Testosterone Cream is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone.

INDICATIONS AND USAGE OF TESTOSTERONE CREAM

  • 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 Cream in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.
  • Safety and efficacy of Testosterone Cream in males less than 18 years old have not been established.
  • Topical testosterone products may have different doses, strengths, or application instructions that may result in different systemic exposure.

Administration Instructions of Testosterone Cream for testosterone replacement therapy

Testosterone Cream should be applied to clean, dry, intact skin of the upper arms and shoulders. Do not apply Testosterone Cream to any other parts of the body, including the abdomen, genitals, chest, armpits (axillae), or knees. Area of application should be limited to the area that will be covered by the patient’s short sleeve t-shirt. Patients should be instructed to use the palm of the hand to apply Testosterone Cream and spread across the maximum surface area as directed (for pump)

The prescribed daily dose of should be applied to the right and left upper arms and shoulders as shown in the shaded areas.testosterone cream

Once the application site is dry, the site should be covered with clothing. Wash hands thoroughly with soap and water. Avoid fire, flames or smoking until the gel has dried since alcohol based products, including Testosterone Cream, are flammable.

The patient should avoid swimming or showering or washing the administration site for a minimum of 2 hours after application.

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 three times. Safely discard the gel from the first three actuations. It is only necessary to prime the pump before the first dose.

After the priming procedure, fully depress the actuator once for every 20.25 mg of Testosterone Cream. Testosterone Cream should be delivered directly into the palm of the hand and then applied to the application sites.

Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from Testosterone Cream-treated skin:

  • Children and women should avoid contact with unwashed or unclothed application site(s) of men using Testosterone Cream.
  • Testosterone Cream should only be applied to the upper arms and shoulders. The area of application should be limited to the area that will be covered by a short sleeve t-shirt.
  • Patients should wash their hands with soap and water immediately after applying Testosterone Cream.
  • Patients should cover the application site(s) with clothing (e.g., a t-shirt) after the gel has dried.
  • Prior to situations in which direct skin-to-skin contact 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 Testosterone Cream 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.

CONTRAINDICATIONS of Testosterone Cream for testosterone replacement therapy

  • Testosterone Cream for testosterone replacement therapy is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate.
  • Testosterone Cream is contraindicated in women who are or may become pregnant, or who are breastfeeding. Testosterone Cream may cause fetal harm when administered to a pregnant woman. Testosterone Cream may cause serious adverse reactions in nursing infants. Exposure of a 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 Testosterone Cream. If a pregnant woman is exposed to Testosterone Cream, she should be apprised of the potential hazard to the fetus.

WARNINGS AND PRECAUTIONS

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. Evaluation of patients for prostate cancer prior to initiating and during treatment with androgens is appropriate.

5.2 Potential for Secondary Exposure to Testosterone cream

Cases of secondary exposure resulting in virilization of children have been reported in postmarketing surveillance of testosterone cream 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 Testosterone Cream for testosterone replacement therapy.

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.

5.3 Polycythemia

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.

5.4 Venous Thromboembolism

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 Testosterone Cream. 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 Cream and initiate appropriate workup and management.

5.5 Cardiovascular Risk

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 the 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 Testosterone Cream.

5.6 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.

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.

5.7Testosterone Cream Use for testosterone replacement therapy in Women

Due to the lack of controlled evaluations in women and potential virilizing effects, Testosterone Cream is not indicated for use in women.

5.8 Potential for Adverse Effects on Spermatogenesis

With large doses of exogenous androgens, including Testosterone Cream, spermatogenesis may be suppressed through feedback inhibition of pituitary FSH possibly leading to adverse effects on semen parameters including sperm count.

5.9 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 intramuscular testosterone enanthate has produced multiple hepatic adenomas. Testosterone Cream is not known to cause these adverse effects.

5.10 Edema

Androgens, including Testosterone Cream, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease.

5.11 Gynecomastia

Gynecomastia may develop and persist in patients being treated with androgens, including Testosterone Cream, for hypogonadism.

5.12 Sleep Apnea

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.

5.13 Lipids

Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy.

5.14 Hypercalcemia

Androgens, including AndroGel 1.62 %, 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.

5.15 Decreased Thyroxine-binding Globulin

Androgens, including Testosterone Cream, 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.

5.16 Flammability

Alcohol-based products, including Testosterone Cream, are flammable; therefore, patients should be advised to avoid fire, flame or smoking until the Testosterone Cream has dried.

DRUG INTERACTIONS with Testosterone Cream for testosterone replacement therapy

7.1 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 decrease insulin requirements.

7.2 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 anticoagulants, especially at the initiation and termination of androgen therapy.

7.3 Corticosteroids

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.

DESCRIPTION of Testosterone Cream for testosterone replacement therapy

Testosterone Cream for testosterone replacement therapy use is a clear, colorless gel containing testosterone. Testosterone is an androgen. Testosterone Cream is available in a metered-dose pump or unit dose packets.

The active pharmacologic ingredient in Testosterone Cream is testosterone. Testosterone USP is a white to almost white powder chemically described as 17-beta hydroxyandrost-4-en-3-one.

Patients should be informed of the following:

17.1 Use in Men with Known or Suspected Prostate or Breast Cancer

Men with known or suspected prostate or breast cancer should not use Testosterone Cream.

17.2 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 have been reported in children.

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 testosterone gel should be brought to the attention of a healthcare provider.
  • Testosterone Cream for testosterone replacement therapy 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 Testosterone Cream in men

  • Children and women should avoid contact with unwashed or unclothed application site(s) of men using Testosterone Cream.
  • Patients using Testosterone Cream should apply the product as directed and strictly adhere to the following:
    • Wash hands with soap and water immediately 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 Testosterone Cream 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.

17.3 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 the urine stream, passing urine many times during the day, having an urge 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.
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