Methyltestosterone

The androgens are steroids that develop and maintain primary and secondary male sex characteristics.

Androgens are derivatives of cyclopentanoperhydrophenanthrene. Endogenous androgens are C-19 steroids with a side chain at C-17, and with two angular methyl groups. Testosterone is the primary endogenous androgen. In their active form, all drugs in the class have a 17-beta hydroxy group. 17-alpha alkylation (Methyltestosterone) increases the pharmacologic activity per unit weight compared to testosterone when given orally.

Methyltestosterone, a synthetic derivative of testosterone, is an androgenic preparation given by the oral route in a capsule form. Each capsule contains 10 mg of Methyltestosterone USP. It has the following structural formula:

C20H30O2     M.W. 302.46

17-β-hydroxy-17-methylandrost-4-en-3-one

Methyltestosterone occurs as white or creamy white crystals or powder, which is soluble in various organic solvents but is practically insoluble in water.

Each capsule, for oral administration, contains 10 mg of Methyltestosterone. In addition, each capsule contains the following inactive ingredients: Corn starch NF, Gelatin NF, FD&C Blue #1, FD&C Red #40.

Take methyltestosterone exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Methyltestosterone dose your doctor recommends will be based on the following (use any or all that apply):

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Methyltestosterone is available in the following doses:

• Conjugated Estrogens-methyltestosterone 0.625 Mg-1.25 Mg Oral Tablet
• Conjugated Estrogens-methyltestosterone 0.625 Mg-5 Mg Oral Tablet
• Conjugated Estrogens-methyltestosterone 1.25 Mg-10 Mg Oral Tablet
• Esterified Estrogens-methyltestosterone 0.625 Mg-1.25 Mg Oral Tablet
• Esterified Estrogens-methyltestosterone 1.25 Mg-2.5 Mg Oral Tablet
• Methyltestosterone 10 Mg Oral Capsule
• Methyltestosterone 10 Mg Oral Tablet
• Methyltestosterone 25 Mg Oral Tablet
• Methyltestosterone Compounding Powder

Methyltestosterone is available in the following forms:

• Buccal Tablet
• Oral Capsule
• Oral Tablet
• Sublingual Tablet

Other drugs may interact with methyltestosterone, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

• Store at room temperature.
• Protect from light.
• Protect from heat.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take methyltestosterone or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to methyltestosterone. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Endogenous androgens are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis, and scrotum. The development of male hair distribution, such as beard, pubic, chest, and axillary hair; laryngeal enlargement, vocal chord thickening, alterations in body musculature, and fat distribution. Drugs in this class also cause retention of nitrogen, sodium, potassium, 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 the eventual termination of linear growth which is brought about by fusion of the epiphyseal growth centers. In children, exogenous androgens accelerate linear growth rates, but may cause a disproportionate advancement in bone maturation. Use over long periods may result in fusion of the epiphyseal growth centers and termination of growth process. Androgens have been reported to stimulate the production of red blood cells by enhancing the production of erythropoietic stimulating 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).

There is a lack of substantial evidence that androgens are effective in fractures, surgery, convalescence and functional uterine bleeding.

Pharmacokinetics

Testosterone given orally is metabolized by the gut and 44 percent is cleared by the liver of the first pass. Oral doses as high as 400 mg per day are needed to achieve clinically effective blood levels for full replacement therapy. The synthetic androgen, Methyltestosterone, is less extensively metabolized by the liver and has a longer half-life. It is more suitable than testosterone for oral administration.

Testosterone in plasma is 98 percent bound to a specific testosterone-estradiol binding globulin, and about 2 percent is free. Generally, the amount of this sex-hormone binding globulin in the plasma will determine the distribution of testosterone between free and bound forms, and the free testosterone concentration will determine its half-life.

About 90 percent of a dose of testosterone is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; and 6 percent of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. Testosterone is metabolized to various 17-keto steroids through two different pathways. There are considerable variations of the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes.

In many tissues the activity of testosterone appears to depend on reduction to dihydrotestosterone, which binds to cytosol receptor proteins. The steroid-receptor complex is transported to the nucleus where it initiates transcription events and cellular changes related to androgen action.

In patients with breast cancer, androgen therapy may cause hypercalcemia by stimulating osteolysis. In this case, the drug should be discontinued.

