Data from FDA - Curated by EPG Health - Last updated 12 March 2018

Indication(s)

1 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” (also referred to as “late-onset hypogonadism”) have not been established. Safety and efficacy of AXIRON in males <18 years old have not been established [see Use in Specific Populations (8.4)]. AXIRON® is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired) (1) Hypogonadotropic hypogonadism (congenital or acquired) (1) Limitations of use: Safety and efficacy of AXIRON in men with “age-related hypogonadism” have not been established. (1) Safety and efficacy of AXIRON in males <18 years old have not been established. (8.4)

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Advisory information

contraindications
4 CONTRAINDICATIONS AXIRON is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precaution (5.1)]. AXIRON is contraindicated in women who are, or who may become pregnant, or who are breastfeeding. AXIRON may cause fetal harm when administered to a pregnant woman. AXIRON may cause serious adverse reactions in nursing infants. If a pregnant woman is exposed to AXIRON, she should be apprised of the potential hazard to the fetus. [See Use in Specific Populations (8.1, 8.3)]. Men with carcinoma of the breast or known or suspected carcinoma of the prostate (4, 5.1) Pregnant or breastfeeding women. Testosterone may cause fetal harm (4, 8.1, 8.3)
Adverse reactions
6 ADVERSE REACTIONS Most common adverse reactions (incidence >4%) are skin application site reactions, increased hematocrit, headache, diarrhea, vomiting, and increased serum PSA (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. Clinical Trials in Hypogonadal Men Table 2 shows the treatment emergent adverse reactions that were reported by either >4% of 155 patients in a 120 day, Phase 3 study or by >4% of 71 patients who continued to use AXIRON for up to 180 days. These data reflect the experience primarily with a testosterone dose of 60 mg, which was taken by all patients at the start of the study, and was the maintenance dose for 97 patients. However, the doses used varied from 30 mg to 120 mg. Table 2: Adverse Reactions Seen With the Use of AXIRON in either the 120 Day Clinical Trial or in the Extension to 180 Days (>4%) Event 120 Days (155 Patients) 180 Days (71 Patients) Application Site Irritation 11 (7%) 6 (8%) Application Site Erythema 8 (5%) 5 (7%) Headache 8 (5%) 4 (6%) Hematocrit Increased 6 (4%) 5 (7%) Diarrhea 4 (3%) 3 (4%) Vomiting 4 (3%) 3 (4%) PSA Increased 2 (1%) 3 (4%) Other less common adverse reactions reported by at least 2 patients in the 120 day trial included: application site edema, application site warmth, increased hemoglobin, hypertension, erythema (general), increased blood glucose, acne, nasopharyngitis, anger and anxiety. Other less common adverse reactions reported in fewer than 1% of patients in the 120 day trial included: asthenia, affect lability, folliculitis, increased lacrimation, breast tenderness, increased blood pressure, increased blood testosterone, neoplasm prostate and elevated red blood cell count. During the 120 day trial one patient discontinued treatment because of affect lability/anger which was considered possibly related to AXIRON administration. During the 120 day clinical trial there was an increase in mean PSA values of 0.13 ± 0.68 ng/mL from baseline. At the end of the 180 day extension clinical trial, there was an overall increase in mean PSA values of 0.1 ± 0.54 ng/mL. Following the 120 day study, seventy-one (71) patients entered a two-month extension study with AXIRON. Two patients (3%) had adverse reactions that led to discontinuation of treatment during the period from Day 120 to Day 180. These reactions were: one patient with application site irritation (considered possibly related to AXIRON application) and one patient with dry skin and erythema, but not at the application site (considered not related to AXIRON administration) and application site erythema (considered possibly related to AXIRON administration). No serious adverse reactions to AXIRON were reported during either the 120 day trial, or the extension to 180 days. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of AXIRON. 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. Cardiovascular Disorders: myocardial infarction, stroke [see Warnings and Precautions (5.5)]. Vascular Disorders: Venous thromboembolism [see Warnings and Precautions (5.4)].

