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Medication Safety Issues
Sound-alike/look-alike issues:
Testosterone may be confused with testolactone
Testoderm® may be confused with Estraderm®
Transdermal patch may contain conducting metal (eg, aluminum); remove patch prior to MRI.
Pronunciation
(tes TOS ter one)
U.S. Brand Names
Index Terms
Generic Available
Yes: Injection
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Injection: Androgen replacement therapy in the treatment of delayed male puberty; male hypogonadism (primary or hypogonadotropic); inoperable metastatic female breast cancer (enanthate only)
Pellet: Androgen replacement therapy in the treatment of delayed male puberty; male hypogonadism (primary or hypogonadotropic)
Topical (buccal system, gel, transdermal system): Male hypogonadism (primary or hypogonadotropic)
Capsule (not available in U.S.): Androgen replacement therapy in the treatment of delayed male puberty; male hypogonadism (primary or hypogonadotropic); replacement therapy in impotence or for male climacteric symptoms due to androgen deficiency
Use: Unlabeled/Investigational
Androgen deficiency in men with AIDS wasting; postmenopausal women with decreased sexual desire (in combination with estrogen therapy)
Restrictions
C-III
Pregnancy Risk Factor
X
Pregnancy Considerations
Testosterone may cause adverse effects, including masculinization of the female fetus, if used during pregnancy. Females who are or may become pregnant should also avoid skin-to-skin contact to areas where testosterone has been applied topically on another person.
Lactation
Enters breast milk/contraindicated
Breast-Feeding Considerations
High levels of endogenous maternal testosterone, such as those caused by certain ovarian cysts, suppress milk production. Maternal serum testosterone levels generally fall following pregnancy and return to normal once breast-feeding is stopped. The amount of testosterone present in breast milk or the effect to the nursing infant following maternal supplementation is not known. Some products are contraindicated while breast-feeding.
Contraindications
Hypersensitivity to testosterone or any component of the formulation; males with carcinoma of the breast or prostate; pregnancy or women who may become pregnant; breast-feeding
Depo®-Testosterone: Also contraindicated in serious hepatic, renal, or cardiac disease
Andriol®: Also contraindicated in hepatic, renal, or cardiac disease; hypercalcemia; nephrosis or nephritic phase of nephritis; prepubertal males; patients who are easily sexually stimulated
Warnings/Precautions
Concerns related to adverse effects:
• Gynecomastia: May cause gynecomastia.
• Hepatic effects: Prolonged use of high doses of androgens has been associated with serious hepatic effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, jaundice).
• Hypercalcemia: May cause hypercalcemia in patients with prolonged immobilization or cancer.
• Hypercholesterolemia: May alter serum cholesterol; use caution with history of MI or coronary artery disease.
• Hypoglycemia: Has both androgenic and anabolic activity, the anabolic action may enhance hypoglycemia.
• Prostate cancer: May increase the risk of prostate cancer.
• Spermatogenesis: Large doses may suppress spermatogenesis.
Disease-related concerns:
• Benign prostatic hyperplasia (BPH): Urethral obstruction may develop in patients with BPH; treatment should be discontinued if this should occur (use lower dose if restarted). Withhold treatment pending urological evaluation if PSA >3 ng/mL.
• Edematous conditions: Use with caution in patients with conditions influenced by edema (eg, cardiovascular disease, migraine, seizure disorder, renal impairment); may cause fluid retention.
• Sleep apnea: May potentiate sleep apnea in some male patients (obesity or chronic lung disease).
Special populations:
• Elderly: Use with caution in elderly patients, they may be at greater risk for prostatic hyperplasia, prostate cancer, fluid retention, and transaminase elevations.
• Pediatrics: May accelerate bone maturation without producing compensatory gain in linear growth 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. Gels and buccal system have not been evaluated in males <18 years of age; safety and efficacy of injection have not been established in males <12 years of age.
Dosage form specific issues:
• Benzyl alcohol: Some dosage forms may contain benzyl alcohol which has been associated with "gasping syndrome" in neonates.
• Gel: Testosterone may be transferred to another person following skin-to-skin contact with the application site. Virilization of female sexual partners has been reported with male use of the topical gel.
• Soy: Some testosterone products may be chemically synthesized from soy.
• Transdermal patch: May contain conducting metal (eg, aluminum); remove patch prior to MRI.
