Testosterone

Pronunciation: (tes-TOS-ter-one)
Class: Androgen Testosterone

Trade Names

Androderm
- Transdermal system 2.5 mg per 24 h
- Transdermal system 5 mg per 24 h

Testopel
- Implant pellets 75 mg

Testosterone Cypionate

Depo-Testosterone
- Injection 100 mg/mL
- Injection 200 mg/mL

Testosterone Enanthate

Delatestryl
- Injection 200 mg/mL

Testosterone Gel

AndroGel
- Gel, topical 1%

Testim
- Gel, topical 1%

Testosterone Buccal System

Striant
- Mucoadhesive 30 mg

Pharmacology

Promotes growth and development of male reproductive organs, maintains secondary sex characteristics, increases protein anabolism, and decreases protein catabolism.

Pharmacokinetics

Absorption

Testosterone transdermal T _max is 2 to 4 h. Slowly released following buccal application, reaching the C _max within 10 to 12 h. Approximately 10% of the testosterone gel dose applied on the skin surface is absorbed into systemic circulation. After initial application, there is an increase in serum testosterone within 30 min, and serum testosterone is within normal range by 4 h.

Distribution

After transdermal administration, steady-state testosterone levels occur in 3 to 4 wk; 98% is bound to proteins.

Metabolism

Gel and transdermal testosterone are metabolized in the liver. The major active metabolites are estradiol and DHT.

Elimination

Transdermal testosterone half-life is 10 to 100 min. Approximately 90% is excreted in urine, and approximately 6% is excreted in feces.

Special Populations

Renal Function Impairment

For testosterone gel, no formal studies were conducted in patients with renal insufficiency.

Hepatic Function Impairment

For testosterone gel, no formal studies were conducted in patients with hepatic insufficiency.

Elderly

There are no observed differences in the average daily serum testosterone concentration at steady state based on age in patients treated with testosterone gel.

Children

For testosterone gel, no formal studies were conducted in patients younger than 18 yr of age.

Indications and Usage

Men

Replacement therapy in primary hypogonadism and hypogonadotropic hypogonadism (testosterone enanthate [ Delatestryl ], testosterone pellets [ Testopel ], testosterone gel [ AndroGel , Testim ], testosterone transdermal system [ Androderm ], testosterone buccal system [ Striant ], testosterone cypionate [ Depo-Testosterone ]); stimulation of puberty (testosterone enanthate [ Delatestryl ], testosterone pellets [ Testopel ]).

Women

Ablation of ovaries in metastatic breast cancer (testosterone enanthate [ Delatestryl ]).

Contraindications

Hypersensitivity to product; serious cardiac, hepatic, or renal disease; men with carcinoma of the breast or prostate; women who are or may become pregnant or who are breast-feeding; testosterone gel and buccal system are contraindicated in women.

Dosage and Administration

Androgen Replacement Therapy
Adults

IM 50 to 400 mg every 2 to 4 wk (testosterone enanthate, testosterone cypionate). Subcutaneous 150 to 450 mg every 3 to 6 mo (testosterone pellets). Transdermal 5 mg applied daily ( Androderm ). Topical Start by applying testosterone 5 g gel (to deliver testosterone 50 mg) once daily to clean, dry skin of shoulders and/or upper arms. AndroGel may also be applied to the abdomen. Based on measurements of serum testosterone levels and clinical response 14 days after initiation of therapy, dose may be increased from 5 to 10 g ( Testim ) or from 5 to 7.5 g ( AndroGel ) and from 7.5 to 10 g ( AndroGel ). Buccal 30 mg applied to the gum region twice daily, morning and evening (about 12 h apart). Place in a comfortable position just above one of the incisor teeth.

Breast Cancer
Adults

IM 200 to 400 mg every 2 to 4 wk (testosterone enanthate).

Delayed Puberty
Adolescents

IM 50 to 200 mg every 2 to 4 wk for limited duration (testosterone enanthate). Subcutaneous 150 to 450 mg every 4 to 6 mo (testosterone pellets).

General Advice

• Injection
• For deep IM administration into gluteal muscle only. Not for intradermal, subcutaneous, IV, or intra-arterial administration.
• Rotate injection sites.

• Topical
• Do not apply testosterone gel to the genitals.
• Allow application site to dry for a few minutes prior to dressing. Cover the application sites with clothing after the gel has dried.
• Wash hands with soap and water after application.
• Do not wash application sites for at least 2 h after application.

Storage/Stability

Store AndroGel and Testim at 59° to 86°F. Store transdermal systems in protective pouch at 59° to 86°F. Protect systems from excessive heat or pressure, which can cause bursting of the drug reservoir. Store blister packs ( Striant ) at 68° to 77°F. Protect from heat and moisture. Do not remove buccal system from blister pack until ready to apply. Store vials and prefilled syringes at 68° to 77°F. Protect from light. Store pellets in a cool place.

Drug Interactions

Anticoagulants (eg, warfarin)

The anticoagulant effect of warfarin may be increased. Monitor coagulation parameters and adjust the warfarin dose as needed.