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Prior to initiating AXIRON, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range. 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 (2). 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. (2.1) Apply to clean, dry intact skin of the axilla, not to any other parts of the body including the abdomen or genitals (2.2) 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. (2.2) 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. (2.2) The application site and dose of AXIRON are not interchangeable with other topical testosterone products. (2.1) 2.1 Dosing and Dose Adjustment The recommended starting dose of AXIRON (testosterone) topical solution is 60 mg of testosterone (2 pump or 2 twist actuations) applied once daily. To ensure proper dosing, serum testosterone concentrations should be measured after initiation of therapy to ensure that the desired concentrations (300 ng/dL-1050 ng/dL) are achieved. The AXIRON dose can be adjusted 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. If the measured serum testosterone concentration is below 300 ng/dL, the daily testosterone dose may be increased from 60 mg (2 pump or 2 twist actuations) to 90 mg (3 pump or 3 twist actuations) or from 90 mg to 120 mg (4 pump or 4 twist actuations). If the serum testosterone concentration exceeds 1050 ng/dL, the daily testosterone dose should be decreased from 60 mg (2 pump or 2 twist actuations) to 30 mg (1 pump or 1 twist actuation) as instructed by a physician. If the serum testosterone concentration consistently exceeds 1050 ng/dL at the lowest daily dose of 30 mg (1 pump or 1 twist actuation), AXIRON therapy should be discontinued. The application site and dose of AXIRON are not interchangeable with other topical testosterone products. 2.2 Administration Instructions AXIRON is applied to the axilla, preferably at the same time each morning, to clean, dry, intact skin. Do not apply AXIRON to other parts of the body including to the scrotum, penis, abdomen, shoulders or upper arms. After applying the solution, the application site should be allowed to dry completely prior to dressing. Avoid fire, flames or smoking until the solution has dried since alcohol based products, including AXIRON, are flammable. When deodorants or antiperspirants are used as part of a regular program for personal hygiene, they should not interfere with the efficacy of AXIRON in treating hypogonadism. If patients use an antiperspirant or deodorant (stick or roll-on) then it should be applied at least 2 minutes prior to the application of AXIRON to avoid contamination of the stick or roll-on product. Patients should be advised to avoid swimming or washing the application site until two hours following application of AXIRON [see Clinical Pharmacology (12.3)]. To reduce the likelihood of interpersonal transfer of testosterone, the application site should always be washed prior to any skin-to-skin contact regardless of the length of time since application. [See Warnings and Precautions (5.2)]. AXIRON is available in two presentations (i.e., pump actuated or twist actuated metered-dose pump). Pump Actuated Metered-Dose Pump AXIRON is applied to the axilla using an applicator. When using AXIRON for the first time, patients should be instructed to prime the pump by depressing the pump three times, discard any product dispensed directly into a basin, sink, or toilet and then wash the liquid away thoroughly. This priming should be done only prior to the first use of each pump. After priming, patients should completely depress the pump one time (1 pump actuation) to dispense 30 mg of testosterone. Ensure that the liquid is directed into the cup. The cup should be filled with no more than 30 mg (1 pump actuation) of testosterone. Dosing that requires greater than one pump actuation must be applied in increments of 30 mg as is shown in Table 1. Keeping the applicator upright, patients should place it up into the axilla and wipe steadily down and up into the axilla. If the solution drips or runs, it can be wiped back up with the applicator cup. The solution should not be rubbed into the skin with fingers or hand. The process is then repeated with application of 30 mg of testosterone (1 pump actuation) to the other axilla to achieve a total of 60 mg of testosterone applied. For patients prescribed the 90 mg dose of testosterone, the procedure is the same, but three applications are required. To dose 120 mg of testosterone, four applications are required alternating left and right for each application as shown in Table 1. When repeat application to the same axilla is required, the axilla should be allowed to dry completely before more AXIRON is applied. After use, the applicator should be rinsed under room temperature, running water and then patted dry with a tissue. The applicator and cap are then replaced on the bottle for storage. Twist Actuated Metered-Dose Pump AXIRON is applied to the axilla using an applicator. When using AXIRON for the first time, patients should be instructed to prime the pump by twisting the dose dial and discarding any product dispensed directly into a basin, sink, or toilet, and then washing the liquid away thoroughly. This should be repeated two additional times. This priming should be done only prior to the first use of each bottle. After priming, patients should completely twist (180° turn) the dose dial one time (1 twist actuation) to dispense 30 mg of testosterone. The applicator should be filled with no more than 30 mg (1 twist actuation) of testosterone. Dosing that requires greater than one twist actuation must be applied in increments of 30 mg as is shown in Table 1. Keeping the applicator upright, patients should place it up into the axilla and wipe steadily down and up into the axilla. If the solution drips or runs, it can be wiped back up with the applicator. The solution should not be rubbed into the skin with fingers or hand. The process is then repeated with application of 30 mg of testosterone (1 twist actuation) to the other axilla to achieve a total of 60 mg of testosterone applied. For patients prescribed the 90 mg dose of testosterone, the procedure is the same, but three applications are required. To dose 120 mg of testosterone, four applications are required alternating left and right for each application as shown in Table 1. When repeat application to the same axilla is required, the axilla should be allowed to dry completely before more AXIRON is applied. After use, the applicator should be wiped with a disposable tissue. The lid is then replaced on the bottle for storage. Table 1: Application Technique Daily Prescribed Dose of Testosterone Number of Twist Actuations Number of Pump Actuations Application 30 mg (once daily) 1 1 Apply once to one axilla only (left OR right) 60 mg (once daily) 2 2 Apply once to the left axilla and then apply once to the right axilla. 90 mg (once daily) 3 3 Apply once to the left and once to the right axilla, wait for the product to dry, and then apply once again to the left OR right axilla. 120 mg (once daily) 4 4 Apply once to the left and once to the right axilla, wait for the product to dry, and then apply once again to the left AND once to the right axilla. Hands should be washed thoroughly with soap and water after AXIRON has been applied [see Warnings and Precautions (5.2)]. Strict adherence to the following precautions is advised in order to minimize the potential for secondary exposure to testosterone from AXIRON treated skin: Children and women should avoid contact with the unclothed or unwashed application sites on the skin of men using AXIRON. Patients should wash their hands immediately with soap and water after application of AXIRON. Patients should cover the application site(s) with clothing (e.g., a T-shirt) after the solution has dried. Prior to any situation in which direct skin-to-skin contact is anticipated, patients should wash the application site 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. While interpersonal testosterone transfer can occur with a T-shirt on, it has been shown that transfer can be substantially reduced by wearing a T-shirt and the majority of residual testosterone is removed from the skin surface by washing with soap and water.
Use in special populations
8 USE IN SPECIFIC POPULATIONS There are insufficient long-term safety data in geriatric patients using AXIRON to assess the potential risks of cardiovascular disease and prostate cancer (8.5). 8.1 Pregnancy Pregnancy Category X [see Contraindications (4)] — 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. 8.3 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. [See Contraindications (4)]. 8.4 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. 8.5 Geriatric Use 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. 8.6 Renal Impairment No formal studies were conducted involving patients with renal impairment. 8.7 Hepatic Impairment No formal studies were conducted involving patients with hepatic impairment. 8.8 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.
Pregnancy and lactation
8.3 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. [See Contraindications (4)].

