General Information

Aveed (testosterone undecanoate) injection is an ester of the androgen testosterone. 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.

Aveed is specifically indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone:

• primary hypogonadism (congenital or acquired)
• hypogonadotropic hypogonadism (congenital or acquired).

Aveed is supplied as a solution for intramuscular administration. The recommended dose of Aveed is 3 mL (750 mg) injected intramuscularly, followed by 3 mL (750 mg) injected after four weeks, then 3 mL (750 mg) injected every 10 weeks thereafter. Aveed should be injected deeply into the gluteal muscle.

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).

Side Effects

Adverse events associated with the use of Aveed may include, but are not limited to, the following:

• Acne
• Injection site pain
• Prostatic specific antigen increased
• Estradiol increased
• Hypogonadism
• Fatigue
• Irritability
• Hemoglobin increased
• Insomnia
• Mood swings

The Aveed drug label comes with the following Black Box Warning: Serious Pulmonary Oil Microembolism (POME) reactions, involving urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope; and episodes of anaphylaxis, including life-threatening reactions, have been reported to occur during or immediately after the administration of testosterone undecanoate injection.  These reactions can occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose. 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. Because of the risks of serious POME reactions and anaphylaxis, Aveed is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Aveed REMS Program.

Clinical Trial Results

The FDA approval of Aveed was based on an 84-week, single-arm, open-label, multicenter study of 130 hypogonadal men.  Eligible patients weighed at least 65 kg, were 18 years of age and older (mean age 54.2 years), and had a morning serum total testosterone concentration <300 ng/dL (mean screening testosterone concentration 215 ng/dL).  All patients received injections of Aveed 750 mg at baseline, at 4 weeks, and then every 10 weeks thereafter. The primary endpoint was the percentage of patients with average serum total testosterone concentration (Cavg) within the normal range (300-1000 ng/dL) after the third injection, at steady state. The secondary endpoint was the percentage of patients with maximum total testosterone concentration (Cmax) above 3 pre-determined limits: greater than 1500 ng/dL, between 1800 and 2499 ng/dL, and greater than 2500 ng/dL.

A total of 117 out of 130 hypogonadal men completed study procedures through Week 24 and were included in the evaluation of testosterone pharmacokinetics after the third Aveed injection. Ninety-four percent (94%) of patients maintained a Cavg within the normal range (300 to 1000 ng/dL).  The percentages of patients with Cavg below the normal range (less than 300 ng/dL) and above the normal range (greater than 1000 ng/dL) were 5.1% and 0.9%, respectively.