Testosterone gel 1% is indicated for replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range.
Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations, but have gonadotropins in the normal or low range. Limitations of use: Safety and efficacy of testosterone gel 1% in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.
Safety and efficacy of testosterone gel 1% in males less than 18 years old have not been established [see Use in Specific Populations ( 8.4 )] . Topical testosterone products may have different doses, strengths or application instructions that may result in different systemic exposure ( 1 , 12.3 ). Testosterone gel 1% is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired).
( 1 ) Hypogonadotropic hypogonadism (congenital or acquired). ( 1 ) Limitations of use: Safety and efficacy of testosterone gel 1% in men with “age-related hypogonadism” have not been established. ( 1 ) Safety and efficacy of testosterone gel 1% in males less than 18 years old have not been established. ( 8.4 ) Topical testosterone products may have different doses, strengths or application instructions that may result in different systemic exposure.
( 1 , 12.3 )
Contraindications
Testosterone gel 1% is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions ( 5.4 ), Adverse Reactions ( 6.1 ), and Nonclinical Toxicology ( 13.1 )] . Testosterone gel 1% is contraindicated in women who are pregnant. Testosterone gel 1% can cause virilization of the female fetus when administered to a pregnant woman. Pregnant women need to be aware of the potential for transfer of testosterone from men treated with testosterone gel 1%.
If a pregnant woman is exposed to testosterone gel 1%, she should be apprised of the potential hazard to the fetus [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )] . Men with carcinoma of the breast or known or suspected prostate cancer. ( 4 , 5.4 ) Women who are pregnant. Testosterone may cause fetal harm. ( 4 , 8.1 )
Warnings and precautions
Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer: Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH. ( 5.4 ) Potential for Secondary Exposure to Testosterone: Avoid unintentional exposure of women or children to testosterone gel 1%. Secondary exposure to testosterone can produce signs of virilization. Testosterone gel 1% should be discontinued until the cause of virilization is identified.
( 5.1 ) Venous Thromboembolism (VTE): VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients using testosterone products. Evaluate patients with signs or symptoms consistent with DVT or PE. ( 5.3 ) Blood Pressure Increases: Testosterone gel 1% can increase blood pressure, which can increase cardiovascular risk over time. Measure blood pressure periodically. Not recommended for use in men with uncontrolled hypertension ( 5.5 ) Potential for Adverse Effects on Spermatogenesis: Exogenous administration of androgens may lead to azoospermia.
( 5.8 ) Edema: Edema, with or without congestive heart failure (CHF), may be a complication in patients with preexisting cardiac, renal, or hepatic disease. ( 5.10 , 6.2 ) Sleep apnea: Sleep apnea may occur in those with risk factors. ( 5.12 ) Monitor serum testosterone, prostate specific antigen (PSA), hemoglobin, hematocrit, liver function tests, and lipid concentrations periodically. ( 5.4 , 5.2 , 5.9 , 5.13 ) Flammability: Testosterone gel 1% is flammable until dry.
( 5.16 )
5.1Potential for Secondary Exposure to Testosterone Cases
of secondary exposure resulting in virilization of children have been reported in postmarketing surveillance. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with removal of the exposure to testosterone gel. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age.
The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of the topical testosterone product. Children and women should avoid contact with unwashed or unclothed application sites in men using testosterone gel 1% [see Dosage and Administration ( 2.2 ), Use in Specific Populations (8.1) and Clinical Pharmacology (12.3)] . Inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone gel should also be brought to the attention of a physician.
Testosterone gel should be promptly discontinued until the cause of virilization has been identified.
5.2Polycythemia Increases
in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating treatment. It would also be appropriate to re-evaluate the hematocrit 3 to 6 months after starting treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable concentration. An increase in red blood cell mass may increase the risk of thromboembolic events.
5.3Venous Thromboembolism
There have been postmarketing reports of venous thromboembolic events (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products such as testosterone gel 1%. In the Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) Study, a randomized, double-blind, placebo-controlled, cardiovascular (CV) outcomes study, compared to placebo, testosterone gel 1% was associated with a numerically higher incidence of VTE (1.7% vs 1.2%) which included DVT (0.6% vs 0.5%) and PE events (0.9% vs 0.5%) [see Adverse Reactions ( 6.1 )] .
Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with testosterone gel 1% and initiate appropriate workup and management [see Adverse Reactions ( 6.2 )] .
5.4 Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens [see Contraindications ( 4 ), Adverse Reactions ( 6.1 ) and Nonclinical Toxicology ( 13.1 )] .
5.5Blood Pressure Increases
Testosterone gel 1% can increase blood pressure. In an ambulatory blood pressure monitoring (ABPM) study, testosterone gel 1% increased the mean systolic/diastolic blood pressure by 1.9/1.3 mm Hg from baseline after 16 weeks of treatment. In patients with hypertension on antihypertensive therapy, testosterone gel 1% increased the mean systolic/diastolic BP by 3.0/2.2 mm Hg from baseline. Blood pressure increases can increase cardiovascular (CV) risk over time.
