Oxandrin^Ò oral tablets contain 2.5 mg or 10 mg of the anabolic steroid oxandrolone.

Oxandrolone is 17b-hydroxy-17a-methyl-2-oxa-5a-androstan-3-one with the following structural formula:

Inactive ingredients include cornstarch, lactose, magnesium stearate, and hypromellose.

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).

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.

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).

Manufactured for BTG Pharmaceuticals by: DSM Pharmaceuticals, Inc. Greenville, NC 27834 G.D. Searle LLC A Subsidiary of PHARMACIA Corporation Chicago, IL 60680 Address medical inquires to BTG Pharmaceuticals One Tower Center Fourteenth Floor East Brunswick, NJ 08816 2003, BTG Pharmaceuticals Printed in USA BTG PHARMACEUTICALS OXANDRINÒ (oxandrolone tablets, USP), 517213, FDA Revision: 6/20/2005.

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, and increases in serum bilirubin, aspartate aminotransferase (AST, SGOT) and alkaline phosphatase.

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.

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/Laboratory test interactions

Anabolic steroids may decrease levels of thyroxine-binding globulin, resulting in decreased total T₄ serum levels and increased resin uptake of T₃ and T₄. Free thyroid hormone levels remain unchanged. In addition, a decrease in PBI and radioactive iodine uptake may occur.

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

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.

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 and 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).

Women should be observed for signs of virilization (deepening of the voice, hirsutism, acne, clitoromegaly). Discontinuation of drug therapy at the time of evidence of mild virilism is necessary to prevent irreversible virilization. Some virilizing changes in women are irreversible even after prompt discontinuance of therapy and are not prevented by concomitant use of estrogens. Menstrual irregularities may also occur.

Anabolic steroids may cause suppression of clotting factors II, V, VII, and X, and an increase in prothrombin time.

INFORMATION FOR PATIENTS

The physician should instruct patients to report immediately any use of warfarin and any bleeding.

The physician should instruct patients to report any of the following side effects of androgens: Males: Too frequent or persistent erections of the penis, appearance or aggravation of acne. Females: Hoarseness, acne, changes in menstrual periods, or more facial hair. All patients: Nausea, vomiting, changes in skin color, or ankle swelling.

Women with disseminated breast carcinoma should have frequent determination of urine and serum calcium levels during the course of therapy. (See WARNINGS).

Because of the hepatotoxicity associated with the use of 17-alpha-alkylated androgens, liver function tests should be obtained periodically.

Periodic (every 6 months) x-ray examinations of bone age should be made during treatment of children to determine the rate of bone maturation and the effects of androgen therapy on the epiphyseal centers.

Serum lipids and high-density lipoprotein cholesterol determinations should be done periodically as androgenic anabolic steroids have been reported to increase low-density lipoproteins. Serum cholesterol levels may increase during therapy. Therefore, caution is required when administering these agents to patients with a history of myocardial infarction or coronary artery disease. Serial determinations of serum cholesterol should be made and therapy adjusted accordingly.

Hemoglobin and hematocrit should be checked periodically for polycythemia in patients who are receiving high doses of anabolic steroids.

Carcinogenesis, mutagenesis, impairment of fertility

Animal data

Oxandrolone has not been tested in laboratory animals for carcinogenic or mutagenic effects. In 2-year chronic oral rat studies, a dose-related reduction of spermatogenesis and decreased organ weights (testes, prostate, seminal vesicles, ovaries, uterus, adrenals, and pituitary) were shown.

Human data

Liver cell tumors have been reported in patients receiving long-term therapy with androgenic anabolic steroids in high doses (See WARNINGS). Withdrawal of the drugs did not lead to regression of the tumors in all cases.

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

Pregnancy: Teratogenic effects-Pregnancy Category X (See CONTRAINDICATIONS).

Nursing mothers

It is not known whether anabolic steroids are excreted in human milk. Because of the potential of serious adverse reactions in nursing infants from oxandrolone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric use

Anabolic agents may accelerate epiphyseal maturation more rapidly than linear growth in children and the effect may continue for 6 months after the drug has been stopped. Therefore, therapy should be monitored by x-ray studies at 6-month intervals in order to avoid the risk of compromising adult height. Androgenic anabolic steroid therapy should be used very cautiously in children and only by specialists who are aware of the effects on bone maturation (See WARNINGS).

Oxandrin, at daily doses of 5 mg bid and 10 mg bid, was evaluated in four clinical trials involving a total of 339 patients with different underlying medical conditions. The maximum duration of treatment was 4 months with the average duration of treatment from 68.5 days to 94.7 days across the studies. A total of 172 elderly patients ( ≥65 years of age) received Oxandrin treatment. Mean weight gain was similar in those ≥65 and those < 65 years of age. No significant differences in efficacy were detected between the 5 mg bid and 10 mg bid daily doses. The adverse event profiles were similar between the two age groups although the elderly, particularly in women, had a greater sensitivity to fluid retention and increases in hepatic transaminases. A single dose pharmacokinetic study in elderly volunteers revealed an increased half-life when compared to younger volunteers. (see CLINICAL PHARMACOLOGY) Based on greater sensitivity to drug-induced fluid retention and transaminase elevations, a lower dose is recommended in the elderly (see DOSAGE AND ADMINISTRATION).

