS. THE CHANGES MAY increases in the INR or prothrombin time androgens, endogenous testosterone release is masculinization of female animal BE VERY MARKED AND COULD HAVE (PT). When oxandrolone is prescribed to inhibited through inhibition of pituitary offspring when given in doses 9 times A SERIOUS IMPACT ON THE RISK OF patients being treated with warfarin, doses luteinizing hormone (LH). At large doses, the human dose. ATHEROSCLEROSIS AND CORONARY of warfarin may need to be decreased spermatogenesis may be suppressed through 4. Nephrosis, the nephrotic phase of ARTERY DISEASE. significantly to maintain the desirable INR feedback inhibition of pituitary follicle- nephritis. level and diminish the risk of potentially stimulating hormone (FSH). 5. Hypercalcemia. Cholestatic hepatitis and jaundice may occur serious bleeding (See PRECAUTIONS: with 17-alpha-alkylated androgens at a Drug Interactions). Anabolic steroids have been reported to increase WARNINGS relatively low dose. If cholestatic hepatitis low-density lipoproteins and decrease high- with jaundice appears or if liver function tests General: density lipoproteins. These levels revert to PELIOSIS HEPATIS, A CONDITION IN become abnormal, oxandrolone should be Women should be observed for signs of normal on discontinuation of treatment. WHICH LIVER AND SOMETIMES discontinued and the etiology should be virilization (deepening of the voice, SPLENIC TISSUE IS REPLACED WITH determined. Drug-induced jaundice is hirsutism, acne, clitoromegaly). In a single dose pharmacokinetic study of BLOOD-FILLED CYSTS, HAS BEEN reversible when the medication is Discontinuation of drug therapy at the time of Oxandrin in elderly subjects, the mean REPORTED IN PATIENTS RECEIVING discontinued. evidence of mild virilism is necessary to elimination half-life was 13.3 hours. In a ANDROGENIC ANABOLIC STEROID prevent irreversible virilization. Some previous single dose pharmacokinetic study in THERAPY. THESE CYSTS ARE virilizing changes in women are irreversible younger volunteers, the mean elimination half- even after prompt discontinuance of therapy serum calcium levels during the course of patient already receiving treatment with the development of prostatic hypertrophy and and are not prevented by concomitant use of therapy. (See WARNINGS). warfarin, the INR or prothrombin time (PT) prostatic carcinoma. estrogens. Menstrual irregularities may also should be monitored closely and the dose of occur. Because of the hepatotoxicity associated with warfarin adjusted as necessary until a stable Pregnancy: Teratogenic effects-Pregnancy the use of 17-alpha-alkylated androgens, liver target INR or PT has been achieved. Category X (See CONTRAINDICATIONS). Anabolic steroids may cause suppression of function tests should be obtained periodically. Furthermore, in patients receiving both drugs, clotting factors II, V, VII, and X, and an careful monitoring of the INR or PT, and Nursing mothers: increase in prothrombin time. Periodic (every 6 months) x-ray examinations of adjustment of the warfarin dosage if indicated It is not known whether anabolic steroids are bone age should be made during treatment of are recommended when the oxandrolone dose is excreted in human milk. Because of the Information for patients: children to determine the rate of bone changed or discontinued. Patients should be potential of serious adverse reactions in nursing The physician should instruct patients to report maturation and the effects of androgen therapy closely monitored for signs and symptoms of infants from oxandrolone, a decision should be immediately any use of warfarin and any on the epiphyseal centers. occult bleeding. made whether to discontinue nursing or to bleeding. discontinue the drug, taking into account the The physician should instruct patients to report Androgenic anabolic steroids have been Oral hypoglycemic agents: importance of the drug to the mother. any of the following side effects of androgens: reported to increase low-density lipoproteins Oxandrolone may inhibit the metabolism of oral Males: Too frequent or persistent erections of and decrease high-density lipoproteins. hypoglycemic agents. Pediatric use: the penis, appearance or aggravation of acne. Therefore, caution is required when Anabolic agents may accelerate epiphyseal Females: Hoarseness, acne, changes in administering these agents to patients with a Adrenal steroids or ACTH: maturation more rapidly than linear growth in menstrual periods, or more facial hair. history of cardiovascular disease or who are at In patients with edema, concomitant children and the effect may continue for 6 All patients: Nausea, vomiting, changes in risk for cardiovascular disease. Serum administration with adrenal cortical steroids or months after the drug has been stopped. skin color, or ankle swelling. determination of lipid levels should be ACTH may increase the edema. Therefore, therapy should be monitored by x- performed periodically and therapy adjusted ray studies at 6-month intervals in order to Geriatric Use: accordingly. avoid the risk of compromising adult height. Oxandrin, at daily doses of 5 mg bid and 10 mg Drug/Laboratory test interactions: Androgenic anabolic steroid therapy should be bid, was evaluated in four clinical trials Hemoglobin and hematocrit should be checked Anabolic steroids may decrease levels of used very cautiously in children and only by involving a total of 339 patients with different periodically for polycythemia in patients who thyroxine-binding globulin, resulting in specialists who are aware of the effects on bone underlying medical conditions. The maximum are receiving high doses of anabolic steroids. decreased total T4 serum levels and increased maturation (See WARNINGS). duration of treatment was 4 months with the resin uptake of T3 and T4. Free thyroid average duration of treatment from 68.5 days to Drug interactions hormone levels remain unchanged. In addition, ADVERSE