Fortesta - Product Information
|Manufacture:||Endo Pharmaceuticals Inc.|
|Class:||Androgens and anabolic steroids|
|Form:||Cream, gel, liniment or balm, lotion, ointment, etc|
|Ingredients:||testosterone, propylene glycol, purified water, ethanol, 2-propanol, oleic acid, carbomer 1382, triethanolamine, butylated hydroxytoluene.|
Indications and Usage
FORTESTA is an androgen indicated for replacement therapy in 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, heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH)) above the normal range.
- Hypogonadotropic hypogonadism (congenital or acquired) – idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low serum testosterone concentrations but have gonadotropins in the normal or low range.
Important limitations of use: — Safety and efficacy of FORTESTA in males <18 years old have not been established [see Use in Specific Populations].
Dosage and Administration
Dosing and Dose Adjustment
The recommended starting dose of FORTESTA is 40 mg of testosterone (4 pump actuations) applied once daily to the thighs in the morning. The dose can be adjusted between a minimum of 10 mg of testosterone and a maximum of 70 mg of testosterone. To ensure proper dosing, the dose should be titrated based on the serum testosterone concentration from a single blood draw 2 hours after applying FORTESTA and at approximately 14 days and 35 days after starting treatment or following dose adjustment. In addition, serum testosterone concentration should be assessed periodically thereafter. Table 1 describes the dose adjustments required at each titration step.
|Total Serum Testosterone Concentration 2 hours Post FORTESTA Application||Dose Titration|
|Equal to or greater than 2,500 ng/dL
Equal to or greater than 1,250 and less than 2,500 ng/dL
|Decrease daily dose by 20 mg (2 pump actuations)
Decrease daily dose by 10 mg (1 pump actuation)
|Equal to or greater than 500 and less than 1,250 ng/dL||No change: continue on current dose|
|Less than 500 ng/dL||Increase daily dose by 10 mg (1 pump actuation)|
The application site and dose of FORTESTA are not interchangeable with other topical testosterone products.
FORTESTA should be applied directly to clean, dry, intact skin of the front and inner thighs. Do not apply FORTESTA to the genitals or other parts of the body. Patients should be instructed to use one finger to gently rub FORTESTA evenly onto the front and inner area of each thigh as directed in Table 2.
|Total Dose of
|Pump Actuations per Thigh|
|Thigh #1||Thigh #2|
Once the application site is dry, the site should be covered with clothing [see Clinical Pharmacology]. Wash hands thoroughly with soap and water. Avoid applying the gel to the thigh adjacent to the scrotum. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including FORTESTA, are flammable.
The patient should avoid swimming or showering or washing the administration site for a minimum of 2 hours after application [see Clinical Pharmacology].
To obtain a full first dose, it is necessary to prime the canister pump. To do so, with the canister in the upright position, slowly and fully depress the actuator eight times. The first three actuations may result in no discharge of gel. Safely discard the gel from the first eight actuations. It is only necessary to prime the pump before the first dose.
Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from FORTESTA-treated skin:
- Children and women should avoid contact with unwashed or unclothed application site(s) of men using FORTESTA.
- FORTESTA should only be applied to the front and inner thighs (area of application should be limited to the area that will be covered by the patient’s shorts or pants).
- Patients should wash their hands immediately with soap and water after applying FORTESTA.
- Patients should cover the application site(s) with clothing (e.g., shorts of sufficient length or pants) after the gel has dried.
- Prior to any situation in which skin-to-skin contact with the application site is anticipated, patients should wash the application site(s) thoroughly with soap and water to remove any testosterone residue.
- In the event that unwashed or unclothed skin to which FORTESTA has been applied comes in direct 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.
Dosage Forms and Strengths
FORTESTA (testosterone) Gel for topical use only, is supplied in a metered-dose pump. One pump actuation delivers 10 mg of testosterone.
- FORTESTA is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions , Adverse Reactions].
- FORTESTA is contraindicated in women who are or may become pregnant, or who are breastfeeding. FORTESTA may cause fetal harm when administered to a pregnant woman. FORTESTA may cause serious adverse reactions in nursing infants. Exposure of a female fetus or nursing infant to androgens may result in varying degrees of virilization. Pregnant women or those who may become pregnant need to be aware of the potential for transfer of testosterone from men treated with FORTESTA. If a pregnant woman is exposed to FORTESTA, she should be apprised of the potential hazard to the fetus [see Use in Specific Populations].
Warnings and Precautions
Warning: Secondary Exposure to Testosterone
- Virilization has been reported in children who were secondarily exposed to testosterone gel [see Warnings and Precautions and Adverse Reactions].
- Children should avoid contact with unwashed or unclothed application sites in men using FORTESTA [see Dosage and Administration and Warnings and Precautions].
- Healthcare providers should advise patients to strictly adhere to recommended instructions for use [see Dosage and Administration, Warnings and Precautions and Patient Counseling Information].
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.
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, for hypogonadism.
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 thyroid dysfunction.
Alcohol based products, including FORTESTA, are flammable; therefore, patients should be advised to avoid smoking, fire or flame until the FORTESTA gel has dried.
Clinical 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 clinical practice.
