ranolazine


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ranolazine

Pharmacologic class: Piperazine derivative

Therapeutic class: Antianginal

Pregnancy risk category C

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.

ranolazine

(ra-nole-a-zeen) ,

Ranexa

(trade name)

Classification

Therapeutic: antianginals
Pregnancy Category: C

Indications

Chronic angina pectoris.

Action

Does not ↓ BP or heart rate; remainder of mechanism is not known.

Therapeutic effects

Decreased frequency of angina.

Pharmacokinetics

Absorption: Highly variable.
Distribution: Unknown.
Metabolism and Excretion: Metabolized in the gut (P-glycoprotein) and by the liver (primarily CYP3A and less by CYP2D6); <5% excreted unchanged in urine and feces.
Half-life: 7 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown2–5 hr12 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Concurrent use of potent inhibitors of CYP3A;Concurrent use of inducers of CYP3A;Hepatic impairment; Lactation: Lactation.
Use Cautiously in: Renal impairment; Obstetric: Use only when potential benefit outweighs risk to fetus; Pediatric: Safety not established; Geriatric: ↑ risk of adverse reactions in patients >75 yr.

Adverse Reactions/Side Effects

Central nervous system

  • dizziness
  • headache

Ear, Eye, Nose, Throat

  • tinnitus

Cardiovascular

  • torsades de pointes (life-threatening)
  • palpitations
  • QTc prolongation

Gastrointestinal

  • abdominal pain
  • constipation
  • dry mouth
  • nausea
  • vomiting

Interactions

Drug-Drug interaction

Ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir 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.St. John's wort significantly ↓ levels (contraindicated).Grapefruit juice↑ levels (do not exceed ranolazine dose of 500 mg twice daily).

Route/Dosage

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

Availability (generic available)

Extended-release tablet: 500 mg

Nursing implications

Nursing 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.
    • May cause transient eosinophilia.
    • May cause small mean ↓ in hematocrit.

Potential Nursing Diagnoses

Ineffective tissue perfusion (Indications)
Activity intolerance (Indications)

Implementation

  • Ranolazine should be used in combination with amlodipine, beta blockers, or nitrates.
    • Do not administer with grapefruit juice or grapefruit products.
  • Oral: May be administered without regard to food. Tablets should be swallowed whole; do not break, crush, or chew.

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.

Evaluation/Desired Outcomes

  • Decrease in frequency of angina attacks.

ranolazine

an antianginal.
indications This drug is used in combination with other antianginals (such as amlodipine, beta-blockers, or nitrates) to treat chronic stable angina pectoris in those who have not responded to other treatment options.
contraindications Preexisting Q-T prolongation, hepatic disease (Child-Pugh class A, B, or C), hypokalemia, renal failure, torsades de pointes, ventricular arrhythmia, ventricular tachycardia, and known hypersensitivity to this drug prohibit its use.
adverse effects Adverse effects of this drug include headache, dizziness, palpitations, nausea, vomiting, constipation, dry mouth, peripheral edema, and dyspnea. A life-threatening side effect of this drug is Q-T prolongation.

ranolazine

Cardiology An anti-anginal metabolic modulator, which inhibits partial fatty acid oxidation, maintaining glucose oxidation without lactic acid buildup. See CARISA.
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Gilead) announced results from HARMONY, a randomized, double-blind, placebo-controlled Phase 2 study that evaluates the effect of ranolazine and low-dose dronedarone, each given alone and in combination, on atrial fibrillation burden (AFB) in patients with paroxysmal atrial fibrillation (AF).
Biopharmaceutical company Gilead Sciences Inc (NasdaqGS:GILD) stated on Monday the use of the LogPad System on the Phase 4 TERISA trial that measured the antianginal effect of Ranolazine in T2DM patients in the therapeutic areas of cardiology and endocrinology.
Results of TERISA (Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina), presented by Dr.
The most extensively investigated agents of this group of drugs are trimetazidine and ranolazine.
Therefore, we investigated the relationship between ST2 and presenting clinical characteristics; markers of myocyte injury, inflammation, and hemodynamic stress; and cardiovascular outcomes in the large, multinational, randomized, placebo-controlled Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLINTIMI 36) trial (12).
Its lead drug, Ranolazine, underwent successful human trials last November and may be approved for sale by the end of next year.
Despite promising trial data, Ranexa is not expected to achieve significant market share, owing primarily to the entry of generic ranolazine in 2019.
The Food and Drug Administration has approved a revised indication and several label additions for the angina drug ranolazine, including a statement that the drug reduced hemoglobin [A.
This group of agents consists of the partial fatty acid oxidation inhibitors trimetazidine and ranolazine, as well as dichloroacetate, which promotes carbohydrate utilization.
Nasdaq: GILD) and the Cardiovascular Research Foundation (CRF) today announced the initiation of RIVER-PCI (Ranolazine for Incomplete VEssel Revascularization post-PCI), a Phase 3 clinical trial evaluating the utility of ranolazine to prevent major adverse cardiovascular events (MACE) in patients with a history of chronic angina who have incomplete revascularization following percutaneous coronary intervention (PCI).
NEW ORLEANS -- Ranolazine may have earned a product labeling upgrade from second-line to first-tier status for treatment of chronic angina on the strength of its reassuring safety performance in the 6,560-patient MERLIN trial.