Testosterone

Testosterone is an androgen indicated as a treatment for replacement therapy in the male in conditions associated with symptoms of low testosterone levels in the body or absence of endogenous testosterone. It is a sexual hormone produced by the testes that encourage the development of male sexual characteristics. High levels of the hormone are beneficial to men's health. Healthy levels of the hormone promote good health by lowering the dangers of high blood pressure and heart attack, in addition to a heart-healthy diet. Still, testosterone may be given as a treatment for specific medical conditions and low levels of testosterone in both men and women.

• Primary hypogonadism (congenital or acquired)-testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy.
• Hypogonadotropic hypogonadism (congenital or acquired)- gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.
• Safety and efficacy of DEPO-Testosterone (testosterone cypionate) in men with "age-related hypogonadism" (also referred to as "late-onset hypogonadism") have not been established.
• Testosterone is available under the following different brand names: Aveed, Depo-Testosterone, Delatestryl, and Testopel.

Dosages of Testosterone:

Dosages of Testosterone Should Be Given As Follows:

Adult and Pediatric Dosage Forms & Strengths

Injectable solution (cypionate): Schedule III

• 100mg/mL (Depo-Testosterone)
• 200mg/mL (Depo-Testosterone)

Injectable solution (enanthate): Schedule III

• 200mg/mL (Delatestryl)

Injectable solution (undecanoate): Schedule III

• 250mg/mL (Aveed)

Pellet implant: Schedule III

• 75mg (Testopel)
• 12.5mg, 25mg, 37.5mg, 50mg (generic)

Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility, and aggression.

Primary hypogonadism (congenital or acquired): Testicular failure due to diseases and conditions in the body such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter Syndrome, chemotherapy, or toxic damage from alcohol or heavy metals; these men usually have low serum testosterone levels and gonadotropins (FSH, LH) above normal range Hypogonadotropic hypogonadism (congenital or acquired): Gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation; these men have low testosterone serum concentrations but have gonadotropins in the normal or low range.

• Testosterone cypionate: 50-400 mg IM every 2-4 weeks
• Testosterone enanthate: 50-400 mg IM every 2-4 weeks
• Testosterone undecanoate (restricted availability): 750 mg IM initial dose, repeat after 4 weeks, and then q10wk thereafter
• Pellet: 150-450 mg SC every 3-6 months; 150 mg of pellet approximately equivalent to 25 mg of testosterone propionate weekly

<12 years

• Safety and efficacy not established

≥12 years

• testosterone cypionate: 50-400 mg IM every 2-4 weeks
• Testosterone enanthate: 50-400 mg IM every 2-4 weeks
• Testosterone undecanoate (restricted availability): 750 mg IM initial dose, repeat after 4 weeks, and then q10wk thereafter
• Pellet: 150-450 mg SC every 3-6 months; 150 mg of pellet approximately equivalent to 25 mg of testosterone propionate weekly

• 50-200 mg IM every 2-4 weeks for 4-6 months
• Alternative: 150-450 mg SC every 3-6 months

<12 years

• Safety and efficacy not established

≥12 years

• 50-200 mg IM every 2-4 weeks for 4-6 months
• Alternate dosing schedule: 150-450 mg SC every 3-6 months

200-400 mg enanthate IM every 2-4 weeks

• Physiologic testosterone replacement in androgen-deficient HIV+ patients with associated weight loss

Orphan sponsor

• Watson Laboratories, Research Park, 417 Wakara Way, Salt Lake City, UT 8410

Treatment of constitutional delay in growth and puberty in adolescent boys aged 14-17 years of life (testosterone undecanoate)

Orphan sponsor

• SOV Therapeutics, Inc, 101 Guymon Court, Morrisville, NC 27560

Side effects of testosterone include:

• Acne
• Abnormal dreams
• Aggressive behavior
• Hair loss
• Anaphylaxis
• Anger
• Memory loss (amnesia)
• Anxiety
• Bladder irritability
• Breast soreness
• Deep venous thrombosis
• Excessive frequency and duration of erection
• Fatigue
• Growth acceleration
• Enlarged breasts in men (gynecomastia)
• Headache
• Excessive hair growth
• Hot flashes
• Hypersensitivity
• High cholesterol (high fat in the blood)
• High blood pressure
• Insomnia
• Liver function alterations
• Male pattern baldness
• Menstrual irregularities
• Prolonged erection
• Itching
• Rash
• Scalp rash
• Suppression of factors II, V, VII, X
• Vasodilation
• Development of male characteristics in women
• Water retention
• Blood clot

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

If your doctor has directed you to use this medication, 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, health care provider, or pharmacist first.

Serious interactions of testosterone include:

• cyclosporine
• ivacaftor
• warfarin

Moderate interactions of testosterone include:

• axitinib
• carbamazepine
• daclatasvir
• eliglustat
• flibanserin
• insulin degludec
• insulin degludec/insulin aspart
• insulin inhaled
• ivacaftor
• lomitapide
• mipomersen
• ombitasvir/paritaprevir/ritonavir
• ponatinib

Testosterone has moderate interactions with at least 41 different drugs.