Corticosteroids

Use with caution because of increased risk of edema.

Disulfiram, metronidazole

Because testosterone gel contains alcohol, topical use of testosterone gel and ingestion of disulfiram or systemic use of metronidazole may produce acute and severe alcohol intolerance. Avoid concurrent use of testosterone gel and disulfiram or metronidazole oral or intravaginal.

Insulin, oral hypoglycemics

May decrease glucose levels and antidiabetic drug requirements. Monitor blood glucose and adjust the insulin dose as needed.

Propranolol

Coadministration of an injectable testosterone may increase propranolol Cl, resulting in decreased plasma levels. Monitor the response of the patient. If an interaction is suspected, adjust the propranolol dose as needed.

Laboratory Test Interactions

Androgens may decrease levels of thyroxin-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.

Adverse Reactions

Cardiovascular

Hot flashes (postmarketing).

Topical gel

Hypertension (3%); BP diastolic decreased, hot flushes (1%).

CNS

Anxiety, depression, generalized paresthesia, headache, increased or decreased libido; amnesia, anxiety, dizziness, hostility, insomnia, malaise, sleep apnea (postmarketing).

Buccal

Headache (3%).

Topical gel

Headache (4%); asthenia, decreased libido, emotional lability, nervousness (3%); depression, insomnia, mood swings (1%).

Dermatologic

Acne, hirsutism, male pattern baldness, seborrhea; discolored hair, erythema, paresthesia, rash (postmarketing).

Topical gel

Acne (8%); dry skin, pruritus (2%); alopecia (1%).

Transdermal

Pruritus at application site (37%); burn-like blister reaction under system (12%); erythema at application site (7%); vesicles at application site (6%); prostate abnormalities (5%); allergic contact dermatitis (4%); burning and induration at application site (3%).

EENT

Topical gel

Lacrimation increased, smell disorder, taste disorder (1%).

Endocrine

Inhibition or gonadotropin secretion.

GI

Nausea; nausea (postmarketing).

Transdermal

GI bleeding (2%).

Genitourinary

Amenorrhea and other menstrual irregularities, virilization (women); excessive frequency and duration of penile erection, gynecomastia, oligospermia (men).

Topical gel

Enlarged prostate (12%); prostate disorder including benign prostatic hypertrophy and elevated prostate-specific antigen (PSA) (5%); urinary symptoms including nocturia, urinary hesitancy, urinary incontinence, urinary retention, urinary urgency, weak urinary stream (4%); breast pain, gynecomastia, testis disorder including left varicocele and slight testis sensitivity (3%); benign prostatic hyperplasia, prostate carcinoma, spontaneous penile erection (1%).

Hematologic-Lymphatic

Polycythemia, suppression of clotting factors II, V, VII, and X.

Topical gel

Anemia (3%).

Hepatic

Alterations in LFTs, cholestatic jaundice, hepatocellular neoplasms, peliosis hepatitis.

Lab Tests

Topical gel

Decreased HDL, elevated AST or ALT, elevated cholesterol, elevated HDL, elevated testosterone, elevated serum creatinine, elevated triglycerides, elevated total bilirubin, elevated cholesterol/LDL ratio, elevated glucose, hyperlipidemia, hypokalemia, and elevated hemoglobin or hematocrit (6% to 9%).

Local

Inflammation and pain at injection site.

Buccal

Gum or mouth disorder (9%); bitter taste (4%); gum pain, gum tenderness (3%); gum edema, taste perversion (2%).

Topical gel

Application-site reactions (6%).

Metabolic-Nutritional

Increased serum cholesterol, retention of calcium, chloride, potassium, sodium, and water, electrolyte changes (eg, calcium nitrogen, phosphorus, potassium, sodium), increased weight (postmarketing).

Respiratory

Dyspnea (postmarketing).

Miscellaneous

Anaphylactic reactions; edema, hirsutism (postmarketing).

Precautions

Monitor Regularly monitor serum calcium concentrations in patients with cancer at risk of hypercalcemia. Observe women for signs of virilization (eg, clitoral enlargement, deepening of voice). In patients with delayed puberty, monitor effect on bone maturation by assessing bone age of the wrist and hand every 6 mo. In patients receiving high doses, periodically check hemoglobin and hematocrit for polycythemia. Periodically monitor liver function, serum lipid profile, and PSA. To ensure proper dosing, measure serum testosterone concentrations.

Pregnancy

Category X .

Lactation

Undetermined. Testosterone gel, cypionate, buccal, and transdermal are not indicated for women.

Children

Use drug with great caution; may affect bone maturation.

Androderm

Safety and efficacy not established in children younger than 15 yr of age.

Testosterone cypionate

Safety and efficacy not established in children younger than 12 yr of age.

Testosterone gel and buccal system

Safety and efficacy not established.

Elderly

Elderly men may be at increased risk of developing prostatic hypertrophy or carcinoma.

Acute intermittent porphyria

Acute intermittent porphyria has been reported. Use drug with caution in patients known to have this condition.

Athletic performance

Abuse of these agents to enhance athletic performance has potential risk of serious adverse reactions.

