Brand names: Androderm, AndroGel, Axiron, Delatestryl, Depo-testosterone, ... show all 11 brands Fortesta, Natesto, Striant, Testim, Testopel, Vogelxo
Drug class: Androgens
VA class: HS100
CAS number: 58-22-0

Medically reviewed by Drugs.com on Nov 17, 2023. Written by ASHP.

Introduction

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

Uses for Testosterone

Male Hypogonadism

Management of congenital or acquired primary hypogonadism such as that resulting from orchiectomy 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} 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^{† [off-label]}.¹²²

Safety and efficacy of testosterone replacement therapy in men with late-onset hypogonadism (i.e., low testosterone concentrations related to aging) not established.^{133 175} Further study needed to elucidate the role of testosterone replacement therapy in treatment of this condition.¹⁷⁶

Not indicated for the treatment of erectile dysfunction^{† [off-label]} 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, Abuse, and Dependence

Has been misused and abused by athletes, bodybuilders, weight lifters, and others to enhance athletic performance or physique^{† [off-label]}.^{100 101 102 103 104 105 106 107 108 109 110 111 112 114 115 116 120 194}

Based on review of data, FDA concluded that misuse and abuse of androgens associated with serious adverse cardiovascular, hepatic, endocrine, and mental health effects.¹⁹⁴ 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} (See Misuse, Abuse, and Dependence under Cautions.)

Testosterone Dosage and Administration

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 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 chronologic 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, intrabuccally, or intranasally.^{133 135 157 161 166 186 187 188 190 192}

Administer testosterone cypionate, testosterone enanthate, and testosterone undecanoate by deep IM injection;^{117 162 189} not for IV administration.¹¹⁷

Administer testosterone pellets subcutaneously as a biodegradable implant.¹³⁶

IM Administration

Administer by deep IM injection into the upper outer quadrant of the gluteus maximus.^{117 162 189}

Restricted Distribution Program

Distribution of testosterone undecanoate injection (Aveed) is restricted because of the potential for serious pulmonary oil microembolism reactions and anaphylaxis.¹⁸⁹ (See Pulmonary Oil Microembolism Reactions and also Sensitivity Reactions under Cautions.)

Must be obtained through the Aveed Risk Evaluation and Mitigation Strategy (REMS) Program designed to minimize risk of pulmonary oil microembolism reactions and anaphylaxis.¹⁸⁹ Clinicians and institutions must enroll in and comply with all requirements of the Aveed REMS Program.¹⁸⁹ Institutions required to have appropriate equipment for immediate treatment of serious pulmonary oil microembolism and anaphylactic reactions.¹⁸⁹

For additional information or to enroll in the Aveed REMS program, contact 855-755-0494 or visit www.AveedREMS.com.¹⁸⁹

Sub-Q Administration

Administer sub-Q as a biodegradable implant into hip or other fatty area.^{136 191}

Topical Administration

Gel

AndroGel: Apply gel topically once daily, preferably in the morning, to clean, dry, intact skin; apply AndroGel 1% only on shoulders and upper arms and/or abdomen, and AndroGel 1.62% only on shoulders and upper arms.^{135 190} Do not apply to other body parts (e.g., genitals, chest, axilla, knees, back).^{135 190}

Testim, Vogelxo: Apply gel topically once daily to clean, dry, intact skin on shoulders and/or upper arms.¹⁵⁷ Do not apply to abdomen or genitals.¹⁵⁷

Fortesta: Apply gel topically once daily, in the morning, to clean, dry, intact skin on front and inner thighs.¹⁹² Do not apply to other body parts (e.g., genitals).¹⁹²

AndroGel unit-dose packet: Upon opening the packet, squeeze entire contents into the palm of the hand and immediately apply to application site.^{135 190} 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.^{135 190}

AndroGel and Vogelxo metered-dose pump: Collect gel in the palm of the hand by pressing the pump firmly and fully; apply to application site.^{187 190} Prime pump by pressing 3 times before using the pump for the first dose; discard gel so that household members or pets avoid exposure (i.e., rinse down sink).^{187 190}

Testim and Vogelxo unit-dose tube or packet: Upon opening the unit-dose tube (Testim, Vogelxo) or packet (Vogelxo), squeeze the entire contents into the palm of the hand and immediately apply to application site.^{157 187}