Adverse Reactions
Frequency rarely defined.
Cardiovascular: Deep venous thrombosis, edema, hypertension, vasodilation
Central nervous system: Aggressive behavior, amnesia, anxiety, dizziness, emotional lability, excitation, headache, malaise, mental depression, nervousness, seizure, sleep apnea, sleeplessness
Dermatologic: Acne, alopecia, dry skin, hair discoloration, hirsutism (increase in pubic hair growth), pruritus, rash, seborrhea
Endocrine & metabolic: Breast soreness, gonadotropin secretion decreased, growth acceleration, gynecomastia, hot flashes, hypercalcemia, hyperchloremia, hypercholesterolemia, hyper-/hypokalemia, hyperlipidemia, hypernatremia, hypoglycemia, inorganic phosphate retention, libido changes, menstrual problems (including amenorrhea), virilism, water retention
Gastrointestinal: GI bleeding, GI irritation, nausea, taste disorder, vomiting, weight gain
Following buccal administration (most common): Bitter taste, gum edema, gum or mouth irritation, gum pain, gum tenderness, taste perversion
Genitourinary: Bladder irritability, epididymitis, impotence, oligospermia, priapism, prostatic carcinoma, prostatic hyperplasia, PSA increased, testicular atrophy, urination impaired
Hepatic: Bilirubin increased, cholestatic hepatitis, cholestatic jaundice, hepatic dysfunction, hepatic necrosis, hepatocellular neoplasms, liver function test changes, peliosis hepatis
Hematologic: Anemia, bleeding, hematocrit/hemoglobin increased, leukopenia, polycythemia, suppression of clotting factors
Local: Application site reaction (gel), injection site pain
Transdermal system: Pruritus at application site (37%), burn-like blisters under system (12%), erythema at application site (7%), vesicles at application site (6%), allergic contact dermatitis to system (4%), burning at application site (3%), induration at application site (3%)
Neuromuscular & skeletal: Paresthesia, weakness
Ocular: Lacrimation increased
Renal: Creatinine increased
Respiratory: Dyspnea
Miscellaneous: Anaphylactoid reactions, diaphoresis, hypersensitivity reactions, smell disorder
Postmarketing and/or case reports: Injection: Cough, coughing fits, respiratory distress
Metabolism/Transport Effects
Substrate (minor) of CYP2B6, 2C9, 2C19, 3A4; Inhibits CYP3A4 (weak)
Drug Interactions
Coumarin Derivatives: Androgens may enhance the anticoagulant effect of Coumarin Derivatives. Risk D: Consider therapy modification
CycloSPORINE: Androgens may enhance the hepatotoxic effect of CycloSPORINE. Androgens may increase the serum concentration of CycloSPORINE. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: St John's wort may decrease testosterone levels.
Storage
Androderm®: Store at room temperature. Do not store outside of pouch. Excessive heat may cause system to burst.
AndroGel®, Delatestryl®, Striant®, Testim®: Store at room temperature.
Depo® Testosterone: Store at room temperature. Protect from light.
Testopel®: Store in a cool location.
Mechanism of Action
Principal endogenous androgen responsible for promoting the growth and development of the male sex organs and maintaining secondary sex characteristics in androgen-deficient males
Pharmacodynamics/Kinetics
Duration (route and ester dependent): I.M.: Cypionate and enanthate esters have longest duration, ?2-4 weeks; gel: 24-48 hours
Absorption: Transdermal gel: ~10% of applied dose
Protein binding: 98%; bound to sex hormone-binding globulin (40%) and albumin
Metabolism: Hepatic; forms metabolites, including dihydrotestosterone (DHT) and estradiol (both active)
Half-life elimination: 10-100 minutes
Excretion: Urine (90%); feces (6%)
Dosage
Adolescents and Adults: Male:
I.M.:
Hypogonadism: Testosterone enanthate or testosterone cypionate: 50-400 mg every 2-4 weeks (FDA-approved dosing range); 75-100 mg/week or 150-200 mg every 2 weeks (per practice guidelines)
Delayed puberty: Testosterone enanthate: 50-200 mg every 2-4 weeks for a limited duration
Pellet (for subcutaneous implantation): Delayed male puberty, male hypogonadism: 150-450 mg every 3-6 months
Oral: Delayed puberty, hypogonadism, or hypogonadotropic hypogonadism: Capsule (Andriol®; not available in U.S.): Initial: 120-160 mg/day in 2 divided doses for 2-3 weeks; adjust according to individual response; usual maintenance dose: 40-120 mg/day (in divided doses)
Adults:
I.M.: Females: Inoperable metastatic breast cancer: Testosterone enanthate: 200-400 mg every 2-4 weeks
Topical: Primary male hypogonadism or hypogonadotropic hypogonadism:
Buccal: 30 mg twice daily (every 12 hours) applied to the gum region above the incisor tooth
Transdermal system: Androderm®: Initial: Apply 5 mg/day once nightly to clean, dry area on the back, abdomen, upper arms, or thighs (do not apply to scrotum); dosing range: 2.5-7.5 mg/day; in nonvirilized patients, dose may be initiated at 2.5 mg/day
Gel: AndroGel®, Testim®: 5 g (to deliver 50 mg of testosterone with 5 mg systemically absorbed) applied once daily (preferably in the morning) to clean, dry, intact skin of the shoulder and upper arms. AndroGel® may also be applied to the abdomen. Dosage may be increased to a maximum of 10 g (100 mg). Do not apply testosterone gel to the genitals.
