"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 "...
Serious Pulmonary Oil Microembolism (POME) Reactions And Anaphylaxis
Serious POME reactions, involving cough, urge to cough, dyspnea, hyperhidrosis, throat tightening, chest pain, dizziness, and syncope, have been reported to occur during or immediately after the injection of intramuscular testosterone undecanoate 1000 mg (4 mL). The majority of these events lasted a few minutes and resolved with supportive measures; however, some lasted up to several hours and some required emergency care and/or hospitalization. To minimize the risk of intravascular injection of Aveed, care should be taken to inject the preparation deeply into the gluteal muscle, being sure to follow the recommended procedure for intramuscular administration [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS].
In addition to serious POME reactions, episodes of anaphylaxis, including life-threatening reactions, have also been reported to occur following the injection of intramuscular testosterone undecanoate.
Both serious POME reactions and anaphylaxis can occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose. Patients with suspected hypersensitivity reactions to Aveed should not be re-treated with Aveed.
Following each injection of Aveed, observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions and anaphylaxis.
Aveed Risk Evaluation And Mitigation Strategy (REMS) Program
Aveed is available only through a restricted program called the Aveed REMS Program because of the risk of serious POME and anaphylaxis.
Notable requirements of the Aveed REMS Program include the following:
- Healthcare providers who prescribe Aveed must be certified with the REMS Program before ordering or dispensing Aveed.
- Healthcare settings must be certified with the REMS Program and have healthcare providers who are certified before ordering or dispensing Aveed. Healthcare settings must have on-site access to equipment and personnel trained to manage serious POME and anaphylaxis.
Further information is available at www.AveedREMS.com or call 1-855-755-0494.
Worsening Of Benign Prostatic Hyperplasia (BPH) And Potential Risk Of Prostate Cancer
Patients with BPH treated with androgens are at an increased risk of worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms.
Increases in hematocrit, reflective of increases in red blood cell mass, may require 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.
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 Aveed. 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 Aveed and initiate appropriate workup and management.
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 Aveed.
Use In Women
Due to lack of controlled evaluations in women and potential virilizing effects, Aveed is not indicated for use in women.
Potential For Adverse Effects On Spermatogenesis
With large doses of exogenous androgens, including Aveed, 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.
Hepatic Adverse Effects
Prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate, which elevates blood levels for prolonged periods, has produced multiple hepatic adenomas. Aveed is not known to produce these adverse effects. Nonetheless, patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue Aveed while the cause is evaluated.
Androgens, including Aveed, may promote retention of sodium and water. Edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required.
Changes in serum lipid profile may require dose adjustment of lipid lowering drugs or discontinuation of testosterone therapy.
Androgens, including Aveed, 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 Aveed, may decrease concentrations of thyroxine-binding globulin, resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.
Patient Counseling Information
See FDA-Approved Medication Guide
Advise patients of the following:
Risks Of Serious Pulmonary Oil Microembolism (POME) And Anaphylaxis
- Serious pulmonary oil microembolism (POME) reactions, involving cough, urge to cough, shortness of breath, sweating, throat tightening, chest pain, dizziness, and syncope, have been reported to occur during or immediately after the injection of intramuscular testosterone undecanoate. The majority of these events lasted a few minutes and resolved with supportive measures; however, some lasted up to several hours and some required emergency care and/or hospitalization.
- Episodes of anaphylaxis, including life-threatening reactions, have also been reported to occur following the injection of intramuscular testosterone undecanoate.
- Both serious POME reactions and anaphylaxis can occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose.
- Advise the patient to read the Aveed REMS information sheet titled “What You Need to Know About AVEED® Treatment: A Patient Guide”.
- Instruct patients to remain at the healthcare setting for 30 minutes after each Aveed injection.
Men With Known Or Suspected Carcinoma Of The Prostate Or Breast
Potential Adverse Reactions To Androgens
Patients should be informed that treatment with androgens may lead to adverse reactions which include:
- Changes in urinary habits, such as increased urination at night, trouble starting the urine stream, passing urine many times during the day, having an urge to go the bathroom right away, having a urine accident, or being unable to pass urine or weak urine flow
- Breathing disturbances, including those associated with sleep or excessive daytime sleepiness
- Too frequent or persistent erections of the penis
- Nausea, vomiting, changes in skin color, or ankle swelling
Patients Should Be Advised Of The Following Instructions For Use
- Read the Medication Guide before starting Aveed therapy and reread the Guide before each injection.
- Adhere to all recommended monitoring.
- Report any changes in their state of health, such as changes in urinary habits, breathing, sleep, and mood.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats.
Mutagenic effects of testosterone undecanoate were not detected in a battery of in vitro tests including bacterial mutation assays (Ames test) and chromosomal aberration tests in human lymphocytes. Testosterone undecanoate was also negative in an in vivo bone marrow micronucleus assay in mice. Testosterone was negative in the in vitro Ames and in the in vivo mouse micronucleus assays.
Impairment of Fertility
The administration of exogenous testosterone has been reported to suppress spermatogenesis in the rat, dog and non-human primates, which was reversible on cessation of the treatment.
Use In Specific Populations
Pregnancy Category X
Aveed is contraindicated in pregnant women or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm. Exposure of a fetus to androgens, such as testosterone, may result in varying degrees of virilization. If this drug is used in pregnancy or if the patient becomes pregnant while taking this drug, the patient should be made aware of the potential hazard to the fetus.
Although it is not known how much testosterone transfers into human milk, Aveed is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants.
Safety and effectiveness of Aveed in pediatric patients less than 18 years old have not been established. Improper use may result in acceleration of bone age and premature closure of epiphyses.
There have not been sufficient numbers of geriatric patients in controlled clinical studies with Aveed to determine whether efficacy or safety in those over 65 years of age differs from younger subjects. Of the153 patients enrolled in the pivotal clinical study utilizing Aveed, 26 (17.0%) were over 65 years of age. Additionally, there are insufficient long-term safety data in geriatric patients to assess the potentially increased risk of cardiovascular disease and prostate cancer.
Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH [see WARNINGS AND PRECAUTIONS].
No studies were conducted in patients with renal impairment.
No studies were conducted in patients with hepatic impairment.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 11/7/2016
Additional Aveed Information
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