Fortesta metered-dose pump: Apply gel directly to application site by pressing the pump firmly and fully; avoid thigh area adjacent to scrotum.¹⁹² Use one finger to gently and evenly rub gel into application site.¹⁹² Prime pump by pressing 8 times before using the pump for the first dose; discard gel so that household members or pets avoid exposure (i.e., rinse down sink).¹⁹²

Immediately wash hands with soap and water after application of the gel.^{135 157 170 171 190}

Allow site to dry after application of gel.^{135 170 171 190} After gel has dried, cover site with clothing to prevent transfer to another individual.^{135 157 187 190 192}

Manufacturer of AndroGel 1 and 1.62% recommends waiting ≥5 and 2 hours, respectively,^{135 190} and the manufacturers of Fortesta, Testim, and Vogelxo recommend waiting ≥2 hours after application before showering, swimming, or washing application site.^{135 157 187 190 192}

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.^{135 157 170 171 187 190 192} 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.^{135 157 170 171 187 190 192}

Consider the possibility of secondary exposure to testosterone topical gel.^{135 157 170 171 187 190 192} (See Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.)

Solution

Axiron: Apply solution topically once daily to clean, dry, intact skin only on the axilla.¹⁸⁶ Do not apply to other body parts (i.e., genitals, abdomen, shoulders, upper arms).¹⁸⁶ If concomitant deodorant or antiperspirant (stick or roll-on) products are used, apply deodorant or antiperspirant prior to application of Axiron to avoid contamination.¹⁸⁶

Axiron metered-dose pump: Collect solution into applicator cup and wipe cup steadily up and down the application site.¹⁸⁶ Do not rub solution into the application site with hands or fingers.¹⁸⁶ If solution drips or runs, collect excess solution using the applicator cup.¹⁸⁶ Allow application sites to dry completely prior to another application.¹⁸⁶ Prime pump by pressing 3 times before using the pump for the first dose; discard solution so that household members or pets avoid exposure (i.e., rinse down sink, basin, toilet).¹⁸⁶

Immediately wash hands with soap and water after application of solution.¹⁸⁶

Allow application site to dry after administration of solution.¹⁸⁶ After solution has dried, cover site with clothing to prevent transfer to another individual.¹⁸⁶

Manufacturer of Axiron recommends waiting ≥2 hours after administration before showering, swimming, or washing application site.¹⁸⁶

Wash application site(s) thoroughly with soap and water to remove any testosterone residue in anticipation of skin-to-skin contact with other individuals at application site.¹⁸⁶ If unwashed or unclothed skin at application site comes in contact with skin of another individual, wash general area of contact with soap and water as soon as possible.¹⁸⁶

Consider possibility of secondary exposure to testosterone topical solution.¹⁸⁶ (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

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

Intranasal

Administer intranasally 3 times daily.¹⁸⁸ Do not apply to other body parts.¹⁸⁸

Clear nasal passages prior to administration.¹⁸⁸

Place right index finger on pump of actuator and slowly insert actuator into left nostril until the finger reaches base of the nose.¹⁸⁸ Apply gel to lateral wall of nostril by slowly pressing the pump; to ensure adequate gel application, wipe tip of actuator along lateral nostril wall upon removal from the nose.¹⁸⁸ Repeat procedure using left index finger for administration to right nostril.¹⁸⁸ Press nostrils just below the nasal bridge to lightly massage application site.¹⁸⁸

Prime pump by pressing 10 times before using it for the first dose; discard gel so that household members or pets avoid exposure (i.e., rinse down sink).¹⁸⁸

Wash hands with soap and water after gel application.¹⁸⁸

Wait 1 hour after application before blowing the nose or sniffing.¹⁸⁸

Concomitant administration of testosterone nasal gel with other nasally administered drugs, except for topical sympathomimetic nasal decongestants (e.g., oxymetazoline) not studied; concomitant use with such drugs not recommended.¹⁸⁸ (See Specific Drugs under Interactions.)

Dosage

Available as testosterone; dosage expressed in terms of testosterone.^{133 135 157 161} Also available as testosterone cypionate, testosterone enanthate, or testosterone undecanoate; dosage expressed in terms of the salts.^{117 162 189}

AndroGel 1% unit-dose packets contain 2.5 or 5 g of gel (25 or 50 mg of testosterone).¹³⁵

AndroGel 1.62% unit-dose packets contain 1.25 or 2.5 g of gel (20.25 or 40.5 mg of testosterone).¹⁹⁰ Each actuation of the metered-dose pump delivers 1.25 g of gel (20.25 mg of testosterone) after priming.¹⁹⁰

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

Vogelxo unit-dose packets or tubes contain 5 g of gel (50 mg of testosterone).¹⁸⁷ Each actuation of the metered-dose pump delivers 1.25 g of gel (12.5 mg of testosterone) after priming.¹⁸⁷

Fortesta metered-dose pump delivers 0.5 g of gel (10 mg of testosterone) per actuation of the metered-dose pump.¹⁹²

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 limited period of time (e.g., 4–6 months).^{a 162}

Usual dosage of testosterone pellets for sub-Q implantation: Generally in the lower end of 150–450 mg and administered for limited period of time (e.g., 4–6 months).¹³⁶

Adults

Male Hypogonadism

IM

Usual dosage: 50–400 mg of testosterone cypionate or testosterone enanthate every 2–4 weeks or 750 mg of testosterone undecanoate every 4 weeks for first 2 doses, then every 10 weeks thereafter.^{117 162 189}

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

Sub-Q

150–450 mg for sub-Q implantation every 3–6 months.¹³⁶

Topical (Gel)

AndroGel 1%, Testim, and Vogelxo: 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.^{135 157 187}

AndroGel 1.62%: Apply 40.5 mg of testosterone (2.5 g of 1.62% gel) once daily in the morning.¹⁹⁰

Fortesta: Apply 40 mg of testosterone (2 g of gel) once daily in the morning.¹⁹²

Adjust dosage according to serum testosterone concentrations obtained at regular intervals after initiating daily application of AndroGel 1%,¹³⁵ approximately 14 days after initiating daily application of Testim or Vogelxo,^{157 187} approximately 14 and 28 days after initiating daily application or dosage adjustment of Androgel 1.62%,¹⁹⁰ and approximately 14 and 35 days after initiating daily application or dosage adjustment of Fortesta.¹⁹²

AndroGel 1%: If serum testosterone concentrations are below the normal range, 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.¹³⁵ 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.¹³⁵

Testim or Vogelxo: If serum testosterone concentrations are below the normal range, may increase dosage to 100 mg of testosterone (10 g of 1% gel).^{157 187}

Androgel 1.62%: For serum testosterone concentrations >750 ng/dL, decrease dosage to 20.25 mg of testosterone (1.25 g of 1.62% gel).¹⁹⁰ For serum testosterone concentrations <350 ng/dL, increase dosage initially to 60.75 mg of testosterone (3.75 g of 1.62% gel) and, if necessary, subsequently to 81 mg of testosterone (5 g of 1.62% gel).¹⁹⁰

Fortesta: For serum testosterone concentrations ≥2500 ng/dL, decrease dosage by 20 mg of testosterone (1 g of gel).¹⁹² For serum testosterone concentrations ≥1250, but <2500 ng/dL, decrease testosterone dosage by 10 mg (0.5 g of gel).¹⁹² If a daily testosterone dosage of 10 mg requires further reduction, discontinue gel.¹⁹² For serum testosterone concentrations <500 ng/dL, adjust dosage of testosterone in 10-mg increments (0.5 g of gel).¹⁹²

Topical (Solution)

Apply 60 mg of testosterone (3 mL of solution) once daily.¹⁸⁶

Adjust dosage according to serum testosterone concentrations obtained after initiating therapy and at least 14 days after initiating daily application or dosage adjustment of testosterone solution.¹⁸⁶ For serum testosterone concentrations >1050 ng/dL, decrease dosage from 60 mg (3 mL of solution) to 30 mg (1.5 mL of solution).¹⁸⁶ If serum testosterone concentrations consistently >1050 ng/dL at a daily dosage of 30 mg, discontinue solution.¹⁸⁶ For serum testosterone concentrations <300 ng/dL, adjust dosage of testosterone in 30-mg increments (1.5 mL of solution).¹⁸⁶

Topical (Transdermal System)

