Testosterone enanthate

Males

DELATESTRYL® (Testosterone Enanthate Injection, USP) is indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone.

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 luteinizing hormone-releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. (Appropriate adrenal cortical and thyroid hormone replacement therapy are still necessary, however, and are actually of primary importance.)

If the above conditions occur prior to puberty, androgen replacement therapy will be needed during the adolescent years for development of secondary sexual characteristics. Prolonged androgen treatment will be required to maintain sexual characteristics in these and other males who develop testosterone deficiency after puberty.

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

Delayed puberty – DELATESTRYL® (Testosterone Enanthate Injection, USP) may be used to stimulate puberty in carefully selected males with clearly delayed puberty. These patients usually have a familial pattern of delayed puberty that is not secondary to a pathological disorder; puberty is expected to occur spontaneously at a relatively late date. Brief treatment with conservative doses may occasionally be justified in these patients if they do not respond to psychological support. The potential adverse effect on bone maturation should be discussed with the patient and parents prior to androgen administration. An X-ray of the hand and wrist to determine bone age should be obtained every six months to assess the effect of treatment on the epiphyseal centers (see WARNINGS).

Females

Metastatic mammary cancer – DELATESTRYL® (Testosterone Enanthate Injection, USP) may be used secondarily in women with advancing inoperable metastatic (skeletal) mammary cancer who are one to five years postmenopausal. Primary goals of therapy in these women include ablation of the ovaries. Other methods of counteracting estrogen activity are adrenalectomy, hypophysectomy, and/or antiestrogen therapy. This treatment has also been used in premenopausal women with breast cancer who have benefited from oophorectomy and are considered to have a hormone-responsive tumor. Judgment concerning androgen therapy should be made by an oncologist with expertise in this field.

• Breast Cancer
• Breastfeeding (and Formula Feeding)

You should not receive testosterone if you are allergic to it, or if you have:

• prostate cancer;

• male breast cancer;

• a serious heart condition;

• severe liver disease;

• severe kidney disease; or

• if you are pregnant or may become pregnant.

To make sure testosterone is safe for you, tell your doctor if you have:

• diabetes;

• enlarged prostate;

• heart disease or coronary artery disease;

• a history of heart attack, stroke, or blood clot;

• high cholesterol or triglycerides (a type of fat in the blood);

• breast cancer (in men, or in women who have hypercalcemia);

• liver or kidney disease;

• if you are bedridden or otherwise debilitated; or

• if you take a blood thinner (warfarin, Coumadin, Jantoven).

This medicine can harm an unborn baby or cause birth defects. Do not use testosterone if you are pregnant or may become pregnant. Tell your doctor right away if you become pregnant during treatment. Use effective birth control while you are receiving testosterone.

It is not known whether testosterone injection passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Testosterone is injected into a muscle. Testosterone injection is usually given every 2 to 4 weeks.

Misuse of testosterone can cause dangerous or irreversible effects, such as enlarged breasts, small testicles, infertility, high blood pressure, heart attack, stroke, liver disease, bone growth problems, addiction, and mental effects such as aggression and violence.

Testosterone injections should be given only by a healthcare professional.

The length of treatment with testosterone injection will depend on the condition being treated.

Testosterone will not enhance athletic performance and should not be used for that purpose.

While receiving testosterone, you will need frequent blood tests.

Testosterone can affect bone growth in boys who are treated for delayed puberty. Bone development may need to be checked with x-rays every 6 months during treatment.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Other drugs may interact with testosterone, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

General

• Confirm diagnosis of hypogonadism by laboratory testing prior to initiation of therapy.133 175

• Measure serum testosterone concentrations in the morning on at least 2 separate days.133 175 To confirm diagnosis, measurements must be consistently below the normal range.133 175 Serum testosterone concentrations may be low later in the day in men with or without hypogonadism; avoid measuring testosterone concentrations later in the day.175

Male Hypogonadism

• Individualize dosage according to the condition being treated; the severity of symptoms; the patient’s age, gender, and history of prior androgenic therapy; and the specific testosterone preparation being used.a

• Monitor every 3–4 months during the first year of testosterone replacement and periodically thereafter (e.g., every 4–6 months) for response and tolerance.123

Delayed Puberty

• Prior to initiation of therapy, fully discuss the potential risk of therapy with the patient and his parents.a 162

• Take into consideration the chronological and skeletal ages of the patient, both in determining the initial dosage and in adjusting the dosage.117 162 a

• Perform radiographic examination of the hand and wrist at 6-month intervals to determine the rate of bone maturation and to assess the effect of therapy on the epiphyseal centers.117 162 a (See Pediatric Use under Cautions.)