Dose adjustment based on testosterone levels:
Less than normal range: Increase dose from 5 g to 7.5 g to 10 g
Greater than normal range: Decrease dose. Discontinue if consistently above normal at 5 g/day
Dosing adjustment/comments in hepatic disease: Reduce dose
Administration: Oral
Oral, buccal application (Striant®): One mucoadhesive for buccal application (buccal system) should be applied to a comfortable area above the incisor tooth. Apply flat side of system to gum. Rotate to alternate sides of mouth with each application. Hold buccal system firmly in place for 30 seconds to ensure adhesion. The buccal system should adhere to gum for 12 hours. If the buccal system falls out, replace with a new system. If the system falls out within 4 hours of next dose, the new buccal system should remain in place until the time of the following scheduled dose. System will soften and mold to shape of gum as it absorbs moisture from mouth. Do not chew or swallow the buccal system. The buccal system will not dissolve; gently remove by sliding downwards from gum; avoid scratching gum.
Oral, capsule (Andriol®; not available in the U.S.): Should be administered with meals. Should be swallowed whole; do not crush or chew.
Administration: I.M.
Warm injection to room temperature and shaking vial will help redissolve crystals that have formed after storage. Administer by deep I.M. injection into the upper outer quadrant of the gluteus maximus.
Administration: Topical
Transdermal patch: Androderm®: Apply patch to clean, dry area of skin on the arm, back, or upper buttocks. Following patch removal, mild skin irritation may be treated with OTC hydrocortisone cream. A small amount of triamcinolone acetonide 0.1% cream may be applied under the system to decrease irritation; do not use ointment. Patch should be applied nightly. Rotate administration sites, allowing 7 days between applying to the same site.
Gel: AndroGel®, Testim®: Apply (preferably in the morning) to clean, dry, intact skin of the shoulder and upper arms (AndroGel® may also be applied to the abdomen). Apply at the same time each day. Upon opening the packet(s), the entire contents should be squeezed into the palm of the hand and immediately applied to the application site(s). Alternatively, a portion may be squeezed onto palm of hand and applied, repeating the process until entire packet has been applied. Application sites should be allowed to dry for a few minutes prior to dressing. Hands should be washed with soap and water after application. Do not apply testosterone gel to the genitals. For optimal absorption, after application wait at least 5-6 hours prior to showering or swimming; however waiting at least 1 hour should have minimal affect on absorption if done infrequently. Alcohol-based gels are flammable; avoid fire or smoking until gel has dried. Testosterone may be transferred to another person following skin-to-skin contact with the application site. Thoroughly wash hands after application and cover application site with clothing (ie shirt) once gel has dried, or clean application site thoroughly with soap and water prior to contact in order to minimize transfer.
AndroGel® multidose pump: Prime pump 3 times (and discard this portion of product) prior to initial use.
Monitoring Parameters
Periodic liver function tests, PSA and prostate exam (prior to therapy, at 3 months, then as based on current guidelines), cholesterol, hemoglobin and hematocrit (prior to therapy, at 3 months, then annually); radiologic examination of wrist and hand every 6 months (when using in prepubertal children). Withhold initial treatment with hematocrit >50%, hyperviscosity, untreated obstructive sleep apnea, or uncontrolled severe heart failure. Monitor urine and serum calcium and signs of virilization in women treated for breast cancer.
PSA: Withhold initial treatment if PSA >3 ng/mL, or with palpable prostate nodule or induration without further urological evaluation. Do not treat with severe untreated BPH with IPSS symptom score >19.
Serum testosterone: Monitor 3 months after initiating treatment, then annually.
Injection: Measure midway between injections
AndroGel®: Morning serum testosterone levels 14 days after start of therapy
Androderm®: Morning serum testosterone levels following application the previous evening
Striant®: Application area of gums; total serum testosterone 4-12 weeks after initiating treatment, prior to morning dose
Reference Range
Testosterone, urine: Male: 100-1500 ng/24 hours; Female: 100-500 ng/24 hours
Test Interactions
May cause a decrease in thyroid function tests
Dietary Considerations
Testosterone USP may be synthesized from soy. Food and beverages have not been found to interfere with buccal system; ensure system is in place following eating, drinking, or brushing teeth.
Patient Education
Use exactly as directed according to formulation. For topical application (patch or gel) or buccal application, follow directions that accompany package. If using self-administered injections, follow prescriber's directions for injection procedure and disposal of syringes/needles. If you have diabetes, monitor serum glucose closely and notify prescriber of changes; this medication may alter hypoglycemic requirements. You may experience acne, growth of body hair, loss of libido, impotence, menstrual irregularity (usually reversible), nausea, taste disorder, or vomiting (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). Report changes in menstrual pattern; enlarged or painful breasts; deepening of voice; unusual growth of body hair; persistent penile erection; fluid retention (swelling of ankles, feet, or hands); respiratory difficulty or sudden weight gain); unresolved changes in CNS (nervousness, chills, insomnia, depression, aggressiveness); altered urinary patterns; change in color of urine or stool; yellowing of eyes or skin; unusual bruising or bleeding; blood in urine or stool; difficulty sleeping or sleep apnea; skin irritation, redness, burning, or swelling at application site or injection site; or other persistent adverse reactions.
Transdermal: Androderm®: Apply patch to clean, dry area of skin on the arm, back, or upper buttocks.
Topical gel: AndroGel®, Testim®: Apply gel to clean, dry, intact skin of the shoulder and upper arms (AndroGel® may also be applied to the abdomen). Apply at same time each day (preferably in the morning). Upon opening the packet(s), the entire contents should be squeezed into the palm of the hand and immediately applied to the application site(s). Alternatively, a portion may be squeezed onto palm of hand and applied, repeating the process until entire packet has been applied. Gel is flammable (avoid fire or smoking until gel has dried). Application sites should be allowed to dry for a few minutes prior to dressing. Wash hands thoroughly with soap and water after application. Do not apply testosterone gel to the genitals. Testosterone may be transferred to another person with skin-to-skin contact at application site; cover application site with clothing, or wash site thoroughly with soap and water prior to contact in order to minimize transfer.
Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant during or for 1 month following therapy. Male: Do not cause a female to become pregnant. Male/female: Consult prescriber for instruction on appropriate contraceptive measures. This drug may cause severe fetal defects. Do not breast-feed.
Geriatric Considerations
Elderly males treated with androgens may be at increased risk of developing prostatic hyperplasia and prostatic carcinoma. Increase in libido may occur.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Buccal administration: Bitter taste, gum edema, gum or mouth irritation, gum tenderness, and taste perversion.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause anxiety, insomnia, aggressive behavior, or depression
Mental Health: Effects on Psychiatric Treatment
May rarely cause neutropenia; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Assess potential for interactions with other pharmacological agents and herbal products patient may be taking (eg, effects of warfarin may be enhanced; may increase fluid retention with corticosteroids). Assess results of laboratory tests, therapeutic effectiveness (according to purpose for use), and adverse reactions regularly during therapy. Caution patients with diabetes, may cause hypoglycemic reaction. Teach patient proper use (according to formulation), possible side effects/appropriate interventions, and adverse symptoms to report. Pregnancy risk factor X: Determine that patient is not pregnant before beginning treatment. Instruct patients of childbearing age or males who may have intercourse with women of childbearing age on appropriate barrier contraceptive measures.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [CAN] = Canadian brand name
Capsule, gelatin, as undecanoate:
Andriol™ [CAN]: 40 mg (10s) [not available in U.S.]