In a controlled multicenter, open label, non-comparative 90-day clinical study, 149 hypogonadal patients were treated with FORTESTA [see Clinical Studies]. Adverse reactions occurred in 22.8% (34/149) of patients. The most common adverse reaction reported in this study was skin reactions associated with the site of application (16.1%; 24/149) of which 79% (19/24) were mild, and the remainder were moderate (21%; 5/24) Table 3.
|Adverse Reaction||Number (%) of Patients
N = 149
|Skin reaction||24 (16.1%)|
|Prostatic specific antigen increased||2 (1.3%)|
|Abnormal dreams||2 (1.3%)|
During the 90 day trial 5 patients (3.4%) discontinued treatment because of adverse reactions. These reactions were: 1 patient with contact dermatitis (considered probably related to FORTESTA application), 1 with application site reaction (considered probably related to FORTESTA application), 1 with gastrointestinal hypomotility (considered possibly related to FORTESTA application), 1 with severe dyspnea (considered not related to FORTESTA application), and 1 with moderate contusion (considered not related to FORTESTA application).
The following adverse reactions have been identified during post approval use of FORTESTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure Table 4.
|System Organ Class||Adverse Reaction|
|Blood and lymphatic system disorders||Polycythemia|
|Eye disorders||Vitreous detachment|
|Gastrointestinal disorders||Abdominal symptoms|
|General disorders and administrative site conditions||Application site erythema, irritation, pruritus, and swelling; fatigue, influenza like illness, and malaise.|
|Investigations||Decreased serum testosterone, increased hematocrit and hemoglobin|
|Musculoskeletal and connective tissue disorders||Pain in extremity|
|Nervous system disorders||Dizziness, headache, and migraine|
|Reproductive system and breast disorders||Erectile dysfunction, and priapism|
|Skin and subcutaneous tissue disorders||Allergic dermatitis, erythema, rash, and papular rash.|
Secondary Exposure to Testosterone in Children
Cases of secondary exposure to testosterone resulting in virilization of children have been reported in postmarketing surveillance of testosterone gel products. Signs and symptoms of these reported cases have included enlargement of the clitoris (with surgical intervention) or the penis, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases with a reported outcome, these signs and symptoms were reported to have regressed with removal of the testosterone gel exposure. 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. In some of the cases, direct contact with the sites of application on the skin of men using testosterone gel was reported. In at least one reported case, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user’s shirts and/or other fabric, such as towels and sheets [see Warnings and Precautions].
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.
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.
The concurrent administration 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.
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 BPH.
No studies were conducted in patients with renal impairment.
No studies were conducted in patients with hepatic impairment.
Drug Abuse and Dependence
FORTESTA contains testosterone, a Schedule III controlled substance as defined under the Anabolics Steroid Control Act.
Anabolic steroids, such as testosterone, are abused. Abuse is often associated with adverse physical and psychological effects.
Although drug dependence is not documented in individuals using therapeutic doses of anabolic steroids for approved indications, dependence is observed in some individuals abusing high doses of anabolic steroids. In general, anabolic steroid dependence is characterized by any three of the following:
- Taking more drug than intended
- Continued drug use despite medical and social problems
- Significant time spent in obtaining adequate amounts of drug
- Desire for anabolic steroids when supplies of the drugs are interrupted
- Difficulty in discontinuing use of the drug despite desires and attempts to do so
- Experience of a withdrawal syndrome upon discontinuation of anabolic steroid use.
There is a single report of acute overdosage after parenteral administration of an approved testosterone product in the literature. This subject had serum testosterone concentrations of up to 11,400 ng/dL, which were implicated in a cerebrovascular accident. There were no reports of overdose in the FORTESTA clinical trial.
Treatment of overdosage would consist of discontinuation of FORTESTA, washing the application site with soap and water, and appropriate symptomatic and supportive care.
How Supplied/Storage and Handling
FORTESTA is supplied in 60 g canisters with a metered dose pump that delivers10 mg of testosterone per complete pump actuation. The metered dose pump is capable of dispensing 120 metered pump actuations. One pump actuation dispenses 0.5 g of gel.
FORTESTA is available in packages of 1, 2 and 3 canisters (NDC 63481-183-16, NDC 63481-183-17 and NDC 63481-183-18, respectively).
Store at controlled room temperature 20-25oC (68-77oF); excursions permitted to 15o-30oC (59o-86oF). [See USP]. Do Not Freeze.
Used FORTESTA canisters should be discarded in household trash in a manner that prevents accidental application or ingestion by children or pets.
Patient Counseling Information
See FDA-approved Medication Guide.
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 Precaution].
Potential for Secondary Exposure to Testosterone and Steps to Prevent Secondary Exposure
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 healthcare provider.
- 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:
- 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 skin-to-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 mood.
- FORTESTA is prescribed to meet the patient’s specific needs, therefore, the patient should never share FORTESTA with anyone.
Manufactured by: Pharbil Waltrop GmbH, Im Wirrigen 25, 45731 Waltrop, Germany
Manufactured for: Endo Pharmaceuticals Inc., 100 Endo Boulevard, Chadds Ford, PA 19317