Breast Cancer

• Administer only under supervision of a qualified clinician experienced in the treatment of breast cancer.162 a

• May occasionally appear to accelerate progression of the disease;162 a monitor patients closely.162

• Discontinue the drug if hypercalcemia occurs, since this may indicate progression of metastases to the bone.162

Administration

Administer testosterone topically or intrabuccally.133 157 161 166

Administer testosterone cypionate and testosterone enanthate by deep IM injection;117 162 not for IV administration.117

IM Administration

Administer by deep IM injection into the upper outer quadrant of the gluteus maximus.117 162

Topical Administration

AndroGel: Apply gel topically once daily, preferably in the morning, to clean, dry, intact skin on the shoulders and upper arms and/or abdomen.166 Do not apply to the genitals.166

AndroGel unit-dose packet: Upon opening the unit-dose packet, squeeze the entire contents into the palm of the hand and immediately apply to the application site.135 Alternatively, squeeze a portion of the contents into the palm of the hand and immediately apply to application site; repeat procedure until entire contents of the packet applied.135

AndroGel metered-dose pump: Collect gel in the palm of the hand by pressing the pump firmly and fully; apply to application site.135 This can be done one pump actuation at a time or after completion of all pump actuations needed for the daily dose.135 Alternatively, apply the gel directly to application site (direct application prevents loss of gel during transfer to hand).135 Prime pump by depressing 3 times before using the pump for the first dose; discard gel so that household members or pets are not exposed to the gel (i.e., rinse down sink).135

Testim: Apply gel topically once daily, preferably in the morning, to clean, dry, intact skin on the shoulders and/or upper arms157 Do not apply to abdomen or genitals.157 Upon opening the unit-dose tube, squeeze the entire contents into the palm of the hand and immediately apply to the application site.157

Immediately wash hands with soap and water after application of the gel.157 166 170 171

Allow the application site to dry for a few minutes after application of gel.166 170 171 After the gel has dried, cover site with clothing (e.g., a shirt) to prevent transfer to another individual.157 166

Manufacturer of AndroGel recommends waiting ≥5–6 hours166 and the manufacturer of Testim recommends waiting ≥2 hours after application before showering or swimming.157 However, showering or swimming after the elapse of just 1 hour should have a minimal effect on the amount of testosterone gel absorbed if done very infrequently.135

Wash the application site(s) thoroughly with soap and water to remove any testosterone residue prior to situations in which skin-to-skin contact with other individuals is anticipated at the site of testosterone gel application.170 171 If unwashed or unclothed skin at the site of testosterone gel application comes in contact with the skin of another individual, wash the general area of contact with soap and water as soon as possible.157 166 170 171

Consider the possibility of secondary exposure to testosterone topical gel.157 166 170 171 (See Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.)

Apply the transdermal system to clean, dry area of skin on the back, abdomen, upper arm, or thigh by firmly pressing the system with the adhesive side touching the skin.133 Do not apply to the scrotum or to oily, damaged, or irritated areas of the skin.133 134

To avoid burn-like blisters, do not apply systems over bony prominences or on a part of the body that may be subject to prolonged pressure during sleep or sitting (e.g., the deltoid region of the upper arm, the greater trochanter of the femur, the ischial tuberosity).133

Apply once daily at night (e.g., 10 p.m.).133 Leave transdermal system in place for 24 hours; after 24 hours, remove system and apply a new system.133 Apply system immediately after removal from its protective pouch and removal of the protective liner.133

If transdermal system becomes loose, smooth down by firmly rubbing a finger around the edges.133 If system inadvertently comes off before noon following application the previous evening, apply a new system until the next scheduled application that evening.133 If system inadvertently comes off later in the day, do not replace until the next scheduled application that evening.133 Do not reapply with tape.133

To minimize and/or prevent potential skin irritation, apply each transdermal system at a different site, with ≥1 week between applications to a particular site.133

Mild skin irritation may be ameliorated with topical OTC hydrocortisone cream after system removal; alternatively, apply a small amount of triamcinolone acetonide 0.1% cream to the skin under the drug reservoir (do not use ointment formulations because they may reduce testosterone absorption).133 143

Transdermal system does not need to be removed during sexual intercourse or while showering or bathing; however, avoid swimming, showering, or washing the administration site for at least 3 hours following application.133

Remove transdermal system before undergoing magnetic resonance imaging (MRI).133 (See Magnetic Resonance Imaging under Cautions.)