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.

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.

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 even after prompt discontinuance of therapy and are not prevented by concomitant use of estrogens. Menstrual irregularities may also occur.

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.

The physician should instruct patients to report immediately any use of warfarin and any bleeding.

The physician should instruct patients to report any of the following side effects of androgens: Males: Too frequent or persistent erections of the penis, appearance or aggravation of acne. Females: Hoarseness, acne, changes in menstrual periods, or more facial hair. All patients: Nausea, vomiting, changes in skin color, or ankle swelling.

Please also refer to the WARNINGS and PRECAUTIONS sections.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

OXANDROLONE - ORAL

(ox-AN-droe-lone)

COMMON BRAND NAME(S): Oxandrin

WARNING: Rarely, this drug has caused serious, sometimes fatal liver problems including liver failure, liver cysts, and liver tumors. Tell your doctor promptly if you have any early signs of liver problems such as yellowing eyes/skin, dark urine, unusual tiredness, or sudden/persistent stomach/abdominal pain.

This drug may also affect your cholesterol and may increase your risk of heart or blood vessel problems (coronary artery disease). Your doctor will monitor your cholesterol level closely.

USES: This medication is used to help people regain weight they have lost due to certain medical conditions (e.g., surgery, chronic infection, trauma). It is also used to relieve bone pain due to bone loss (osteoporosis). Oxandrolone belongs to a class of drugs known as anabolic steroids. These drugs are similar to male hormones made by the body. They work by helping and speeding up muscle growth.

Abuse of this medication (e.g., to improve athletic performance or physical appearance) is very dangerous and may cause serious, sometimes fatal problems.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to treat breast cancer in women. It may also be used to treat swelling of the abdomen/arms/face/airway due to a certain inherited disease (hereditary angioedema).

HOW TO USE: Take this medication by mouth as directed by your doctor. It may be taken with food or milk if stomach upset occurs.

Dosage is based on your medical condition and response to treatment. In children, dosage is also based on weight.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.

Tell your doctor if your condition does not improve or if it worsens.

SIDE EFFECTS: Nausea, vomiting, trouble sleeping, changes in skin color, and changes in sexual interest may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

For males, in the very unlikely event you have a painful or prolonged erection lasting 4 or more hours, stop using this drug and seek immediate medical attention, or permanent problems could occur.

Women may experience signs of masculinization (male characteristics) from oxandrolone. To prevent these changes from becoming permanent, stop taking this medication and tell your doctor immediately if any of the following occur: hoarseness, deepening voice, sore throat, facial hair growth, new or worsening acne, enlarged clitoris.

Women often stop having regular menstrual periods while taking this medication. Menstrual periods usually return after stopping the drug.

Tell your doctor immediately if any of these unlikely but serious side effects occur: swelling ankles/feet, unusual tiredness, breast tenderness/swelling in men, easy bruising/bleeding, severe muscle spasms, mental/mood changes, seizures.

Tell your doctor immediately if any of these rare but very serious side effects occur: stomach/abdominal pain or swelling, dark urine, persistent nausea/vomiting, yellowing eyes/skin.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking oxandrolone, tell your doctor or pharmacist if you are allergic to it; or to other anabolic steroids (e.g., testosterone); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: prostate cancer, male breast cancer, mineral imbalance (high calcium blood level), kidney disease (nephropathy).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: high blood cholesterol levels, liver disease, heart disease, coronary artery disease, lung disease (chronic obstructive pulmonary disease-COPD), diabetes.

If you have diabetes, you must closely monitor urine and blood sugar while taking this medication and report any changes to your doctor.

Caution is advised when using this drug in the elderly because they may be at greater risk for enlarged prostate, prostate cancer, and swelling of arms/legs.

Caution is advised when using this drug in children because they may be more sensitive to the effects of the drug, especially on bone growth and sexual development. Oxandrolone may stop or stunt growth in children younger than 18 years. Therefore, this medication should be used in this age group only when prescribed by a medical specialist.

Oxandrolone must not be used during pregnancy. It may harm the unborn baby. If you become pregnant or think you may be pregnant, tell your doctor immediately.

It is not known whether this drug passes into breast milk. Due to the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: ACTH, adrenal cortical steroid, "blood thinners" (e.g., warfarin), sulfonylureas (e.g., glipizide).

This medication may interfere with certain laboratory tests (including thyroid function tests), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others. It is against the law.

Laboratory and/or medical tests (e.g., cholesterol levels, liver function tests, urine and blood calcium levels) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.