Androxy

Overdose

There have been no reports of acute overdosage with androgens.

Contraindications

Androgens are contraindicated in men with carcinomas of the breast or with known or suspected carcinomas of the prostate and in women who are or may become pregnant. When administered to pregnant women, androgens cause virilization of the external genitalia of the female fetus. This virilization includes clitoromegaly, abnormal vaginal development, and fusion of genital folds to form a scrotal-like structure. The degree of masculinization is related to the amount of drug given and the age of the fetus and is most likely to occur in the female fetus when the drugs are given in the first trimester. If the patient becomes pregnant while taking androgens, she should be apprised of the potential hazard to the fetus.

Undesirable effects

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 cause virilization of external genitalia of the female fetus.

Gynecomastia, and excessive frequency and duration of penile erections. Oligospermia may occur at high dosages (see CLINICAL PHARMACOLOGY).

Hirsutism, male pattern baldness, and acne.

Retention of sodium, chloride, water, potassium, calcium (see WARNINGS), and inorganic phosphates.

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

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

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

Increased serum cholesterol.

Hypersensitivity; rarely, anaphylactoid reactions.

ANDROXY™ Tablets are classified as a Schedule III controlled substance under the Anabolic Steroids Control Act of 1990.

Therapeutic indications

ANDROXY™ Tablets are indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone.

Primary hypogonadism (congenital or acquired)—Testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy.

Hypogonadotropic hypogonadism (congenital or acquired)—Idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. (Appropriate adrenal cortical and thyroid hormone replacement therapy are still necessary, however, and are actually of primary importance.)

If the above conditions occur prior to puberty, androgen replacement therapy will be needed during the adolescent years for development of secondary sexual characteristics. Prolonged androgen treatment will be required to maintain sexual characteristics in these and other males who develop testosterone deficiency after puberty.

Delayed puberty - ANDROXY™ (Fluoxymesterone Tablets, USP) may be used to stimulate puberty in carefully selected males with clearly delayed puberty. These patients usually have a familial pattern of delayed puberty that is not secondary to a pathological disorder; puberty is expected to occur spontaneously at a relatively late date. Brief treatment with conservative doses may occasionally be justified in these patients if they do not respond to psychological support. The potential adverse effect on bone maturation should be discussed with the patient and parents prior to androgen administration. An X-ray of the hand and wrist to determine bone age should be obtained every six months to assess the effect of treatment on the epiphyseal centers (see WARNINGS).

Metastatic mammary cancer - ANDROXY™ (Fluoxymesterone Tablets, USP) may be used secondarily in women with advancing inoperable metastatic (skeletal) mammary cancer who are one to five years postmenopausal. Primary goals of therapy in these women include ablation of the ovaries. Other methods of counteracting estrogen activity are adrenalectomy, hypophysectomy, and/or antiestrogen therapy. This treatment has been used in premenopausal women with breast cancer who have benefited from oophorectomy and are considered to have a hormone-responsive tumor. Judgment concerning androgen therapy should be made by an oncologist with expertise in this field.

Date of revision of the text

Name of the medicinal product

Fertility, pregnancy and lactation

Category X (see CONTRAINDICATIONS)

Qualitative and quantitative composition

ANDROXY™ (Fluoxymesterone Tablets, USP) 10 mg are round, green, scored compressed tablets debossed with 832 and 86 and are available in bottles of 100.

Dispense in a tight, light-resistant container as defined in the USP.

Store at controlled room temperature 15 – 30°C (59 – 86°F).

Keep out of reach of children.

Manufactured by : UPSHER-SMITH LABORATORIES, INC., Maple Grove, MN 55369. Revised: Jul 2013

Special warnings and precautions for use

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.

In patients with breast cancer and in immobilized patients, androgen therapy may cause hypercalcemia by stimulating osteolysis. In patients with cancer, hypercalcemia may indicate progression of bony metastasis. If hypercalcemia occurs, the drug should be discontinued and appropriate measures instituted.

Prolonged use of high doses of androgens has been associated with the development of peliosis hepatis and hepatic neoplasms including hepatocellular carcinoma (see PRECAUTIONS, Carcinogenesis). Peliosis hepatis can be a life-threatening or fatal complication.

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

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

Due to sodium and water retention, edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required. If the administration of fluoxymesterone is restarted, a lower dosage should be used.

