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ADPKD Pregnancy: Contraindicated — effective contraception mandatory

Tolvaptan (ADPKD)

Brand names: Jinarc

Adult dose

Dose: 45 mg on waking + 15 mg 8 hours later; titrate to 60+30 mg/day, then 90+30 mg/day as tolerated
Route: Oral
Frequency: Split dose — on waking then 8 hours later
Max: 90 mg + 30 mg per day
Vasopressin V2-receptor antagonist. Licensed for ADPKD with rapidly progressing disease (CKD stage 1-3 typically). Aquaretic effect is prominent — patients must have constant access to water. MHRA Black Box: serious hepatotoxicity including fatal cases.

Paediatric dose

Route: Oral
Seek specialist opinion — not licensed for ADPKD in children

Dose adjustments

Renal

Avoid if eGFR <25 mL/min. Monitor carefully in CKD stage 3-4 — aquaretic effect can cause acute AKI if dehydrated.

Hepatic

Contraindicated in hepatic impairment — serious hepatotoxicity including fatal cases reported (MHRA Black Box)

Clinical pearls

  • TEMPO 3:4 trial (Torres et al. NEJM 2012): tolvaptan vs placebo in ADPKD — 49% reduction in total kidney volume growth rate; 26% reduction in eGFR decline composite. Landmark ADPKD trial.
  • REPRISE trial (Torres et al. NEJM 2017): later CKD stage (eGFR 25-65) — 35% reduction in eGFR decline vs placebo. Confirmed benefit at later stages.
  • HEPATOTOXICITY: MHRA mandates LFTs monthly for 18 months, then every 3 months. Three cases of serious liver injury in TEMPO trial including one requiring transplant. Must be prescribed via restricted access programme (RAP).
  • Aquaresis counselling: patients must drink ~3L/day; nocturia is common and limiting. Avoid driving after night-time dose if alertness affected by nocturia.
  • UK eligibility: rapidly progressing ADPKD defined by eGFR decline >5 mL/min/year, total kidney volume doubling <10 years, or Mayo Classification 1C/1D/1E

Contraindications

  • Liver disease or elevated LFTs >2x ULN at baseline
  • Anuria
  • Volume depletion
  • Hypersensitivity to tolvaptan or benzazepines

Side effects

  • Aquaresis — polyuria, polydipsia, nocturia (expected class effect)
  • Hepatotoxicity (SERIOUS — MHRA Black Box; monthly LFT monitoring mandatory)
  • Thirst
  • Dry mouth
  • Hypernatraemia
  • Hyperuricaemia/gout

Interactions

  • Strong CYP3A4 inhibitors (ketoconazole, itraconazole) — significantly increase tolvaptan levels; avoid
  • Strong CYP3A4 inducers (rifampicin) — reduce efficacy
  • P-gp inhibitors (cyclosporin) — increase levels
  • Digoxin — tolvaptan increases digoxin AUC ~20%

Monitoring

  • LFTs monthly for 18 months, then every 3 months (MHRA mandate)
  • eGFR
  • Serum sodium (hypernatraemia risk)
  • Uric acid
  • Fluid intake and urine output

Reference: BNFc; BNF 90; TEMPO 3:4 Trial (Torres et al. NEJM 2012); REPRISE Trial (Torres et al. NEJM 2017); MHRA DSU (Hepatotoxicity); NICE TA506; SPC Jinarc. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

Pathways