Intrabuccal Administration

Press the extended-release buccal (transmucosal) tablet against the gum above the upper left or right incisor twice daily (morning and evening) about 12 hours apart.161 These tablets will adhere to the gum and do not dissolve completely; do not chew or swallow.161 Dislodge and remove the tablet after 12 hours.161 Alternate application sites above the left and right upper incisors.161

Consult manufacturer’s patient information for instructions on proper intrabuccal administration and removal of the tablet.161

If the tablet fails to properly adhere to the gum or falls off within the first 8 hours, replace the old tablet with a new one.161 The new tablet may remain in place until the time of the next regularly scheduled dose (i.e., 12 hours after the original buccal tablet was administered).161 If the buccal tablet falls off after 8 hours but before 12 hours, replace the original tablet with one that can serve as the second dose for that day.161

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as testosterone; dosage expressed in terms of testosterone.133 135 157 161 Also available as testosterone enanthate or testosterone cypionate; dosage expressed in terms of the salts.117 162

AndroGel unit-dose packets contain 2.5 or 5 g of gel (25 or 50 mg of testosterone).135 Each depression of the metered-dose pump delivers 1.25 g of gel (12.5 mg of testosterone) after priming.135

Androderm 2 mg transdermal system contains 9.7 mg of testosterone for delivery of testosterone 2 mg/24 hours.133 Androderm 4 mg transdermal system contains 19.5 mg of testosterone for delivery of testosterone 4 mg/24 hours.133

Testim unit-dose tubes contain 5 g of gel (50 mg of testosterone).157

Pediatric Patients

Dosage regimens vary.117 162 a Some clinicians recommend that lower dosages be used initially, followed by gradual increases in dosage as puberty progresses; subsequently, the dosage may be decreased to maintenance levels.117 162 a Other clinicians state that higher dosages are required initially to induce pubertal changes and lower dosages can then be used for maintenance therapy after puberty.117 162 a

Usual dosage of testosterone enanthate: 50–200 mg every 2–4 weeks for a limited period of time (e.g., 4–6 months).a 162

Adults

Usual dosage: 50–400 mg of testosterone cypionate or testosterone enanthate every 2–4 weeks.117 162

Some clinicians recommend testosterone cypionate or testosterone enanthate dosage of 50–100 mg every 7–10 days or 100–150 mg every 2 weeks.f While dosage of 300 mg every 3 weeks also may be considered for convenience, such dosing is associated with wider testosterone fluctuations and generally is inadequate to ensure a consistent clinical response.123 Serum total testosterone concentrations generally should exceed lower limit of normal (in the range of 250–300 ng/dL) just before the next dose.123

Adult males with prepubertal onset of hypogonadism who are going through puberty for the first time with testosterone replacement: Initially, 50 mg every 3–4 weeks;f increase dosage gradually in subsequent months as tolerated up to full replacement within 1 year.123

Attainment of full virilization may require up to 3–4 years of IM testosterone replacement.123

AndroGel and Testim: Apply 50 mg of testosterone (5 g of 1% gel) once daily, preferably in the morning; this dose delivers about 5 mg of testosterone systemically.135 157 Adjust dosage according to serum testosterone concentrations obtained at regular intervals after initiating daily application of AndroGel166 and approximately 14 days after initiating Testim.157

AndroGel: If serum testosterone concentrations are below the normal range or the clinical response is inadequate, the dosage can be increased initially to 75 mg of testosterone (7.5 g of 1% gel) and, if necessary, subsequently to 100 mg of testosterone (10 g of 1% gel).135 If serum testosterone concentrations exceed the normal range, the daily dosage may be decreased.166 If serum testosterone concentrations consistently exceed the normal range at a daily dosage of 50 mg of testosterone (5 g of 1% gel), discontinue application of the gel.166

