AVEED® (testosterone undecanoate) injection

AVEED® (testosterone undecanoate) injection

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AVEED® (testosterone undecanoate) injection

AVEED (testosterone undecanoate) injection contains testosterone undecanoate (17β-undecanoyloxy-4-androsten-3-one) which is an ester of the androgen, testosterone. Testosterone is formed by cleavage of the ester side chain of testosterone undecanoate.

Testosterone undecanoate is a white to off-white crystalline substance. The empirical formula of testosterone undecanoate is C30H48O3 and a molecular weight of 456.7.

Indications and usage

Aveed (testosterone undecanoate) injection is an androgen indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

  • Primary hypogonadism (congenital or acquired): testicular failure due to 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 (follicle-stimulating hormone [FSH], luteinizing hormone [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.

Aveed should only be used in patients who require testosterone replacement therapy and in whom the benefits of the product outweigh the serious risks of pulmonary oil microembolism and anaphylaxis

Limitations of Use

  • Safety and efficacy of Aveed in men with “age-related hypogonadism” have not been established
  • Safety and efficacy of Aveed in males less than 18 years old have not been established

Mechanism of Action

Endogenous androgens, including testosterone and dihydrotestosterone (DHT) are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as facial, pubic, chest, and axillary hair; laryngeal enlargement; vocal cord thickening; and alterations in body musculature and fat distribution.

Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has 2 main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

Dosage and administration

  • Prior to initiating Aveed, 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
  • For intramuscular use only
  • Three (3) mL (750 mg) is to be injected intramuscularly at initiation, at 4 weeks, and every 10 weeks thereafter
  • 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 or anaphylaxis
  • Inject Aveed deeply into the gluteal muscle following the usual precautions for intramuscular administration of oily solutions

Contraindications

  • Men with carcinoma of the breast or known or suspected carcinoma of the prostate
  • Women who are pregnant. Testosterone may cause fetal harm
  • Known hypersensitivity to Aveed or its ingredients (testosterone undecanoate, refined castor oil, benzyl benzoate)

Warnings and precautions

  • 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.
  • Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH
  • Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients using testosterone products. Evaluate patients with signs or symptoms consistent with DVT or PE.
  • Some postmarketing studies have shown an increased risk of myocardial infarction and stroke associated with use of testosterone replacement therapy
  • Exogenous administration of androgens may lead to azoospermia
  • Edema with or without congestive heart failure may be a complication in patients with preexisting cardiac, renal, or hepatic disease
  • Sleep apnea may occur in those with risk factors
  • Monitor prostatic specific antigen (PSA), hemoglobin, hematocrit, and lipid concentrations periodically

Adverse reactions

The most commonly reported adverse reactions (≥2%) are acne, injection site pain, prostatic specific antigen (PSA) increased, estradiol increased, hypogonadism, fatigue, irritability, hemoglobin increased, insomnia, and mood swings

Drug interaction

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, may necessitate a decrease in the dose of anti-diabetic medication.

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Oral Anticoagulants: Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking warfarin, especially at the initiation and termination of androgen therapy.

Corticosteroids: The concurrent use of testosterone with corticosteroids may result in increased fluid retention and requires careful monitoring, particularly in patients with cardiac, renal or hepatic disease.

Use in specific populations

Pregnancy: AVEED is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm based on data from animal studies and its mechanism of action. Exposure of a female fetus to androgens may result in varying degrees of virilization.

Lactation: AVEED is not indicated for use in females.

Infertility: During treatment with large doses of exogenous androgens, including AVEED, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis, possibly leading to adverse effects on semen parameters including sperm count. Reduced fertility is observed in some men taking testosterone replacement therapy. Testicular atrophy, subfertility, and infertility have also been reported in men who abuse anabolic androgenic steroids. With either type of use, the impact on fertility may be irreversible.

Pediatric Use: 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.

Drug abuse and dependence

Controlled Substance: AVEED contains testosterone, a Schedule III controlled substance in the Controlled Substances Act.

Abuse

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 of 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 adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility.

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.

Dependence

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.

Overdosage

There have been no reports of overdosage in the AVEED clinical trials. There is 1 report of acute overdosage with use of an approved injectable testosterone product: this subject had serum testosterone levels of up to 11,400 ng/dL with a cerebrovascular accident.

Treatment of overdosage would consist of discontinuation of AVEED together with appropriate symptomatic and supportive care.

Storage and handling

Store at controlled room temperature 25°C (77°F); excursions permitted to 15°C – 30°C (59°F – 86°F) [See USP controlled room temperature] in its original carton until the date indicated. Before use, each vial should be visually inspected.

Only vials free from particles should be used.

Single Use Vial. Discard unused portion.

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