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

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

Intranasal

1 actuation of pump (0.122 g of gel containing 5.5 mg of testosterone) per nostril (total dose: 11 mg) 3 times daily.¹⁸⁸

Adjust dosage according to serum testosterone concentrations obtained at least 1 month after initiating therapy and periodically thereafter.¹⁸⁸ For serum testosterone concentrations consistently >1050 ng/dL, discontinue use of nasal gel.¹⁸⁸ For serum testosterone concentrations consistently <300 ng/dL, discontinue nasal gel and consider alternative therapy.¹⁸⁸

If severe rhinitis occurs, temporarily interrupt use of nasal gel until resolution of symptoms.¹⁸⁸ For persistent severe rhinitis, discontinue nasal gel and consider alternative therapy.¹⁸⁸

Breast Cancer

IM

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

Prescribing Limits

Adults

Male Hypogonadism

Topical

Axiron: Maximum 120 mg of testosterone (6 mL of solution) once daily.¹⁸⁶

Fortesta: Maximum 70 mg of testosterone (3.5 g of gel) once daily.¹⁹²

Special Populations

No special population dosage recommendations at this time.^{157 166}

Cautions for Testosterone

Contraindications

• Men with breast cancer or known or suspected prostate cancer.^{117 133 135 136 157 161 162 186 187 188 189 190 192}

• Known hypersensitivity to testosterone, testosterone cypionate, testosterone enanthate, testosterone undecanoate, or any ingredient in the formulation.^{117 157 161 162 166 189 a}

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

• Manufacturer of testosterone enanthate injection (preparation indicated for the treatment of breast cancer) states that androgens are contraindicated in women who are or may become pregnant.¹⁶²

• Manufacturers of testosterone topical gel, topical solution, nasal gel, transdermal system, and buccal tablets and testosterone undecanoate injection state that testosterone is contraindicated in women who are or may become pregnant, or who are breast-feeding.^{133 135 157 161 186 187 188 189 190 192}

• Manufacturers of testosterone topical gel, topical solution, nasal gel, transdermal system, and buccal tablets and testosterone undecanoate injection state that these preparations not be used in women.^{133 135 157 161 186 187 188 189 190 192}

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity

May cause fetal harm;^{117 133 135 157 162} 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 first 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 products (e.g., gel, solution).^{135 157 170 171 172 173 186 187 190 192} 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 topical testosterone preparations.^{166 170 171 186} 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 topical testosterone preparations.^{170 186} Advise men using topical testosterone preparations 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.^{170 171 186} (See Administration under Dosage and Administration.)

If unwashed or unclothed skin to which testosterone gel or solution 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.^{157 166 186}

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 topical gel or solution promptly at least until the cause of virilization in such children and women is identified.^{170 171 186}

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 1% during postmarketing surveillance.¹³⁵

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 associated with increases in PSA (0.1–0.5 ng/mL) in men with hypogonadism.^{135 163 186 188 189 190} Increased serum PSA concentrations observed in 18% of hypogonadal men receiving AndroGel 1% 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} Routinely perform rectal prostate examinations along with assessment of prostate-related symptoms every 6–12 months.¹²³ Annual determinations of PSA also recommended in older men.¹²³ Manufacturers of testosterone transdermal system, nasal gel, and topical solution recommend evaluation for prostate cancer prior to therapy initiation, 3–6 months after initiation, and then in accordance with current standards of care.^{133 186 188} Manufacturers of testosterone topical gel and buccal tablets and testosterone undecanoate injection recommend evaluation for prostate cancer prior to therapy initiation and during therapy.^{161 187 189 190 192}

Gynecomastia frequently develops and occasionally persists.^{117 135 157 161 162} Consider surgery in some patients.¹²³

Postmarketing reports with AndroGel 1% 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 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

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.^{135 157 161}

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, Abuse, and Dependence

Serious adverse effects (e.g., increased aggression, antisocial behavior, manic episode, hostility, depression, changes in libido, increased risk of cardiovascular events, hepatotoxicity, testicular atrophy, sperm abnormalities) associated with misuse and abuse of androgens (see Misuse, Abuse, and Dependence under Uses);^{100 101 102 104 107 108 109 116 135 193 194} testosterone preparations currently subject to control as schedule III (C-III) drugs.^{113 164}

