#antianginal

Brand Name: Ranexa

Generic Available

Common Dosage Forms:

Tablets, extended release: 500 mg, 1000 mg

FDA Indications/Dosages:

For the treatment of chronic angina: Start with 500 mg twice daily. May increase to 1000 mg twice a day based on clinical symptoms.

Monitor: BP, RFT

Pharmacology/Pharmacokinetics: The exact mechanism of action of ranolazine in the treatment of angina is not fully understood. Its effects do not appear to be related to reductions in heart rate or blood pressure. At therapeutic levels, ranolazine inhibits the cardiac late sodium current but it is not known how this may relate to its anti-angina effects. Ranolazine has been shown to prolong the QT interval via ventricular action potential. Ranolazine is extensively metabolized in the intestines and liver, primarily by CYP3A and to a lesser extent, CYP2D6. Peak plasma levels are reached in 2-5 hours post oral dose. The apparent terminal half-life of ranolazine is 7 hours. Steady state is usually reached in 3 days. Food does not alter pharmacokinetics. Ranolazine is moderately bound to plasma proteins (62%).

Drug Interactions: Do not use with strong CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, indinavir, and saquinavir). Moderate CYP3A inhibitors (diltiazem, verapamil, erythromycin, fluconazole, and grapefruit juice) may increase free ranolazine. Do not use with CYP3A inducers such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John’s Wort. Lower doses of CYP3A substrates (simvastatin, cyclosporine, tacrolimus, sirolimus) and CYP2D6 substrates (tricyclic antidepressants and antipsychotics) should not be used when combined with ranolazine. Doses of ranolazine at 1000 mg twice a day increases plasma concentrations of metformin (limit metformin to 1700 mg daily).

Contraindications/Precautions: Contraindicated in patients with liver cirrhosis and in use with strong CYP3A inhibitors or CYP3A inducers. Do not use in patients with acute renal failure. Use with caution in patients with moderate to severe renal impairment (CrCl <60 mL/min). May cause QT interval prolongation therefore use caution in patients with a history of QT prolongation or with drugs that may cause QT interval prolongation. No data available in pregnant or lactating women.

Adverse Effects: The most common adverse effects are dizziness, headache, constipation, and nausea.

Patient Consultation:

May cause dizziness and lightheadedness. Use caution when operating automobiles or machinery or engaging in activities that require mental alertness.

Notify a physician if you experience fainting spells.

Swallow whole do not crush, chew, or break tablets.

May be taken with or without meals.

Inform your physician and pharmacists of any and all other medications, including over the counter medications, taken concurrently with ranolazine.

If a dose is missed, skip it and return to your normal dosing schedule. Do not double doses.

Brand Name: Imdur

Generic Available

Common Dosage Forms:

Tablets, extended-release: 30 mg, 60 mg, 120 mg

*Isosorbide is also available as the dinitrate salt

FDA Indications/Dosages:

For the prophylactic treatment of angina pectoris due to coronary artery disease: Normal daily dose is 30-120 mg once daily in the morning. The starting dose is 30-60 mg given once daily in the morning. After several days the dose may be increased to 120 mg given as a single daily dose in the morning. Maximum daily dose is 240 mg. Tablets may be halved but they should not be crushed or chewed. Each dose should be followed by 4 ounces of fluid. The onset of action of isosorbide mononitrate is not sufficiently rapid enough to be useful in aborting acute anginal attacks.

Pharmacology/Pharmacokinetics: Isosorbide acts by reduction of myocardial oxygen demand through the relaxation of vascular smooth muscle. This relaxation causes dilation of peripheral arteries and veins which results in a reduction of left ventricular back pressure and more efficient blood flow within the myocardium. Terminal elimination half-life is between 6-7 hours. Tmax is 3-4 hours. Metabolism occurs via d-nitration and glucuronidation in the liver with elimination primarily occurring in the urine.

Drug Interactions: Alcohol may increase hypotensive effects. Additive effects may occur with other vasodilators, especially calcium-channel blockers.

Contraindications/Precautions: Contraindicated in patients who are hypersensitive to nitrates. Use is not recommended in patients during the acute phase of myocardial infarction or in those with congestive heart failure. Use with caution in patients with hypotension or volume depletion. Tolerance and physical dependence may occur after prolonged use. Pregnancy Category B.

Adverse Effects: The most common adverse effects are headache (~50%) and dizziness (~10%). Less common effects include rash, cutaneous vasodilation with flushing, nausea, vomiting, dry mouth, tinnitus, blurred vision, acne, or anxiety.

Patient Consultation:

May cause dizziness, headache, or flushing. Headaches are a sign of drug effectiveness. Do not adjust dosage to treat headache--use aspirin or acetaminophen as needed. Dizziness is more common when standing from a recumbent or seated position.

Swallow whole or halved, do not crush or chew.

Avoid alcohol while taking this medication.

Store in a cool, dry place away from sunlight and children.

If a dose is missed, take it as soon as possible. If it is closer to the time of your next dose than the dose you missed, skip the missed dose and return to your dosing schedule. Do not double doses.