Dosing & Uses
Dosage Forms & Strengths
oral capsule (undecanoate): Schedule III
- 158mg (Jatenzo)
- 198mg (Jatenzo)
- 237mg (Jatenzo)
injectable solution (cypionate): Schedule III
- 100mg/mL (Depo-Testosterone)
- 200mg/mL (Depo-Testosterone)
injectable solution (enanthate): Schedule III
- 50 mg/0.5mL (Xyosted)
- 75 mg/0.5mL (Xyosted)
- 100 mg/0.5mL (Xyosted)
- 200mg/mL (generic)
injectable solution (undecanoate): Schedule III
- 750mg/3mL (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 (generic): 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
Xyosted
- Starting dose: 75 mg SC qWeek
- Adjust dose based upon total testosterone minimum (trough) concentrations (Cmin) (measured 7 days after most recent dose) obtained following 6 weeks of dosing and periodically thereafter
- Trough concentration (350-650 ng/dL) generally provides testosterone exposures in normal range during entire dosing interval
- Decrease dose by 25 mg if (Cmin) is ≥650 ng/dL Increase dose by 25 mg if the total testosterone Cmin <350 ng/dL
- Maintain same dose if total testosterone Cmin ≥350 ng/dL and <650 ng/dL
Jatenzo
- Starting dose: 237 mg PO BID with food
- To ensure proper dose adjustment, measure serum testosterone concentrations 6 hr after morning dose in plain tubes, clotted at room temperature for 30 minutes prior to centrifugation; adjust dose based on serum testosterone measurement
- Wait 7 days after starting treatment or adjusting the dose before checking the serum testosterone concentration; thereafter, periodically monitor serum testosterone concentrations 6 hr after morning dose
- Adjust dose based on testosterone level as follows
- <425 ng/dL
- Current BID dose 158 mg: Increase to 198 mg BID
- Current BID dose 198 mg: Increase to 237 mg BID
- Current BID dose 237 mg: Increase to 316 mg (two 158-mg cap) BID
- Current BID dose 316 mg: Increase to 396 mg (two 198-mg cap) BID
- 425-970 ng/dL
- No dose change
- >970 ng/dL
- Current BID dose 396 mg: Decrease to 316 mg BID
- Current BID dose 316 mg: Decrease to 237 mg BID
- Current BID dose 237 mg: Decrease to 198 mg BID
- Current BID dose 198 mg: Decrease to 158 mg BID
- Current BID dose 158 mg: Discontinue treatment
Delayed Puberty in Males
Testosterone enanthate (generic): 50-200 mg IM every 2-4 weeks for 4-6 months
Inoperable Mammary Cancer in Women
Testosterone enanthate (generic): 200-400 mg 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
Dosing Considerations
Before initiating: Confirm diagnosis of hypogonadism by ensuring serum testosterone has been measured in the morning on at least 2 separate days and that these concentrations are below the normal range
Dosage Forms & Strengths
injectable solution (cypionate): Schedule III
- 100mg/mL (Depo-Testosterone)
- 200mg/mL (Depo-Testosterone)
injectable solution (enanthate): Schedule III
- 200mg/mL (generic)
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 (generic): 50-400 mg IM every 2-4 weeks
- 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
Dosing Considerations
Limitations of use (Xyosted, Aveed)
- Safety and efficacy not established in adult males with “age-related hypogonadism” (also referred as “late-onset hypogonadism”) and males <18 years
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse 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
Reproductive system: Azoospermia, benign prostatic hyperplasia
Warnings
Black Box Warnings
Blood pressure increase
- Blood pressure (BP) increases reported that can increase the risk for major adverse cardiovascular events (MACE) (eg, nonfatal myocardial infarction, nonfatal stroke, cardiovascular death) with greater risk for MACE in patients with cardiovascular risk factors or established cardiovascular disease
- Before initiating treatment, consider patient’s baseline cardiovascular risk and ensure adequate blood pressure controlled
- Starting ~6 weeks after initiating therapy, periodically monitor for and treat new onset hypertension or exacerbations of pre-existing hypertension
- Re-evaluate whether benefits outweigh its risks in patients who develop cardiovascular risk factors or cardiovascular disease while on treatment
- Due to this risk, use only for treatment of men with hypogonadal conditions associated with structural or genetic etiologies
Serious pulmonary oil microembolism reactions and anaphylaxis
- Aveed only
