Metabolic Anti-Anginal Pregnancy: Avoid — limited data; not recommended in pregnancy

Trimetazidine

Brand names: Vastarel

Adult dose

Dose: 35 mg twice daily (modified-release) with meals

Route: Oral

Frequency: Twice daily with meals

Max: 70 mg/day

Metabolic anti-anginal — inhibits 3-ketoacyl CoA thiolase (3-KAT), shifting myocardial metabolism from free fatty acid oxidation to glucose oxidation. Glucose oxidation requires less oxygen for equivalent ATP production — improves ischaemic myocardial efficiency. Does NOT affect heart rate or blood pressure.

Paediatric dose

Route: Oral

Seek specialist opinion — not licensed in children

Dose adjustments

Renal

eGFR 30-60: 35 mg once daily. eGFR <30: AVOID — metabolite accumulation causes Parkinson-like symptoms.

Hepatic

No dose adjustment for mild-moderate impairment; limited data in severe hepatic impairment

Clinical pearls

Mechanism — myocardial metabolic switch: normal myocardium obtains 60-70% energy from fatty acid oxidation (FAO). In ischaemia, FAO becomes inefficient (requires more O2 per ATP than glucose oxidation) and accumulates toxic intermediates. Trimetazidine inhibits the last enzyme of FAO (3-KAT), forcing myocardium to use glucose oxidation — reduces O2 consumption for equivalent work output.
MHRA 2012 withdrawal recommendation: initially MHRA considered withdrawing trimetazidine due to Parkinsonism reports. Decision reversed — trimetazidine retained with new contraindications (Parkinson's disease, extrapyramidal symptoms) and dose reduction in CKD. It remains licensed in UK for add-on treatment of stable angina.
EMA review: European Medicines Agency (EMA) in 2012 confirmed trimetazidine remains available but restricted — not for dizziness/tinnitus indications, only for stable angina as add-on. Assess benefit at 3 months; stop if no improvement.
Haemodynamic neutrality advantage: trimetazidine does NOT lower BP or HR. This makes it uniquely useful in patients with refractory angina who are already limited by bradycardia (on maximum beta-blocker) or hypotension (on maximum CCB/nitrate) — no further haemodynamic compromise.
Evidence in heart failure: TRIMPOL trial and meta-analyses suggest trimetazidine may improve EF and exercise tolerance in ischaemic HFrEF as add-on therapy. Not yet a guideline-recommended HF therapy but area of ongoing interest.

Contraindications

Parkinson's disease or parkinsonian symptoms (MHRA 2012 — trimetazidine can cause/worsen extrapyramidal symptoms)
eGFR <30
Hypersensitivity to trimetazidine

Side effects

Parkinsonism (tremor, rigidity, gait disturbance — MHRA 2012 warning; higher risk in elderly and CKD)
Restless legs syndrome
GI upset (nausea, diarrhoea)
Dizziness
Headache

Interactions

No significant pharmacokinetic drug interactions — purely metabolic mechanism

Monitoring

Angina frequency and severity (efficacy at 3 months)
Neurological symptoms (tremor, rigidity, restless legs)
eGFR (renal dose adjustment)
Blood pressure and HR (unchanged by trimetazidine — monitor for other medication effects)

Reference: BNFc; BNF 90; TRIMPOL Trial; EMA Review 2012 (Trimetazidine); MHRA DSU 2012 (Parkinsonism); ESC Stable CAD Guidelines 2019; SPC Vastarel. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways