Class I Antiarrhythmics
Contraindicated
Textbook
Increased risk of significant Q-T interval prolongation.
Should not be used along with other Q-T prolonging drugs.
Source: KDT 7e · p554
Drug reference
Ranolazine
Anti-anginal agent (late sodium current inhibitor) · Antianginal
START
Baseline ECG (QTc), creatinine, LFTs. Verify no CYP3A4 inhibitors/inducers or diltiazem/verapamil use. Counsel on taking WITH food.
TYPICAL MAX
1000mg BID. QT prolongation is dose-related—do not exceed. Monitor ECG at baseline and after dose increase.
STOP IF
QTc >500ms, syncope, severe constipation, signs of torsades de pointes, anaphylaxis, hepatotoxicity (jaundice, LFTs >3x ULN).
WATCH
QTc interval at baseline and during titration (dose-related QT prolongation). Dizziness and constipation are most common side effects. Renal impairment increases levels—use caution if CrCl <30. Does NOT reduce BP or HR—useful when these are already optimized.
CDSCO approvedATC C01EB18
KDIGO 2024 + manufacturer label
- ONSET
- 30min · Onset ~30 min
- PEAK
- 3.5h · Tmax 2-5 hours
- t½
- 7h · t½ ~7 hours
- DURATION
- 12h · 12 hours (BID)
EXCRETION
Renal as metabolites (~75%)
route + CYP
INTERACTIONS
12 major
incl. contraindicated
PREGNANCY
Limited data; use only if clearly needed. Animal studies show no teratogenicity at therapeutic doses.
FDA category + note
Top interactionssee all 12 →
- Class I AntiarrhythmicsContraindicatedTextbookKDT 7e · p554
- Class Iii AntiarrhythmicsContraindicatedTextbookKDT 7e · p554
- Hiv Protease InhibitorsContraindicatedTextbookG&G 14e · p619
- Imidazole AntibioticsContraindicatedTextbookG&G 14e · p619
Available in India
76 branded formulations. Look up specific brands in the Drugs workspace.
Mechanism
Inhibits the late inward sodium current (INa) in cardiac myocytes, reducing intracellular sodium accumulation. This decreases calcium overload via the sodium-calcium exchanger, improving myocardial relaxation and reducing wall tension and oxygen demand. Does NOT significantly affect heart rate, blood pressure, or contractility at therapeutic doses.
Indications
Chronic stable angina (add-on therapy when angina inadequately controlled with beta-blockers, calcium channel blockers, and/or nitrates)
Dosing
- Adult
- 500mg PO BID initially with meals; increase to 1000mg BID after 1-2 weeks if tolerated and angina persists. Max 1000mg BID.
- Pediatric
- Not established in children.
- Renal adjustment
- CrCl 30-80: no adjustment. CrCl <30: use caution; limited data; increased levels.
- Hepatic adjustment
- Mild: no adjustment. Moderate-severe cirrhosis: contraindicated.
- Geriatric
- No specific adjustment; monitor for dizziness, constipation, and QT prolongation.
- Max dose
- 1000mg BID (2000mg/day)
Pharmacokinetics
Onset
Angina reduction within 1-2 weeks
Peak effect
Tmax 2-5 hours; steady-state in 2-3 days
Duration
12 hours (BID dosing)
Half-life
~7 hours
Bioavailability
~35-50% (food increases by ~20-30%)
Protein binding
~62%
Metabolism
Extensive hepatic via CYP3A4 (major) and CYP2D6 (minor) to active and inactive metabolites
Excretion
~75% renal (metabolites); ~25% fecal
Contraindications
- Concomitant strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, nefazodone)
- Concomitant CYP3A4 inducers (rifampicin, phenytoin, phenobarbital, carbamazepine, St. John's wort)
- Concomitant diltiazem or verapamil (moderate CYP3A4 inhibitors)
- Hepatic cirrhosis
- QT prolongation / congenital long QT syndrome
- Hypersensitivity to ranolazine
Side effects
Common
DizzinessHeadacheConstipationNauseaAsthenia / fatigueQT prolongation (dose-related)
Serious
- QT prolongation / torsades de pointes
- Severe constipation / intestinal obstruction
- Acute renal failure (rare)
- Hepatotoxicity (rare)
- Anaphylaxis
- Syncope
Pregnancy & lactation
Pregnancy
Limited data; use only if clearly needed. Animal studies show no teratogenicity at therapeutic doses.
Lactation
Excretion in breast milk unknown; use with caution during breastfeeding.
Drug interactions
Class Iii Antiarrhythmics
Contraindicated
Textbook
Increased risk of significant Q-T interval prolongation.
Should not be used along with other Q-T prolonging drugs.
Source: KDT 7e · p554
Hiv Protease Inhibitors
Contraindicated
Textbook
Enhanced ranolazine exposure and potential for increased ranolazine toxicity.
Ranolazine should not be used together with strong CYP3A4 inhibitors.
Source: G&G 14e · p619
Imidazole Antibiotics
Contraindicated
Textbook
Enhanced ranolazine exposure and potential for increased ranolazine toxicity.
Ranolazine should not be used together with strong CYP3A4 inhibitors.
Source: G&G 14e · p619
Lopinavir
Contraindicated
Textbook
Increased plasma levels and toxicity of ranolazine, including QT prolongation.
Should not be given to patients taking CYP3A4 inhibitors.
Source: KDT 7e · p554
Macrolide Antibiotics
Contraindicated
Textbook
Enhanced ranolazine exposure and potential for increased ranolazine toxicity.
Ranolazine should not be used together with strong CYP3A4 inhibitors.
Source: G&G 14e · p619
Diltiazem
Contraindicated
Database
Moderate CYP3A4 inhibitors; increase ranolazine levels and QT prolongation risk; also additive AV nodal effects.
Contraindicated. Consider amlodipine or beta-blocker instead.
Source: Kimi deep-research + Cla
Ketoconazole
Contraindicated
Database
Increased plasma levels and toxicity of ranolazine, including QT prolongation.
Should not be given to patients taking CYP3A4 inhibitors.
Source: DDInter
Cyp3a4 Inducers
Contraindicated
Database
Reduces ranolazine levels by >95%, eliminating efficacy.
Contraindicated. Use alternative anti-anginal.
Source: Kimi deep-research + Cla
Strong Cyp3a4 Inhibitors
Contraindicated
Database
Increases ranolazine levels 2-3 fold; marked QT prolongation risk.
Contraindicated. Use alternative anti-anginal if these drugs needed.
Source: Kimi deep-research + Cla
Aminoglutethimide
Severe
Database
Drug interaction classified as: metabolism
Source: DDInter
Amiodarone
Severe
Database
Drug interaction classified as: synergy
Source: DDInter
Related guidelines
Ask House about Ranolazine
Continue into a citation-backed clinical answer with the drug context already attached.
Sources: KD Tripathi 7e, Goodman & Gilman 14e, Harrison 22e, Katzung·Verified: 2026-05-19 · House clinical team·Cockpit curated: 2026-05-19