The CV risk associated with testosterone gel 1% was evaluated in TRAVERSE, a randomized, double-blind, placebo-controlled, CV outcomes study in men with a history of CV disease or multiple CV risk factors. In TRAVERSE, mean systolic blood pressure in the group treated with testosterone gel 1% was increased by 1.0 mm Hg from baseline to 36 months, whereas a mean decrease from baseline of 0.5 mm Hg was observed in the placebo group at this timepoint, for a mean between-group difference of 1.5 mm Hg.
However, the incidences of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction [MI] and non-fatal stroke, were similar between treatment groups (7% for testosterone gel 1% vs 7.3% for placebo) [See Adverse Reactions ( 6.1 )]. Monitor blood pressure periodically in men using testosterone gel 1%, especially men with hypertension. Testosterone gel 1% is not recommended for use in patients with uncontrolled hypertension.
5.6Abuse of Testosterone and Monitoring of Serum Testosterone Concentrations
Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see Drug Abuse and Dependence ( 9 )]. If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range.
However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.
5.7 Not for use in Women Due to lack of controlled evaluations in women and potential virilizing effects, testosterone gel 1% is not indicated for use in women [see Contraindications ( 4 ) and Use in Specific Populations ( 8.1 , 8. 2 )] . 5. 8 Potential for Adve rse Effects on Spermatogenesis With large doses of exogenous androgens, including testosterone gel 1%, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (FSH) which could possibly lea
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Interactions
7 DRU G INTERACTIONS Androgens may decrease blood glucose and therefore may decrease insulin requirements in diabetic patients. ( 7.1 ) Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of INR and prothrombin time is recommended. ( 7.2 ) Use of testosterone with adrenocorticotrophic hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease.
( 7.3 )
7.1Insulin Changes
in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease insulin requirements.
7.2Oral Anticoagulants Changes
in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking anticoagulants, especially at the initiation and termination of androgen therapy.
7.3Corticosteroids
The concurrent use of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may result in increased fluid retention and requires careful monitoring particularly in patients with cardiac, renal or hepatic disease.
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
Testosterone gel 1% is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action [see Contraindications (4) and Clinical Pharmacology ( 12.1 )] . Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring.
These studies did not meet current standards for nonclinical development toxicity studies. Data Animal Data In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring.
Structural impairments observed in females included increased ano-genital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes.
Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant female rats and their offspring exposed to doses approximately twice those used for testosterone replacement therapy.
Adverse reactions
6 AD VERSE REACTIONS Most common adverse reactions (incidence ≥ 5%) are acne, application site reaction, abnormal lab tests, and prostatic disorders. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Cli nical Trials in Hypogonadal Men Table 2 shows the incidence of all adverse events judged by the investigator to be at least possibly related to treatment with testosterone gel 1% and reported by > 1% of patients in a 180 Day, Phase 3 study.
Table 2: Adverse Events Possibly, Probably or Definitely Related to Use of Testosterone Gel 1% in the 180-Day Controlled Clinical Trial Dose of Testosterone Gel 1% Adverse Event 50 mg 75 mg 100 mg N = 77 N = 40 N = 78 Acne 1% 3% 8% Alopecia 1% 0% 1% Application Site Reaction 5% 3% 4% Asthenia 0% 3% 1% Depression 1% 0% 1% Emotional Lability 0% 3% 3% Gynecomastia 1% 0% 3% Headache 4% 3% 0% Hypertension 3% 0% 3% Lab Test Abnormal* 6% 5% 3% Libido Decreased 0% 3% 1% Nervousness 0% 3% 1% Pain Breast 1% 3% 1% Prostate Disorder** 3% 3% 5% Testis Disorder*** 3% 0% 0% * Lab test abnormal occurred in nine patients with one or more of the following events reported: elevated hemoglobin or hematocrit, hyperlipidemia, elevated triglycerides, hypokalemia, decreased HDL, elevated glucose, elevated creatinine, elevated total bilirubin. ** Prostate disorders included five patients with enlarged prostate, one with BPH, and one with elevated PSA results. *** Testis disorders were reported in two patients: one with left varicocele and one with slight sensitivity of left testis.
Other less common adverse reactions, reported in fewer than 1% of patients included: amnesia, anxiety, discolored hair, dizziness, dry skin, hirsutism, hostility, impaired urination, paresthesia, penis disorder, peripheral edema, sweating, and vasodilation. In this 180-day clinical trial, skin reactions at the site of application were reported with testosterone gel 1%, but none was severe enough to require treatment or discontinuation of drug.
Six patients (4%) in this trial had adverse events that led to discontinuation of testosterone gel 1%. These events included: cerebral hemorrhage, convulsion (neither of which were considered related to testosterone gel 1% administration), depression, sadness, memory loss, elevated prostate specific antigen, and hypertension. No testosterone gel 1% patient discontinued due to skin reactions. In a separate uncontrolled pharmacokinetic study of 10 patients, two had adverse events associated with testosterone gel 1%; these were asthenia and depression in one patient and increased libido and hyperkinesia in the other.
