ranolazine (Ranexa)
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Indications
- adjuvant therapy of chronic angina pectoris after other options exhausted[3]
- rhythm control in atrial fibrillation[5]
- may accelerate chemical cardioconversion with amiodarone in patients with recent-onset atrial fibrillation[7]
Contraindications
- pre-existing QT prolongation (a QTc of 440 msec is acceptable)
- hepatic insufficiency (Child-Pugh classes A,B,C)
- coadministration of drugs that prolong QT interval
- no benefit for acute onset coronary artery disease
- no benefit for patients with incomplete revascularization after PCI[4]
- may be of benefit for angina pectoris after coronary stent[3]
Dosage
Tabs: 500 (orange)
Pharmacokinetics
- metabolized by cyt P450 3A4 & to a lesser extent cyt P450 2D6
Monitor
ECG, baseline and follow-up
Adverse effects
- increased QT interval
- dizziness (6%), headache (6%), constipation (4%), nausea (4%)
- others < 2%
- palpitations, tinitus, vertigo, abdominal pain, xerostomia, vomiting, peripheral edema, dyspnea
Drug interactions
- drugs that inhibit cyt P450 3A4 increase ranolazine levels (diltiazem, verapamil, HIV protease inhibitors, macrolides)
- drugs that inhibit cyt P450 2D6 do not increase ranolazine levels significantly
- ranolazine inhibits cyt P450 3A4 & cyt P450 2D6, thus may increase levels of drugs metabolized by these enzymes (simvastatin levels doubled)
- ranolazine inhibits P-glycoprotein and may increase levels of drugs eliminated in part by P-glycoprotein (digoxin levels increased 1.5 fold)
- avoid other drugs that prolong QT interval (amiodarone, erythromycin, quinidine, sotalol, etc)
Mechanism of action
- inhibits late myocyte Na+ current
- no significant effect on heart rate or blood pressure
- facilitates myocardium functioning during ischemia
- reduces intracellular Na+ & Ca+2 during myocardial ischemia
- partially inhibits fatty acid oxidation, thus increases glucose oxidation
- may decrease myocardial oxygen demand
- inhibits P-glycoprotein
More general terms
References
- ↑ Prescriber's Letter 13(3): 2006 New Drug: Ranexa (ranolazine) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220302&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Morrow DA et al, Effects of ranolazine on recurrent cardiovascular events in patients with non ST_segment elevation acute coronary syndromes: The MERLIN-TIMI 36 randomized trial, JAMA 2007, 297:1775 PMID: https://pubmed.ncbi.nlm.nih.gov/17456819
- ↑ 3.0 3.1 3.2 Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
Medical Knowledge Self Assessment Program (MKSAP) 20 American College of Physicians, Philadelphia 2025 - ↑ 4.0 4.1 Weisz G et al. Ranolazine in patients with incomplete revascularisation after percutaneous coronary intervention (RIVER-PCI): A multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2015 Oct 13; PMID: https://pubmed.ncbi.nlm.nih.gov/26474810
Alexander KP et al. Effects of ranolazine on angina and quality of life after percutaneous coronary intervention with incomplete revascularization: Results from the ranolazine for incomplete vessel revascularization (RIVER-PCI) trial. Circulation 2015 Nov 10; PMID: https://pubmed.ncbi.nlm.nih.gov/26555329
Head SJ, Kappetein AP. Coronary artery disease: A dam in the river for ranolazine. Lancet 2015 Oct 13; PMID: https://pubmed.ncbi.nlm.nih.gov/26474812 - ↑ 5.0 5.1 Guerra F, Romandini A, Barbarossa A et al Ranolazine for rhythm control in atrial fibrillation: A systematic review and meta-analysis. Int J Cardiol. 2017 Jan 15;227:284-291.Review. PMID: https://pubmed.ncbi.nlm.nih.gov/27839812
- ↑ Trivedi C, Upadhyay A, Solanki K. Efficacy of ranolazine in preventing atrial fibrillation following cardiac surgery: Results from a meta-analysis. J Arrhythm. 2017 Jun;33(3):161-166. Review. PMID: https://pubmed.ncbi.nlm.nih.gov/28607609 Free PMC Article
- ↑ 7.0 7.1 Gong M, Zhang Z, Fragakis N, Korantzopoulos P et al Role of ranolazine in the prevention and treatment of atrial fibrillation: A meta-analysis of randomized clinical trials. Heart Rhythm. 2017 Jan;14(1):3-11. Epub 2016 Oct 13. PMID: https://pubmed.ncbi.nlm.nih.gov/27746384