Xyosted
(Testosterone Enanthate)Xyosted Prescribing Information
XYOSTED (testosterone enanthate) 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.
- Safety and efficacy of XYOSTED in men with “age-related hypogonadism” has not been established.
- Safety and efficacy of XYOSTED in males less than 18 years old have not been established [see Use in Specific Populations (.)]
8.4 Pediatric UseSafety and effectiveness of XYOSTED 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.
XYOSTED injection is available as 0.5 mL of a sterile, preservative-free and nonpyrogenic, clear, colorless to yellow solution containing testosterone enanthate. It is supplied in a single-dose syringe assembled in an autoinjector for subcutaneous administration. XYOSTED is available in three dosage strengths:
50 mg/0.5 mL
75 mg/0.5 mL
100 mg/0.5 mL
XYOSTED is contraindicated in:
- Men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions (.)]
5.4 Blood Pressure IncreasesXYOSTED can increase blood pressure. Ambulatory blood pressure monitoring (ABPM) demonstrated XYOSTED increased systolic/diastolic BP by an average of 3.9/1.5 mm Hg from baseline after 12 weeks of treatment in clinical trials
[see Adverse Reactions ].In patients with hypertension on antihypertensive therapy, XYOSTED increased the mean systolic/diastolic BP by 3.9/1.3 mm Hg from baseline.The CV risk associated with topical testosterone gel was evaluated in TRAVERSE, a randomized, double-blind, placebo-controlled, CV outcomes study in men with a history of CV disease or multiple CV risk factors. In TRAVERSE, topical testosterone gel increased mean systolic blood pressure by 1.0 mm Hg from baseline to 36 months, whereas a mean decrease from baseline of 0.5 mm Hg was observed in the placebo group at this timepoint, for a mean between-group difference of 1.5 mm Hg. However, the incidences of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction [MI] and non-fatal stroke, were similar between treatment groups (7% for topical testosterone gel vs 7.3% for placebo)
[See Adverse Reactions ].Monitor blood pressure periodically in men using XYOSTED, especially men with hypertension. XYOSTED is not recommended for use in patients with uncontrolled hypertension.
- Women who are pregnant. Testosterone can cause virilization of the female fetus when administered to a pregnant woman [see Use in Specific Populations (.)]
8.1 PregnancyRisk SummaryXYOSTED is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies and its mechanism of action
[see Contraindications and Clinical Pharmacology ]. Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies.DataAnimal DataIn developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. Structural impairments observed in females included increased ano-genital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes.
Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant females and offspring in rats exposed to doses approximately twice those used for testosterone replacement therapy.
- Men with known hypersensitivity to XYOSTED or any of its ingredients (testosterone enanthate and sesame oil).
XYOSTED (testosterone enanthate) injection contains testosterone enanthate, an ester derivative of an endogenous androgen, testosterone. Testosterone enanthate is a white to creamy white crystalline powder described by the chemical name (17β)-17-[(1-Oxoheptyl) oxy]-androst-4-en-3-one. Testosterone enanthate has the molecular formula C26H40O3, the molecular weight 400.59, and the molecular structure with the chemical formula:
XYOSTED (testosterone enanthate) injection is a sterile, preservative-free, and nonpyrogenic colorless to pale yellow solution supplied in a single-dose syringe assembled in a pressure-assisted autoinjector for subcutaneous administration. Each XYOSTED autoinjector contains 50 mg, 75 mg, or 100 mg of testosterone in sesame oil to form 0.5 mL solution providing three product strengths of 50 mg/0.5 mL, 75 mg/0.5 mL, and 100 mg/0.5 mL.
XYOSTED was evaluated in a 52-week, open-label study (NCT02159469) to evaluate its efficacy and safety when administered subcutaneously once weekly to 150 adult males with hypogonadism. The study included a Screening Phase, a Treatment Titration Phase, and an Extended Treatment Phase.
Patients were trained on proper use of XYOSTED to self-administer the initial dose of 75 mg once weekly on the same day of the week and at approximately the same time (7:00 am ± 2 hours). The dose was increased by 25 mg at Week 7 if the Week 6 serum total testosterone concentration at the end of the dosing interval (Ctrough) was <350 ng/dL, and was decreased by 25 mg if the Ctrough was ≥650 ng/dL.
The primary endpoint was the percentage of patients with a time-averaged serum total testosterone concentration (Cavg) over the 7-day dosing interval (0 to 168 hours) within the normal range (300 to 1100 ng/dL) at Week 12.
Secondary endpoints were the percentage of patients with a maximum total testosterone concentration (Cmax) above three predetermined limits: greater than 1500 ng/dL, between 1800 and 2500 ng/dL, and greater than 2500 ng/dL.
One hundred and thirty five (90%) of the 150 hypogonadal men who received XYOSTED had a serum total testosterone concentration Cavg(0-168h) within the normal range (300 to 1100 ng/dL) at Week 12. There were no patients (0%) with Cmax >1500 ng/dL at Week 12.
XYOSTED (testosterone enanthate) injection is provided as 0.5 mL of a sterile, preservative-free, and nonpyrogenic colorless to pale yellow solution in a single-dose syringe pre-assembled in an autoinjector for a single subcutaneous administration. XYOSTED is packaged in cartons containing four (4) or one (1) autoinjectors. XYOSTED is available in the following strengths and configurations.
- XYOSTED (testosterone enanthate) injection, USP, 50 mg/0.5 mL
- Carton of 4 autoinjectors NDC 54436-250-04
- Autoinjector NDC 54436-250-02
- XYOSTED (testosterone enanthate) injection, USP, 75 mg/0.5 mL
- Carton of 4 autoinjectors NDC 54436-275-04
- Carton of 1 autoinjector NDC 54436-275-05
- Autoinjector NDC 54436-275-02
- XYOSTED (testosterone enanthate) injection, USP, 100 mg/0.5 mL
- Carton of 4 autoinjectors NDC 54436-200-04
- Carton of 1 autoinjector NDC 54436-200-05
- Autoinjector NDC 54436-200-02
Before use, each autoinjector should be visually inspected. XYOSTED should be clear to light yellow in color and free of visible particles. Do not use if the liquid is cloudy or if visible particles are present. You may notice an air bubble, this is normal.