"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 "...
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%)
|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.
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.
Vascular Disorders: Venous thromboembolism [see WARNINGS AND PRECAUTIONS].
Read the Axiron (testosterone topical solution) Side Effects Center for a complete guide to possible side effects
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.
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.
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.
Drug Abuse And Dependence
AXIRON contains testosterone, a Schedule III controlled substance in the Controlled Substances Act.
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.
Abuse-Related Adverse Reactions
Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression.
The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities.
The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty.
Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Behaviors Associated With Addiction
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.
Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.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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