Testim: If serum testosterone concentrations are below the normal range or the clinical response is inadequate, may increase dosage to 100 mg of testosterone (10 g of 1% gel).157

Usual initial dosage is 1 system delivering 4 mg/24 hours applied to the skin nightly.133

Adjust dosage according to morning serum testosterone concentrations approximately 2 weeks following initiation of therapy.133 Depending on requirements, increase dosage to 6 mg once daily (administered nightly as 1 system delivering 4 mg/24 hours plus 1 system delivering 2 mg/24 hours) or decrease dosage to 2 mg once daily (administered nightly as 1 system delivering 2 mg/24 hours).133

Switch patients currently maintained on a dosage of 2.5 mg/24 hours to 1 system delivering 2 mg/24 hours at next scheduled dose.133 Switch patients currently maintained on a dosage of 5 mg/24 hours to 1 system delivering 4 mg/24 hours at next scheduled dose.133 Switch patients currently maintained on a dosage of 7.5 mg/24 hours to 1 system delivering 4 mg/24 hours plus 1 system delivering 2 mg/24 hours at next scheduled dose.133

Approximately 2 weeks after switching therapy, measure patient's morning serum testosterone concentrations following system application the previous evening to ensure proper dosing.133

30 mg (1 extended-release transmucosal tablet) twice daily (morning and evening) about 12 hours apart.161 Serum testosterone concentration may be determined just prior to the morning dose at 4–12 weeks after initiation of intrabuccal therapy; if total serum testosterone concentration is excessive, discontinue intrabuccal therapy and consider alternative treatments.161

200–400 mg of testosterone cypionate or testosterone enanthate every 2–4 weeks.162 a

Special Populations

No special population dosage recommendations at this time.157 166

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• Men with breast cancer or known or suspected prostate cancer.117 133 157 161 162 166

• Known hypersensitivity to testosterone, testosterone cypionate, testosterone enanthate, or any ingredient in the formulation.117 133 157 161 162 166 a

• Some manufacturers state that testosterone is contraindicated in patients with serious cardiac, renal, or hepatic disease.117

• Manufacturers of testosterone cypionate and testosterone enanthate injections (preparations indicated for the treatment of breast cancer) state that androgens are contraindicated in women who are or may become pregnant.117 162

• Manufacturers of testosterone gel (AndroGel, Testim) state that testosterone is contraindicated in women who are or may become pregnant, or who are breastfeeding.157 166

• Manufacturers of buccal and transdermal testosterone preparations state that these preparations should not be used in women.133 161

Warnings/Precautions

Warnings

May cause fetal harm;117 133 157 162 166 dose-related virilization of the external genitalia (e.g., clitoral hypertrophy, abnormal vaginal development, fusion of genital folds to form a scrotal-like structure) of female fetus reported, particularly when exposure to androgens occurs during the 1st trimester.162 166 a

Virilization in children and women can occur following secondary exposure to testosterone in topically administered gel.170 171 172 173 Enlargement of penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age reported in children 9 months to 5 years of age during postmarketing surveillance of testosterone gel.167 168 169 170 171 172 173 Direct contact of children with testosterone gel application sites on men's skin reported in most cases.170 172 173 Secondary exposure to testosterone also possible from contact with items (e.g., shirts, bed linens) of men receiving testosterone gel.170 172 173 Signs and symptoms generally resolved with removal of testosterone exposure.169 170 171 172 In some cases, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronologic age.169 170 171

Children and women should avoid contact with application sites on the skin of men using testosterone gel.166 170 171 Consider also the possibility of secondary exposure from contact with items (e.g., shirts, bed linens) of men using testosterone gel.170 172 173

Risk of testosterone transfer in some cases increased by lack of adherence to precautions for appropriate use of testosterone gel.170 Advise men using topical gel to strictly adhere to the recommended instructions for use and appropriate precautions from the manufacturers to minimize the potential for secondary exposure to testosterone in other individuals.170 171 (See Administration under Dosage and Administration.)

