Xyosted - Drug Monograph

Introduction

Xyosted (testosterone enanthate) is an FDA-approved subcutaneous auto-injector formulation of testosterone indicated for testosterone replacement therapy in adult males with conditions associated with a deficiency or absence of endogenous testosterone. This novel delivery system provides a convenient method for self-administration of testosterone, offering an alternative to traditional intramuscular injections, gels, patches, and pellets.

Mechanism of Action

Testosterone, the primary endogenous androgen, is responsible for the normal growth and development of male sex organs and maintenance of secondary sex characteristics. Xyosted delivers testosterone enanthate, a prodrug that undergoes hydrolysis to release free testosterone into the systemic circulation. Testosterone exerts its effects through binding to intracellular androgen receptors, which then translocate to the nucleus and regulate gene transcription. This results in:

• Promotion of nitrogen retention and protein anabolism
• Development and maintenance of male sexual characteristics
• Stimulation of erythropoiesis
• Regulation of gonadotropin secretion via negative feedback on the hypothalamic-pituitary axis

Indications

Xyosted is 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)

Dosage and Administration

• May increase to 100 mg weekly if testosterone levels below normal range
• May decrease to 50 mg weekly if testosterone levels above normal range

• For subcutaneous injection only in abdominal area
• Rotate injection sites
• Allow auto-injector to reach room temperature before use
• Patient must be trained on proper injection technique

• Geriatric: Use with caution; monitor for increased risk of adverse events
• Renal Impairment: No specific dosage adjustment recommended
• Hepatic Impairment: Use with caution in patients with severe hepatic impairment

Pharmacokinetics

Contraindications

• Men with breast cancer
• Known or suspected prostate cancer
• Pregnancy (may cause fetal harm)
• Hypersensitivity to testosterone enanthate or any product components

Warnings and Precautions

• Increased risk of major adverse cardiovascular events (MACE)
• Potential for abuse leading to serious cardiovascular and psychiatric adverse reactions

• Polycythemia: May increase hematocrit requiring dose reduction or discontinuation
• Cardiovascular risk: Monitor for signs of cardiovascular disease
• Venous thromboembolism: Increased risk of deep vein thrombosis and pulmonary embolism
• Sleep apnea: May occur or worsen in those with risk factors
• Hepatotoxicity: Monitor liver function tests periodically
• Edema: May occur in patients with pre-existing cardiac, renal, or hepatic disease
• Gynecomastia: May develop or worsen
• Lipid changes: May adversely affect lipid profile
• Hypercalcemia: In immobilized patients or those with cancer
• Infertility: Suppression of spermatogenesis with large doses

Drug Interactions

• Anticoagulants: Testosterone may enhance anticoagulant effect
• Corticosteroids: Increased risk of edema
• Insulin: Testosterone may decrease blood glucose; monitor and adjust antidiabetic medications
• CYP3A4 inducers/inhibitors: May affect testosterone metabolism
• Propranolol: May increase clearance of testosterone

Adverse Effects

• Increased hematocrit/hemoglobin
• Hypertension
• Injection site reactions (erythema, pain, pruritus)
• Headache
• Increased PSA

• Major adverse cardiovascular events
• Venous thromboembolism
• Hepatotoxicity
• Psychiatric adverse reactions (including aggression)
• Pulmonary oil microembolism reactions (if injected intravenously)

Monitoring Parameters

• Testosterone levels (on at least two separate mornings)
• Complete blood count (CBC)
• Prostate-specific antigen (PSA)
• Lipid profile
• Liver function tests
• Cardiovascular risk assessment

• Serum testosterone levels (3-4 days post-dose at 2-4 week intervals after initiation, then periodically)
• Hematocrit/hemoglobin (at 3-6 months, then annually)
• PSA (at 3-6 months, then in accordance with guidelines)
• Lipid profile (annually)
• Liver function (periodically)
• Signs and symptoms of fluid retention
• Cardiovascular risk factors

Patient Education

• Proper injection technique and site rotation
• Importance of adherence to prescribed dosing schedule
• Recognition of injection site reactions
• Signs of polycythemia (dizziness, fatigue, headache)
• Symptoms of cardiovascular events (chest pain, shortness of breath)
• Signs of venous thromboembolism (leg swelling, pain, redness)
• Potential for abuse and sharing of medication
• Importance of regular monitoring and follow-up appointments
• Report any mood changes, aggression, or depression
• Inform all healthcare providers about testosterone use
• Store at room temperature; do not freeze

References

1. Xyosted [package insert]. Irving, TX: Antares Pharma, Inc.; 2021. 2. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423-432. 3. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. 4. FDA-approved labeling for Xyosted. Accessible via Drugs@FDA. 5. Kaminetsky J, Jaffe JS, Swerdloff RS. Pharmacokinetic profile of subcutaneous testosterone enanthate delivered via a novel, prefilled auto-injector. Curr Med Res Opin. 2019;35(2):225-231. 6. Corona G, Goulis DG, Huhtaniemi I, et al. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males. Andrology. 2020;8(5):970-987.