- Serious pulmonary oil microembolism reactions (POME) (eg, urge to cough, dyspnea, throat tightening, chest pain, dizziness, syncope reactions and episodes) of anaphylaxis reported during or immediately after administration; 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 anaphylaxis
- 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
Men with carcinoma of the breast or known or suspected carcinoma of the prostate
Men with hypogonadal conditions (eg, “age-related hypogonadism”) that are not associated with structural or genetic etiologies; efficacy has not been established for these conditions, and testosterone can increase BP which can increase the risk of MACE
Women: Pregnancy or prospect of pregnancy
Cautions
May increase blood pressure (BP); before initiating, consider baseline cardiovascular (CV) risk and ensure BP is adequately controlled; check BP ~3 weeks after initiating or increasing dose and periodically thereafter; treat new-onset hypertension or exacerbations; reassess whether the benefits of continued treatment outweigh risks
Increased hematocrit (polycythemia) reflective of increases in RBC mass may require lower dose or discontinuation; evaluate hematocrit ~q3Months, and if elevated hold testosterone until hematocrit returns to normal; if testosterone restarted and again hematocrit increase, permanently discontinue testosterone; increased RBC mass may increase thromboembolic risk
Patients with BPH treated with androgens are at an increased risk for worsening of BPH signs and symptoms
Androgens may increase risk for prostate cancer; evaluate patients for prostate cancer before initiating and during treatment with testosterone
Venous thromboembolic events (VTE) reported, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone replacement; 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 VTE suspected, discontinue testosterone and initiate appropriate workup and management
Testosterone has been subject to abuse, typically at doses higher than recommended for 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 suspected, check serum testosterone concentrations to ensure they are within therapeutic range; consider 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 testosterone associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice); peliosis hepatis can be life-threatening or fatal; long-term therapy with IM testosterone enanthate has produced multiple hepatic adenomas; although not reported with other administration routes, monitor for signs or symptoms of hepatic dysfunction; promptly discontinue testosterone if jaundice occurs while evaluating cause
Gynecomastia may develop and persist in patients treated for hypogonadism
May alter serum lipid profile and require dose adjustment of lipid lowering drugs or discontinuing testosterone; monitor lipid profile, especially after starting testosterone
Androgens may promote sodium and water retention; edema, with or without CHF, may be a serious complication if pre-existing cardiac, renal, or hepatic disease exists; may necessitate discontinuing drug; consider diuretic therapy
Large doses may suppress spermatogenesis
May potentiate sleep apnea in some patients, especially patients who are obese or with chronic lung disease
Use androgens cautiously in patients with cancer with risk of hypercalcemia (and associated hypercalciuria); monitor serum calcium concentrations regularly during treatment
May decrease concentrations of thyroxine-binding globulin, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4; free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction
Due to lack of controlled evaluations in women and potential virilizing effects, not indicated for use in women
Depression and suicidal ideation and behavior, including completed suicide, have occurred during clinical trials
Aveed only: Serious POME reactions reported to occur during or immediately after IM injection of testosterone undecanoate 1000 mg (see Black Box Warnings)
Testopel only: Postmarketing cases associated pellet(s) insertion with implant site infection (cellulitis and abscess), and/or pellet extrusion at or near implantation site; most reported cases occurred within the first month after implantation
Cardiovascular risk
- Long term clinical safety trials have not been conducted to assess CV outcomes of testosterone replacement therapy
- As of March 2019, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of MACE (eg, non-fatal MI or stroke, CV death) with testosterone use compared with non-use
