ranolazine

Absorption: Highly variable.

Distribution: Unknown.

Metabolism/Excretion: Metabolized by the liver primarily by the CYP3A isoenzyme and to a lesser extent by the CYP2D6 isoenzyme; <5% excreted unchanged in urine and feces.

Half-Life: 7 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2–5 hr	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent use of potent CYP3A inhibitors;
Concurrent use of CYP3A inducers;
Hepatic impairment;
Lactation: Lactation.

Use Cautiously in:

Renal impairment;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children;
Geri: risk of adverse reactions in patients >75 yr.

Adv. Reactions/Side Effects ⬆ ⬇

CV: palpitations, QT interval prolongation, TORSADES DE POINTES

EENT: tinnitus

GI: abdominal pain, constipation, dry mouth, nausea, vomiting

GU: acute renal failure

Neuro: dizziness, headache

Interactions ⬆ ⬇

Drug-drug:

Ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, and ritonavir significantly ↑ levels; concurrent use contraindicated.
Rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, and carbamazepine significantly ↓ levels; concurrent use contraindicated.
Verapamil, diltiazem, aprepitant, erythromycin, and fluconazole↑ levels (do not exceed ranolazine dose of 500 mg twice daily).
Cyclosporine may ↑ levels.
Paroxetine may ↑ levels.
May ↑ levels of simvastatin.
May ↓ metabolism and ↑ effects of metoprolol, tricyclic antidepressants, and antipsychotics; dosage adjustments may be necessary.
May ↑ digoxin levels; dose adjustment may be required.

Drug-Natural Products:

St. John's wort significantly ↓ levels (contraindicated).

Grapefruit juice↑ levels (do not exceed ranolazine dose of 500 mg twice daily).

Route/Dosage ⬆ ⬇

PO (Adults ): 500 mg twice daily initially, may be ↑ to 1000 mg twice daily.

Availability ⬆ ⬇

(Generic available)

Extended-release tablets: 500 mg; 1000 mg
Extended-release granules: 500 mg/pkt; 1000 mg/pkt

Assessment ⬆ ⬇

Assess location, duration, intensity, and precipitating factors of anginal pain.
Monitor ECG at baseline and periodically during therapy to evaluate effects on QT interval.

Lab Test Considerations:

Monitor renal function after starting and periodically during therapy in patients with moderate to severe renal impairment (CCr <60 mL/min) for ↑ serum creatinine accompanied by ↑ BUN. Usually has a rapid onset, but does not progress during therapy and is reversible with discontinuation of ranolazine. If acute renal failure develops, discontinue ranolazine.
- May cause transient eosinophilia.
- May cause small mean ↓ in hematocrit.

Implementation ⬆ ⬇

Ranolazine should be used in combination with calcium channel blockers, beta blockers, or nitrates.
- Do not administer with grapefruit juice or grapefruit products.
PO: May be administered without regard to food. DNC: Tablets should be swallowed whole; do not break, crush, or chew.
- Sprinkle granules on one tablespoonful of soft food (applesauce or yogurt) and consume immediately. Do not crush or chew granules.
- Nasogastric (NG) tube: Add content of a sachet to a plastic catheter tip syringe and add 50 mL of water. Gently shake syringe for approximately 15 seconds. Promptly deliver through a 12 French or larger NG tube. Ensure no granules are left in the syringe. Rinse with additional water (about 15 mL) if needed.
- Gastrostomy/Gastric (G) tube: Add content of a sachet to a plastic catheter tip syringe and add 30 mL of water. Gently shake syringe for approximately 15 seconds. Promptly deliver through a 12 French or larger G-tube. Rinse with 20 mL of water in the syringe. Ensure no granules are left in the syringe. Rinse with additional water (about 15 mL) if needed.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take ranolazine as directed. If a dose is missed, take the usual dose at the next scheduled time; do not double doses. Explain to patient that ranolazine is used for chronic therapy and will not help an acute angina episode.
Advise patient to avoid grapefruit juice and grapefruit products when taking ranolazine.
May cause dizziness and light-headedness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
Advise patient to notify health care professional if fainting occurs.
Inform patient that ranolazine may cause changes in the ECG. Patient should inform health care professional if they have a personal or family history of QTc prolongation, congenital long QT syndrome, or proarrhythmic conditions such as hypokalemia.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