Alcohol based products, including FORTESTA, are flammable; therefore, patients should be advised to avoid smoking, fire, or flame until the FORTESTA gel has dried.
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 (14.1)]. 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 PatientsN = 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|
|Vascular disorders||Venous thromboembolism|
|Cardiovascular disorders||Myocardial infarction and stroke|
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 1 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 (5.2)].
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.
FORTESTA is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm 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.
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 anogenital 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.
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