- Some studies, but not all, reported an increased risk of MACE associated with testosterone replacement therapy
- Testosterone can cause BP increases that can increase the risk of MACE
Drug interactions overview
- In diabetic patients, metabolic effects of androgens may decrease blood glucose and, therefore, may necessitate a decrease in dose of antidiabetic medication
- Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking warfarin, especially at initiation and termination of androgen therapy
- Concurrent use of testosterone with corticosteroids may result in increased fluid retention and carefully monitor, particularly in patients with cardiac, renal or hepatic disease
- Some prescription medications and nonprescription analgesic and cold medications contain drugs known to increase blood pressure; coadministration of these medications may lead to additional increases in blood pressure
Pregnancy & Lactation
Pregnancy
Contraindicated in pregnant women
Teratogenic; may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action
Exposure of a female fetus to androgens may result in varying degrees of virilization
Animal data
- In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring
- These studies did not meet current standards for nonclinical development toxicity studies
Infertility
- During treatment with large doses of exogenous androgens, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis
- Observed reduced fertility in some men taking testosterone replacement therapy; impact on fertility may be irreversible
Lactation
Not indicated for women
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
Mechanism of Action
Endogenous androgen; promotes growth and development of male sex organs and maintains secondary sex characteristics in androgen-deficient males
Absorption
Peak plasma concentration: 790 ng/dL (Xyosted)
Peak plasma time: 11.9 hr (Xyosted)
AUC: 92,955 ng·hr/dL (Xyosted)
Steady state reached: 14 days (Aveed)
Distribution
Circulating testosterone is primarily bound in serum to sex hormone-binding globulin (SHBG) and albumin
Protein bound
- Xyosted and Aveed: ~40% (SHBG), 2% (free), and remaining is loosely bound to albumin and other proteins
- Depo-Testosterone and Testopel: 98% (SHBG); 2 % (free)
Metabolism
Testosterone undecanoate: Metabolized to testosterone via ester cleavage of undecanoate group
Testosterone enanthate: Metabolized to testosterone via ester cleavage of enanthate group
Testosterone is metabolized to various 17-keto steroids through two different pathways; major active metabolites of testosterone are estradiol and DHT
Elimination
Half-life: 8 days (Depo-Testosterone); 10-100 minutes (Testopel)
Excretion: Urine (90%); feces (6%)
Inactivation of testosterone occurs primarily in the liver
Administration
Oral Administration
Jatenzo only
Take with food
Implant Administration
Testopel only
Number of pellets to implant depends upon minimal daily requirements of testosterone propionate determined by a gradual reduction of amount administered parenterally
With lower requirements by injection, correspondingly lower amounts may be implanted; found approximately one-third of material is absorbed in the first month, one-fourth in the second month and one-sixth in the third month
Adequate effect of pellets ordinarily continues for 3-4 months, sometimes as long as 6 months
SC Administration
Xyosted only
SC use only; administer in abdominal region only
Avoid IM or IV injection
Visually inspect for particulate matter and discoloration prior to administration
Do not use if liquid is cloudy or if visible particles are present
Do not use if seal is broken
IM Administration
Depo-Testosterone and Aveed only
IM use only; administer IM deep in the gluteal muscle
Do not give IV
The various testosterone salts are not interchangeable; check prescribing information if switching product
Between consecutive injections, alternate injection site between left and right buttock
Visually inspect for particular matter and discoloration prior to administration
Warming and shaking the vial redissolves any crystals that may have formed during storage at temperatures lower than recommended
Storage
All formulations: Store at room temperature 25°C (77°F); excursions permitted to 15-30°C (59-86°F) in its original carton until the date indicated
Xyosted: Protect from light
Jatenzo: Avoid exposing the capsules to moisture (store in a dry place)
Images
Patient Handout
Formulary
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