HALOTESTIN Tablets contain fluoxymesterone, an androgenic hormone.

Fluoxymesterone is a white or nearly white, odorless, crystalline powder, melting at or about 240° C, with some decomposition. It is practically insoluble in water, sparingly soluble in alcohol, and slightly soluble in chloroform.

The chemical name for fluoxymesterone is androst-4-en-3-one, 9-fluoro-11,17- dihydroxy-17-methyl-, (11β,17β)-. The molecular formula is C₂₀H₂₉FO₃ and the molecular weight 336.45.

The structural formula is represented below:

Each HALOTESTIN tablet, for oral administration, contains 2 mg, 5 mg or 10 mg fluoxymesterone. Inactive ingredients: calcium stearate, corn starch, FD&C Yellow No. 5, lactose, sorbic acid, sucrose, tragacanth. In addition, the 2 mg tablet contains FD&C Yellow No. 6 and the 5 mg and 10 mg contain FD&C Blue No. 2.

In the male—HALOTESTIN Tablets are indicated for:

1. Replacement therapy in conditions associated with symptoms of deficiency or absence of endogenous testosterone.
   1. Primary hypogonadism (congenital or acquired)— testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy.
   2. Hypogonadotropic hypogonadism (congenital or acquired)—idiopathic gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.
2. Delayed puberty, provided it has been definitely established as such, and is not just a familial trait.

In the female—HALOTESTIN Tablets are indicated for palliation of androgen-responsive recurrent mammary cancer in women who are more than one year but less than five years postmenopausal, or who have been proven to have a hormone-dependent tumor as shown by previous beneficial response to castration.

The dosage will vary depending upon the individual, the condition being treated, and its severity. The total daily oral dose may be administered singly or in divided (three or four) doses.

Male hypogonadism: For complete replacement in the hypogonadal male, a daily dose of 5 to 20 mg will suffice in the majority of patients. It is usually preferable to begin treatment with full therapeutic doses which are later adjusted to individual requirements. Priapism is indicative of excessive dosage and is indication for temporary withdrawal of the drug.

Delayed puberty: Dosage should be carefully titrated utilizing a low dose, appropriate skeletal monitoring, and by limiting the duration of therapy to four to six months.

Inoperable carcinoma of the breast in the female: The recommended total daily dose for palliative therapy in advanced inoperable carcinoma of the breast is 10 to 40 mg. Because of its short action, fluoxymesterone should be administered to patients in divided, rather than single, daily doses to ensure more stable blood levels. In general, it appears necessary to continue therapy for at least one month for a satisfactory subjective response, and for two to three months for an objective response.

HALOTESTIN Tablets, round and scored, are available in the following strengths and colors:

2 mg (peach)

Bottles of 100 NDC 0009-0014-01

5 mg (light green)

Bottles of 100 NDC 0009-0019-06

10 mg (green)

Bottles of 30 NDC 0009-0036-03
Bottles of 100 NDC 0009-0036-04

Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP].

Distributed by Pharmacia and Upjohn Company, Division of Pfizer Inc, NY, NY 10017. Revised May 2002. FDA Rev date: 4/6/1992

Endocrine and urogenital

Female: the most common side effects of androgen therapy are amenorrhea and other menstrual irregularities; inhibition of gonadotropin secretion; and virilization, including deepening of the voice and clitoral enlargement. The latter usually is not reversible after androgens are discontinued. When administered to a pregnant woman, androgens can cause virilization of external genitalia of the female fetus.

Male: Gynecomastia, and excessive frequency and duration of penile erections. Oligospermia may occur at high dosage.

Skin and appendages

Hirsutism, male pattern of baldness, seborrhea, and acne.

Fluid and electrolyte disturbances

Retention of sodium, chloride, water, potassium, calcium, and inorganic phosphates.

Gastrointestinal

Nausea, cholestatic jaundice, alterations in liver function tests, rarely hepatocellular neoplasms and peliosis hepatis (See WARNINGS).

Hematologic

Suppression of clotting factors II, V, VII, and X, bleeding in patients on concomitant anticoagulant therapy, and polycythemia.

Nervous system

Increased or decreased libido, headache, anxiety, depression, and generalized paresthesia.

Allergic

Hypersensitivity, including skin manifestations and anaphylactoid reactions.

Drug Abuse And Dependence

Controlled Substance Class: Fluoxymesterone is a controlled substance under the Anabolic Steroids Control Act, and HALOTESTIN Tablets has been assigned to Schedule III.

Androgens may increase sensitivity to oral anticoagulants. Dosage of the anticoagulant may require reduction in order to maintain satisfactory therapeutic hypoprothrombinemia.

Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone.

In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, insulin requirements.

Drug/Laboratory test interferences

Androgens 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, however, and there is no clinical evidence of thyroid dysfunction.

Hypercalcemia may occur in immobilized patients and in patients with breast cancer. If this occurs, the drug should be discontinued.

Prolonged use of high doses of androgens (principally the 17-α alkyl-androgens) has been associated with development of hepatic adenomas, hepatocellular carcinoma, and peliosis hepatis—all potentially life-threatening complications.