In a 3-year, flexible dose, extension study, the incidence of all adverse events judged by the investigator to be at least possibly related to treatment with testosterone gel 1% and reported by > 1% of patients is shown in Table 3. Table 3: Adverse Events Possibly, Probably or Definitely Related to Use of Testosterone Gel 1% in the 3 Year, Flexible Dose, Extension Study Percent of Subjects Adverse Event (N = 162) Lab Test Abnormal+
9.3 Skin dry
1.9 Application Site Reaction
5.6 Acne
3.1 Pruritus
1.9 Enlarged Prostate
11.7 Carcinoma of Prostate
1.2 Urinary Symptoms*
3.7 Testis Disorder**
1.9 Gynecomastia
2.5Anemia
2.5 + Lab test abnormal occurred in 15 patients with one or more of the following events reported: elevated AST, elevated ALT, elevated testosterone, elevated hemoglobin or hematocrit, elevated cholesterol, elevated cholesterol/LDL ratio, elevated triglycerides, elevated HDL, elevated serum creatinine. * Urinary symptoms included nocturia, urinary hesitancy, urinary incontinence, urinary retention, urinary urgency and weak urinary stream. ** Testis disorders included three patients.
There were two with a non-palpable testis and one with slight right testicular tenderness. Two patients reported serious adverse events considered possibly related to treatment: deep vein thrombosis (DVT) and prostate disorder requiring a transurethral resection of the prostate (TURP). Discontinuation for adverse events in this study included: two patients with application site reactions, one with kidney failure, and five with prostate disorders (including increase in serum PSA in 4 patients, and increase in PSA with prostate enlargement in a fifth patient).
Increases in Serum PSA Observed in Clinical Trials of Hypogonadal Men During the initial 6-month study, the mean change in PSA values had a statistically significant increase of 0.26 ng/mL. Serum PSA was measured every 6 months thereafter in the 162 hypogonadal men on testosterone gel 1% in the 3-year extension study. There was no additional statistically significant increase observed in mean PSA from 6 months through 36 months.
However, there were increases in serum PSA observed in approximately 18% of individual patients. The overall mean change from baseline in serum PSA values for the entire group from month 6 to 36 was 0.11 ng/mL. Twenty-nine patients (18%) met the per-protocol criterion for increase in serum PSA, defined as > 2X the baseline or any single serum PSA > 6 ng/mL. Most of these (25/29) met this criterion by at least doubling of their PSA from baseline.
In most cases where PSA at least doubled (22/25), the maximum serum PSA value was still < 2 ng/mL. The first occurrence of a pre-specified, post-baseline increase in serum PSA was seen at or prior to Month 12 in most of the patients who met this criterion (23 of 29; 79%). Four patients met this criterion by having a serum PSA > 6 ng/mL and in these, maximum serum PSA values were 6.2 ng/mL, 6.6 ng/mL, 6.7 ng/mL, and 10.7 ng/mL.
In two of these patients, prostate cancer was detected on biopsy. The first patient’s PSA levels were 4.7 ng/mL and 6.2 ng/mL at baseline and at Month 6/Final, respectively. The second patient’s PSA levels were 4.2 ng/mL, 5.2 ng/mL, 5.8 ng/mL, and 6.6 ng/mL at baseline, Month 6, Month 12, and Final, respectively. Blood Pressure Increases In a 4-month clinical study, 24-hour ambulatory blood pressure monitoring (ABPM) was conducted on 246 patients.
ABPM was conducted at baseline and at Week 16 of testosterone gel 1% therapy. A total of 169 patients had acceptable ABPM recordings at both baseline and Week 16 and also were at least 85% compliant with study drug. In that group, the mean change in 24-hour systolic blood pressure (BP) and diastolic BP from baseline to end-of-treatment at Week 16 (n=169) was 1.9 mm Hg (95% CI 0.6, 3.1) and 1.3 mm Hg (95% CI 0.5, 2.1), respectively.
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Composition
Active ingredients
TESTOSTERONE 50MG/5GM PACKET
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
At a glance
Brand name
Testosterone
Drug class
3-oxoandrosten (4) derivatives, Androgens and estrogens
In patients with a history of hypertension who were being treated with antihypertensive therapy, the mean ABPM systolic and diastolic BP increased by 3.0 mm Hg [95% CI 0.8, 5.2] and 2.2 mm Hg [95% CI 0.8, 3.5], respectively [n=72]). In patients with no history of hypertension at baseline, the mean systolic and diastolic blood pressure increased by 1.2 mm Hg [95% CI -0.2, 2.7] and 0.9 mm Hg [95% CI -0.1, 1.8], respectively [n=91]).
Four patients (2.8%) on testosterone gel 1%, all of whom were receiving antihypertensive medications at baseline, either started new antihypertensive medications (n=2) or had their antihypertensive regimen adjusted during the ABPM study. Of the 246 patients who used testosterone gel 1% during the study, 10 patients (4.1%) were reported to have either an adverse reaction of hypertension (5 patients, 2.0%) or increased blood pressure (5 patients, 2.0%).
Cardiovascular Outcomes TRAVERSE was a randomized, double-blind, cardiovascular outcomes study to assess the CV safety of testosterone gel 1% compared to placebo in 5198 hypogonadal men aged 45 to 80 years with a history of CV disease or with multiple CV risk factors. Th