Manifestations of withdrawal (e.g., depressed mood, major depression, fatigue, cravings, restlessness, irritability, anorexia, insomnia, decreased libido, hypogonadotropic hypogonadism) may occur if androgens are discontinued abruptly or dosage is substantially reduced in physically dependent patients or those taking supratherapeutic doses of the drug; withdrawal symptoms may persist for weeks or months.¹³⁵

Evaluate serum testosterone concentrations if misuse or abuse of androgens is suspected (e.g., patients experiencing serious adverse cardiovascular or psychiatric reactions).^{133 135 136 157 161 162 186 187 188 189 190 192 194} Serum testosterone concentrations may be below or within the normal range in patients abusing synthetic derivatives of testosterone.^{133 135 136 157 161 162 186 187 188 189 190 192 194}

Flammability

Testosterone topical gels and solution contain alcohol and are flammable until dry; keep away from open flame.^{135 157 186 187 190 192}

Pulmonary Oil Microembolism Reactions

Serious pulmonary oil microembolism reactions reported during or immediately following any IM injection of testosterone undecanoate.¹⁸⁹ Manifestations include cough, urge to cough, dyspnea, hyperhidrosis, throat tightening, chest pain, dizziness, syncope.¹⁸⁹ Serious pulmonary oil microembolism reactions generally last a few minutes and resolve following supportive measures; some reactions may require emergency care and/or hospitalization.¹⁸⁹

Observe patients for 30 minutes in a healthcare setting following each IM injection of testosterone undecanoate.¹⁸⁹

Local Effects

Mild to moderate adverse nasal effects (e.g., nasal discomfort, nasal scabbing, rhinorrhea, epistaxis, nasopharyngitis, bronchitis, upper respiratory tract infection, sinusitis) commonly occur following administration of testosterone nasal gel.¹⁸⁸ Long-term effects of testosterone nasal gel unknown.¹⁸⁸

Gum/mouth irritation, bitter taste, gum pain/tenderness reported in patients receiving testosterone buccal tablets.¹⁶¹ Gum edema or taste perversion also may occur.¹⁶¹ Most gum-related adverse effects are transient; gum irritation and tenderness generally resolve in 1–8 and 1–14 days, respectively.¹⁶¹

Sensitivity Reactions

Allergic contact dermatitis possible with transdermal systems.^{133 137 142} Hypersensitivity reactions (e.g., anaphylactoid reactions, skin manifestations) rarely reported with testosterone.^a

General Precautions

Cardiovascular Effects

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.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.^{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 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, 6–12 months after initiating therapy, and then annually thereafter; adjust therapy accordingly.^{123 157 161 162} Changes in serum lipid profiles may require dosage adjustment or discontinuance of testosterone therapy.¹³⁵

Hematologic Effects

Supraphysiologic concentrations of testosterone can stimulate erythropoiesis^{123 135} and may increase the risk for a thromboembolic event.¹³⁵ Increases in hematocrit may require dosage reduction or discontinuance of testosterone.¹³⁵ To detect polycythemia, perform periodic hemoglobin and hematocrit determinations in patients receiving long-term therapy.^{117 123 133 135 157 161 162} Perform hematocrit determinations 3–6 months after therapy initiation and annually thereafter.^{133 135 157 161 186 187 188 189 190 192}

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 or solution to their sexual partners or other individuals in close physical contact.^{135 157 186 187 190 192} (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

Magnetic Resonance Imaging

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

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.^{135 157 186 187 190 192} (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.^{135 157 186 187 190 192}

Lactation

Not known whether testosterone is distributed into milk.¹⁶² Potential for serious adverse reactions in nursing infants.^{135 162} Testosterone also may adversely affect lactation.¹³⁵

Manufacturers of testosterone cypionate injection, testosterone enanthate injection, and testosterone pellets recommend discontinuing nursing or the drug taking into account the importance of the drug to the woman.^{117 136 162} Use of testosterone topical gel, topical solution, nasal gel, transdermal system, and buccal tablets and testosterone undecanoate injection not recommended in nursing women.^{117 133 135 157 161 186 187 188 189 190 192}

Pediatric Use

Safety and efficacy not established for testosterone topical gel, topical solution, nasal gel, buccal tablets and transdermal system and testosterone undecanoate injection in children <18 years of age.^{133 157 161 186 188 189} Testosterone cypionate injection not recommended in children <12 years of age.¹¹⁷

