New FDA approval: oral testosterone

In March 2019 FDA approved the first oral testosterone supplementation for male patients with documented central (primary) or peripheral (secondary) hypogonadism. The medication is given twice a day orally. The recommended starting dose is about 250 mg every 12 hours. The minimum dose is about 150 mg BID with a maximum dose of 400 mg BID.

Follow up blood work needs to be done at least 7 days after initiation and 6 hours after the morning dose. Side effects may include elevated blood pressure, increased red blood cell mass, prostate enlargement, and GI upset. The approval comes with a black box warning for increased risk of hypertension and cardiovascular events.

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FDA APPROVAL 

DRUG THERAPY

March 2019

General Information

Jatenzo (testosterone undecanoate) is an endogenous androgen. It is specifically indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone. Jatenzo is supplied as a capsule for oral administration. 

Prior to initiating Jatenzo, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these concentrations are below the normal range. Take Jatenzo with food.

The starting dose is 237 mg orally BID, once in the morning and once in the evening. Adjust the dose to a minimum of 158 mg twice daily and a maximum of 396 mg twice daily based on serum testosterone drawn 6 hours after the morning dose at least 7 days after starting treatment or following dose adjustment and periodically thereafter. 

Clinical Results:

The FDA approval of Jatenzo was based on an open label study in 166 adult hypogonadal males of approximately 4 months duration. The study included a Screening Phase, a Treatment Titration Phase, and a Treatment Maintenance Phase.

Jatenzo was taken orally at a starting dose of 237 mg twice per day with meals. The dose was adjusted on Days 21 and 56 between a minimum of 158 mg twice per day and a maximum of 396 mg twice per day on the basis of the average testosterone concentration obtained over 24 hours post-morning dose.

  • Primary endpoint was the percentage of patients with mean plasma total testosterone concentration (Cavg) over 24-hours within the normal eugonadal range on the final PK visit of the study.

  • Secondary endpoints were the percentage of patients with a maximum total testosterone (TT concentration (Cmax) above three predetermined limits:

    • <1500 ng/dL

    • 1800-2500 ng/dL

    • >2500 ng/dL.

145 (87%) of the 166 hypogonadal men who received jatenzo had a mean total testosterone (TT) concentration (Cavg) within the normal eugonadal range at the end of treatment.

The percentage of patients who received Jatenzo and had Cmax <1500 ng/dL, 1800 -2500 ng/dL, and >2500 ng/dL at the final PK visit were 83%, 3%, and 3%, respectively.

Side Effects

  • Polycythemia

  • Hypertension

  • Peripheral edema

  • Prostate Enlargement

  • Headache

  • GI upset

    • Diarrhea

    • Dyspepsia

    • Eructation

    • Nausea

 

Black Box Warning:

  • Jatenzo can cause blood pressure (BP) increases that can increase the risk of major adverse cardiovascular events (MACE), including non-fatal MI, non-fatal stroke and CVD death.

  • Before initiating Jatenzo, consider the patient’s baseline cardiovascular risk and ensure blood pressure is adequately controlled. Periodically monitor for and treat new-onset hypertension or exacerbations of pre-existing hypertension and re-evaluate whether the benefits of Jatenzo outweigh its risks in patients who develop cardiovascular risk factors or cardiovascular disease on treatment.

  • Due to this risk, use Jatenzo only for the treatment of men with hypogonadal conditions associated with structural or genetic etiologies.

 

Mechanism of Action

Jatenzo (testosterone undecanoate) is an endogenous androgen. 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, alterations in body musculature and fat distribution.

Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has two main etiologies.

  • Primary hypogonadism is caused by defects of the gonads, such as Klinefelter syndrome or Leydig cell aplasia, whereas

  • Secondary hypogonadism (also known as hypogonadotropic hypogonadism) is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

 
Oral Testosterone