If unwashed or unclothed skin to which testosterone gel was applied comes in contact with the skin of another individual, wash the general area of contact with soap and water as soon as possible.157 166

Inform clinicians of inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, substantial increases in acne, or other signs of virilization in women.166 170 171 Consider the possibility of secondary exposure to testosterone as the cause of virilization in these patients.166 170 171 Discontinue testosterone gel promptly at least until the cause of virilization in such children and women is identified.170 171

Potentially serious and/or life-threatening adverse hepatic effects (e.g., peliosis hepatis, hepatic adenomas, hepatocellular carcinoma, cholestatic hepatitis, jaundice) associated with prolonged use of high dosages of androgens (e.g., testosterone enanthate).117 133 134 135 157 161 162 Abnormal liver function tests (e.g., ALT, AST, gamma-glutamyltranspeptidase [GGTP], bilirubin) reported with AndroGel during postmarketing surveillance.166

If cholestatic jaundice or hepatitis occurs or if liver function test results become abnormal during therapy, discontinue the drug and investigate the etiology of these disorders.162 Drug-induced jaundice usually is reversible following discontinuance of the drug.162 Discontinuance of androgen therapy following development of hepatocellular carcinoma does not always result in regression of the tumor.117 133 135 157 161 162

Priapism or excessive sexual stimulation possible, especially in geriatric men.117 133 135 a Oligospermia and decreased ejaculatory volume may also occur in men receiving excessive dosage or prolonged administration of testosterone.117 a If any of these adverse effects occur, discontinue the drug temporarily.117 a If therapy is restarted, use lower dosages.117 a

Possible increased risk for the development of prostatic hyperplasia and prostate cancer, particularly in geriatric patients.117 133 134 135 157 161 162 Testosterone therapy associated with increases in PSA (of 0.3 ng/mL) in men with hypogonadism.135 163 Increased serum PSA concentrations observed in 18% of hypogonadal men receiving AndroGel for up to 42 months; most increases occurred within the first year of therapy.166 Evaluate geriatric patients and other patients with known clinical or demographic risk factors for prostate cancer for the presence of the disease prior to initiation of testosterone replacement therapy.133 135 157 161 162 Perform rectal prostate examinations at baseline and periodically thereafter.123 Baseline and annual determinations of PSA also recommended in older men, particularly in those >50 years of age.123 Manufacturer of testosterone transdermal system (Androderm) recommends evaluation for prostate cancer prior to therapy initiation, 3–6 months after initiation, and then in accordance with current standards of care.133

Acute urethral obstruction possible in patients with benign prostatic hypertrophy who receive IM testosterone cypionate.117

Gynecomastia frequently develops and occasionally persists.117 135 157 161 162 Consider concomitant use of an aromatase inhibitor or surgery.123

Postmarketing reports with AndroGel include impaired urination, prostatic enlargement, testicular atrophy, oligospermia, priapism, gynecomastia, and mastodynia.166

Edema, with or without CHF, possible as a result of sodium and water retention and may be a serious complication in patients with preexisting cardiac, renal, and/or hepatic disease.117 133 157 161 162 166 (See Contraindications under Cautions.)

If edema occurs and is considered a serious complication, discontinue the drug and, if necessary, initiate diuretic therapy.133 135 157 161 162 a

Possible hypercalcemia resulting from osteolysis, especially in immobile patients and in women with metastatic breast cancer.161 166 a In patients with cancer, hypercalcemia may indicate progression of metastases to the bone.161 a Monitor urine and serum calcium concentrations frequently during the course of androgen therapy in women with metastatic breast cancer.162 166

If hypercalcemia occurs, discontinue the drug and institute appropriate measures to reduce serum calcium concentrations.162 a

May potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases.157 161 166

If manifestations of sleep apnea occur or worsen during therapy, perform sleep studies.123 144 If sleep apnea is confirmed, decrease the dosage or discontinue the drug.123 144

Some clinicians consider a history of sleep apnea to be a relative contraindication to testosterone therapy.123

Potential for serious adverse effects (e.g., increased aggression,100 101 102 104 107 108 109 116 antisocial behavior,100 101 102 104 107 108 109 116 manic episode,102 104 105 106 107 108 112 114 depression,102 104 105 106 107 108 112 114 changes in libido,101 102 107 109 116 increased risk of cardiovascular disease,100 101 102 104 107 108 111 112 114 116 119 hepatotoxicity100 101 102 104 107 108 109 110 112 114 116 ) associated with misuse and abuse of androgens (see Misuse and Abuse under Uses); testosterone preparations currently subject to control under the Federal Controlled Substances Act of 1970, as amended by the Anabolic Steroids Control Act of 1990 and 2004, as schedule III (C-III) drugs.113 164

