Makindo Medical Notes

Ranolazine (Anti-anginal) — Clinician Guide

Always check the up-to-date BNF entry ➝ Ranolazine | BNF. This page gives practical, exam-ready pearls with UK context and safety cues.

Mode of Action (Why it helps angina)

• Late Na⁺ current inhibition in ventricular myocytes ↓ intracellular Na⁺ ➝ ↓ Na⁺/Ca²⁺ exchange ➝ ↓ diastolic Ca²⁺ overload ➝ improved lusitropy (relaxation) and subendocardial perfusion.
• Anti-ischaemic effect is largely haemodynamically neutral (minimal effect on HR/BP) — useful where bradycardia or hypotension limit β-blockers/CCBs.
• Exam pearl: Ranolazine reduces angina frequency without lowering heart rate or blood pressure — think of it when HR/BP already low or rate-limiting drugs not tolerated.

Indications (UK/NICE-aligned use)

• Chronic stable angina as:
  • Add-on if symptoms persist on first-line (β-blocker and/or dihydropyridine CCB).
  • Alternative when first-line drugs are contraindicated or not tolerated (e.g., bradycardia, hypotension, bronchospasm).
• Not for acute angina/ACS relief (no role in acute haemodynamic control).

Dose & Titration (modified-release tablets)

Start low, go slow; titrate to symptom control if tolerated. Check ECG/QT and interactions during up-titration.

• Missed dose: Take next scheduled dose (don’t double).
• Swallow whole (do not crush or chew).

Renal & Hepatic Considerations

• Hepatic impairment: Contraindicated in moderate–severe hepatic impairment/cirrhosis (↑ exposure and QT). Avoid in any clinically significant liver disease unless specialist advises.
• Renal impairment: Avoid/stop in severe renal impairment (e.g., CrCl <30 mL/min) or if acute renal failure develops; use cautiously in mild–moderate impairment with closer monitoring (U&E, creatinine).

Key Interactions (check BNF before prescribing)

• CYP3A interactions (major):
  • Strong inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) ➝ contraindicated.
  • Moderate inhibitors (e.g., diltiazem, verapamil, erythromycin) ➝ limit ranolazine to ≤500 mg BD; monitor QT and adverse effects.
  • Inducers (e.g., rifampicin, carbamazepine, phenytoin, St John’s wort) ➝ avoid (loss of efficacy).
  • Grapefruit juice ➝ avoid (↑ levels).
• CYP2D6 inhibition (by ranolazine): ↑ levels of metoprolol, TCAs, some antipsychotics — consider dose reductions/monitoring.
• P-gp/OCT2 effects:
  • Digoxin levels may rise — check levels and clinical status after initiation/titration.
  • Simvastatin exposure ↑ — consider max 20 mg daily or switch statin.
  • Metformin exposure ↑ — consider dose limits/monitor glucose and GI tolerance.
• QT-prolonging drugs: Additive risk (e.g., class Ia/III antiarrhythmics, some macrolides, fluoroquinolones, antipsychotics) — avoid or monitor ECG and electrolytes.

Contraindications

• Moderate–severe hepatic impairment/cirrhosis.
• Concomitant strong CYP3A inhibitors/inducers.
• Known congenital long-QT syndrome or baseline prolonged QTc; uncorrected hypokalaemia/hypomagnesaemia.
• Severe renal impairment or acute renal failure.

Cautions

• Elderly, low body weight, renal impairment ➝ higher exposure.
• History of arrhythmia, QT-risk combinations, electrolyte imbalance.
• Hepatic disease (any degree) ➝ prefer alternatives unless specialist advises.
• Driving/operating machinery: may cause dizziness or syncope.

Adverse Effects (counsel & monitor)

• Common: Constipation, nausea, vomiting, dyspepsia; dizziness, headache; asthenia; palpitations.
• Cardiac: QT prolongation (dose-related; torsades rare) — more likely with interacting drugs or electrolyte disturbance.
• Lab: Small creatinine rise (tubular handling), usually benign; monitor renal function if impaired.

Monitoring Plan (pragmatic)

• Before start: Medication review for CYP3A/QT risks; baseline ECG (QTc), U&E (K⁺, Mg²⁺), renal function; BP/HR (document haemodynamics).
• After each up-titration: Assess angina frequency, dizziness/GI effects; consider repeat ECG if risk factors or higher doses/combos.
• Ongoing: Periodic ECG/electrolytes in high-risk patients; drug-specific monitoring (e.g., digoxin level, metformin exposure/renal function).

Clinical Reasoning Pearls (UK context)

• When HR low or BP borderline (limits β-blocker/CCB), ranolazine is a logical add-on.
• Polypharmacy check is crucial (CYP3A & QT) — most failures are interaction-related.
• In diabetic patients, ranolazine may have a modest HbA1c-lowering effect, but it is not a glycaemic drug; don’t use it for diabetes control.
• Persistent angina despite optimal therapy warrants review of adherence, interactions, anaemia, thyroid, renal function and consideration of functional testing or re-vascularisation discussion.

Patient Counselling (30-second script)

• “This helps your heart muscle relax and get more oxygen without slowing the heart or dropping BP.”
• “Take it twice daily, same times; swallow whole; don’t drink grapefruit juice.”
• “Tell us if you feel faint, very dizzy, or notice palpitations — we may check your ECG and bloods.”

References

• BNF: Ranolazine — dosing, cautions, interactions (check each time)
• NICE CG for stable angina (use as add-on/alternative when first-line not tolerated or inadequate)

Revisions

• Reviewed & expanded: 01/09/2025 (UK context, safety & interactions emphasised)