Included as part of the "PRECAUTIONS" Section
Worsening Of Benign Prostatic Hyperplasia (BPH) And Potential Risk Of Prostate Cancer
- Patients with BPH treated with androgens are at an increased risk of 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. Evaluation of the
patients for the presence of prostate cancer prior to initiating and during treatment with androgens is
appropriate [see CONTRAINDICATIONS].
Potential For Secondary Exposure To Testosterone
Cases of secondary exposure resulting in virilization of children have been reported in postmarketing
surveillance of testosterone gel products. 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 FORTESTA [see DOSAGE AND ADMINISTRATION, Use In Specific Populations and CLINICAL PHARMACOLOGY].
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.
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.
There have been Postmarketing reports of venous thromboembolic events, including deep vein
thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as
FORTESTA. 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 FORTESTA and initiate appropriate
workup and management.
Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of
testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled
trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE),
such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of
testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE
in association with use of testosterone replacement therapy in men. Patients should be informed of this
possible risk when deciding whether to use or to continue to use FORTESTA.
Abuse 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].
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.
Use In Women
Due to the lack of controlled evaluations in women and potential virilizing effects, FORTESTA is not
indicated for use in women [see CONTRAINDICATIONS and Use In Specific Populations].
Potential For Adverse Effects On Spermatogenesis
With large doses of exogenous androgens, including FORTESTA, spermatogenesis may be suppressed
through feedback inhibition of pituitary FSH which could possibly lead to adverse effects on semen
parameters including sperm count.
Hepatic Adverse Effects
Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g. methyltestosterone) has
been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic
hepatitis and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term
therapy with testosterone enanthate has produced multiple hepatic adenomas. FORTESTA is not known
to cause these adverse effects.
Androgens, including FORTESTA, may promote retention of sodium and water. Edema, with or without
congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal, or
hepatic disease [see ADVERSE REACTIONS].
Gynecomastia may develop and persist in patients being treated with androgens, including FORTESTA,
The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients,
especially those with risk factors such as obesity or chronic lung diseases.
Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy.
Androgens, including FORTESTA, should be used with caution in cancer patients at risk of
hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is
recommended in these patients.
Decreased Thyroxine-Binding Globulin
Androgens, including FORTESTA, may decrease concentrations of thyroxin-binding globulins,
resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free
thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of
Alcohol based products, including FORTESTA, are flammable; therefore, patients should be advised to
avoid smoking, fire or flame until the FORTESTA gel has dried.
Patient Counseling Information
See FDA-approved PATIENT INFORMATION.
Patients should be informed of the following information:
Use In Men With Known Or Suspected Prostate Or Breast Cancer
Men with known or suspected prostate or breast cancer should not use FORTESTA [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].
Potential For Secondary Exposure To Testosterone And Steps To Prevent Secondary
Secondary exposure to testosterone in children and women can occur with the use of testosterone gel in
men. Cases of secondary exposure to testosterone in children have been reported.
Physicians should advise patients of the reported signs and symptoms of secondary exposure which may
include the following:
- In children; unexpected sexual development including inappropriate enlargement of the penis or
clitoris, premature development of pubic hair, increased erections, and aggressive behavior.
- In women; changes in hair distribution, increase in acne, or other signs of testosterone effects.
- The possibility of secondary exposure to FORTESTA should be brought to the attention of a
- FORTESTA should be promptly discontinued until the cause of virilization is identified.
Strict adherence to the following precautions is advised to minimize the potential for secondary
exposure to testosterone from FORTESTA in men [see PATIENT INFORMATION]:
- Children and women should avoid contact with unwashed or unclothed application site(s) of men using FORTESTA.
- Patients using FORTESTA should apply the product as directed and strictly adhere to the following:
- Wash hands with soap and water after application.
- Cover the application site(s) with clothing after the gel has dried.
- Wash the application site(s ) thoroughly with soap and water prior to any situation where skinto-
skin contact of the application site with another person is anticipated.
- In the event that unwashed or unclothed skin to which FORTESTA has been applied comes in
contact with the skin of another person, the general area of contact on the other person should be
washed with soap and water as soon as possible [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
Potential Adverse Reactions With Androgens
Patients should be informed that treatment with androgens may lead to adverse reactions which include:
- Changes in urinary habits such as increased urination at night, trouble starting your urine stream,
passing urine many times during the day, having an urge that you have to go to the bathroom right
away, having a urine accident, being unable to pass urine and weak urine flow.
- Breathing disturbances, including those associated with sleep, or excessive daytime sleepiness.
- Too frequent or persistent erections of the penis.
- Nausea, vomiting, changes in skin color, or ankle swelling.
Patients Should Be Advised Of The Following Instructions For Use
- Read the Medication Guide before starting FORTESTA therapy and reread it each time the
prescription is renewed.
- FORTESTA should be applied and used appropriately to maximize the benefits and to
minimize the risk of secondary exposure in children and women.
- Keep FORTESTA out of the reach of children.
- FORTESTA is an alcohol based product and is flammable; therefore avoid fire, flame or
smoking until the gel has dried.
- It is important to adhere to all recommended monitoring.
- Report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and
- FORTESTA is prescribed to meet the patient’s specific needs, therefore, the patient should never
share FORTESTA with anyone.
- Wait 2 hours before swimming or washing following application of FORTESTA. This will ensure
that the greatest amount of FORTESTA is absorbed into their system.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice,
implant induced cervical-uterine tumors metastasized in some cases. There is suggestive evidence that
injection of testosterone into some strains of female mice increases their susceptibility to hepatoma.
Testosterone is also known to increase the number of tumors and decrease the degree of differentiation
of chemically induced carcinomas of the liver in rats. Testosterone was negative in the in vitro Ames
and in the in vivo mouse micronucleus assays. The administration of exogenous testosterone has been
reported to suppress spermatogenesis in the rat, dog and non-human primates, which was reversible on
cessation of the treatment.
Use In Specific Populations
Pregnancy Category X [see CONTRAINDICATIONS]. – FORTESTA is contraindicated during pregnancy or
in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure
of a female fetus to androgens may result in varying degrees of virilization. If this drug is used during
pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be made aware
of the potential hazard to the fetus.
Although it is not known how much testosterone transfers into human milk, FORTESTA is
contraindicated in nursing women because of the potential for serious adverse reactions in nursing
infants. Testosterone and other androgens may adversely affect lactation [see CONTRAINDICATIONS].
The safety and efficacy of FORTESTA in pediatric patients <18 years old has not been established.
Improper use may result in acceleration of bone age and premature closure of epiphyses.
There have not been sufficient numbers of geriatric patients involved in controlled clinical studies
utilizing FORTESTA to determine whether efficacy in those over 65 years of age differs from
younger subjects. Of the 149 patients enrolled in the pivotal clinical study utilizing FORTESTA, 20
were over 65 years of age. Additionally, there are insufficient long-term safety data in geriatric patients
to assess the potential risks of cardiovascular disease and prostate cancer.
Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of
No studies were conducted in patients with renal impairment.
No studies were conducted in patients with hepatic impairment.