Vogelxo Drug Information

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 practice. In a controlled clinical study, 304 patients were treated with testosterone gel 50 mg or 100 mg or placebo gel for up to 90 days. Two hundred-five patients received testosterone gel 50 mg or 100 mg daily and 99 patients received placebo.

Subjects could be counted in both testosterone gel treatment groups if they received both 50 mg and 100 mg at different points in the study and experienced an adverse reaction at both dose levels. Adverse reactions reported by ≥1% of the testosterone gel patients and greater than placebo are listed in Table 3. Table 3: Incidence of Adverse Reactions (Reported by ≥1% of the Testosterone Gel Patients and Greater than Placebo) in the Controlled Clinical Trial Through 90 Days Testosterone Gel 50 mg Testosterone Gel 100 mg Placebo Event (n=103) (n=149) (n=99) Application Site Reactions 2% 4% 3% Blood Pressure Increased 1% 1% 0% Gynecomastia 1% 0% 0% Headache 1% 1% 0% Hematocrit/Hemoglobin Increased 1% 2% 0% Hot Flushes 1% 0% 0% Insomnia 1% 0% 0% Mood Swings 1% 0% 0% Smell Disorder 1% 0% 0% Spontaneous Penile Erection 1% 0% 0% Taste Disorder 1% 1% 0% The following adverse reactions occurred in fewer than 1% of patients but were greater in testosterone gel groups compared to the placebo group: activated partial thromboplastin time prolonged, blood creatinine increased, prothrombin time prolonged, appetite increased, sensitive nipples, and acne. In this clinical trial of testosterone gel, six patients had adverse events that led to their discontinuation.

These events included: depression with suicidal ideation, urinary tract infection, mood swings and hypertension. No testosterone gel patients discontinued due to skin reaction. In one foreign Phase 3 trial, one subject discontinued due to a skin-related adverse event.

In the pivotal U.S. and European Phase 3 trials combined, at the 50 mg dosage strength, the percentage of subjects reporting clinically notable increases in hematocrit or hemoglobin were similar to placebo. However, in the 100 mg dose group, 2.3% and 2.8% of patients had a clinically notable increase in hemoglobin (≥ 19 g/dL) or hematocrit (≥ 58%), respectively, compared to 1.0% and 1.5% of patients in the placebo group, respectively. In the combined U.S. and European open label extension studies, approximately 140 patients received testosterone gel for at least 6 months.

The results from these studies are consistent with those reported for the U.S. controlled clinical trial.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of testosterone gel products. Because the 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. 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 of 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 fabrics, such as towels and sheets . Cardiovascular Disorders: Myocardial infarction, stroke Vascular Disorders: Venous thromboembolism.

Insulin 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 necessitate a decrease in the dose of anti-diabetic medication.

Oral 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 warfarin, especially at the initiation and termination of androgen therapy.

Corticosteroids

The concurrent use of testosterone with corticosteroids may result in increased fluid retention and requires careful monitoring particularly in patients with cardiac, renal or hepatic disease.

Pregnancy Risk Summary Vogelxo 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 . 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 or decreased 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.

Pediatric Use The safety and efficacy of Vogelxo in pediatric patients less than 18 years old have not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.

Vogelxo is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate . Vogelxo is contraindicated in women who are pregnant. Vogelxo can cause virilization of the female fetus when administered to a pregnant woman. Pregnant women need to be aware of the potential for skin transfer of testosterone from men treated with Vogelxo.

If a pregnant woman is exposed to Vogelxo, she should be apprised of the potential hazard to the fetus. Men with known carcinoma of the breast or known or suspected carcinoma of the prostate. Women who are pregnant.

Testosterone may cause fetal harm.

There were no reports of overdose in the testosterone gel clinical trials. There is a single report in the literature of acute overdosage after injection of testosterone enanthate. This subject had serum testosterone concentrations of up to 11,400 ng/dL, which were implicated in a cerebrovascular accident.

Treatment of overdosage would consist of discontinuation of Vogelxo, washing the application site with soap and water, and appropriate symptomatic and supportive care.