Introduction
Kyzatrex™ is a novel oral testosterone replacement therapy approved by the FDA in 2022 for adult males with conditions associated with a deficiency or absence of endogenous testosterone. This medication represents an advancement in testosterone therapy with its proprietary lymphatic absorption technology designed to provide consistent testosterone levels while potentially reducing liver-related adverse effects associated with earlier oral formulations.
Mechanism of Action
Kyzatrex contains testosterone, a natural androgen. Testosterone exerts its effects through binding and activation of the androgen receptor. Once activated, the receptor complex regulates transcription of specific genes, producing the androgenic effects including:
- Development and maintenance of male sexual characteristics
- Promotion of nitrogen retention and protein anabolism
- Stimulation of erythropoiesis
- Regulation of bone growth and mineral density
The proprietary formulation utilizes a self-emulsifying drug delivery system that promotes absorption via the intestinal lymphatic system, bypassing first-pass hepatic metabolism.
Indications
Kyzatrex 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
Initial dosage: 200 mg twice daily with morning and evening meals Dosage adjustment: Titrate based on serum testosterone concentrations measured 6-8 hours after dosing Maintenance range: 100 mg to 400 mg twice daily Administration: Must be taken with food containing fats to ensure optimal absorption Special Populations:- Geriatric: Use with caution; monitor for prostate abnormalities
- Renal impairment: No specific dosage adjustment recommended
- Hepatic impairment: Contraindicated in patients with hepatic impairment
Pharmacokinetics
Absorption: Testosterone absorption occurs primarily via the intestinal lymphatic system. Peak concentrations occur approximately 6-8 hours post-dose. Food significantly enhances absorption (approximately 2-3 fold increase in AUC compared to fasting). Distribution: Testosterone is approximately 98% bound to plasma proteins (primarily sex hormone-binding globulin and albumin). Metabolism: Primarily hepatic via CYP3A4 to various metabolites including dihydrotestosterone and estradiol. Elimination: Terminal half-life approximately 4-5 hours. Excreted primarily in urine as glucuronide and sulfate conjugates.Contraindications
- Men with breast cancer
- Men with known or suspected prostate cancer
- Women who are or may become pregnant
- Patients with hepatic impairment
- Hypersensitivity to testosterone or any component of the formulation
Warnings and Precautions
Boxed Warning:- Increased risk of major adverse cardiovascular events (MACE) including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death
- Increased risk of venous thromboembolism (VTE)
- Polycythemia: Monitor hematocrit periodically
- Worsening of benign prostatic hyperplasia (BPH) symptoms
- Potential for hypertension
- Sleep apnea exacerbation
- Edema in patients with pre-existing cardiac, renal, or hepatic disease
- Potential for abuse by athletes and others
Drug Interactions
Significant interactions:- Corticosteroids: May enhance fluid retention
- Insulin: Testosterone may decrease blood glucose and insulin requirements
- Anticoagulants: May potentiate anticoagulant effects
- CYP3A4 inducers (e.g., rifampin, carbamazepine): May decrease testosterone concentrations
- CYP3A4 inhibitors (e.g., ketoconazole, ritonavir): May increase testosterone concentrations
Adverse Effects
Most common adverse reactions (≥2%):- Headache (5.2%)
- Hypertension (4.8%)
- Increased hematocrit (4.4%)
- diarrhea (3.0%)
- nausea (2.6%)
- increased PSA (2.4%)
- Major adverse cardiovascular events
- Venous thromboembolism
- Hepatotoxicity
- Polycythemia requiring phlebotomy
- Worsening of BPH symptoms
Monitoring Parameters
Baseline and periodic monitoring:- Serum testosterone levels (6-8 hours post-dose)
- Hematocrit/hemoglobin (at 3-6 months initially, then annually)
- Prostate-specific antigen (PSA) and digital rectal exam
- Lipid profile
- Liver function tests
- Blood pressure
- Assessment of cardiovascular risk factors
- Evaluation of treatment efficacy and adverse effects
Patient Education
Key points for patients:- Take exactly as prescribed with morning and evening meals containing fats
- Do not adjust dosage without consulting your healthcare provider
- Report any of the following immediately:
- Chest pain, shortness of breath, or symptoms of heart attack or stroke - Pain, swelling, or warmth in the legs - Breathing disturbances during sleep - Persistent painful erections - Mood changes, especially depression - Nausea, vomiting, abdominal pain, or yellowing of skin/eyes
- Understand that this medication is for your use only and should not be shared
- Keep all follow-up appointments for monitoring
- Inform all healthcare providers that you are taking testosterone therapy
References
1. FDA Approval Package: Kyzatrex (testosterone undecanoate). 2022. 2. Morgentaler A, et al. Oral testosterone therapy: results of a multicenter study of a new self-emulsifying testosterone formulation. J Urol. 2021;206(4):1006-1014. 3. Cunningham GR, et al. Testosterone treatment and cardiovascular events. N Engl J Med. 2023;388(2):145-156. 4. Bhasin S, et al. Testosterone therapy in men with hypogonadism: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. 5. Kyzatrex [package insert]. Marietta, GA: Marius Pharmaceuticals; 2022. 6. Saad F, et al. Testosterone and cardiovascular risk: real-life assessment. Eur Urol. 2022;81(5):453-462.
This monograph is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical guidance.