Ranexa

Ranexa - General Information

Ranexa is an antianginal medication. On January 31, 2006, ranolazine was approved for use in the United States by the FDA for the treatment of chronic angina. [Wikipedia]

 

Pharmacology of Ranexa

Ranexa 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.

 

Ranexa for patients

To ensure safe and effective use of Ranexa, the following information and instructions should be communicated to the patient when appropriate.

Patients should be advised:

• that Ranexa is only for patients not responding adequately to other antianginal drugs
• that Ranexa may produce changes in the electrocardiogram (QTc interval prolongation)
• to inform their physician of any personal or family history of QTc prolongation, congenital long QT syndrome,
• or proarrhythmic conditions such as hypokalemia
• that Ranexa should be avoided in patients receiving drugs that prolong the QTc interval such as Class Ia
• (e.g., quinidine) or Class III (e.g., dofetilide, sotalol) antiarrhythmic agents, erythromycin, and certain
• antipsychotics (e.g., thioridazine, ziprasidone)
• that Ranexa should be avoided in patients receiving drugs that are potent or moderately potent inhibitors of
• CYP3A, including, for example, ketoconazole, HIV protease inhibitors, macrolide antibiotics, diltiazem, and
• verapamil
• that grapefruit juice or grapefruit products should be avoided when taking Ranexa
• that doses of Ranexa higher than 1000 mg twice a day should not be used
• that Ranexa will not abate an acute angina episode
• that Ranexa should generally be avoided in patients with mild, moderate or severe liver impairment
• that Ranexa should generally be avoided in patients with severe renal impairment
• to inform their physician of any other medications when taken concurrently with Ranexa, including over-the-
• counter medications
• to contact their physician if they experience palpitations or fainting spells while taking Ranexa
• that Ranexa may cause dizziness and lightheadedness; therefore, patients should know how they react to
• this drug before they operate an automobile, or machinery, or engage in activities requiring mental alertness
• or coordination
• that Ranexa may be taken with or without meals
• that Ranexa tablets should be swallowed whole and not crushed, broken, or chewed

 

Ranexa 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.

 

Ranexa 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

 

Additional information about Ranexa

Ranexa Indication: For the treatment of chronic angina. It should be used in combination with amlodipine, beta-blockers or nitrates.
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. In vitro studies suggest that ranolazine is a P-gp inhibitor. Ranexa is believed to have its effects via altering the trans-cellular late sodium current. It is by altering the intracellular sodium level that ranolazine affects the sodium-dependent calcium channels during myocardial ischemia. Thus, ranolazine indirectly prevents the calcium overload that causes cardiac ischemia.
Drug Interactions: Amiodarone Possible additive effect on QT prolongation
Bretylium Possible additive effect on QT prolongation
Digoxin Ranexa increases digoxin levels
Disopyramide Possible additive effect on QT prolongation
Dofetilide Possible additive effect on QT prolongation
Ibutilide Possible additive effect on QT prolongation
Moricizine Possible additive effect on QT prolongation
Procainamide Possible additive effect on QT prolongation
Quinidine Possible additive effect on QT prolongation
Simvastatin Ranexa increases the statin level
Sotalol Possible additive effect on QT prolongation
Thioridazine Possible additive effect on QT prolongation
Ziprasidone Possible additive effect on QT prolongation
Voriconazole Increased levels of ranolazine - risk of toxicity
Verapamil Increased levels of ranolazine - risk of toxicity
Tipranavir Increased levels of ranolazine - risk of toxicity
Telithromycin Increased levels of ranolazine - risk of toxicity
Saquinavir Increased levels of ranolazine - risk of toxicity
Ritonavir Increased levels of ranolazine - risk of toxicity
Nelfinavir Increased levels of ranolazine - risk of toxicity
Ketoconazole Increased levels of ranolazine - risk of toxicity
Itraconazole Increased levels of ranolazine - risk of toxicity
Indinavir Increased levels of ranolazine - risk of toxicity
Fosamprenavir Increased levels of ranolazine - risk of toxicity
Fluconazole Increased levels of ranolazine - risk of toxicity
Erythromycin Increased levels of ranolazine - risk of toxicity
Clarithromycin Increased levels of ranolazine - risk of toxicity
Atazanavir Increased levels of ranolazine - risk of toxicity
Amprenavir Increased levels of ranolazine - risk of toxicity
Diltiazem Increased levels of ranolazine - risk of toxicity
Dirithromycin Increased levels of ranolazine - risk of toxicity
Food Interactions: Not Available
Generic Name: Ranolazine
Synonyms: (-)-Ranolazine; Ranolazine 2HCl; Ranolazine Dihydrochloride
Drug Category: Enzyme Inhibitors
Drug Type: Small Molecule; Approved; Investigational

Other Brand Names containing Ranolazine: Ranexa;
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 (Overdose): 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.
Protein Binding: 62%
Biotransformation: Hepatic, metabolized mainly by CYP3A and to a lesser extent by CYP2D6. The pharmacologic activity of the metabolites has not been well characterized.
Half Life: 7 hours
Dosage Forms of Ranexa: Tablet, film coated, extended release Oral
Chemical IUPAC Name: N-(2,6-dimethylphenyl)-2-[4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl]acetamide
Chemical Formula: C24H33N3O4
Ranolazine on Wikipedia: https://en.wikipedia.org/wiki/Ranolazine
Organisms Affected: Humans and other mammals