Ranolazine

Ranolazine is a prescription drug used for the treatment of chronic angina (chest pain associated with heart disease). It should only be used in people who have not achieved an adequate response with other drugs used to treat angina. Ranolazine will not relieve an acute (sudden onset) episode of angina.

Ranolazine is marketed as Ranexa by CV Therapeutics in the United States.

Uses
Ranolazine is used for the treatment of chronic (long-standing) angina. It should only be used in people who have not responded to other medications used to treat angina. It is not effect in relieving acute (sudden onset) angina symptoms. The drug should be used in combination with other drugs used to treat angina, such as amlodipine, beta-blockers, or nitrates.

How Ranolazine is Taken
Ranolazine is available in 500 and 1000 mg tablets. Tablets should be taken by mouth, swallowed whole, and can be taken with or without food. If a dose is missed, the prescribed dose should be taken at the next scheduled time. The next dose should not be doubled.

Ranolazine dosing is typically started at 500 mg twice daily and increased to 1000 mg twice daily, as needed to control the symptoms of angina. The maximum dose is 1000 mg taken twice a day.

How Ranolazine Works
Ranolazine works to prevent attacks of angina and to prevent decreased blood flow to heart muscle. How the drug accomplishes this is not known at this time.

How the Body Affects Ranolazine
Peak levels of the drug in the bloodstream are reached between two and five hours after a dose.

Ranolazine is metabolized in the liver (by the liver enzyme CYP3A) and intestine. Approximately 75% of the original dose is excreted in urine and 25% in feces in the form of metabolites.

Side Effects
The most frequently reported side effects (unwanted effects) occurring in more than 2% of people taking ranolazine include the following:


 * dizziness
 * headache
 * constipation
 * nausea

Risks and Precautions
Ranolazine, like other drugs used to treat heart disease, has been associated with changes in the way electrical impulses are sent through the heart to produce a heart beat. This phenomenon is called prolongation of the QTc interval (as measured on an electrocardiogram) which in some people can lead to an arrhythmia (abnormal rhythm of the heart).

Because ranolazine is metabolized by the CYP3A enzyme system in the liver, people on other medications that affect this system, such as rifampin or diltiazem, should not take ranolazine. People with significant liver disease should also avoid ranolazine.

Ranolazine should be used with caution in the elderly.

There has been one published study showing that mice given a large dose of ranolazine were more likely to develop intestinal tumors compared with untreated mice. The clinical significance of this finding is unclear.

It is not known whether ranolazine is excreted in human milk and what effect the drug might have on a developing infant. The decision to use ranolazine in women who are breast feeding must take into account any possible effects on the child and the importance of the drug to the mother.

The safety and effectiveness of ranolazine in children has not been studied.

Drug Interactions
The following drugs may interact with ranolazine:


 * Ketoconazole
 * Diltiazem
 * Verapamil
 * Cimetidine
 * Rifampin
 * Digoxin
 * Paroxetine
 * Simvastatin
 * Warfarin

In addition, ranolazine is primarily metabolized by the liver enzyme CYP3A. Concurrent use of ranolazine and an inducer of CYP3A (such as rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, and [[St. John's Wort|St. John's Wort) is not recommended.

Effectiveness
In a pivotal study (CARISA) of 823 patients with chronic angina, subjects received either ranolazine (750 mg or 1000 mg twice a day) or placebo along with other antianginal drugs. The conclusion was that those taking ranolazine had increased exercise capacity and required less nitroglycerin use than those taking placebo.

In another pivotal trial (ERICA), 565 patients with chronic angina were treated with either ranolazine or placebo along with another heart medication, amlodipine. The researchers concluded that ranolazine significantly reduced the frequency of angina and nitroglycerin use compared with placebo.

The MERLIN-TIMI 36 study, the largest study of Ranexa in patients with chronic angina, demonstrated that Ranexa significantly reduced the risk of recurrent ischemia and worsening angina in over 3500 angina patients.