Secondary exposure to testosterone in children can occur with use of testosterone topical gel or solution in other individuals.^{135 157 170 171 186 187 190 192} (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, testosterone undecanoate injection, and testosterone topical gel (AndroGel, Fortesta), topical solution, nasal gel, and transdermal system have not included sufficient numbers of adults ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^{133 135 162 186 188 189 192}

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

Insufficient long-term safety data with testosterone enanthate injection, testosterone undecanoate injection, and testosterone topical gel (AndroGel, Fortesta, Testim, Vogelxo), topical solution, nasal gel, and transdermal system to determine the potential risks of cardiovascular disease, prostate cancer, and prostatic hyperplasia in geriatric adults.^{133 135 157 162 186 187 188 189 192}

Common Adverse Effects

Acne, edema,^a local irritation at application site (with topical, intranasal, or intrabuccal administration), headache, injection site pain (with IM administration), increased serum PSA or serum estradiol concentrations, increased hematocrit or hemoglobin, insomnia, mood swings, irritability, fatigue, hypogonadism, back pain, diarrhea, vomiting, taste perversion (with intrabuccal administration) reported.^{133 135 137 138 139 140 143 157 161 186 187 188 189 190}

With intranasal therapy, rhinorrhea, epistaxis, nasal discomfort, nasopharyngitis, bronchitis, upper respiratory tract infection, sinusitis, nasal scabbing reported.¹⁸⁸

Drug Interactions

Specific Drugs

Testosterone Pharmacokinetics

Absorption

Bioavailability

Testosterone is absorbed systemically through the skin following topical application as a gel,^{135 157 187 190 192} solution,¹⁸⁶ or transdermal system^{123 133 137 145 146 147 148 149 150 151 152} and through the gum and cheek following administration as an extended-release buccal (transmucosal) tablet.¹⁶¹

Following oral administration, bioavailability is low secondary to metabolism in the GI mucosa during absorption and on first pass through the liver.^a

Following topical application of testosterone gel or solution (AndroGel 1%, Testim, Vogelxo, Axiron) to the skin, the skin surface serves as a reservoir for sustained release of the hormone into systemic circulation; approximately 10% of a testosterone dose applied topically to the skin as the 1% gel is absorbed into systemic circulation.^{135 157 186 187}

Showering 3 hours after application of testosterone transdermal system (Androderm) did not substantially alter peak concentrations or systemic exposure of testosterone compared with not showering 3 hours after application.¹³³

Cypionate, enanthate, and undecanoate esters of testosterone are absorbed slowly from the lipid tissue phase at the IM injection site.^{117 162 189 a} Peak serum concentrations are achieved about 72 hours after IM injection.^a Peak plasma concentrations following IM administration of testosterone undecanoate are achieved after a median of 7 days.¹⁸⁹

Onset

Increases in serum testosterone concentrations are apparent within 30 minutes of topical application of a 100-mg testosterone dose of AndroGel 1% gel; physiologic concentrations generally are achieved within 4 hours.¹³⁵

Physiologic concentrations are achieved within 24 hours of topical application of a 50- or 100-mg testosterone dose Testim gel; percutaneous absorption continues for the entire 24-hour dosing interval.¹⁵⁷

Following intranasal application of testosterone nasal gel, peak plasma concentrations achieved in approximately 40 minutes.¹⁸⁸

Following topical application of the transdermal testosterone system, peak plasma concentrations achieved in 6–12 hours.¹³³

Following application of an extended-release buccal (transmucosal) tablet, peak plasma concentrations achieved in 10–12 hours.¹⁶²

Duration

Following discontinuance of daily topical application of AndroGel 1% gel, serum testosterone concentrations remain within the normal range for 24–48 hours but return to pretreatment levels by the 5th day after the last application.¹³⁵

Following discontinuance of daily application of testosterone topical solution, serum testosterone concentrations return to pretreatment levels 7–10 days after the last application.¹⁸⁶

Testosterone concentrations return toward baseline within about 24 hours following removal of the transdermal system.¹³³

Following removal of the extended-release buccal (transmucosal) tablet, serum testosterone concentrations decline to below normal range within 2–4 hours.¹⁶¹

Testosterone cypionate and enanthate have a prolonged (up to 2–4 weeks) duration of action following IM administration.^a

Plasma Concentrations

Administration of 10 or 5 g of AndroGel 1% gel daily results in average daily serum testosterone concentrations of 792 or 566 ng/dL, respectively, at day 30.¹³⁵

Administration of 10 or 5 g of Testim gel daily results in average daily serum testosterone concentrations of 612 or 365 ng/dL, respectively, at day 30.¹⁵⁷

Administration of 11 mg of Natesto nasal gel 3 times daily results in average daily serum testosterone concentrations of 421 ng/dL.¹⁸⁸

In patients receiving the transdermal system, average daily serum testosterone concentrations reportedly are 498 ng/dL at steady state.¹³³

In patients receiving the extended-release buccal tablet, average daily serum testosterone concentrations are 520–550 ng/dL at steady state.¹⁶¹

Distribution

Plasma Protein Binding

Approximately 30–40% of testosterone in plasma is bound to sex hormone binding globulin (SHBG), 2% remains unbound (free), and the rest is bound to albumin and other proteins.^{123 135 157 161}

Special Populations

SHBG-binding capacity is high in prepubertal children, declines during puberty and adulthood, and increases again during the later decades of life.^{135 161}

Elimination

Metabolism

Metabolized principally in the liver to various 17-ketosteroids via 2 different pathways.^{162 a}

Elimination Route

Excreted principally in urine (90%) and also in feces (6%).^{117 133 135 157 161 162 a}

Half-life

Testosterone: Plasma half-life ranges from 10–100 minutes.^{133 135 157 162 a}

Testosterone cypionate after IM injection: Plasma half-life is approximately 8 days.¹¹⁷

Stability

Storage

Buccal (Transmucosal)

Extended-release Tablets

20–25°C.¹⁶¹ Protect from heat and moisture.¹⁶¹

Topical

Gel

20–25°C (may be exposed to 15–30°C).^{135 157 187 190 192}

Solution

25°C (may be exposed to 15–30°C).¹⁸⁶

Transdermal System

20–25°C.¹³³ Protect from excessive heat.¹³³

Nasal

Gel

20–25°C (may be exposed to 15–30°C).¹⁸⁸

Parenteral

IM Injection

Testosterone cypionate: 20–25°C.¹¹⁷ Protect from light.¹¹⁷

Testosterone enanthate: Room temperature.¹⁶²

Testosterone undecanoate: 25°C (may be exposed to 15–30°C).¹⁸⁹

A precipitate may form if testosterone cypionate or testosterone enanthate injection is stored at low temperatures; the precipitate will dissolve after shaking and warming to room temperature.^{117 162}

Pellets for Sub-Q Implantation

25°C (may be exposed to 15–30°C).¹³⁶

Actions

• Replaces diminished or absent endogenous testicular hormone in hypogonadal males.^{117 133 135 a}

• Endogenous androgens are essential hormones that are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics.^{117 133 135 157 161 162 a}

• Androgens are responsible for the growth spurt that occurs during adolescence and for the eventual termination of linear growth that results from fusion of the epiphyseal growth centers.^{117 133 135 157 161 162 a}

• Large doses of androgens may suppress spermatogenesis.^{117 133 135 157 161 162 a}

• Increases protein anabolism and decreases amino acid catabolism; improves nitrogen balance only when there is sufficient intake of calories and protein.^{117 133 135 157 161 162 a}

• Androgens reportedly stimulate the production of erythrocytes, apparently by enhancing production of erythropoietic-stimulating factor.^{117 133 135 157 161 162 a}

• Importance of advising patients to read the manufacturer's medication guide before beginning treatment and each time the prescription for topical testosterone gel or solution is refilled or each time IM testosterone undecanoate (Aveed) is administered.^{135 157 186 187 189 190 192}

• Importance of advising patients of the potential for serious adverse effects associated with misuse and abuse of testosterone.¹⁹⁴

• Risk of MI or stroke.^{133 175} Contact clinician if symptoms suggestive of MI or stroke (e.g., chest pain, shortness of breath, unilateral weakness, difficulty talking) occur.¹⁷⁵