Interactions

7 DRUG INTERACTIONS Androgens may decrease blood glucose and insulin requirement in diabetic patients (7.1). Changes in anticoagulant activity may be seen with androgens. More frequent monitoring of International Normalized Ratio (INR) and prothrombin time is recommended (7.2). Use of testosterone with Adrenocorticotropic Hormone (ACTH) or corticosteroids may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease (7.3). 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, insulin requirement. 7.2 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. 7.3 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.

More information

Category Value
Authorisation number NDA022504
Agency product number 3XMK78S47O
Orphan designation No
Product NDC 0002-1975,0002-1977
Date Last Revised 04-01-2018
Type HUMAN PRESCRIPTION DRUG
Storage and handling 16.2 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. Used AXIRON bottles and applicators should be discarded in household trash in a manner that prevents accidental exposure of children or pets.
Marketing authorisation holder Eli Lilly and Company
Warnings WARNING: SECONDARY EXPOSURE TO TESTOSTERONE • Virilization has been reported in children who were secondarily exposed to topical testosterone products [see Warnings and Precautions (5.2)]. • Children should avoid contact with unwashed or unclothed application sites in men using AXIRON [see Dosage and Administration (2.2) and Warnings and Precautions (5.2)]. • Healthcare providers should advise patients to strictly adhere to recommended instructions for use [see Dosage and Administration (2.2), Warnings and Precautions (5.2) and Patient Counseling Information (17)]. WARNING: SECONDARY EXPOSURE TO TESTOSTERONE See full prescribing information for complete boxed warning. Virilization has been reported in children who were secondarily exposed to topical testosterone products (5.2) Children should avoid contact with unwashed or unclothed application sites in men using AXIRON (2.2, 5.2) Healthcare providers should advise patients to strictly adhere to recommended instructions for use (2.2, 5.2, 17)