Breast cancer and immobilized patients

May develop hypercalcemia.

Edema

Edema with or without CHF may be a serious complication in patients with preexisting cardiac, hepatic, or renal disease. Use with caution in patients with conditions affected by fluid retention (eg, asthma, cardiac or renal function impairment, epilepsy).

Gynecomastia

Frequently occurs and may persist. Use drug with caution in patients with preexisting gynecomastia.

Hepatic effects

Prolonged use of high doses of androgens may result in potentially life-threatening peliosis, cholestatic jaundice, hepatitis, hepatic neoplasms, or hepatocellular carcinoma.

Hypercalcemia

Use with caution in cancer patients at risk of hypercalcemia.

Oligospermia and reduced ejaculatory volume

May occur after prolonged use.

Product interchange

Do not interchange products because of their differences in duration of action.

Serum cholesterol

Levels may increase with androgen use; use drug with caution in patients with history of MI or coronary artery disease.

Sleep apnea

Treatment of hypogonadal men may potentiate sleep apnea, particularly in patients with risk factors (eg, chronic lung diseases, obesity).

Virilization

May occur in women.

Overdosage

Symptoms

Testosterone enanthate

Cerebrovascular accident.

Patient Information

• Advise patient to read patient information leaflet before using the first time and with each refill.
• Instruct patient with diabetes to monitor blood glucose more frequently when drug is started or dose is changed, and to inform health care provider of significant changes in readings.
• Caution patient that testosterone has not been shown to be safe or effective for enhancing athletic performance and, because of potential for serious health risks, to not use for this purpose.
• Instruct patient to inform health care provider if any of the following occurs: ankle swelling; any change in skin color; breast enlargement; breathing problems, including any associated with sleep; changes in body hair distribution, increase in acne, or other unusual changes in female partner; difficulty urinating; mood changes; too frequent or persistent erections of the penis; unexplained nausea and/or vomiting.

• Buccal system
• Review application and removal process with patient.
• Instruct patient to apply buccal system twice daily, morning and evening (approximately 12 h apart).
• Caution patient not to chew or swallow the buccal system.
• Advise patient to avoid dislodging the buccal system and check to see if the system is in place following brushing teeth, using mouthwash, and eating or drinking.
• Advise patient that if the buccal system fails to properly adhere to the gum or falls off during the 12-hour dosing interval, the old system should be discarded and a new one applied. If the buccal system falls out of position within 4 h of the next dose, a new system should be applied and may remain in place until the time of the next regularly scheduled dose.
• Advise patient to regularly inspect gum region where buccal system is applied and to report any abnormality (including gum tenderness or irritation) to health care provider.

• Gel
• Instruct patient to apply gel once daily at about the same time each day. Advise patient that application every morning is preferred. Advise patient that if bathing or showering in the morning, to apply the gel afterward.
• Caution patient that gel is flammable and not to use near fire or open flame.
• Instruct patient in proper application of gel.
• Caution patient not to apply gel to scrotum, penis, or skin that is not normal (eg, inflamed or irritated). AndroGel may be applied to the abdomen.
• Advise patient to rinse eyes with warm, clean water if gel accidentally gets into the eyes and to notify health care provider if eye irritation develops.
• Advise patient not to swim or bathe within 2 h of applying gel because swimming or bathing too soon after application of gel may reduce effectiveness.
• Instruct patient to wash application site thoroughly with soap and water to remove drug residue before any situation in which direct skin-to-skin contact is anticipated.
• Advise patient in the event that unwashed or unclothed skin to which the gel has been applied comes in contact with the skin of another person, especially a pregnant or breast-feeding partner, to thoroughly wash the general area of contact on the other person with soap and water as soon as possible.
• Advise patient that if a dose is missed and it is more than 12 h before the next scheduled dose, to apply the dose and resume the regular dose the next day. If it is less than 12 h before the next scheduled dose, advise patient to skip that dose and apply the next dose at the regularly scheduled time. Caution patient not to double the dose to catch up.

• Injection and pellets
• Advise patient that medication will be prepared and administered by a health care provider in a medical setting.
• Advise patient to report pain, tenderness, or signs of inflammation at injection/implantation site to health care provider.

• Transdermal system
• Instruct patient to apply patch once daily at about the same time each day. Advise patient that application at night is preferred.
• Instruct patient in proper application of patch: open packet and remove patch immediately prior to application; remove release liner to expose adhesive side of patch; apply to clean, dry skin area of back, abdomen, thigh, or upper arm using firm pressure with fingers or palm, making sure there is good contact with the skin, especially around the edge of the patch.
• Caution patient not to apply patch to scrotum, penis, skin that is not normal (eg, inflamed or irritated), skin over a bony prominence, or skin that could be subject to prolonged pressure during sleep or sitting.
• Instruct patient to discard used patches in household trash in manner that prevents accidental ingestion by children or pets.
• Advise patient that patch does not have to be removed during sexual intercourse, nor while showering, bathing, or swimming.
• Advise patient that mild skin irritation can be relieved by using OTC hydrocortisone. Instruct patient to notify health care provider if irritation persists or worsens.

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