ranolazine

Action

Unclear. Appears to modulate myocardial metabolism by partially inhibiting fatty acid oxidation, thereby increasing glucose oxidation and generating more adenosine triphosphate.

Availability

Tablets (extended-release): 500 mg, 1,000 mg

Indications and dosages

➣ Chronic angina

Adults: Initially, 500 mg P.O. twice daily, increased to maximum recommended dosage of 1,000 mg P.O. twice daily if needed

Dosage adjustment

• Concurrent use of moderate CYP3A inhibitors, such as diltiazem, verapamil, and erythromycin

• Concurrent use of P-gp inhibitors such as cyclosporine

Contraindications

• Liver cirrhosis

• Concurrent use of strong CYP3A inhibitors (such as ketoconazole, clarithromycin, nelfinavir)

• Concurrent use of CYP3A inducers (such as rifampin, phenobarbital, St. John's wort)

Precautions

Use cautiously in:

• concurrent digoxin therapy, QT-interval prolongation, drugs that prolong QT interval, moderate CYP3A inhibitors (including diltiazem, verapamil, aprepitant, erythromycin, fluconazole, grapefruit juice, or grapefruit-containing products)

• patients age 75 and older

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

• Administer without regard to meals.

• Don't give with grapefruit juice.

Adverse reactions

CNS: dizziness, headache, vertigo

CV: palpitations

EENT: tinnitus, dry mouth

GI: nausea, vomiting, constipation, abdominal pain

Respiratory: dyspnea

Other: peripheral edema

Interactions

Drug-drug. CYP3A inducers such as carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentin: decreased ranolazine plasma concentration

CYP3A inhibitors such as diltiazem, ketoconazole, macrolide antibiotics, paroxetine, protease inhibitors, verapamil: increased ranolazine blood level

Digoxin, simvastatin: increased blood levels of these drugs

P-gp inhibitors (such as cyclosporine): increased ranolazine exposure

Drug-food. Grapefruit juice and grapefruit-containing products: increased ranolazine blood level

Patient monitoring

• Obtain baseline and follow-up ECGs to evaluate drug effects on QT interval.

• Monitor blood pressure regularly in patients with severe renal impairment.

Patient teaching

• Inform patient that drug can be taken with or without food, but not with grapefruit juice or grapefruit-containing products.

• Advise patient not to chew or crush tablets.

• Instruct patient to consult prescriber before taking other prescription or over-the-counter drugs or herbal products.

• Inform patient that drug isn't intended for acute angina episodes.

• Caution patient to avoiding driving and other hazardous activities until drug effects are known.

• Advise female with childbearing potential to tell prescriber if she is pregnant or plans to become pregnant.

• Advise female not to breastfeed during therapy.

• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs and foods mentioned above.