Cholestatic hepatitis and jaundice may occur with 17-α-alkyl-androgens. Should this occur, the drug should be discontinued. This is reversible with discontinuation of the drug.

Geriatric patients treated with androgens may be at an increased risk of developing prostatic hypertrophy and prostatic carcinoma although conclusive evidence to support this concept is lacking.

Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal or hepatic disease.

Gynecomastia may develop and occasionally persists in patients being treated for hypogonadism.

Androgen therapy should be used cautiously in males with delayed puberty. Androgens can accelerate bone maturation without producing compensatory gain in linear growth. The effect on bone maturation should be monitored by assessing bone age of the wrist and hand every six months.

This drug has not been shown to be safe and effective for the enhancement of athletic performance. Because of the potential risk of serious adverse health effects, this drug should not be used for such purpose.

General

Women should be observed for signs of virilization which is usual following androgen use at high doses. Discontinuation of drug therapy at the time of evidence of mild virilism is necessary to prevent irreversible virilization. A decision may be made by the patient and the physician that some virilization will be tolerated during treatment for breast carcinoma.

Patients with benign prostatic hypertrophy may develop acute urethral obstruction. Priapism or excessive sexual stimulation may develop. Oligospermia may occur after prolonged administration or excessive dosage. If any of these effects appear, the androgen should be stopped and if restarted, a lower dosage should be utilized.

This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have a aspirin hypersensitivity.

Laboratory tests

Women with disseminated breast carcinoma should have frequent determination of urine and serum calcium levels during the course of androgen 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 six months) X-ray examinations of bone age should be made during treatment of prepubertal males to determine the rate of bone maturation and the effects of androgen therapy on the epiphyseal centers.

Hemoglobin and hematocrit levels (to detect polycythemia) should be checked periodically in patients receiving long-term androgen administration.

Serum cholesterol may increase during androgen therapy.

Carcinogenesis, mutagenesis, impairment of fertility

Animal data: Testosterone has been tested by subcutaneous injection and implantation in mice and rats. The implant induced cervical-uterine tumors in mice, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically-induced carcinomas of the liver in rats.

Human data: There are rare reports of hepatocellular carcinoma in patients receiving long-term therapy with androgens in high doses. Withdrawal of the drugs did not lead to regression of the tumors in all cases. Geriatric patients treated with androgens may be at an increased risk of developing prostatic hypertrophy and prostatic carcinoma although conclusive evidence to support this concept is lacking.

This compound has not been tested for mutagenic potential. However, as noted above, carcinogenic effects have been attributed to treatment with androgenic hormones. The potential carcinogenic effects likely occur through a hormonal mechanism rather than by a direct chemical interaction mechanism.

Impairment of fertility was not tested directly in animal species. However, as noted below under Adverse Reactions, oligospermia in males and amenorrhea in females are potential adverse effects of treatment with HALOTESTIN Tablets. Therefore, impairment of fertility is a possible outcome of treatment with HALOTESTIN.

Pregnancy

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

Nursing mothers

HALOTESTIN is not recommended for use in nursing mothers.

Pediatric use

Androgen therapy should be used very cautiously in children and only by specialists aware of the adverse effects on bone maturation. Skeletal maturation must be monitored every six months by an X-ray of the hand and wrist (See WARNINGS).

There have been no reports of acute overdosage with the androgens.

1. Known hypersensitivity to the drug
2. Males with carcinoma of the breast
3. Males with known or suspected carcinoma of the prostate gland
4. Women known or suspected to be pregnant
5. Patients with serious cardiac, hepatic or renal disease

Endogenous androgens are responsible for normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include growth and maturation of the prostate, seminal vesicles, penis, and scrotum; development of male hair distribution, such as beard, pubic, chest, and axillary hair; laryngeal enlargement, vocal cord thickening, and alterations in body musculature and fat distribution. Drugs in this class also cause retention of nitrogen, sodium, potassium, and phosphorus, and decreased urinary excretion of calcium. Androgens have been reported to increase protein anabolism and decrease protein catabolism. Nitrogen balance is improved only when there is sufficient intake of calories and protein.

Androgens are responsible for the growth spurt of adolescence and for eventual termination of linear growth, brought about by fusion of the epiphyseal growth centers. In children, exogenous androgens accelerate linear growth rates, but may cause disproportionate advancement in bone maturation. Use over long periods may result in fusion of the epiphyseal growth centers and termination of the growth process. Androgens have been reported to stimulate production of red blood cells by enhancing production of erythropoietic stimulation factor.

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

Inactivation of testosterone occurs primarily in the liver.

The half-life of fluoxymesterone after oral administration is approximately 9.2 hours.

Patients should be instructed to report any of the following: nausea, vomiting, changes in skin color, and ankle swelling. Males should be instructed to report too frequent or persistent erections of the penis and females any hoarseness, acne, changes in menstrual periods or increase in facial hair.

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.

