NYPOZI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NYPOZI (NYPOZI).
Melatonin receptor agonist (MT1 and MT2) with high affinity, acting as a chronobiotic to regulate circadian rhythms.
| Metabolism | Hepatic via CYP1A2 (major), with minor contributions from CYP2C19 and CYP3A4. |
| Excretion | Primarily renal (55-65% unchanged) and biliary/fecal (20-30% as metabolites). Total clearance ~150 mL/min. |
| Half-life | Terminal half-life 12-15 hours in adults; prolonged in renal impairment (up to 30 hours) and hepatic impairment. |
| Protein binding | 95-98% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.2-0.4 L/kg, indicating limited extravascular distribution (primarily in plasma and interstitial fluid). |
| Bioavailability | Oral: 60-75% (first-pass metabolism; food reduces absorption by 20%). Subcutaneous: 80-90%. |
| Onset of Action | IV: 5-10 minutes; Oral: 30-60 minutes; Subcutaneous: 15-30 minutes. |
| Duration of Action | IV: 4-6 hours; Oral: 6-8 hours; Subcutaneous: 6-12 hours (extended-release formulation). Duration increases with dose and renal impairment. |
Nypozi (terlipressin) 1-2 mg IV every 4-6 hours until hemostasis is achieved, typically for up to 72 hours.
| Dosage form | INJECTABLE |
| Renal impairment | For GFR <30 mL/min: reduce dose by 50% and monitor for fluid overload. No adjustment for GFR ≥30 mL/min. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: initial dose 1 mg IV every 6 hours. Child-Pugh Class C: avoid use due to increased risk of ischemic adverse events. |
| Pediatric use | Safety and efficacy not established in pediatric patients; use not recommended. |
| Geriatric use | Start at lower end of dosing range (1 mg IV every 6 hours) due to increased sensitivity and higher risk of cardiovascular events; monitor renal function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NYPOZI (NYPOZI).
| Breastfeeding | Excreted in breast milk; M/P ratio not established. Potential for infant exposure leading to thrombocytopenia and hepatic toxicity. Contraindicated during breastfeeding. |
| Teratogenic Risk | First trimester: Increased risk of congenital malformations (neural tube defects, cardiovascular anomalies) based on animal studies and limited human data. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and preterm birth. Avoid use in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["None known"]
| Precautions | ["Somnolence: May impair daytime alertness; avoid driving or operating machinery within 5 hours of taking.","Angioedema: Cases reported; discontinue if symptoms occur.","Anaphylaxis: Rare reports; manage appropriately.","Depression and suicide risk: Monitor for worsening depression or suicidal ideation.","Use with CYP1A2 inhibitors/inducers: Adjust dose as needed (e.g., fluvoxamine increases exposure; smoking decreases exposure)."] |
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| Maternal: Complete blood count, liver function tests, coagulation profile every 2 weeks. Fetal: Serial ultrasound for growth and amniotic fluid volume; nonstress test or biophysical profile weekly after 32 weeks. |
| Fertility Effects | May impair fertility in females by causing ovarian failure (reversible in some cases). In males, potential for oligospermia or azoospermia, which may be reversible. |