Products
Ranolazine is commercially available in the form of sustained-release tablets (Ranexa). It was approved in the United States as early as 2006, in the EU in July 2008, and in many countries in April 2010.
Structure and properties
Ranolazine or ()–(2, 6-dimethylphenyl)-4(2-hydroxy-3-(2-methoxyphenoxy)-propyl)-1-piperazine acetamide (C24H33N3O4, Mr = 427.54 g/mol) is a piperazine derivative and a racemate.
Effects
Ranolazine (ATC CO1EB18) has antianginal and antiischemic properties. The mechanism of action is not precisely known. The effects are likely the result of inhibition of late sodium flow into cardiac cells. This also allows fewer calcium ions to enter the cells, resulting in relaxation of the myocardium and improved blood flow. Ranolazine, unlike beta blockers and calcium channel blockers, has no effect on heart rate, blood pressure, or vasodilation, so it has a different, novel mechanism of action.
Indications
As adjunctive therapy for symptomatic treatment of patients with stable angina who are inadequately controlled or cannot tolerate first-line antianginal agents (such as beta blockers and/or calcium antagonists).
Dosage
Ranolazine may be taken with meals or independently of meals. It is administered twice daily. The maximum daily dose is 1500 mg.
Contraindications
- Hypersensitivity
- Severe renal dysfunction
- Moderate to severe liver dysfunction
- Concurrent use of strong CYP3A4 inhibitors, e.g., itraconazole, ketoconazole, voriconazole, posaconazole, HIV protease inhibitors, clarithromycin, telithromycin, nefazodone.
- Concurrent use of certain class Ia (e.g., quinidine) or class III (e.g., sofetilide, sotalol) antiarrhythmic agents, except amiodarone.
Refer to the SmPC for complete precautions.
Interactions
Ranolazine is a substrate of CYP3A4. Concomitant administration of inhibitors may result in potentiation of adverse effects. Combination with potent inhibitors is contraindicated. Conversely, inducers may attenuate the effect. Because ranolazine is partially metabolized by CYP2D6, interactions via CYP2D6 are also possible. Ranolazine is also a substrate of P-glycoprotein (P-gp). Co-administration of potent inhibitors of the transporter, such as ciclosporin, quinidine, and verapamil, also increases plasma concentrations. Ranolazine is itself a moderate to strong inhibitor of P-gp and a weak CYP3A4 and CYP2D6 inhibitor. Interactions are therefore possible with digoxin and simvastatin, for example. Furthermore, possible interactions with other drugs that prolong the QT interval must be considered. Full details of interactions can be found in the SmPC.
Adverse effects
The most common adverse effects include dizziness, headache, constipation, vomiting, nausea, and weakness. Ranolazine may prolong the QT interval.