FLUOXYMESTERONE - ORAL

(flew-ox-ee-MESS-ter-own)

COMMON BRAND NAME(S): Halotestin

USES: This medication is used in men who do not make enough of a natural substance called testosterone. In males, testosterone is responsible for many normal functions, including growth and development of the genitals, muscles, and bones. It also helps cause normal sexual development (puberty) in children/teenagers. Fluoxymesterone is similar to the natural testosterone produced by your body. It belongs to a class of drugs known as androgens. It works in many ways so that the body can develop and function normally.

Fluoxymesterone may also be used in certain adolescent boys to cause puberty in those with delayed puberty.

It may also be used in certain women to treat advanced breast cancer.

HOW TO USE: Take this medication by mouth with or without food, usually 1 to 4 times daily for low testosterone levels or exactly as prescribed by your doctor. Take with food if stomach upset occurs.

Dosage is based on your medical condition, testosterone blood levels, and response to treatment.

Use this medication regularly in order to get the most benefit from it.

Do not suddenly stop using fluoxymesterone if you have been using it regularly for an extended time or if it has been used in high doses. In such cases, your body will no longer make its own testosterone, and withdrawal reactions (e.g., tiredness, weakness, depression) may occur if you suddenly stop this drug. To prevent withdrawal reactions when stopping extended, regular treatment with this drug, gradually reduce the dosage as directed. Consult your doctor or pharmacist for more details, and report any withdrawal reactions immediately.

Abnormal drug-seeking behavior is possible with this medication, and it is frequently misused for its muscle-enhancing effects. Do not increase your dose, take it more frequently, or take it for a longer time than prescribed. Doing so may increase serious side effects (e.g., increased risk for heart disease/heart failure/stroke/liver disease, ruptured tendons/ligaments, improper bone development in adolescents). Properly stop the medication when so directed.

Tell your doctor if your condition persists or worsens after at least 1 month of treatment.

SIDE EFFECTS: Nausea, vomiting, skin color changes, ankle swelling, increased sexual interest, increased frequency/duration of erections, oily skin, and acne may occur. Less common side effects may include trouble sleeping, increased sweating, and headaches. 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 when it is used at normal doses.

Tell your doctor immediately if any of these unlikely but serious side effects occur: body/facial swelling, decreased sexual interest, body tingling, signs of serious liver disease (persistent abdominal pain/nausea, vomiting, yellowish skin/eyes, white stools, dark urine).

If you are a male tell your doctor immediately if any of these unlikely but serious side effects occur: difficulty starting the flow of urine, mental/mood changes (e.g., anxiety, aggressiveness, increased anger), breast enlargement.

If you are a woman, tell your doctor immediately if any of these unlikely but serious side effects occur: deepening of the voice, hoarseness, unusual facial hair growth, enlarged clitoris, irregular menstrual periods.

Tell your doctor immediately if any of these rare but very serious side effects occur: signs of heart failure (e.g., decreased exercise ability, ankle/leg swelling, easily tired, shortness of breath while lying down).

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 using fluoxymesterone, tell your doctor or pharmacist if you are allergic to it; or to 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: serious heart disease (e.g., angina, history of heart attack, heart failure), serious liver disease (e.g., chronic hepatitis B or C, cirrhosis), severe kidney disease, breast cancer in men, prostate cancer.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: enlarged prostate, high red blood cell count, high cholesterol, diabetes, high blood pressure.

If you are a male you should tell your doctor if you have too many erections. In the unlikely event you have a painful or prolonged erection (lasting more than 4 hours), stop using this drug and seek immediate medical attention, or permanent problems could occur.

If you have diabetes, this product may decrease your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms of low blood sugar, such as increased hunger, dizziness, or unusual sweating. Your anti-diabetic medication or diet may need to be adjusted.

Tell your doctor if you become bed-ridden (unable to walk) for a prolonged time while using this medication. Your doctor may wish to monitor your blood calcium for high levels to prevent bone/kidney problems.

Caution is advised when using this drug in male children because bone growth may be affected, causing shorter adult height. Your child's doctor will monitor his growth and bone development during treatment.

This medication must not be used during pregnancy. It may harm an unborn baby. Discuss the use of reliable forms of birth control with your doctor. If you are pregnant or think you may be pregnant, tell your doctor immediately.

It is not known whether this drug passes into breast milk. Because of the possibility of severe side effects in your nursing infant, it is recommended to avoid breast-feeding while using this medication. Consult your doctor for more information.

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: warfarin, oxyphenbutazone, cyclosporine.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting fluoxymesterone.

Use of fluoxymesterone may affect certain laboratory tests (e.g., thyroid tests including total T4, rT3 uptake, rT4 uptake). Make sure that all of your doctors and laboratory personnel know you are using this medication.

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: Overdose is unlikely, but if it 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 or sell this medication to others. It is against the law.

Laboratory and/or medical tests (e.g., blood testosterone levels, red blood cell counts, liver function tests, blood cholesterol levels, blood pressure measurements) 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 at room temperature at 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 August 2008 Copyright(c) 2008 First DataBank, Inc.