Brands, Medical Use, Clinical Data
Drug Category
Dosage Forms
- Tablets (extended release - 500 mg)
Brands / Synonyms
(-)-Ranolazine
; Ranexa; Ranolazine 2HCl; Ranolazine Dihydrochloride
Indications
For the treatment of chronic angina. It should be used in combination with amlodipine, beta-blockers or nitrates.
Pharmacology
Ranolazine has antianginal and anti-ischemic effects that do not depend upon reductions in heart rate or blood pressure. It is the first new anti-anginal developed in over 20 years.
Mechanism of Action
The mechanism of action of ranolazine is unknown. It does not increase the rate-pressure product, a measure of myocardial work, at maximal exercise.
Absorption
Absorption is highly variable. After oral administration of ranolazine as a solution, 73% of the dose is systemically available as ranolazine or metabolites. The bioavailability of oral ranolazine relative to that from a solution is 76%.
Toxicity
In the event of overdose, the expected symptoms would be dizziness, nausea/vomiting, diplopia, paresthesia, and confusion. Syncope with prolonged loss of consciousness may develop.
Biotrnasformation / Drug Metabolism
Hepatic, metabolized mainly by CYP3A and to a lesser extent by CYP2D6. The pharmacologic activity of the metabolites has not been well characterized.
Contraindications
Ranexa is contraindicated in patients: - With pre-existing QT prolongation
- With hepatic impairment (Child-Pugh Classes A [mild], B [moderate] or C [severe])
- On QT prolonging drugs
- On potent and moderately potent CYP3A inhibitors, including diltiazem
Drug Interactions
Pharmacokinetic Interactions:Effects of Other Drugs on Ranolazine
Ketoconazole
As a potent inhibitor of CYP3A, ketoconazole (200 mg b.i.d.) increases average steady-state plasma concentrations of ranolazine 3.2-fold.Ranexa should not be used during treatment with ketoconazole.
Diltiazem
As a moderate inhibitor of CYP3A, diltiazem (180 to 360 mg daily) causes dose-dependent mean increases in average ranolazine steady-state concentrations of about 1.8- to 2.3-fold.
Verapamil
Verapamil 120 mg t.i.d. increases ranolazine steady-state plasma concentrations about 2-fold.
Cimetidine
Co-administration of cimetidine does not increase the plasma concentrations of ranolazine.No dose adjustment of Ranexa is required in patients treated with cimetidine.
Digoxin
Co-administration of digoxin does not increase the plasma concentration of ranolazine.No dose adjustment of Ranexa is required in patients treated with digoxin.
Paroxetine
Paroxetine, a potent inhibitor of CYP2D6, increased average steady-state plasma concentrations of ranolazine 1.2-fold.No dose adjustment of Ranexa is required in patients treated with paroxetine or other CYP2D6 inhibitors.
Pharmacokinetic Interactions:Effects of Ranolazine on Other Drugs
Digoxin
As a result of an interaction at the P-gp level, co-administration of ranolazine and digoxin results in a 1.5-fold elevation of digoxin plasma concentrations.The dose of digoxin may have to be adjusted when ranolazine is co- administered with digoxin.
Simvastatin
Co-administration of ranolazine and simvastatin results in about a 2-fold increase in plasma concentrations of simvastatin, and its active metabolite.
Warfarin
Ranolazine has no significant effect on the pharmacokinetics of (+) R and (-) S warfarin.
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