ZAROXOLYN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZAROXOLYN (ZAROXOLYN).
Inhibits sodium reabsorption in the distal convoluted tubule by blocking the thiazide-sensitive sodium-chloride symporter (NCC).
| Metabolism | Metabolized primarily via cytochrome P450 (CYP) enzymes, including CYP3A4, with minor contribution from CYP1A2 and CYP2C8. |
| Excretion | Primarily renal (approximately 70% as unchanged drug and metabolites) and biliary (approximately 30% as unchanged drug and metabolites into feces). |
| Half-life | Terminal elimination half-life ranges from 6 to 15 hours (mean ~8 hours) in patients with normal renal function. In renal impairment, half-life is prolonged and accumulation may occur. |
| Protein binding | Approximately 95% bound, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: Approximately 75% (range 60-90%), with food potentially decreasing absorption. |
| Onset of Action | Oral: Diuresis begins within 1 hour, with peak effect at 2-4 hours. |
| Duration of Action | Oral: Duration of diuretic effect is 12-24 hours, with blood pressure reduction lasting up to 24 hours. Clinical note: Use once daily for hypertension. |
2.5 to 5 mg orally once daily; may increase up to 20 mg daily based on response.
| Dosage form | TABLET |
| Renal impairment | eGFR 10-50 mL/min: use with caution; eGFR <10 mL/min: not recommended due to ineffectiveness. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B or C: consider dose reduction due to reduced clearance. |
| Pediatric use | Not established; safety and efficacy not determined in pediatric patients. |
| Geriatric use | Start at lower end of dosing range (2.5 mg) due to increased risk of electrolyte imbalance and hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZAROXOLYN (ZAROXOLYN).
| Breastfeeding | Excreted in breast milk in low concentrations; M/P ratio not established. Theoretical risk of electrolyte imbalance in neonate. Use caution; consider alternative agents if breastfeeding. |
| Teratogenic Risk | Pregnancy Category D. Crosses placenta. First trimester: No evidence of teratogenicity in humans, but animal studies show fetal toxicity (skeletal anomalies, growth retardation) at high doses. Second/third trimesters: Associated with decreased placental perfusion, fetal jaundice, electrolyte disturbances, and possible neonatal thrombocytopenia. Not recommended in pregnancy, especially for gestational hypertension or preeclampsia due to maternal hypovolemia risk. |
■ FDA Black Box Warning
No FDA black box warnings reported.
| Serious Effects |
["Anuria","Hypersensitivity to metolazone or sulfonamide-derived drugs","Hepatic coma or pre-coma"]
| Precautions | ["May cause hypokalemia, hyponatremia, and metabolic alkalosis.","Can precipitate azotemia in patients with impaired renal function.","Risk of hyperuricemia and new-onset gout.","Use with caution in patients with hepatic impairment due to risk of hepatic encephalopathy."] |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes (sodium, potassium, chloride, magnesium), renal function, and uric acid. Fetal assessment includes ultrasound for growth restriction and amniotic fluid volume (oligohydramnios risk). In neonates, monitor for jaundice, thrombocytopenia, and electrolyte disturbances. |
| Fertility Effects | No specific human data; animal studies show no effect on fertility. Potential indirect effects via electrolyte imbalance or hemodynamic changes affecting pregnancy outcomes. |