Aprocitentan

FDA label

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Renal No adjustment for eGFR ≥15 mL/min (mild–severe); not recommended in kidney failure (eGFR <15) or on dialysis

Hepatic No adjustment in mild (Child-Pugh A); not recommended in moderate–severe (Child-Pugh B/C)

Do not take two doses on the same day

Instructions

• Swallow tablets whole; with or without food
• Missed dose: skip; do not take two doses on the same day
• Exclude pregnancy before initiation; effective contraception during and for 1 month after treatment
• Measure aminotransferases and total bilirubin before starting and periodically; do not initiate if ALT/AST >3x ULN or in moderate–severe hepatic impairment
• Measure hemoglobin before starting and periodically; initiation not recommended in severe anemia

Contraindications

• Pregnancy

Cautions

• Hepatotoxicity (ERA class effect) — monitor LFTs; stop and evaluate for symptoms of hepatotoxicity; discontinue for sustained/clinically relevant elevations, bilirubin >2x ULN, or clinical symptoms
• Fluid retention/peripheral edema (9%) — risk higher with older age and CKD; not recommended in NYHA III–IV heart failure, unstable cardiac function, or NT-proBNP ≥500 pg/mL; may require diuretics; consider discontinuation if significant
• Hemoglobin decrease (>2 g/dL drop in 7%) — do not start in severe anemia; monitor hemoglobin
• Decreased sperm counts (ERA class) — counsel males on potential fertility effects
• Initial small eGFR decrease within first 6 weeks, then stabilizes

Adverse reactions

• Edema/fluid retention (9.1% vs 2.1% placebo)
• Anemia (3.7% vs 0)
• Hypersensitivity reactions (rash, erythema, allergic edema; 0.8%)
• Mean hemoglobin decrease ~0.8 g/dL

Pregnancy Contraindicated — can cause embryo-fetal toxicity incl. birth defects and fetal death (ERA-class teratogenicity in animals at all doses tested); discontinue as soon as pregnancy detected

Lactation Do not breastfeed during treatment (excreted in rat milk; potential for serious adverse reactions in breastfed infants)