|Labeler Name||Eli Lilly and Company|
|Dosage & Substance||solution testosterone|
|Date First Marketed||November 23, 2010|
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.
- AXIRON is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate.
- 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..
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.
|Event||120 Days |
|180 Days |
|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.
Vascular Disorders: Venous thromboembolism.
5.1 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..
5.2 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.
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..
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.
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 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.
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 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.
5.6 Abuse of Testosterone and Monitoring of Serum Testosterone Concentrations
5.7 Use in Women
Due to lack of controlled studies in women and potential virilizing effects, AXIRON is not indicated for use in women.
5.8 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.
5.9 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.
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 may develop and may persist in patients being treated with androgens, including AXIRON, 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 and chronic lung disease.
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.
5.15 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.
This Medication Guide has been approved by the U.S. Food and Drug Administration
|Medication Guide |
topical solution, for topical use CIII
What is the most important information I should know about AXIRON?
|Stop using AXIRON and call your healthcare provider right away if you see any signs and symptoms in a child or a woman that may have occurred through accidental exposure to AXIRON: |
Signs and symptoms in children may include:
|Signs and symptoms in women may include: |
|What is AXIRON? |
|Do not use AXIRON if you: |
|Women who are pregnant or who may become pregnant should avoid contact with the area of the skin where AXIRON has been applied. |
Talk to your healthcare provider before taking this medicine if you have any of the above conditions.
|Before you use AXIRON, tell your healthcare provider about all of your medical conditions, including if you: |
|Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. |
Using AXIRON with other medicines can affect each other.
Especially tell your healthcare provider if you take:
|Know the medicines you take. Ask your healthcare provider or pharmacist for a list of all of your medicines if you are not sure. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.|
|How should I use AXIRON? |
| AXIRON |
|Find Your Dose as Prescribed by Your Healthcare Provider||Each application equals 1 press (depression) of the pump. |
|30 mg||Apply 1 application one time, to one armpit only (left or right).|
|60 mg||Apply 2 applications: one to the left armpit and then one to the right armpit.|
|90 mg||Apply 3 applications: one to the left and one to the right armpit, wait for the product to dry, and then apply again one to the left or right armpit.|
|120 mg||Apply 4 applications: one to the left and one to the right armpit, wait for the product to dry, and then apply again one to the left and one to the right armpit.|
|What are the possible side effects of AXIRON? |
|Call your healthcare provider right away if you have any of the serious side effects listed above. |
The most common side effects of AXIRON include:
|Other side effects include more erections than are normal for you or erections that last a long time. |
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of AXIRON.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
|How should I store AXIRON? |
|Keep AXIRON and all medicines out of the reach of children.|
|General information about the safe and effective use of AXIRON. |
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use AXIRON for a condition for which it was not prescribed. Do not give AXIRON to other people, even if they have the same symptoms you have. It may harm them.
You can ask your pharmacist or healthcare provider for information about AXIRON that is written for health professionals.
|What are the ingredients in AXIRON? |
Active ingredient: testosterone.
Inactive ingredients: ethanol, isopropyl alcohol, octisalate, and povidone.
The bottle and the applicator cup are not made with natural rubber latex.
Marketed by: Lilly USA, LLC Indianapolis, IN 46285, USA
For more information, go to www.axiron.com or call 1-800-545-5979.
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.
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 structural formula is:
The inactive ingredients are ethanol, isopropyl alcohol, octisalate, and povidone.