• Risk of virilization in females.^{133 135 157 161 162 186} Advise female patients receiving testosterone therapy and female partners of patients treated with topical testosterone preparations (e.g., gel, solution, transdermal systems) to contact their clinician if they notice changes in body hair distribution, substantial increases in acne, or other manifestations of virilization.^{117 133 135 157 161 162 186}

• Risk of virilization in children resulting from secondary exposure to testosterone.^{135 167 168 169 170 171 172 173 186} Contact clinician if inappropriate changes in genital size, development of pubic hair, increased erections and libido, or aggressive behavior occur in children when transfer of topically administered testosterone gel or solution from another individual is possible.^{117 133 135 157 161 162 186}

• Importance of children and women avoiding contact with application sites on the skin of men using testosterone gel or solution.^{135 170 171 186} If contact with unwashed or unclothed skin at the site of testosterone gel or solution application occurs with the skin of another individual, importance of washing the general area of contact with soap and water as soon as possible.^{135 157 170 171 186}

• Importance of promptly discontinuing testosterone gel or solution when virilization occurs in children or women in contact with men using topical testosterone products until the cause of virilization is identified.^{135 170 171 186}

• Risk of developing benign prostatic hyperplasia or prostate cancer.^{133 135 157} Importance of evaluating patients for prostate cancer, especially geriatric patients and those with clinical or demographic characteristics associated with increased risk, prior to initiating and during testosterone therapy.^{133 135 157}

• Importance of informing patients that changes in urinary habits may occur with testosterone therapy, including increased urinary frequency, urgency, incontinence, nocturia.¹³³

• Risk of priapism; importance of adult or adolescent males informing their clinician if too frequent or persistent penile erections occur.¹³³

• Importance of periodic assessments to determine the rate of bone maturation in prepubertal males receiving testosterone therapy for delayed puberty.¹⁶¹

• Importance of patients informing their clinician of nausea, vomiting, changes in skin color, ankle swelling, or breathing disturbances (e.g., sleep apnea).^{117 133 135 157 161 162}

• Importance of instructing patients in the proper use (see Administration under Dosage and Administration) and disposal of testosterone preparations and of providing patients a copy of manufacturer’s patient information.^{133 135 157 161}

• Importance of advising patients receiving therapy with extended-release buccal tablets to regularly inspect the gum region where the tablet is applied and to report any abnormality to their clinician.¹⁶¹

• For patients using topical testosterone preparations, importance of strictly adhering to the recommended instructions for use and precautions from the manufacturers.^{135 170 171 186}

• For patients using topical testosterone preparations, importance of washing hands immediately with soap and water following application of gel or solution and covering the application site with clothing after allowing gel or solution to dry.^{135 170 135}

• For patients using topical testosterone preparations, importance of avoiding fire, flames, and smoking until gel or solution has dried.^{135 186}

• Risk of serious pulmonary oil microembolism reactions and anaphylaxis following administration of IM testosterone undecanoate; importance of patients informing their clinician of cough, urge to cough, dyspnea, sweating, throat tightening, chest pain, dizziness, syncope during or immediately following administration.¹⁸⁹

• Risk of adverse nasal reactions following administration of testosterone nasal gel; importance of patients informing their clinician of nasopharyngitis, rhinorrhea, epistaxis, nasal discomfort, nasal scabbing.¹⁸⁸

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{117 133 135 157 161 162}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.^{117 133 135 157 161 162}

• Importance of informing patients of other important precautionary information.^{117 133 135 157 161 162} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of testosterone undecanoate injection (Aveed) is restricted.¹⁸⁹ (See REMS and also see Restricted Distribution Program under Dosage and Administration.)

Most preparations containing testosterone or its salts, esters, or ethers are 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} However, manufacturers of certain preparations containing androgenic anabolic steroid hormones (principally combinations that also include estrogens) have applied for and obtained for their products(s) an exemption from the record-keeping and other regulatory requirements of the Federal Controlled Substances Act.^{121 165} Under provisions of the Act, specific products can be exempted from such control by the Attorney General, in consultation with the Secretary of Health and Human Services, if the product is determined not to possess any significant potential for abuse because of concentration, preparation, combination, and/or delivery system. Because regulatory requirements for a given preparation containing an androgenic anabolic steroid may be subject to change based on these provisions, the manufacturer should be contacted when specific clarification about a preparation’s status is required.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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