Testosterone gels contain alcohol and are flammable until dry; keep away from open flame.166

Sensitivity Reactions

Allergic contact dermatitis possible with transdermal systems.133 137 142 Topical application of testosterone gel (i.e., AndroGel) is not associated with phototoxicity.135 Hypersensitivity reactions (e.g., anaphylactoid reactions, skin manifestations) rarely reported with testosterone.a

General Precautions

Long-term safety studies not conducted to date to determine the cardiovascular effects of testosterone replacement therapy in men.133 Epidemiologic data and results from randomized, controlled clinical trials inconclusive to date for determining risk of serious adverse cardiovascular events (i.e., nonfatal MI, nonfatal stroke, death) with testosterone use compared with nonuse.133

Based on review of data, FDA concluded that testosterone therapy is associated with possible increased risk of serious adverse cardiovascular events.175 177 178 179 180 181 182 183 Inform patients of this potential increased cardiovascular risk when deciding whether to use or continue to use therapy.133

Unclear whether potential cardiovascular risk is confined to a certain subset of patients; some experts suggest that clinicians use testosterone therapy with caution in patients at high risk for cardiovascular disease (e.g., older men, those with diabetes mellitus or obesity).176 Additional evidence needed to further elucidate the cardiovascular risk associated with testosterone use.175 176

Cardiovascular events (e.g., MI, stroke) reported during postmarketing experience with testosterone transdermal system (Androderm).133 Advise patients to immediately report symptoms suggestive of MI or stroke (e.g., chest pain, shortness of breath, unilateral weakness, difficulty talking) to their clinician.175

Venous thromboembolism (i.e., PE, DVT) reported during postmarketing experience with testosterone preparations, including testosterone transdermal system (Androderm).133 185 Evaluate patients reporting symptoms of pain, edema, warmth, erythema in a lower extremity for DVT, or presenting with acute shortness of breath for PE.133 If venous thromboembolism suspected, discontinue drug and institute appropriate evaluation and management.133

Virilization, including deepening of the voice, hirsutism, and clitoral enlargement, occurs commonly in females receiving testosterone therapy; these changes may not be reversible following discontinuance of the drug.162 a

Monitor women receiving testosterone therapy for signs of virilization (e.g., deepening of the voice, hirsutism, clitoromegaly, menstrual irregularities).161 If virilization occurs, discontinue therapy.161

See Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.

Androgens may alter serum cholesterol concentration.117 162 Although lipid abnormalities generally do not develop during testosterone replacement therapy because of aromatization of testosterone to estradiol,123 consider the possibility that such changes could occur and use testosterone with caution in patients with a history of MI or CAD.162

Perform a lipid profile at baseline and after 6–12 months; adjust therapy accordingly.123 135 157 161 162 Changes in serum lipid profiles may require dosage adjustment or discontinuance of testosterone therapy.166

Supraphysiologic concentrations of testosterone can stimulate erythropoiesis123 166 and may increase the risk for a thromboembolic event.166 Increases in hematocrit may require dosage reduction or discontinuance of testosterone.166 To detect polycythemia, perform periodic hemoglobin and hematocrit determinations in patients receiving long-term therapy.117 123 133 135 157 161 162 Manufacturer of testosterone transdermal system (Androderm) recommends performing hematocrit determinations 3–6 months after therapy initiation and annually thereafter.133

Some clinicians consider hyperviscosity to be a relative contraindication to testosterone therapy.123

Possible transfer of testosterone from patients treated with topical gel to their sexual partners or other individuals in close physical contact.157 166 (See Pregnancy and also see Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.)

Androderm transdermal system has an occlusive backing that prevents the partner from coming in contact with testosterone in the system; the system does not need to be removed during sexual intercourse.133 Transfer of the transdermal system itself from the patient’s body to that of his partner is unlikely.133

Skin burns may occur at application site of testosterone transdermal system (Androderm) if worn during MRI, since system contains aluminum.133 Advise patients to remove the transdermal system before undergoing MRI.133

Specific Populations

Category X.117 133 135 157 161 162 (See Fetal/Neonatal Morbidity and also see Contraindications under Cautions.)

