"The US Food and Drug Administration (FDA) has approved class-wide labeling changes for all prescription testosterone products, the agency announced today.
New safety information from published literature and case reports on the risks "...
Worsening Of Benign Prostatic Hyperplasia And Potential Risk Of Prostate Cancer
Patients treated with Androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating treatment. It would be appropriate to reevaluate patients 3 to 6 months after initiation of treatment, and then in accordance with prostate cancer screening practices. [See CONTRAINDICATIONS].
Potential For Secondary Exposure To Testosterone
Cases of secondary exposure to testosterone in children and women have been reported with topical testosterone products applied to the abdomen or upper arms, including cases of secondary exposure resulting in virilization of children. 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. 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 AXIRON [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 should also be brought to the attention of a physician. Testosterone therapy should be promptly discontinued at least until the cause of virilization has been identified. [See DOSAGE AND ADMINISTRATION].
Increases in hematocrit, reflective of increases in red blood cell mass, may require lowering or discontinuation of testosterone. Check hematocrit prior to initiating testosterone treatment. It would be appropriate to re-evaluate the hematocrit 3 to 6 months after starting testosterone treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable level. 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 AXIRON. 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 AXIRON and initiate appropriate workup and management [see ADVERSE REACTIONS].
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 AXIRON.
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 lack of controlled studies in women and potential virilizing effects, AXIRON is not indicated for use in women [see CONTRAINDICATIONS and Use in Specific Populations].
Potential For Adverse Effects On Spermatogenesis
At large doses of exogenous androgens, including AXIRON, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle-stimulating hormone (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 (methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatitis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatitis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. AXIRON is not known to cause these adverse effects.
Reference ID: 4003434 6 Androgens, including AXIRON, 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].
Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy.
Androgens, including AXIRON, 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 AXIRON, may decrease concentrations of thyroxin-binding globulins, resulting in decreased total T4 serum concentration and increased resin uptake of T3 and T4. Free thyroid hormone concentration remain unchanged, however there is no clinical evidence of thyroid dysfunction.
Alcohol based products, including AXIRON, are flammable; therefore, patients should be advised to avoid smoking, fire or flame until the AXIRON dose applied has dried.
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
Potential For Secondary Exposure To Testosterone And Steps To Prevent Secondary Exposure
Cases of secondary exposure to testosterone in children and women have been reported with topical testosterone products applied to the abdomen, shoulders or upper arms, including cases of secondary exposure resulting in virilization of children, with signs and symptoms including enlargement of the penis or clitoris, premature development of pubic hair, increased erections, aggressive behavior and advanced bone age. Inappropriate changes in genital size or premature development of pubic hair or libido in children, or changes in hair distribution, increase in acne, or other signs of testosterone effects in adult women should be brought to the attention of a physician and the possibility of secondary exposure to AXIRON also should be brought to the attention of a physician. AXIRON should be promptly discontinued at least until the cause of virilization is identified.
Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from AXIRON treated skin:
- AXIRON should only be applied to the axilla, not to any other part of the body.
- Children and women should avoid contact with the unwashed skin of the axilla or unclothed application sites of men where AXIRON has been applied.
- Patients should wash their hands immediately with soap and water after application of AXIRON.
- Patients should cover the axilla application site(s) with clothing (e.g., a shirt) after waiting 3 minutes for the solution to dry.
- Prior to any situation in which direct skin-to-skin contact of the axilla is anticipated, patients should wash the axilla to which AXIRON has been applied thoroughly with soap and water to remove any testosterone residue.
- In the event that unwashed or unclothed skin to which AXIRON 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. [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 urine accident, being unable to pass urine and having a 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 These Application Instructions
- The pump should be primed by depressing it 3 times prior to its first use. No priming is needed with subsequent uses of that pump.
- AXIRON should NOT be applied to the scrotum, penis, abdomen, shoulders or upper arms.
- With testosterone doses greater than 60 mg, which require two applications of AXIRON to the same axilla, the product should be allowed to dry after the first application before the second is applied.
- AXIRON should be applied once daily at approximately the same time each day. AXIRON should be applied to clean, dry skin.
- Patients may use an antiperspirant or deodorant spray before applying AXIRON. If patients use a stick or roll-on antiperspirant or deodorant, then it should be applied prior to application of AXIRON to avoid contamination of the stick or roll-on product.
- Avoid swimming or washing the application site until two hours following application of AXIRON [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].
- Avoid splashing in the eyes. In case of contact with eyes, flush thoroughly with water. If irritation persists, seek medical advice.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors, which 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] - AXIRON 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 apprised of the potential hazard to a fetus.
Although it is not known how much testosterone transfers into human milk, AXIRON 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].
Safety and efficacy of AXIRON has not been established in males < 18 years of age. 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 AXIRON to determine whether efficacy in those over 65 years of age differs from younger patients. Of the 155 patients enrolled in the pivotal clinical study utilizing AXIRON, 21 were over 65 years of age. Additionally, there were insufficient long-term safety data in these patients utilizing AXIRON to assess a potential incremental risk of cardiovascular disease and prostate cancer.
No formal studies were conducted involving patients with renal impairment.
No formal studies were conducted involving patients with hepatic impairment.
Use In Men With Body Mass Index (BMI) > 35 kg/m²
Safety and efficacy of AXIRON in males with BMI > 35 kg/m² has not been established.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 2/6/2017
Additional Axiron Information
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