Fluoxymesterone

Brand name: Androxy
Drug class: Androgens
ATC class: G03BA01
VA class: HS100
Chemical name: 11β, 17β Androst-4-en-3-one, 9-fluoro-11, 17-dihydroxy-17 methyl
Molecular formula: C₂₀ H₂₉ FO₃
CAS number: 76-43-7

Introduction

Synthetic androgenic anabolic steroid hormone.

Uses for Fluoxymesterone

Male Hypogonadism

Management of congenital or acquired primary hypogonadism such as that resulting from orchiectomy or from testicular failure caused by cryptorchidism, bilateral torsion, orchitis, or vanishing testis syndrome.

Management of congenital or acquired hypogonadotropic hypogonadism such as that resulting from idiopathic gonadotropin or gonadotropin releasing hormone (luteinizing hormone releasing hormone) deficiency or from pituitary-hypothalamic injury caused by tumors, trauma, or radiation.

If any of these conditions occur before puberty, androgen replacement therapy will be necessary during adolescence for the development of secondary sexual characteristics; prolonged therapy required to maintain these characteristics. Prolonged androgen therapy also required to maintain sexual characteristics in other males who develop testosterone deficiency after puberty.

May be used to stimulate puberty in carefully selected males with delayed puberty (family history of delayed puberty not secondary to a pathologic disorder). Brief treatment with conservative doses of an androgen occasionally may be justified in these males if they do not respond to psychologic support.

Breast Cancer

Palliative treatment of androgen-responsive, advanced, inoperable, metastatic (skeletal) breast cancer in women who are 1–5 years postmenopausal and in premenopausal women who have benefited from oophorectomy and are considered to have a hormone-responsive tumor.

Poorly tolerated (see Virilization under Cautions); other hormonal agents (e.g., tamoxifen, anastrozole, letrozole, exemestane) currently are preferred for this use.

Misuse, Abuse, and Dependence

Has been misused and abused by athletes, bodybuilders, weight lifters, and others to enhance athletic performance and physique^{† [off-label]}.

Based on review of data, FDA concluded that misuse and abuse of androgens associated with serious adverse cardiovascular, hepatic, endocrine, and mental health effects. (See Misuse, Abuse, and Dependence under Cautions.)

Medical and sport experts (e.g., International Olympic Committee) consider such use to be inappropriate and unacceptable because of known adverse effects and potential for long-term sequelae. Such use by athletes is contrary to the rules and ethical principles of athletic competition.

Evaluate serum testosterone concentrations if misuse or abuse of androgens suspected (e.g., patients experiencing serious adverse cardiovascular or psychiatric effects). Serum testosterone concentrations may be below or within the normal range in patients abusing synthetic derivatives of testosterone.

Fluoxymesterone Dosage and Administration

General

• Individualize dosage according to condition being treated, severity of symptoms, and patient age, gender, and history of prior androgenic therapy.

• Adjust dosage carefully according to individual therapeutic response and appearance of adverse effects.

Delayed Puberty

• Take into consideration the chronological and skeletal ages of the patient, both in determining the initial dosage and in adjusting the dosage.

• Perform radiographic examination of the hand and wrist at 6-month intervals to determine the rate of bone maturation and to assess the effect of therapy on the epiphyseal centers. (See Pediatric Use under Cautions.)

Breast Cancer

• Administer only under the supervision of a qualified clinician experienced in the treatment of breast cancer.

• Occasionally, may appear to accelerate progression of the disease; monitor patients closely.

Administration

Oral Administration

Administer orally, usually as a single daily dose or in 3 or 4 divided doses.

Dosage

Pediatric Patients

Male Hypogonadism

Hypogonadism

Oral

For development of secondary sexual characteristics during adolescence: 5–20 mg daily. Generally, therapy initiated at a higher level within the range (e.g., 10 mg daily). Prolonged therapy is required to maintain sexual characteristics.

Delayed Puberty

Oral

Use dosages in the lower end of the usual range for replacement (i.e., 10 mg daily) for 4–6 months. Usual range: 2.5–20 mg daily; however, most patients respond to 2.5–10 mg daily. Titrate carefully using low doses.

