Ranolazine
- Atc Codes:C01EB18
- CAS Codes:95635-55-5
- PHARMGKB ID:95635-55-5
Table of contents
- Brand Names
- Chemistry
- Pharmacologic Category
- Mechanism of Action
- Therapeutic Use
- Pregnancy and Lactation Implications
- Contraindications
- Warnings and Precautions
- Adverse Reactions
- Caution and personalized dose adjustment in patients with the following genotypes
- Substrate of
- Inhibits
- Drug Interactions
- Nutrition/Nutraceutical Interactions
- Dosage
- Pharmacokinetics and Pharmacodynamics
- Special Considerations
Brand Names
Europe
Austria: Ranexa; Bulgaria: Ranexa; Czech Republic: Latixa, Ranexa; Estonia: Ranexa; Germany: Latixa, Ranexa; Greece: Ranexa; Hungary: Ranexa; Ireland: Ranexa; Latvia: Ranexa; Lithuania: Ranexa; Luxembourg: Ranexa; Malta: Ranexa; Netherlands: Ranexa; Poland: Ranexa; Portugal: Ranexa; Romania: Ranexa; Slovakia: Ranexa; Slovenia: Ranexa; Sweden: Ranexa; UK: Ranexa.
North America
USA: Ranexa.
Drug combinations
Chemistry
Ranolazine: C~24~H~33~N~3~O~4~. Mw: 427.54. (1) 1-Piperazineacetamide, N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-; (2)(±)-N-(2,6-Dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-1-piperazineacetamide. CAS-95635-55-5 (2004).
Pharmacologic Category
Cardiac Drugs, Miscellaneous. (ATC-Code: C01EB18).
Mechanism of action
Ranolazine exerts antianginal and anti-ischemic effects without changing hemodynamic parameters (heart rate or blood pressure). At therapeutic levels, ranolazine inhibits late phase of inward sodium channel (late I~Na~) in ischemic cardiac myocytes during cardiac repolarization reducing intracellular sodium concentrations and thereby reducing calcium influx via Na^+^-Ca^2+^ exchange. Decreased intracellular calcium reduces ventricular tension and myocardial oxygen consumption. It is thought that ranolazine produces myocardial relaxation and reduces anginal symptoms through this mechanism although this is uncertain. At higher concentrations, ranolazine inhibits rapid delayed rectifier potassium current (I~Kr~) thus prolonging ventricular action potential duration and subsequent prolongation of QT interval.
Therapeutic use
Treatment of chronic angina.
Pregnancy and lactiation implications
Adverse effects observed in animal studies. There are no adequate, well-controlled studies in pregnant women. Not recommended in nursing women.
Unlabeled use
Contraindications
Clinically significant hepatic impairment. Concurrent strong CYP3A inhibitors. Concurrent inducers of CYP3A.
Warnings and precautions
Prolongs QT interval in dose/plasma concentration-related manner. Hepatically-impaired patients may have more significant increase in QT interval. Ranolazine plasma levels increase by 30% in mild and by 60% in moderate hepatic impairment. Use contraindicated with clinically significant hepatic impairment. Use with caution in renal dysfunction (plasma levels may increase by 50%). Primarily metabolized by CYP3A; use contraindicated with inducers and strong inhibitors of CYP3A. Ranolazine is a substrate for and a moderate inhibitor of ABCB1; inhibitors of ABCB1 may increase serum concentrations of ranolazine. Ranolazine may increase serum concentrations of substrates for ABCB1 (e.g. digoxin). Ranolazine has potential to prolong QT interval (use caution when administered concomitantly with QT-prolonging drugs). Use caution when administering ranolazine in history of malignant neoplasms or adenomatous polyps.