REACTIONS 94.7 days across the studies. A total of 172 a decrease in PBI and radioactive iodine uptake Patients with moderate to severe COPD or elderly patients ( ≥ 65 years of age) received Anticoagulants: may occur. COPD patients who are unresponsive to Oxandrin treatment. Mean weight gain was Anabolic steroids may increase sensitivity to bronchodilators should be monitored closely similar in those ≥ 65 and those < 65 years of oral anticoagulants. Dosage of the Carcinogenesis, mutagenesis, impairment of for COPD exacerbation and fluid retention. age. No significant differences in efficacy were anticoagulant may have to be decreased in order fertility detected between the 5 mg bid and 10 mg bid to maintain desired prothrombin time. Patients The following adverse reactions have been daily doses. The adverse event profiles were receiving oral anticoagulant therapy require Animal data: associated with use of anabolic steroids: similar between the two age groups although the close monitoring, especially when anabolic Oxandrolone has not been tested in laboratory Hepatic: Cholestatic jaundice with, rarely, elderly, particularly in women, had a greater steroids are started or stopped. animals for carcinogenic or mutagenic effects. hepatic necrosis and death. Hepatocellular sensitivity to fluid retention and increases in In 2-year chronic oral rat studies, a dose-related neoplasms and peliosis hepatis with long-term hepatic transaminases. A single dose Warfarin: A multidose study of reduction of spermatogenesis and decreased therapy (See WARNINGS). Reversible pharmacokinetic study in elderly volunteers oxandrolone, given as 5 or 10 mg BID in 15 organ weights (testes, prostate, seminal vesicles, changes in liver function tests also occur revealed an increased half-life when compared healthy subjects concurrently treated with ovaries, uterus, adrenals, and pituitary) were including increased bromsulfophthalein (BSP) to younger volunteers. (see CLINICAL warfarin, resulted in a mean increase in S- shown. retention, changes in alkaline phosphatase and PHARMACOLOGY) Based on greater warfarin half-life from 26 to 48 hours and AUC increases in serum bilirubin, aspartate sensitivity to drug-induced fluid retention and from 4.55 to 12.08 ng*hr/mL; similar increases Human data: aminotransferase (AST, SGOT) and alanine transaminase elevations, a lower dose is in R-warfarin half-life and AUC were also Liver cell tumors have been reported in patients aminotransferase (ALT, SGPT) recommended in the elderly (see DOSAGE detected. Microscopic hematuria (9/15) and receiving long-term therapy with androgenic In males: AND ADMINISTRATION). gingival bleeding (1/15) were also observed. A anabolic steroids in high doses (See Prepubertal: Phallic enlargement and increased 5.5-fold decrease in the mean warfarin dose WARNINGS). Withdrawal of the drugs did frequency or persistence of erections. Laboratory Tests: from 6.13 mg/day to 1.13 mg/day not lead to regression of the tumors in all cases. Postpubertal: Inhibition of testicular function, Women with disseminated breast carcinoma (approximately 80-85% reduction of warfarin testicular atrophy and oligospermia, impotence, should have frequent determination of urine and dose), was necessary to maintain a target INR of Geriatric patients treated with androgenic chronic priapism, epididymitis, and bladder 1.5. When oxandrolone therapy is initiated in a anabolic steroids may be at an increased risk for irritability. In females: Children: For children the total daily dosage of Clitoral enlargement, menstrual irregularities. Oxandrin is ≤0.1 mg per kilogram body weight CNS: Habituation, excitation, insomnia, or ≤0.045 mg per pound of body weight. This depression, and changes in libido. may be repeated intermittently as indicated. Hematologic: Bleeding in patients on Geriatric Use:Recommended dose for geriatric concomitant oral anticoagulant therapy. patients is 5 mg bid. Breast: Gynecomastia. Larynx: Deepening of the voice in females. HOW SUPPLIED Hair: Hirsutism and male pattern baldness Oxandrin 2.5 mg tablets are oval, white, and in females. scored with BTG on one side and "11" on each Skin: Acne (especially in females and side of the scoreline on the other side; bottles of prepubertal males). 100 (NDC 54396-111-11). Skeletal: Premature closure of epiphyses Oxandrin 10 mg tablets are capsule shaped, in children (See PRECAUTIONS: white, with BTG on one side and “10” on the Pediatric use). other side; bottles of 60 (NDC 54396-110-60). Fluid and electrolytes: Edema, retention of serum electrolytes (sodium chloride, Rx only Issued: xxxxxxx2005 potassium, phosphate, calcium). Metabolic/Endocrine: Decreased glucose Manufactured for tolerance (See PRECAUTIONS: Laboratory Savient Pharmaceuticals, Inc. by: tests), increased creatinine excretion, increased serum levels of creatinine DSM Pharmaceuticals, Inc. phosphokinase (CPK). Masculinization of Greenville, NC 27834 the fetus. Inhibition of gonadotropin secretion. Pfizer Co. OVERDOSAGE New York, NY 10017 No symptoms or signs associated with overdosage have been reported. It is possible Address medical inquires to that sodium and water retention may occur. Savient Pharmaceuticals, Inc. One Tower Center Fourteenth Floor The oral LD50 of oxandrolone in mice and dogs East Brunswick, NJ 08816 is greater than 5,000 mg/kg. No specific 866-692-6374 antidote is known, but gastric lavage may be used. 2005, Savient Pharmaceuticals, Inc. Printed in USA DOSAGE AND ADMINISTRATION Therapy with anabolic steroids is adjunctive to and not a replacement for conventional therapy. The duration of OXANDRIN® therapy with Oxandrin (oxandrolone) will depend on the response of the patient and the (oxandrolone tablets, USP)CIII 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 Final Draft Labeling – Submitted to FDA desired response may be achieved with as little 5/20/2005. 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.