Some clinicians recommend lower dosages initially, followed by gradual increases in dosage as puberty progresses; subsequently, the dosage may be decreased to maintenance levels. Other clinicians state that higher dosages are required initially to induce pubertal changes and lower dosages can then be used for maintenance therapy after puberty.

Adults

Male Hypogonadism

Oral

Usual dosage: 5–20 mg daily; prolonged therapy is required to maintain sexual characteristics.

Breast Cancer

Oral

Usual dosage: 10–40 mg daily in divided doses.

Generally, ≥1 month of therapy is necessary to obtain a satisfactory subjective response; ≥2–3 months of continuous therapy is required to obtain a satisfactory objective response.

Special Populations

No special population dosage recommendations at this time.

Cautions for Fluoxymesterone

Contraindications

• Males with breast cancer or known or suspected prostate cancer.

• Known or suspected pregnancy.

• Some manufacturers state that fluoxymesterone is contraindicated in patients with serious cardiac, hepatic, or renal disease.

• Known hypersensitivity to fluoxymesterone or any ingredient in the formulation.

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity

May cause fetal harm; dose-related virilization of the external genitalia (e.g., clitoral hypertrophy, labial fusion of the external genital fold to form a scrotal-like structure, abnormal vaginal development, persistence of a urogenital sinus) of female fetus reported, particularly when exposure to androgens occurs during the first trimester. If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard; contraindicated in pregnant women. (See Contraindications under Cautions.)

Hepatic Effects

Potentially serious and/or life-threatening adverse hepatic effects (e.g., peliosis hepatis, hepatic adenomas, hepatocellular carcinoma) associated with prolonged use of high dosages of androgens. Discontinuance of androgen therapy following development of hepatocellular carcinoma dose not always result in regression of the tumor.

If cholestatic hepatitis or jaundice occurs, or if liver function test results become abnormal during therapy, discontinue the drug and investigate the etiology of these disorders. Drug-induced jaundice usually is reversible following discontinuance of the drug.

Periodic liver function evaluation recommended.

GU Effects

Priapism or excessive sexual stimulation possible, especially in geriatric men. Oligospermia and decreased ejaculatory volume also may occur in men receiving excessive dosage or prolonged administration. Acute urethral obstruction possible in patients with benign prostatic hypertrophy. If any of these adverse effects occur, discontinue the drug temporarily. If therapy is restarted, use lower dosages.

Possible increased risk for the development of prostatic hyperplasia and prostate cancer, particularly in geriatric patients.

Possible increased or decreased libido.

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

Fluid Retention

Edema, with or without CHF, possible as a result of sodium and water retention and may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. (See Contraindications under Cautions.) If edema occurs and is considered a serious complication, discontinue drug and, if necessary, initiate diuretic therapy. If therapy is restarted, use lower dosages.

Retention of potassium and inorganic phosphates also has occurred.

Hypercalcemia

Possible hypercalcemia resulting from osteolysis, especially in immobile patients and those with metastatic breast cancer. In patients with cancer, hypercalcemia may indicate progression of metastases to the bone. Monitor urine and serum calcium concentrations frequently during the course of androgen therapy in women with metastatic breast cancer. If hypercalcemia occurs, discontinue the drug and institute appropriate measures.

Misuse, Abuse, and Dependence

Serious adverse effects (e.g., increased aggression, antisocial behavior, manic episode, hostility, depression, changes in libido, increased risk of cardiovascular events, hepatotoxicity, testicular atrophy, sperm abnormalities) associated with misuse and abuse of androgens (see Misuse, Abuse, and Dependence under Uses); fluoxymesterone preparations currently subject to control as schedule III (C-III) drugs.

Manifestations of withdrawal (e.g., depressed mood, major depression, fatigue, cravings, restlessness, irritability, anorexia, insomnia, decreased libido, hypogonadotropic hypogonadism) may occur if androgens discontinued abruptly or dosage substantially reduced in physically dependent patients or in those taking supratherapeutic dosages of such drugs; withdrawal symptoms may persist for weeks or months.

