Testosterone Cypionate

Class: Androgens
Note: This monograph also contains information on Testosterone, Testosterone Enanthate
VA Class: HS100
CAS Number: 58-22-0
Brands: Androderm, AndroGel, Delatestryl, Striant, Testim

• 
  

  Risk of virilization in children and women following secondary exposure to testosterone in topically administered testosterone gel.^{157 166 170 171} Advise children and women to avoid contact with application sites of men using testosterone gel.^{166 170 171} (See Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.)

  
  


• 
  

  Advise men using testosterone gel to strictly adhere to recommended instructions for use.^{170 171} (See Administration under Dosage and Administration.)

  
  

REMS:

FDA approved a REMS for testosterone to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of testosterone and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Androgenic anabolic steroid hormone; the principal endogenous androgen.^a

Uses for Testosterone Cypionate

Male Hypogonadism

Management of congenital or acquired primary hypogonadism such as that resulting from orchidectomy or from testicular failure caused by cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals.^{117 133 135 157 161 162 a}

Management of congenital or acquired hypogonadotropic hypogonadism such as that resulting from idiopathic gonadotropin or gonadotropin-releasing hormone (luteinizing hormone-releasing hormone) deficiency or from pituitary-hypothalamic injury caused by tumors, trauma, or radiation.^{117 133 135 157 161 162 a} Should be used in the treatment of hypogonadotropic hypogonadism only in patients uninterested in or unable to achieve fertility.^f

Considered the androgen of choice for the treatment of androgen deficiency (e.g., hypogonadism) and AIDS wasting in HIV-infected men.¹²⁶

May be used to stimulate puberty when the diagnosis is well established in carefully selected males with delayed puberty (designated an orphan drug by FDA for this use).^{a 162}

Some experts (e.g., American College of Rheumatology) recommend that men who develop low serum testosterone concentrations (<300 ng/mL) while receiving long-term corticosteroid therapy receive testosterone replacement therapy in an attempt to treat hypogonadism and possibly reduce the risk of corticosteroid-induced osteoporosis†.¹²²

Clinical evidence to date regarding testosterone therapy in aging men suggests some beneficial effects (e.g., on body composition, strength, bone density, frailty, cognitive function, mood, sexual function, quality of life), but risks relating to benign prostatic hyperplasia and prostate cancer need to be quantified.¹⁵⁶ The Institute of Medicine states that the nature and extent of therapeutic benefits in older men require additional study.¹⁵⁶

Not indicated for the treatment of erectile dysfunction† in men with normal testosterone concentrations.¹⁵⁸

Breast Cancer

Palliative treatment of androgen-responsive, advanced, inoperable, metastatic (skeletal) breast cancer in women who are 1–5 years postmenopausal and in premenopausal women who have benefited from oophorectomy.^{a 162}

Poorly tolerated (see Virilization under Cautions); other hormonal agents (e.g., tamoxifen, anastrozole, letrozole, exemestane) currently are preferred for this use.^{d e}

Misuse and Abuse

Has been misused and abused by athletes, bodybuilders, weight lifters, and others to enhance athletic performance or physique†.^{100 101 102 103 104 105 106 107 108 109 110 111 112 114 115 116 120}

Medical and sports experts (e.g., International Olympic Committee) consider such use to be inappropriate and unacceptable because of known adverse effects and potential long-term sequelae and because such use by athletes is contrary to the rules and ethical principles of athletic competition.^{101 102 107 114 115 116}

Testosterone Cypionate Dosage and Administration

General

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

Gel

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 has been 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.)

Transdermal System

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

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 hydrocortisone 0.5 or 1% 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.¹³³

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

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

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

Pediatric Patients

Male Hypogonadism

Delayed Puberty

IM

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

Male Hypogonadism

IM

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

Topical (Gel)

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

Topical (Transdermal System)

Usual initial dosage is 1 system delivering 5 mg/24 hours or 2 systems delivering 2.5 mg/24 hours applied to the skin nightly.¹³³

Adjust dosage according to morning serum testosterone concentrations.¹³³ Depending on requirements, increase dosage to 7.5 mg once daily (administered nightly as 1 system delivering 5 mg/24 hours plus 1 system delivering 2.5 mg/24 hours or as 3 systems delivering 2.5 mg/24 hours) or decrease dosage to 2.5 mg once daily (administered nightly as 1 system delivering 2.5 mg/24 hours).¹³³

Intrabuccal

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

Breast Cancer

IM

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}

Cautions for Testosterone Cypionate

Contraindications

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  Men with breast cancer or known or suspected prostate cancer.^{117 133 157 161 162 166}

  
  


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  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

Fetal/Neonatal Morbidity

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 from Secondary Exposure to Testosterone

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 has been 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}

Hepatic Effects

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}

GU Effects

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 has been 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

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

Fluid Retention

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}

Hypercalcemia

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}

Sleep Apnea

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

Misuse and Abuse

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} hepatotoxicity^{100 101 102 104 107 108 109 110 112 114 116} ) 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}

Flammability

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

Virilization in Women Receiving Testosterone Therapy

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.

Lipid Abnormalities

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

Hematologic Effects

Supraphysiologic concentrations of testosterone can stimulate erythropoiesis^{123 166} and may increase the risk for a thromboembolic event.¹⁶⁶ Increases in hematocrit may require dosage reduction or discontinuation 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}

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

Transfer of Topically Administered Testosterone to Other Individuals

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

Specific Populations

Pregnancy

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 has been 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}

Lactation

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}

Pediatric Use

Safety and efficacy not established for topical testosterone gel ^{157 166} or extended-release buccal (transmucosal) testosterone tablets in children <18 years of age;¹⁶¹ testosterone transdermal systems in males <15 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}

Geriatric Use

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) and topical testosterone gel (AndroGel) have not included sufficient numbers of adults ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^{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 and AndroGel to determine the potential risks of cardiovascular disease, prostate cancer, and prostatic hyperplasia in geriatric adults.^{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}

Interactions for Testosterone Cypionate

Specific Drugs

Drug	Interaction	Comment
Anticoagulants, oral	Testosterone may potentiate the action of oral anticoagulantsa and decrease anticoagulant requirements117 133 162	Monitor INR and prothrombin time closely when androgen therapy is initiated or discontinued in patients receiving oral anticoagulants and adjust anticoagulant dosage as needed133 162 166 a