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Antiarrhythmic / AF Pregnancy: Contraindicated — teratogenic in animal studies; effective contraception mandatory during and for 1 month after stopping

Dronedarone

Brand names: Multaq

Adult dose

Dose: 400 mg twice daily with morning and evening meals
Route: Oral
Frequency: Twice daily (with meals — improves bioavailability and reduces GI side effects)
Max: 800 mg/day
Non-iodinated amiodarone derivative. Multichannel blocker (Class I, II, III, IV properties). ATHENA trial: reduces AF recurrence and cardiovascular hospitalisations. MHRA restrictions: CONTRAINDICATED in permanent AF, heart failure with recent decompensation, severe hepatic impairment. Monthly LFT and creatinine monitoring.

Paediatric dose

Route: Oral
Seek specialist opinion — not licensed in children

Dose adjustments

Renal

Dronedarone inhibits tubular secretion of creatinine — serum creatinine rises ~0.1 mg/dL (artefact, NOT true GFR fall — same mechanism as trimethoprim). No dose adjustment needed but interpret rising creatinine carefully.

Hepatic

CONTRAINDICATED in severe hepatic impairment or hepatotoxicity. Hepatotoxicity reported including liver failure (MHRA 2011).

Clinical pearls

  • ATHENA trial (Hohnloser et al. NEJM 2009): dronedarone vs placebo in paroxysmal/persistent AF — 24% reduction in composite of CV hospitalisation or death. No mortality benefit demonstrated.
  • ANDROMEDA trial: dronedarone INCREASED mortality in severe HF (NYHA III-IV with recent decompensation) — trial stopped early. This led to the CONTRAINDICATION in decompensated HF.
  • PALLAS trial: dronedarone in PERMANENT AF — significantly INCREASED mortality, stroke, and HF hospitalisation. Dronedarone is therefore ONLY for paroxysmal or persistent AF (NOT permanent).
  • Amiodarone advantages over dronedarone: no iodine (no thyroid toxicity), no pulmonary toxicity from iodine mechanism, no corneal deposits. However dronedarone has NEW hepatotoxicity risk and is less effective than amiodarone.
  • Creatinine artefact: dronedarone blocks renal tubular creatinine secretion (similar to trimethoprim) — creatinine rises ~10 mcromol/L without true GFR fall. Cystatin C-based eGFR unaffected. Do not stop dronedarone for this isolated creatinine rise — check cystatin C or renal imaging if concerned.

Contraindications

  • Permanent AF (ANDROMEDA trial — increased mortality in permanent AF with HF)
  • Heart failure with recent (<4 weeks) decompensation or NYHA Class IV
  • Severe hepatic impairment
  • 2nd/3rd degree AV block or SSS (without pacemaker)
  • Bradycardia <50 bpm
  • Concomitant strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir)
  • Concomitant QTc-prolonging drugs
  • Pregnancy
  • Dabigatran — dronedarone is a strong P-gp inhibitor; contraindicated (markedly increases dabigatran levels)

Side effects

  • GI upset (nausea, diarrhoea, vomiting)
  • Hepatotoxicity (rare but serious — liver failure reported; MHRA 2011 warning)
  • QTc prolongation
  • Bradycardia
  • Pulmonary toxicity (rare — interstitial pneumonitis)
  • Peripheral oedema
  • Creatinine rise (artefact — tubular secretion blockade)

Interactions

  • Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin) — CONTRAINDICATED
  • Digoxin — dronedarone inhibits P-gp; increases digoxin levels 2.5-fold; halve digoxin dose and monitor levels
  • Dabigatran — CONTRAINDICATED (strong P-gp inhibition — markedly increases dabigatran exposure)
  • Simvastatin — increases simvastatin levels (CYP3A4 inhibition); simvastatin max 10 mg with dronedarone
  • Warfarin — increases INR; monitor closely
  • Beta-blockers/non-dihydropyridine CCBs — additive bradycardia

Monitoring

  • LFTs (baseline, monthly for 6 months, then every 6 months)
  • Creatinine and eGFR (baseline, 1 week, then periodically — interpret carefully)
  • ECG (QTc, HR, rhythm)
  • Potassium and magnesium
  • Pulmonary symptoms (dyspnoea — pneumonitis)

Reference: BNFc; BNF 90; ATHENA Trial (Hohnloser et al. NEJM 2009); ANDROMEDA Trial; PALLAS Trial; MHRA DSU 2011 (Hepatotoxicity); ESC 2020 AF Guidelines; SPC Multaq. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

Pathways