Axiron (Testosterone)


Indications

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.

contraindications


  • 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..

adverse reactions

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.

Vascular Disorders: Venous thromboembolism.

warnings and precautions

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..

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 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

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.

5.7 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.

5.10 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.

5.11 Gynecomastia

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.

5.13 Lipids

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

5.14 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.

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.

5.16 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.

general medication guide

This Medication Guide has been approved by the U.S. Food and Drug Administration

Revised: 02/2017

Medication Guide
AXIRON® (AXE-e-RON)
(testosterone)
topical solution, for topical use CIII

What is the most important information I should know about AXIRON?
AXIRON can transfer from your body to others. This can happen if other people come into contact with the area where the AXIRON was applied.
Signs of puberty that are not expected (for example, pubic hair) have happened in young children who were accidentally exposed to testosterone through skin to skin contact with men using topical testosterone products like AXIRON.

  • Women and children should avoid contact with the unwashed or unclothed area where AXIRON has been applied. If a woman or child makes contact with the application area, the contact area on the woman or child should be washed well with soap and water right away.
  • To lower the risk of transfer of AXIRON from your body to others, you should follow these important instructions:
    • Apply AXIRON only to your armpits.
    • Wash your hands right away with soap and water after applying AXIRON.
    • After the solution has dried, cover the application area with clothing. Keep the area covered until you have washed the application area well or have showered.
  • If you expect another person to have direct skin-to-skin contact with your armpits, first wash the application area well with soap and water.
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:
  • enlarged penis or clitoris
  • early development of pubic hair
  • increased erections or sex drive
  • aggressive behavior
Signs and symptoms in women may include:
  • changes in body hair
  • a large increase in acne
What is AXIRON?
  • AXIRON is a prescription medicine that contains testosterone. AXIRON is used to treat adult males who have low or no testosterone due to certain medical conditions.
  • Your healthcare provider will test your blood before you start and while you are taking AXIRON.
  • It is not known if AXIRON is safe or effective to treat men who have low testosterone due to aging.
  • It is not known if AXIRON is safe and effective in children younger than 18 years old. Improper use of AXIRON may affect bone growth in children.
  • AXIRON is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Keep your AXIRON in a safe place to protect it. Never give AXIRON to anyone else, even if they have the same symptoms you have. Selling or giving away this medicine may harm others and it is against the law.
  • AXIRON is not meant for use in women.
Do not use AXIRON if you:
  • have breast cancer.
  • have or might have prostate cancer.
  • are pregnant or may become pregnant or are breast-feeding. AXIRON may harm your unborn or breast-feeding baby.
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:
  • have breast cancer
  • have or might have prostate cancer
  • have urinary problems due to an enlarged prostate
  • have heart problems
  • have kidney or liver problems
  • have problems breathing while you sleep (sleep apnea)
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:
  • insulin
  • medicines that decrease blood clotting
  • corticosteroids
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?
  • It is important that you apply AXIRON exactly as your healthcare provider tells you to.
  • Your healthcare provider will tell you how much AXIRON to apply and when to apply it.
  • Your healthcare provider may change your AXIRON dose. Do not change your AXIRON dose without talking to your healthcare provider.
  • AXIRON is to be applied to the armpits only. Do not apply AXIRON to any other parts of your body such as your stomach area (abdomen), penis, scrotum, shoulders or upper arms.
  • Do not apply AXIRON with your fingers or hands.
  • Apply AXIRON at about the same time each morning. AXIRON should be applied after showering or bathing.
  • Avoid swimming or bathing for at least 2 hours after you apply AXIRON.
  • You can use an antiperspirant or deodorant before applying AXIRON. If you use antiperspirant or deodorant, then it should be applied at least 2 minutes before you apply AXIRON.
  • AXIRON is flammable until dry. Let AXIRON dry before smoking or going near an open flame.
  • Avoid splashing in the eyes. In case of contact with eyes, flush thoroughly with water. If irritation persists, seek medical advice.
AXIRON
Figure 1

Applying AXIRON
  • Before using a new bottle of AXIRON for the first time, you will need to prime the pump. To prime the AXIRON pump gently push down on the pump 3 times. Do not use any AXIRON that came out while priming. Wash it down the sink to avoid accidental exposure to others. Your AXIRON pump is now ready to use.

  • Use AXIRON exactly as your healthcare provider tells you to use it. Your healthcare provider will tell you the dose of AXIRON that is right for you. Apply your dose correctly by following the application instructions in the table below.
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.

  • Before applying AXIRON, make sure that your armpit is clean, dry and that there is no broken skin.

Figure 2
  • Remove the cap and the applicator cup from the pump. Then, position the nozzle over the applicator cup and gently press down on (depress) the pump (see Figure 2).

Figure 3
  • To apply the AXIRON solution, keep the applicator upright, place it up into the armpit application site and wipe steadily down and up (see Figure 3).
  • If AXIRON drips or runs, wipe it back up with the applicator cup. Do not rub in the solution with your fingers or hand after it has been applied.

  • Let the application site dry completely before putting on a shirt.
  • After you have finished applying AXIRON, rinse the applicator cup with room temperature running water, and then pat it dry with a tissue. Carefully replace the applicator cup and cap back onto the bottle and make sure you store the bottle safely.
  • Clean up any spilled solution from surfaces such as the sink or floor to make sure others do not come into contact with it.
  • Wash your hands with soap and water right away.
What are the possible side effects of AXIRON?
  • See also “What is the most important information I should know about AXIRON?AXIRON can cause serious side effects including:
  • If you already have enlargement of your prostate gland your signs and symptoms can get worse while using AXIRON. This can include:
    • increased urination at night
    • trouble starting your urine stream
    • having to pass urine many times during the day
    • having an urge that you have to go to the bathroom right away
    • having a urine accident
    • being unable to pass urine or weak urine flow
  • Possible increased risk of prostate cancer. Your healthcare provider should check you for prostate cancer or any other prostate problems before you start and while you use AXIRON.
  • Blood clots in the legs or lungs. Signs and symptoms of a blood clot in your leg can include leg pain, swelling or redness. Signs and symptoms of a blood clot in your lungs can include difficulty breathing or chest pain.
  • Possible increased risk of heart attack or stroke.
  • In large doses AXIRON may lower your sperm count.
  • Swelling of your ankles, feet, or body.
  • Enlarged or painful breasts.
  • Problems breathing while you sleep (sleep apnea).
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:
  • skin redness or irritation where AXIRON is applied
  • increased red blood cell count
  • headache
  • diarrhea
  • vomiting
  • increase in blood level of Prostate Specific Antigen (a test used to screen for prostate cancer)
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?
  • Store AXIRON upright at room temperature between 59°F to 86°F (15°C to 30°C).
  • When it is time to throw away the bottle, safely throw away all parts of the AXIRON dispenser including the bottle applicator cup and cap.
  • Be careful to prevent accidental exposure of children or pets.
  • Keep AXIRON away from fire.
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.

AXR-0003-MG-20170203

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.

description

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.

AXIRON Package Photos

About the Author

Truman Lewis
Truman has been a bureau chief and correspondent in D.C., Los Angeles, Phoenix and elsewhere, reporting for radio, television, print and news services, for more than 30 years. Most recently, he has reported extensively on health and consumer issues for ConsumerAffairs.com and FairfaxNews.com.