General Precautions

Virilization

Virilization, including deepening of the voice, hirsutism, acne, menstrual irregularities, and clitoral enlargement, occurs commonly in females receiving high-dose fluoxymesterone therapy; changes may not be reversible following discontinuance of the drug.

Monitor women receiving fluoxymesterone therapy for signs of virilization. If virilization occurs, discontinue therapy.

Hematologic Effects

Possible polycythemia, especially with high dosages of androgens. Perform periodic hemoglobin and hematocrit determinations in patients receiving high dosages or long-term administration of fluoxymesterone.

Lipid Abnormalities

Androgens may alter serum cholesterol concentration; therefore, administer with caution in patients with history of MI or CAD.

Monitor serum cholesterol throughout therapy; adjust therapy accordingly .

Specific Populations

Pregnancy

Category X. (See Fetal/Neonatal Morbidity and also Contraindications, under Cautions.)

Lactation

Not known whether fluoxymesterone is distributed into milk. Discontinue nursing or the drug.

Pediatric Use

May accelerate bone maturation without producing compensatory gain in linear growth, possibly resulting in compromised adult stature. The younger the child, the greater the risk of fluoxymesterone compromising final mature stature. Use with extreme caution in children and only under the supervision of a specialist who is aware of the adverse effects of fluoxymesterone on bone maturation. Perform radiographic examination of the hand and wrist every 6 months to determine the rate of bone maturation and to assess the effect of treatment on the epiphyseal centers.

Geriatric Use

Possible risk of developing prostatic hypertrophy and carcinoma during androgen therapy.

Males, especially geriatric patients, may become overly sexually stimulated during therapy and such stimulation may be a sign of excessive dosage. Carefully monitor males for the development of excessive sexual stimulation.

Common Adverse Effects

Males: Gynecomastia, frequent or persistent penile erections.

Females: Amenorrhea, other menstrual irregularities, inhibition of gonadotropin secretion, virilization (e.g., deepening of the voice, clitoral enlargement).

Interactions for Fluoxymesterone

Specific Drugs and Laboratory Tests

Fluoxymesterone Pharmacokinetics

Elimination

Metabolism

Metabolized primarily in the liver. Methylation at the 17 position associated with less hepatic metabolism following oral administration compared with testosterone.

Half-life

Following oral administration: Approximately 9.2–10 hours.

Stability

Storage

Oral

Tablets

Tight, light-resistant container at 15–30°C.

Actions

• Replaces diminished or absent endogenous testicular hormone in hypogonadal males.

• Endogenous androgens are essential hormones that are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics.

• Responsible for the growth spurt that occurs during adolescence and for the eventual termination of linear growth that results from the fusion of the epiphyseal growth centers.

• Produces retention of nitrogen, potassium, sodium, and phosphorus; increases protein anabolism; and decreases amino acid catabolism and urinary calcium concentrations.

• Approximately 5 times as potent as methyltestosterone; has androgenic activity equal to that of parenterally administered testosterone.

• Halogenated derivative of 17-α-methyltestosterone and, like methyltestosterone, is less extensively metabolized by the liver than testosterone.

• Stimulates the production of erythrocytes, apparently by enhancing the production of erythropoietic stimulating factor.

• Inhibits the release of endogenous testosterone via feedback inhibition of pituitary LH.

• Large doses of androgens may suppress spermatogenesis.

Advice to Patients

• Importance of advising patients of the potential for serious adverse effects associated with misuse and abuse.

• Risk of virilization in females. Advise female patients to contact their clinician if they notice hoarseness, acne, menstrual changes, or the growth of facial hair.

• Risk of priapism; importance of males informing clinicians if too frequent or persistent penile erections occur.

• Importance of discussing the potential for adverse effects on bone maturation in prepubertal males prior to initiation of therapy.

• Importance of informing clinicians if nausea, vomiting, changes in skin color, or ankle swelling occurs.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Fluoxymesterone is subject to control under the Federal Controlled Substances Act of 1970, as amended by the Anabolic Steroids Control Act of 1990 and 2004, as a schedule III (C-III) drug.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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