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

Cholestatic hepatitis and jaundice occur with 17-alpha-alkylandrogens 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.

There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as Methyltestosterone. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with Methyltestosterone and initiate appropriate workup and management.

Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use Methyltestosterone. 

Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see Drug Abuse and Dependence].

If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.

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.

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 6 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.

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.

• Androgen

Delayed puberty: Adolescent males: Oral: Refer to adult dosing.

Hypogonadotropic hypogonadism (congenital or acquired) and primary hypogonadism (congenital or acquired): Adolescent males: Oral: Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, patients with renal disease may be at an increased risk of fluid retention.

Concerns related to adverse effects:

• Cardiovascular events: Available studies are inconclusive regarding the risk of developing major adverse cardiovascular events (MACE) such as nonfatal MI, stroke, or cardiovascular death following testosterone use. Studies have suggested an increased risk of cardiovascular events among groups of men prescribed testosterone therapy (Basaria 2010; Finkle 2014; Vigen 2013). The Endocrine Society suggests it may be prudent to avoid testosterone therapy in men who have experienced a cardiovascular event (eg, MI, stroke, acute coronary syndrome) in the past six months (The Endocrine Society 2014). These risks are currently under review by the FDA (Drug Safety Communication 2014).

• Gynecomastia: May cause gynecomastia which may persist in patients treated for hypogonadism.

• Hepatic effects: Prolonged use and/or high doses may cause peliosis hepatis, hepatic neoplasms including hepatocellular carcinoma, cholestatic hepatitis, and jaundice. Discontinue if cholestatic hepatitis with jaundice or abnormal liver function tests occur.

• Oligospermia: May cause oligospermia and reduced ejaculatory volume after prolonged administration or excessive dosage.

• Polycythemia: May increase hematocrit requiring dose adjustment or discontinuation. Withhold initial treatment in patients with hematocrit >50%. Discontinue therapy if hematocrit exceeds 54%; may reinitiate at lower dose (Endocrine Society [Bhasin 2010]).

• Priapism: Priapism or excessive sexual stimulation may occur.

• Venous thromboembolism: Venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), have been reported with testosterone products. Evaluate patients with symptoms of pain, edema, warmth, and erythema in the lower extremity for DVT and those with acute shortness of breath for PE. Discontinue therapy if a venous thromboembolism is suspected.

Disease-related concerns:

• Benign prostatic hyperplasia (BPH): Androgens may worsen BPH; do not use in patients with severe lower urinary tract symptoms [(AUA)/International Prostate Symptom Score (IPSS) > 19] (Endocrine Society [Bhasin 2010]). Discontinue therapy if urethral obstruction develops in patients with BPH (use lower dose if restarted).

• Breast cancer: May cause hypercalcemia (by stimulating osteolysis) in patients with breast cancer; discontinue if hypercalcemia occurs.

• Diseases exacerbated by fluid retention: Use with caution in patients with diseases that may be exacerbated by fluid retention, including cardiac impairment; may cause fluid retention. Treatment of androgen deficiency syndromes is not recommended for men with uncontrolled or poorly controlled heart failure (Endocrine Society [Bhasin 2010]).

• Hepatic impairment: Use with caution in patients with hepatic impairment; may cause fluid retention.

• Prostate cancer: May increase the risk of prostate cancer. Withhold therapy pending urological evaluation in patients with palpable prostate nodule or induration, PSA >4 ng/mL, or PSA >3 ng/mL in men at high risk of prostate cancer (Endocrine Society [Bhasin 2010]).

• Renal impairment: Use with caution in patients with renal impairment; may cause fluid retention.

• Sleep apnea: May potentiate sleep apnea in some male patients, especially those with risk factors (eg, obesity or chronic lung disease). Withhold initial treatment in patients with untreated obstructive sleep apnea (Endocrine Society [Bhasin 2010]).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: May be at greater risk for prostatic hyperplasia, and prostate cancer.

• Pediatric: May accelerate bone maturation (without producing compensatory gain in linear growth) and premature closure of the epiphyses in children; in prepubertal children, 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. Use with caution in males with delayed puberty.

• Women: During treatment for metastatic breast cancer, women should be monitored for signs of virilization; discontinue if mild virilization is present to prevent irreversible symptoms.