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. Check with your physician if you have health questions or concerns.

Warnings

Serious pulmonary oil microembolism reactions, involving urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope (POME) reactions and episodes of anaphylaxis reported during or immediately after administration of testosterone undecanoate injection; may occur after the first dose

Observe patients for 30 minutes in a healthcare setting to provide immediate medical treatment in event of serious POME reactions or anaphylaxis

Because of the risks of serious POME reactions and anaphylaxis, testosterone undecanoate is available through a restricted program under evaluation and mitigation strategy (REMS) called the Aveed REMS Program

This medication contains testosterone. Do not take Aveed, Depo-Testosterone, Delatestryl, or Testopel if you are allergic to testosterone or any ingredients.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity to this hormone or formulation components
• Cancer of breast or known or suspected carcinoma of the prostate in men
• Severe cardiac, hepatic, or renal disease
• Women: Pregnancy or prospect of pregnancy

Effects of Drug Abuse

• Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility, and aggression.

Short-Term Effects

• None.

Long-Term Effects

• None.

Cautions

• Do not use testosterone cypionate interchangeably with testosterone propionate.
• Breast cancer patients: Risk of hypercalcemia; discontinue if this condition develops.
• Long-term use (>10 years) of parenteral testosterone for male hypogonadism may increase the risk of breast cancer.
• Observe women for signs of virilization during treatment for metastatic breast cancer; if such signs are noted, discontinue to prevent irreversible virilization.
• Caution in history of myocardial infarction (MI) or coronary artery disease (CAD); some post-marketing studies have shown an increased risk of myocardial infarction and stroke associated with the use of testosterone replacement therapy.
• 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; if testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range; consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.
• Prolonged use of high-dose androgens associated with peliosis hepatitis and hepatic neoplasms (including hepatic cancer).
• Cholestatic hepatitis with jaundice; discontinue if this condition develops.
• Geriatric patients: Benign prostatic hyperplasia (BPH) and prostate cancer; monitor patients with BPH for worsening of signs and symptoms of BPH.

Gynecomastia.

• May alter serum lipid profile (use caution in history of MI or coronary artery disease).
• May increase sensitivity to oral anticoagulants and decreases blood glucose; adjust dosages accordingly.
• May cause hypercalcemia in patients with prolonged immobilization or cancer.
• Use with caution in patients with diseases that may be exacerbated by fluid retention, including cardiac, hepatic, or renal dysfunction; testosterone may cause fluid retention; treatment of androgen deficiency syndromes is not recommended for men with uncontrolled or poorly controlled heart failure.
• May accelerate bone maturation and premature closure of epiphyses in children; in prepubertal children perform radiographic examination.
• Large doses may suppress spermatogenesis.
• May potentiate sleep apnea in some patients.
• Priapism, excessive sexual stimulation, or acute urethral obstruction in patients with BPH.
• Increased hematocrit (polycythemia), reflective of increased red blood cell mass, may require discontinuation; increases risk for thromboembolism; monitor serum testosterone, prostate-specific antigen (PSA), liver function, lipid concentrations, hematocrit, and hemoglobin periodically.
• Skin burns were reported at the application site in patients wearing an aluminized transdermal system during a magnetic resonance imaging scan (MRI); because the transdermal testosterone patch contains aluminum, it is recommended to remove the system before undergoing MRI.
• Venous thromboembolism, including DVT and PE, reported in patients using testosterone products; these observations have included patients with and without polycythemia; evaluate signs or symptoms consistent with DVT or PE; if venous thromboembolic event suspected, discontinue treatment with testosterone and initiate appropriate workup and management.

Cardiovascular Risks

• Evaluate patients for cardiovascular risk factors before initiating therapy and monitor closely for cardiovascular events during therapy; it may be prudent to avoid testosterone therapy in men who have experienced a cardiovascular event.
• January 31, 2014: FDA is investigating the risk of stroke, MI, and death in men taking prescription testosterone; the investigation was prompted by findings from 2 studies suggesting an increased risk of MI in men who take testosterone.
• In one study, analysis of 55,593 men with a history of MI showed that men >65 years had a 2-fold increase in MI risk within 90 days of filing an initial prescription for testosterone; among younger men (<65 years) with a history of heart disease, MI risk was increased 2- to 3-fold
• This study confirmed results of an earlier, much smaller study, which found that older men, many with underlying heart disease, had a 30% increased chance of death, MI, and stroke after receiving testosterone therapy

Edema

• Edema with or without congestive heart failure may be a complication in patients with pre-existing cardiac, renal, or hepatic disease
• Diuretic treatment may be necessary in addition to discontinuance of the drug
• If drug therapy is restarted, use a lower dosage

Healthy males with delayed puberty

• Monitor bone maturation by assessing bone age of wrist and hand every 6 months
• May accelerate bone maturation, compromising final adult height

Pregnancy and Lactation

Do not use testosterone in pregnancy. The risks involved outweigh the potential benefits. Safer alternatives exist. Testosterone is excreted into breast milk; avoid using while breastfeeding.