AXIRON (testosterone) topical solution

AXIRON (testosterone) topical solution

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AXIRON (testosterone) topical solution

AXIRON (testosterone) topical solution is a clear, colorless, single phase solution containing 30 mg of testosterone in 1.5 mL of AXIRON solution for topical administration through the axilla. The active pharmacologic ingredient in AXIRON is testosterone. Testosterone USP is a white to practically white crystalline powder chemically described as 17-beta hydroxyandrost-4-en-3-one.

The inactive ingredients are ethanol, isopropyl alcohol, octisalate, and povidone.

Indications and usage

AXIRON® is 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 or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (FSH, 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 AXIRON in men with “age-related hypogonadism” have not been established.
  • Safety and efficacy of AXIRON in males <18 years old have not been established.

Mechanism of Action

Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics.

Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s Syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

Dosage and administration

Prior to initiating AXIRON, confirm the diagnosis of hypogonadism by ensuring that serum testosterone has been measured in the morning on at least two separate days and that these concentrations are below the normal range

  • Starting AXIRON dose is 60 mg of testosterone (1 pump or 1 twist actuation of 30 mg of testosterone to each axilla), applied once daily, at the same time each morning.
  • Apply to clean, dry intact skin of the axilla, not to any other parts of the body including the abdomen or genitals
  • Dose adjustment: The dose of testosterone may be decreased from 60 mg (2 pump or 2 twist actuations) to 30 mg (1 pump or 1 twist actuation) or increased from 60 mg to 90 mg (3 pump or 3 twist actuations) or from 90 mg to 120 mg (4 pump or 4 twist actuations) based on the serum testosterone concentration from a single blood draw 2 – 8 hours after applying AXIRON and at least 14 days after starting treatment or following dose adjustment.
  • Patients should wash hands immediately with soap and water after applying AXIRON and cover the application site with clothing after the solution has dried. Wash the application site thoroughly with soap and water prior to any situation where skin-to-skin contact of the application site with another person is anticipated.
  • The application site and dose of AXIRON are not interchangeable with other topical testosterone products.

Contraindications

  • Men with carcinoma of the breast or known or suspected carcinoma of the prostate (4,
  • Pregnant or breastfeeding women. Testosterone may cause fetal harm

Adverse reactions

Most common adverse reactions (incidence >4%) are skin application site reactions, increased hematocrit, headache, diarrhea, vomiting, and increased serum PSA.

Warnings and precautions

Worsening of Benign Prostatic Hyperplasia and Potential Risk of Prostate Cancer

  • Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH.
  • 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.

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.

Polycythemia: 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.

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 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.

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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.

Use in Women: Due to lack of controlled studies in women and potential virilizing effects, AXIRON is not indicated for use in women

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.

Edema: 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.

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

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

Hypercalcemia: 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.

Flammability: 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.

Drug interactions

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, insulin requirement.

Oral anticoagulants: Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of INR and prothrombin time is recommended in patients taking anticoagulants, especially at the initiation and termination of androgen therapy.

Corticosteroids: The concurrent use of testosterone with ACTH or corticosteroids may result in increased fluid retention and should be monitored cautiously, particularly in patients with cardiac, renal or hepatic disease.

Use in specific populations

Pregnancy: Pregnancy Category X— 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.

Nursing Mothers: 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

Pediatric Use: 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.

Drug abuse and dependence

Controlled Substance: AXIRON contains testosterone, a Schedule III controlled substance in the Controlled Substances Act.

Abuse

Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse by men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice.

Dependence

Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors:

  • Taking greater dosages than prescribed
  • Continued drug use despite medical and social problems due to drug use
  • Spending significant time to obtain the drug when supplies of the drug are interrupted
  • Giving a higher priority to drug use than other obligations
  • Having difficulty in discontinuing the drug despite desires and attempts to do so
  • Experiencing withdrawal symptoms upon abrupt discontinuation of use

Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism.

Overdosage

No cases of overdose with AXIRON have been reported in clinical trials. There is one report of acute overdosage by injection of testosterone enanthate: testosterone concentrations of up to 11,400 ng/dL were implicated in a cerebrovascular accident. Treatment of overdosage would consist of discontinuation of AXIRON together with appropriate symptomatic and supportive care.

Storage and Handling

Keep AXIRON out of reach of children.

Store upright at 25°C (77°F). Excursions are permitted to 15°C to 30°C (59°F to 86°F). See USP Controlled Room Temperature

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