Ranexa (ranolazine)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Ranolazine, a piperazine derivative, is an antianginal agent.
Ranolazine, a piperazine derivative, is an antianginal agent. Although the exact mechanism of antianginal activity of ranolazine has not been fully elucidated, results of early studies suggested that ranolazine shifted adenosine triphosphate (ATP) production away from fatty acid oxidation (i.e., partial inhibition of fatty acid oxidation) in favor of more oxygen-efficient glucose oxidation, especially when free fatty acid concentrations were elevated (e.g., during ischemia), leading to reduced oxygen demand and symptoms of ischemia without affecting cardiac work. However, these pharmacologic effects generally were observed at concentrations exceeding therapeutic plasma concentrations in clinical studies.
Data suggest that ranolazine may exert its antianginal and anti-ischemic effects through concentration-, voltage-, and frequency-dependent inhibition of the late (i.e., sustained, persistent) sodium current and other cardiac ion channels and transporters. The late sodium current is created by inactivation of the sodium channel protein. However, angina (i.e., ischemia, hypoxia) impairs sodium channel inactivation and increases the amount of sodium in cardiac cells, which facilitates calcium overload via the sodium-calcium exchange pump.
Increased intracellular calcium may result in myocyte hyperexcitability and electrical instability, impaired diastolic relaxation, reduced coronary artery perfusion, impaired myocardial oxygen supply, increased oxygen demand, and ventricular dysfunction. Thus, ranolazine may decrease the magnitude of the late sodium current resulting in a net reduction in intracellular sodium concentrations, reversal of calcium overload, restoration of ventricular pump function, and prevention of ischemia-induced arrhythmias. Unlike other antianginal agents, the antianginal effects of ranolazine are not dependent upon reductions in heart rate or blood pressure.
The QT interval prolongation effect of ranolazine is caused by inhibition of IKr, which prolongs the ventricular action potential.
Ranolazine is extensively metabolized in the intestine and liver by the cytochrome P-450 (CYP) isoenzyme system, mainly by CYP3A and, to a lesser extent, CYP2D6. In vitro studies indicate that ranolazine also is a p-glycoprotein substrate. At least 4 metabolites of ranolazine have been identified.
The pharmacologic activity of these metabolites has not been fully established. Approximately 75% of an oral dose of ranolazine is eliminated in urine and 25% is excreted in feces; less than 5% is recovered in urine and feces as unchanged drug.
USES: Ranolazine is used to treat a certain type of chest pain (chronic angina). It decreases how often you may get chest pain and may help to increase your ability to exercise. Ranolazine works differently than other drugs for angina, so it can be used with your other angina medications (including nitrates, calcium channel blockers such as amlodipine, beta blockers such as metoprolol).
It is thought to work by improving how well the heart uses oxygen so that it can do more work with less oxygen.
Generic name: ranolazine
Pronunciation: (ra-NOE-la-zeen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Ranexa
Indications
The following indications are listed for Ranexa:
- Prevention Of Anginal Pain Associated With Coronary Artery Disease
Also known as: Prevention Of Anginal Pain Associated With Cad.
Dosing
The recommended initial adult dosage of ranolazine for adjunctive therapy in the management of chronic stable angina pectoris is 500 mg twice daily; dosage may be increased based on clinical response up to the maximum recommended dosage of 1 g twice daily. Dosages exceeding 1 g twice daily are poorly tolerated and should not be used.
Ranolazine is contraindicated in patients receiving inducers or strong inhibitors of cytochrome P-450 isoenzyme 3A (CYP3A). Ranolazine dosage should not exceed 500 mg twice daily in patients receiving moderate CYP3A inhibitors. (See Drug Interactions.)
Ranolazine is administered orally without regard to meals. Ranolazine tablets should be swallowed whole and not broken, chewed, or crushed. If a dose of ranolazine is missed, the next dose should be taken at the regularly scheduled time; the dose should not be doubled.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Hepatic cirrhosis.
Concomitant use with inducers or potent inhibitors of cytochrome P-450 (CYP) isoenzyme 3A. (See Drug Interactions.)
Known hypersensitivity to ranolazine or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in 4% or more of patients receiving ranolazine and more frequently than placebo include constipation, dizziness, nausea, and headache.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy not established in children younger than 18 years of age.
Category C. (See Users Guide.)
It is not known whether ranolazine is distributed into milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions to ranolazine in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
A substantial number of patients studied in controlled clinical trials of ranolazine for management of chronic angina were geriatric (i.e., 48% were 65 years of age or older and 11% were 75 years of age or older). No overall differences in efficacy were observed between older and younger patients. In addition, no differences in safety were reported between patients 65 years of age or older and younger patients. However, in patients 75 years of age or older, higher and greater severity of adverse effects and drug discontinuance associated with ranolazine (compared with placebo) was observed. In general, dosage of ranolazine should be selected cautiously in geriatric patients, usually initiating therapy at the low end of the dosage range. The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly also should be considered.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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