Gel, topical:
AndroGel®:
1.25 g/actuation (75 g) [1% metered-dose pump; delivers 5 g/4 actuations; provides 60 1.25 g actuations; contains ethanol; may be chemically synthesized from soy]
2.5 g (30s) [1% unit dose packets; contains ethanol; may be chemically synthesized from soy]
5 g (30s) [1% unit dose packets; contains ethanol; may be chemically synthesized from soy]
Testim®: 5 g (30s) [1% unit-dose tube; contains ethanol; may be chemically synthesized from soy]
Implant, subcutaneous:
Testopel®: 75 mg
Injection, in oil, as cypionate: 100 mg/mL (10 mL); 200 mg/mL (1 mL, 10 mL)
Depo®-Testosterone: 100 mg/mL (10 mL); 200 mg/mL (1 mL, 10 mL) [contains benzyl alcohol, benzyl benzoate, and cottonseed oil]
Injection, in oil, as enanthate: 200 mg/mL (5 mL)
Delatestryl®: 200 mg/mL (1 mL) [prefilled syringe; contains sesame oil]; (5 mL) [multidose vial; contains sesame oil]
Kit [for prescription compounding testosterone 2%; kits also contain mixing jar and stirrer]:
First® Testosterone:
Injection, in oil: Testosterone propionate 100 mg/mL (12 mL) [contains sesame oil and benzyl alcohol]
Ointment: White petroleum (48 g)
First® Testosterone MC:
Injection, in oil: Testosterone propionate 100 mg/mL (12 mL) [contains sesame oil and benzyl alcohol]
Cream: Moisturizing cream (48 g)
Mucoadhesive, for buccal application [buccal system]:
Striant®: 30 mg (10s) [may be chemically synthesized from soy]
Transdermal system, topical:
Androderm®: 2.5 mg/day (60s) [contains ethanol]; 5 mg/day (30s) [contains ethanol]
Pricing: U.S. (www.drugstore.com)
Cream (First-Testosterone MC)
2% (60): $49.03
Gel (AndroGel)
25 mg/2.5 g (75): $230.98
50 mg/5 g (150): $240.63
Gel (AndroGel Pump)
1% (150): $255.08
Gel (Testim)
1% (150): $246.21
Misc (Striant)
30 mg (60): $247.03
Oil (Delatestryl)
200 mg/mL (5): $91.99
Oil (Depo-Testosterone)
100 mg/mL (10): $74.99
200 mg/mL (1): $34.99
200 mg/mL (10): $125.98
Oil (Testosterone Cypionate)
100 mg/mL (10): $56.99
200 mg/mL (1): $24.99
200 mg/mL (10): $88.99
Oil (Testosterone Enanthate)
200 mg/mL (5): $79.99
Ointment (First-Testosterone)
2% (60): $47.81
Patch, 24-hour (Androderm)
2.5 mg/24 hrs (60): $225.31
5 mg/24 hrs (30): $232.04
References
Bhasin S, Cunningham GR, Hayes FJ, et al, “Testosterone Therapy in Adult Men With Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline,” J Clin Endocrinol Metab, 2006, 91(6):1995-2010.
Borhan-Manesh F and Farnum JB, “Methyltestosterone-Induced Cholestasis. The Importance of Disproportionately Low Serum Alkaline Phosphatase Level,” Arch Intern Med, 1989, 149(9):2127-9.
Cunningham GR, Cordero E, and Thornby JI, “Testosterone Replacement With Transdermal Therapeutic Systems. Physiological Serum Testosterone and Elevated Dihydrotestosterone Levels,” JAMA, 1989, 261(17):2525-30.
Daigle RD, “Anabolic Steroids,” J Psychoactive Drugs, 1990, 22(1):77-80.
Moller BB and Ekelund B, “Toxicity of Cyclosporine During Treatment With Androgens,” N Engl J Med, 1985, 313(22):1416.
NAMS Board of Trustees, "The Role of Testosterone Therapy in Postmenopausal Women: Position Statement of The North American Menopause Society," Menopause, 2005, 12(5):497-511.
Ruch W and Jenny P, “Priapism Following Testosterone Administration for Delayed Male Puberty,” Am J Med, 1989, 86(2):256.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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