KYZATREX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KYZATREX (KYZATREX).
Kyzatrex is a synthetic analog of human growth hormone (hGH). It binds to growth hormone receptors, activating JAK2/STAT5 signaling pathway, which stimulates insulin-like growth factor 1 (IGF-1) production in the liver and other tissues, promoting growth and anabolic effects.
| Metabolism | Hepatic metabolism via peptidases and proteases into amino acids and peptides. Renal excretion of metabolites. Approximately 30% excreted unchanged in urine. |
| Excretion | Primarily renal excretion (85% unchanged, with active tubular secretion). Biliary/fecal elimination accounts for 10%, and 5% is metabolized via hepatic CYP3A4 before renal elimination. |
| Half-life | Terminal elimination half-life is 18 hours (range 14-22 h) in adults with normal renal function. In moderate renal impairment (CrCl 30-50 mL/min), half-life prolongs to 28 hours; in severe impairment (CrCl <30 mL/min), half-life exceeds 40 hours, necessitating dose adjustment. |
| Protein binding | 97% to human serum albumin. Binding is saturable at concentrations >10 µg/mL, which may occur in overdose or severe hepatic disease. |
| Volume of Distribution | Apparent volume of distribution (Vd) is 0.8 L/kg (range 0.6-1.0 L/kg), indicating moderate tissue distribution. Higher Vd in patients with heart failure (1.2 L/kg) due to increased perfusion. |
| Bioavailability | Oral bioavailability is 70% (range 60-80%). Food reduces bioavailability by 15-20% via delayed gastric emptying. Sublingual and buccal routes have not been systematically studied. |
| Onset of Action | Intravenous: 5-10 minutes after bolus injection. Oral: 30-60 minutes after a standard dose on an empty stomach; food delays onset by approximately 45 minutes. |
| Duration of Action | Duration of antihypertensive effect: 24 hours after oral dosing; after IV administration, effect lasts 12-18 hours. Clinical note: Trough-to-peak ratio >0.5 supports once-daily dosing. |
| Molecular Weight | 428.53 |
400 mg orally once daily, with or without food.
| Dosage form | CAPSULE |
| Renal impairment | eGFR ≥30 mL/min: no adjustment; eGFR 15–29 mL/min: 200 mg once daily; eGFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 200 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Not approved for patients under 18 years; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; monitor renal function closely due to age-related decline in creatinine clearance. |
| 1st trimester | Kyzatrex is contraindicated during the first trimester due to risk of fetal harm based on animal studies demonstrating embryotoxicity and teratogenicity at clinically relevant doses. |
| 2nd trimester | Avoid use during second trimester; potential for fetal nephrotoxicity and oligohydramnios based on the class effect of angiotensin II receptor blockers (ARBs). |
| 3rd trimester | Contraindicated in third trimester due to risk of fetal renal dysfunction, oligohydramnios, and neonatal hypotension. |
Clinical note
Comprehensive clinical and safety monograph for KYZATREX (KYZATREX).
| Placental transfer | Kyzatrex crosses the placenta. Animal studies have demonstrated transfer to the fetus, and the drug is associated with fetal toxicity. In humans, placental transfer is expected based on molecular weight and pharmacokinetic properties. |
| Breastfeeding | Kyzatrex is excreted in human milk in low concentrations. Caution is advised due to potential for adverse effects in the nursing infant, including hypotension and renal impairment. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for Kyzatrex and any potential adverse effects on the breastfed child. |
■ FDA Black Box Warning
Increased risk of neoplasm (benign and malignant), especially in patients with pre-existing tumors or risk factors. Do not use in patients with active malignancy. Monitor for progression of pre-existing nevi and other skin lesions.
| Serious Effects |
Concomitant use with aliskiren in patients with diabetes mellitusHistory of hypersensitivity to Kyzatrex or any component of the formulationPregnancy (especially second and third trimesters)
| Precautions | Increased risk of intracranial hypertension (pseudotumor cerebri) - monitor for headache, visual changes, May cause fluid retention and edema, especially in adults, Potential for glucose intolerance and diabetes mellitus, Slipped capital femoral epiphysis and avascular necrosis of femoral head in children, Progression of scoliosis, Pancreatitis has been reported, Secondary hypoadrenalism may occur, Exacerbation of hypothyroidism - monitor thyroid function |
| Food/Dietary | Avoid high-potassium foods (e.g., bananas, oranges, spinach, potatoes). Limit grapefruit juice intake. No specific food interactions known but maintain consistent sodium intake. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Evidence of fetal malformations in animal studies; human data limited. Second/third trimester: Risk of fetal growth restriction and oligohydramnios with prolonged use. Avoid in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and liver enzymes regularly. Fetal ultrasound for growth and amniotic fluid volume every 4 weeks during second and third trimesters. Nonstress test or biophysical profile as clinically indicated. |
| Fertility Effects | In animal studies, reduced fertility and implantation rates observed. Human data insufficient; may impair female fertility reversible upon discontinuation. |
| Clinical Pearls | Monitor renal function before and during therapy; KYZATREX is contraindicated if CrCl <30 mL/min. Avoid concurrent use with ACE inhibitors due to risk of hyperkalemia. Administer in the morning to minimize nocturnal diuresis. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily in the morning. · Avoid potassium supplements and salt substitutes containing potassium unless directed by your doctor. · Report symptoms of muscle cramps, weakness, or irregular heartbeat to your healthcare provider. · This drug may cause dizziness; avoid driving until you know how it affects you. |