Makindo Medical Notes

💧 Tolvaptan is a vasopressin (ADH) V2-receptor antagonist that causes “aquaresis” (free-water loss without sodium loss) → serum sodium rises.
🧠 Safety headline: in chronic SIADH the brain adapts to low sodium; correcting too fast can cause osmotic demyelination. Aim for a controlled rise (often ~4–6 mmol/L/day) and keep within recommended limits: ≤10 mmol/L in the first 24 h and ≤8 mmol/L per 24 h thereafter. :contentReference[oaicite:0]{index=0}

📘 About: Always check the BNF link here

• 🇬🇧 In UK practice, tolvaptan for SIADH is generally specialist-initiated with close sodium monitoring.
• ⚠️ MHRA warns about over-rapid rises in sodium and advises close monitoring, especially if baseline Na <120 mmol/L or high ODS risk (malnutrition, alcoholism, hypoxia). :contentReference[oaicite:1]{index=1}
• 🧬 Separate indication: ADPKD (Jinarc®) to slow cyst growth in rapidly progressive disease (requires strict LFT monitoring). :contentReference[oaicite:2]{index=2}

⚙️ Mode of action

• 🚰 Selective V2-receptor antagonist in the renal collecting duct → blocks ADH → ↓ aquaporin insertion → ↑ free-water excretion (“aquaresis”). :contentReference[oaicite:3]{index=3}
• 📈 Serum sodium rises because water is lost more than sodium (not because sodium is “added”). :contentReference[oaicite:4]{index=4}

✅ Indications

• 🧪 Hyponatraemia due to SIADH (euvolaemic hyponatraemia) in adults — specialist use. :contentReference[oaicite:5]{index=5}
• 🫘 ADPKD in adults with CKD stage 1–4 at initiation and evidence of rapidly progressive disease (Jinarc®). :contentReference[oaicite:6]{index=6}

💊 Dose range (check local policy + SmPC)

🧪 Monitoring (SIADH / hyponatraemia use)

• 🩸 Check serum sodium frequently after first dose (common practice: baseline, then ~4–6 h, 6–12 h, and 24 h; then daily until stable).
• ⚠️ MHRA: a rise of >6 mmol/L in the first 6 h or >8 mmol/L in the first 6–12 h may be too rapid → intensify monitoring and consider hypotonic fluid. :contentReference[oaicite:9]{index=9}
• 🧠 If Na rise exceeds 12 mmol/L in 24 h (or 18 mmol/L in 48 h), interrupt/stop and actively manage overcorrection (e.g. hypotonic fluid ± desmopressin per local guideline). :contentReference[oaicite:10]{index=10}
• 🚰 Ensure patient has free access to water and can drink to thirst; monitor urine output, weight, BP, volume status. :contentReference[oaicite:11]{index=11}
• 🧂 Avoid combining with hypertonic/normal saline or high-sodium medicines unless specialist-directed (overcorrection risk). :contentReference[oaicite:12]{index=12}

🧪 Monitoring (ADPKD / Jinarc®)

• 🧫 Liver safety: check ALT/AST and bilirubin before start, then monthly for 18 months, then every 3 months thereafter (and if symptoms). :contentReference[oaicite:13]{index=13}
• 🧠 Counsel on hepatotoxicity symptoms: fatigue, anorexia, RUQ pain, dark urine, jaundice → stop and investigate urgently.
• 🚰 Expect polyuria/nocturia and thirst; counsel hydration and sick-day planning. :contentReference[oaicite:14]{index=14}

🔗 Interactions

• 🧬 Tolvaptan is metabolised by CYP3A4:
  • ⛔ Avoid strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, protease inhibitors) — marked exposure increase. :contentReference[oaicite:15]{index=15}
  • ⚠️ Moderate inhibitors (e.g. diltiazem, verapamil, erythromycin, grapefruit juice) may require dose adjustment/avoidance. :contentReference[oaicite:16]{index=16}
  • ⬇️ CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin, St John’s wort) can reduce effect.
• 🩸 Vasopressin analogues (e.g. desmopressin) may have reduced effect; MHRA highlights interaction potential. :contentReference[oaicite:17]{index=17}
• 🧂 Do not combine routinely with other hyponatraemia treatments (saline, demeclocycline, etc.) unless specialist-directed (overcorrection risk). :contentReference[oaicite:18]{index=18}

⚠️ Cautions

• 💧 Dehydration / hypovolaemia: high urine output can cause hypotension/AKI—monitor closely, especially in frail older adults.
• 🧠 High ODS risk: Na ≤105, malnutrition, alcoholism, hypokalaemia, advanced liver disease → use stricter correction targets and consider “re-lowering” strategy if overshoots. :contentReference[oaicite:19]{index=19}
• 🧫 Abnormal LFTs or underlying liver disease (especially for longer-term ADPKD treatment). :contentReference[oaicite:20]{index=20}
• 🍬 Hyperglycaemia can occur—monitor in diabetes and acute illness.

⛔ Contraindications (high-yield)

• 🚱 Inability to sense/respond to thirst (cannot safely compensate water loss). :contentReference[oaicite:21]{index=21}
• 📉 Hypovolaemic hyponatraemia (treat volume first; tolvaptan can worsen). :contentReference[oaicite:22]{index=22}
• 🚫 Anuria. :contentReference[oaicite:23]{index=23}
• 🧂 Hypernatraemia or urgent need for rapid controlled correction with hypertonic saline (e.g. seizures) — tolvaptan is not the emergency drug.
• 💊 Concomitant strong CYP3A4 inhibitors. :contentReference[oaicite:24]{index=24}

😵 Side effects

• 🚰 Thirst, dry mouth, polyuria, pollakiuria, nocturia.
• 📉 Hypotension, dizziness; dehydration/AKI if intake inadequate. :contentReference[oaicite:25]{index=25}
• 🍬 Hyperglycaemia (occasionally).
• 🧫 Liver injury risk (primarily emphasised in ADPKD long-term use). :contentReference[oaicite:26]{index=26}

📖 References

• MHRA Drug Safety Update — Tolvaptan (Samsca): over-rapid sodium correction
• Society for Endocrinology (2022) — Emergency management of symptomatic hyponatraemia
• EMA product information — Samsca (tolvaptan)
• EMA product information — Jinarc (tolvaptan)
• UKKA (2024) — Tolvaptan for ADPKD commentary