Other warnings/precautions:

• Abuse/misuse/diversion: Anabolic steroids may be abused, typically at doses higher than recommended and in combination with other anabolic androgenic steroids; abuse may be associated with serious cardiovascular and psychiatric adverse reactions. Inform patients of the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids; if abuse is suspected, check serum testosterone levels (testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives). Consider the possibility of abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.

• Dependence: Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented; however dependence may occur when used outside of approved dosage/indications.

Applies to methyltestosterone: compounding powder, oral capsule, oral tablet

Cardiovascular

Cardiovascular effects have included edema (with and without congestive heart failure).[Ref]

Endocrine

Endocrine side effects have included gynecomastia. Cautious use is recommended in patients with existing gynecomastia.

During exogenous administration of androgens, endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone (LH). Large doses of exogenous androgens may suppress spermatogenesis through inhibition of pituitary follicle stimulating hormone (FSH).

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 and there is no clinical evidence of thyroid dysfunction.[Ref]

Renal

Renal side effects have included retention of nitrogen, sodium, potassium, chloride, water, and phosphorus and decreased urinary excretion of calcium. Patients should be instructed to report edema.[Ref]

Hepatic

Hepatic side effects have included life-threatening peliosis hepatitis and hepatic abnormalities including hepatic neoplasms and hepatocellular carcinomas following prolonged therapy with high doses of androgen. Tumor regression did not occur in all cases following medication withdrawal.

Cholestatic hepatitis, jaundice, and abnormal liver function tests have occurred during androgen therapy. Drug-induced jaundice is reversible following drug discontinuation.[Ref]

Genitourinary

Genitourinary side effects have included oligospermia and decreased ejaculatory volume following chronic administration and/or large dosages of androgens. Elderly male patients may experience prostatic enlargement resulting in urinary obstruction. Priapism and excessive stimulation may develop. Methyltestosterone should be discontinued if any of these effects occur. If continued therapy is necessary, resume methyltestosterone at a lower dosage.

In female patients the use of androgens has resulted in virilization, including deepening voice, hirsutism, acne, clitomegaly (not reversible), and menstrual abnormalities. Discontinuation of methyltestosterone at signs of mild virilization may prevent irreversible virilization.[Ref]

Metabolic

Metabolic side effects have included osteolytic-induced hypercalcemia in immobilized patients or those with metastatic breast disease.

Androgens affect electrolyte balance, nitrogen retention, and urinary calcium excretion. Edema, with and without congestive heart failure has occurred during testosterone therapy.

Androgens have precipitated acute intermittent porphyria.

Increased cholesterol levels have occurred during androgen therapy.[Ref]

Dermatologic

Dermatologic side effects have included hirsutism, acne, male-patterned baldness and seborrhea.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea and vomiting.[Ref]

Musculoskeletal

Testosterone is involved in termination of linear bone growth by closure of the epiphyseal growth centers. Monitoring of bone age is recommended during methyltestosterone treatment in healthy males with delayed puberty.

Myalgia and pain have been reported.[Ref]

Hematologic

Hematologic side effects have included alteration in clotting factors II, V, VII and X and polycythemia due to increased red cell production.[Ref]

Hypersensitivity

Hypersensitivity side effects have included rare reports of rash and anaphylactoid reactions.[Ref]

Local

Local side effects have included inflammation and pain at injection or dermal application site.[Ref]

Nervous system

Nervous system side effects have included altered libido (increased/decreased), headache, anxiety, depression, generalized paresthesia, or sleep apnea syndrome.[Ref]

Oncologic

Oncologic side effects have included hepatic neoplasms and hepatocellular carcinomas following prolonged therapy with large doses of androgens.[Ref]

Respiratory

Respiratory side effects have included potentiation of sleep apnea, particularly in obese patients or those with chronic lung disease. Androgen therapy for hypogonadal conditions has been reported to[Ref]

Other

Other side effects have included virilization including deepening voice, hirsutism, acne, clitomegaly (not reversible), and menstrual abnormalities in female patients. Discontinuation of methyltestosterone at signs of mild virilization may prevent irreversible virilization.[Ref]

Some side effects of methyltestosterone may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

80 mg orally per day for 3 to 5 days.

Data not available

Data not available