Gynecomastia frequently develops and occasionally persists in patients being treated for hypogonadism.

Androgen therapy should be used cautiously in healthy males with delayed puberty. The effect on bone maturation should be monitored by assessing bone age of the wrist and hand every six months. In children, androgen treatment may accelerate bone maturation without producing compensatory gain in linear growth. This adverse effect may result in compromised adult stature. The younger the child the greater the risk of compromising final mature height.

Women should be observed for signs of virilization (deepening of the voice, hirsutism, acne, clitoromegaly, and menstrual irregularities). Discontinuation of drug therapy at the time of evidence of mild virilism is necessary to prevent irreversible virilization. Such virilization is usual following androgen use at high doses and is not prevented by concomitant use of estrogens. A decision may be made by the patient and the physician that some virilization will be tolerated during treatment for breast carcinoma.

Because androgens may alter serum cholesterol concentration, caution should be used when administering these drugs to patients with a history of myocardial infarction or coronary artery disease. Serial determinations of serum cholesterol should be made and therapy adjusted accordingly. A causal relationship between myocardial infarction and hypercholesterolemia has not been established.

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 should be checked periodically for polycythemia in patients who are receiving high doses of androgens.

When administered concurrently, the following drugs may interact with androgens:

Anticoagulants, oral—C-17 substituted derivatives of testosterone, such as methandrostenolone, have been reported to decrease the anticoagulant requirement. Patients receiving oral anticoagulant therapy require close monitoring especially when androgens are started or stopped.

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

ACTH and corticosteroids—Enhanced tendency toward edema. Use caution when giving these drugs together, especially in patients with hepatic or cardiac disease.

Oxyphenbutazone—May result in elevated serum levels of oxyphenbutazone.

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.

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 for the development of prostatic hypertrophy and prostatic carcinoma.

Category X (see CONTRAINDICATIONS)

It is not known whether androgens are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from androgens, 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.

Androgen therapy should be used very cautiously in children and only by specialists who are 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 INDICATIONS AND USAGE, and WARNINGS).

Dosage (Posology) and method of administration

ANDROXY™ (Fluoxymesterone Tablets, USP), for oral administration, may be given as a single daily dose or in divided doses. Dosage and duration of therapy will depend on age, sex, diagnosis, patient's response to treatment, and appearance of adverse effects. The following recommendations will serve as a guide to therapy with ANDROXY™ Tablets.

Various dosage regimens have been used, some call for lower dosages initially with gradual increases as puberty progresses, with or without a decrease to maintenance levels. Other regimens call for higher dosage to induce pubertal changes and lower dosage for maintenance after puberty. The chronological and skeletal ages must be taken into consideration, both in determining the initial dose and in adjusting the dose. Dosage is within the range of 2.5 to 20 mg daily, although generally in the lower range of 2.5 to 10 mg daily, and for a limited duration, for example 4 to 6 months. X-rays should be taken at appropriate intervals to determine the amount of bone maturation and skeletal development (see INDICATIONS AND USAGE, and WARNINGS).

As replacement therapy, i.e., for eunuchism, a daily dose of 5 to 20 mg is suggested. It is usually preferable to start therapy at a higher level within the range (e.g., 10 mg), with subsequent adjustment as required.

A daily dose of 10 to 40 mg, given in divided doses, is recommended. To determine if there will be an objective response, treatment should be continued for three months or more. Patients must be followed closely because androgen therapy occasionally appears to accelerate the disease. Thus, many experts prefer to use a shorter acting androgen preparation, such as ANDROXY™ Tablets, rather than those with prolonged activity, particularly during the early stages of androgen therapy.

Hormone therapy is adjunctive to and not a replacement for conventional therapy. Duration of therapy will depend on the response of the condition and the appearance of adverse reactions.

Interaction with other medicinal products and other forms of interaction

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 cause virilization of external genitalia of the female fetus.

Gynecomastia, and excessive frequency and duration of penile erections. Oligospermia may occur at high dosages (see CLINICAL PHARMACOLOGY).

Hirsutism, male pattern baldness, and acne.

Retention of sodium, chloride, water, potassium, calcium (see WARNINGS), and inorganic phosphates.

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

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

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

Increased serum cholesterol.

Hypersensitivity; rarely, anaphylactoid reactions.

ANDROXY™ Tablets are classified as a Schedule III controlled substance under the Anabolic Steroids Control Act of 1990.

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.