testosterone (Aveed, Depo-Testosterone, Delatestryl, Testopel)

Dosing and uses of Depo-Testosterone, Aveed (testosterone cypionate, enanthate or undecanoate)

• Adult
• Pediatric

 

Adult dosage forms and 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)

 

Hypogonadism

Primary hypogonadism (congenital or acquired): Testicular failure due to conditions 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 concentrations 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

 

Delayed Puberty in Males

50-200 mg IM every 2-4 weeks for 4-6 months

Alternative: 150-450 mg SC every 3-6 months

 

Inoperable Mammary Cancer in Women

200-400 mg enanthate IM every 2-4 weeks

 

Androgen Deficiency in HIV+ Patients (Orphan)

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

 

Delayed Growth (Orphan)

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

Orphan sponsor

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

 

Administration

Prior to initiating therapy, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range

The aluminum metal ring or crimp seal around the gray rubber stopper from the vial, should not be removed prior to the administration of the injection

For IM use, should be administered deep in gluteal muscle

Dosages >400 mg/month not recommended

 

Limitations of use

Safety and efficacy of testosterone in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.

Safety and efficacy of testosterone in males less than 18 years old have not been established

 

Pediatric dosage forms and 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)

 

Hypogonadism

<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

 

Delayed Puberty in Males

<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

 

Depo-Testosterone, Aveed (testosterone cypionate, enanthate or undecanoate) adverse (side) effects

Frequency not defined

Acne

Abnormal dreams

Aggressive behavior

Alopecia

Anaphylaxis

Anger

Amnesia

Anxiety

Bladder irritability

Breast soreness

Deep venous thrombosis

Excessive frequency and duration of erection

Fatigue

Growth acceleration

Gynecomastia

Headache

Hirsutism

Hot flashes

Hypersensitivity

Hypercholesterolemia

Hypertension

Insomnia

Liver function alterations

Male pattern baldness

Menstrual irregularities

Priapism

Pruritus

Rash

Seborrhea

Suppression of factors II, V, VII, X

Vasodilation

Virilization

Water retention

 

Postmarketing Reports

Vascular Disorders: Venous thromboembolism

 

Warnings

Black box 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 first dose

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

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

 

Contraindications

Hypersensitivity to product or formulation components

Cancer of breast or known or suspected carcinoma of prostate in men

Severe cardiac, hepatic, or renal disease

Women: Pregnancy or prospect of pregnancy

 

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 postmarketing studies have shown an increased risk of myocardial infarction and stroke associated with use of testosterone replacement therapy

Anabolic steroids may be abused; dependence may occur when used outside of approved dosage/indication

Prolonged use of high-dose androgens associated with peliosis hepatitis and hepatic neoplasms (including hepatic cancer)

Risk of cholestatic hepatitis with jaundice; discontinue if this condition develops

Geriatric patients: Increased risk of benign prostatic hyperplasia (BPH) and prostate cancer; monitor patients with BPH for worsening of signs and symptoms of BPH

Risk of 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 prebubertal children perform radiographic examination

Large doses may suppress spermatogenesis

May potentiate sleep apnea in some patients

Risk of 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 thromboemolism; monitor serum testosterone, prostate specific antigen (PSA), liver function, lipid concentrations, hematocrit and hemoglobin periodically

Skin burns reported at application site in patients wearing an aluminized transdermal system during a magnetic resonance imaging scan (MRI); because transdermal testosterone patch contains aluminum, it is recommended to remove 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 prior to 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 risk of stroke, MI, and death in men taking prescription testosterone drugs; investigation was prompted by findings from 2 studies suggesting increased risk of MI in men who take testosterone
• In one study, analysis of 55,593 men with history of MI showed that men >65 years had 2-fold increase in MI risk within 90 days of filling initial prescription for testosterone drug; among younger men (<65 years) with history of heart disease, MI risk was increased 2- to 3-fold
• This study confirmed results of earlier, much smaller study, which found that older men, many with underlying heart disease, had 30% increased chance of death, MI, and stroke after receiving testosterone therapy

Edema

• Risk of 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 drug
• If drug therapy is restarted, use 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

Pregnancy category: X

Lactation: Drug is excreted into breast milk; avoid using

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Depo-Testosterone, Aveed (testosterone cypionate, enanthate or undecanoate)

Mechanism of action

Endogenous androgen; promotes growth and development of male sex organs and maintains secondary sex characteristics in androgen-deficient males

 

Absorption

Bioavailability: IM, slowly absorbed

Duration: 2-4 wk (IM)

Peak plasma time: 24 hr (IM)

 

Distribution

Protein bound: 98%

Vd: 75-122 L/kg

 

Metabolism

Metabolized in liver to glucuronic and sulfuric acid conjugates

Metabolites: Testosterone glucuronic conjugate (activity unknown), testosterone sulfuric acid conjugate (activity unknown), testosterone-19-d3

 

Elimination

Half-life: 10-100 min

Renal clearance: 2 L/min

Excretion: Urine (90%), feces (6%)