Avoid transfer of testosterone from topical preparations of the drug to pregnant women.157 166 (See Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.)

If unwashed or unclothed skin to which testosterone topical gel was applied comes in direct contact with the skin of a pregnant woman, wash the general area of contact with soap and water as soon as possible.157 166

Not known whether testosterone is distributed into milk.162 Potential for serious adverse reactions in nursing infants.162 166 Testosterone also may adversely affect lactation.166 Discontinue nursing or testosterone enanthate injection taking into account the importance of the drug to the woman.162 Use of testosterone gel, transdermal system, and buccal tablets not recommended.117 133 157 161 166

Safety and efficacy not established for topical testosterone gel,157 166 extended-release buccal (transmucosal) testosterone tablets,161 or testosterone transdermal system in children <18 years of age,133 or testosterone cypionate in children <12 years of age.117 Secondary exposure to testosterone in children can occur with use of testosterone gel in other individuals.170 171 (See Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.)

Testosterone enanthate injection may accelerate bone maturation without producing compensatory gain in linear growth, possibly resulting in compromised adult stature.162 a The younger the child, the greater the risk of testosterone compromising final mature stature.162 a Use with extreme caution in children and only under the supervision of a specialist who is aware of the adverse effects of testosterone on bone maturation.162 a 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.162 a

Possible increased risk of developing prostatic hypertrophy and prostate cancer during androgen therapy.117 133 157 166 161 a (See GU Effects under Cautions.)

Total amount of testosterone delivered over 24 hours in men 65–79 years of age following application of transdermal testosterone system (Androderm) was approximately 20% less than the average amount delivered in younger patients.133

Clinical studies evaluating testosterone enanthate injection (Delatestryl), topical testosterone gel (AndroGel), and testosterone transdermal system (Androderm) have not included sufficient numbers of adults ≥65 years of age to determine whether geriatric patients respond differently than younger adults.133 162 166

No substantial differences in safety and efficacy of extended-release buccal (transmucosal) testosterone tablets (Striant) in geriatric patients relative to younger adults.161 Pharmacokinetic differences observed between geriatric and younger adults in studies with Striant, but not known whether these differences are clinically important.161

Insufficient long-term safety data with Delatestryl, AndroGel, and Androderm to determine the potential risks of cardiovascular disease, prostate cancer, and prostatic hyperplasia in geriatric adults.133 162 166

Common Adverse Effects

Acne, flushing of the skin, gynecomastia, increased or decreased libido, habituation, edema,a local irritation at the site of application (with topical or intrabuccal administration).133 137 138 139 140 143 157 161 166

Endocrine and Urogenital, Female – The most common side effects of androgen therapy are amenorrhea and other menstrual irregularities, inhibition of gonadotropin secretion, and virilization, including deepening of the voice and clitoral enlargement. The latter usually is not reversible after androgens are discontinued. When administered to a pregnant woman, androgens cause virilization of the external genitalia of the female fetus.

Male – Gynecomastia, and excessive frequency and duration of penile erections. Oligospermia may occur at high dosages (see CLINICAL PHARMACOLOGY).

Skin and Appendages – Hirsutism, male pattern baldness, and acne.

Cardiovascular Disorders – Myocardial infarction, stroke.

Fluid and Electrolyte Disturbances – Retention of sodium, chloride, water, potassium, calcium (see WARNINGS), and inorganic phosphates.

Gastrointestinal – Nausea, cholestatic jaundice, alterations in liver function tests; rarely, hepatocellular neoplasms, peliosis hepatis (see WARNINGS).

Hematologic – Suppression of clotting factors II, V, VII, and X; bleeding in patients on concomitant anticoagulant therapy; polycythemia.

Nervous System – Increased or decreased libido, headache, anxiety, depression, and generalized paresthesia.

Metabolic – Increased serum cholesterol.

Vascular Disorders – venous thromboembolism

Miscellaneous – Rarely, anaphylactoid reactions; inflammation and pain at injection site.

To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceutical Corp. at 1-877‑233-2001 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.