ranolazine


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ranolazine

Ranexa

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

Cardiology An anti-anginal metabolic modulator, which inhibits partial fatty acid oxidation, maintaining glucose oxidation without lactic acid buildup. See CARISA.
References in periodicals archive ?
ENPNewswire-August 22, 2019--Zydus receives final approval from the USFDA for Ranolazine Extended-Release Tablets
* Other product sales, which include products from chronic hepatitis B virus (HBV), cardiovascular, oncology and other categories inclusive of Vemlidy[R] (tenofovir alafenamide 25 mg), Viread[R] (tenofovir disoproxil fumarate 300 mg), Letairis[R] (ambrisentan 5 mg and 10 mg), Ranexa[R](ranolazine 500 mg and 1000 mg), Zydelig[R] (idelalisib 150 mg), AmBisome[R] (amphotericin B liposome for injection 50 mg/vial) and Cayston[R] (aztreonam for inhalation solution 75 mg/vial), were $604 millionfor the second quarter of 2019 compared to $807 million for the same period in 2018.
- Israeli generic drug specialist Teva Pharmaceutical Industries Ltd., (NYSE: TEVA) (TASE: TEVA) has launched a generic version of Ranexa1 (ranolazine) Extended-Release Tablets, 500 mg and 1000 mg, in the US, the company said.
18, 2018 (HealthDay News) -- For high-risk patients with implantable cardioverter-defibrillators (ICDs), ranolazine does not significantly reduce the risk of ventricular tachycardia (VT) or ventricular fibrillation (VF) requiring appropriate ICD therapy, or death, according to a study published in the Aug.
His home medications consisted of aspirin, prasugrel, warfarin, rosuvastatin, carvedilol, ranolazine, amlodipine, lisinopril, hydroxychloroquine, prednisone, and cinacalcet.
The following case is of a 66-year-old man with a complicated cardiac history, who for some time has been experiencing limiting angina despite being on maximally titrated medical therapy of aspirin, prasugrel, carvedilol, ranolazine, isosorbidemononitrate (sustained release), atorvastatin, lisinopril, nitroglycerin patch, and as needed sublingual nitroglycerin.
Ranolazine is an antianginal drug with hypoglycemic action used in AF treatment, which was shown to enhance skeletal muscle differentiation [35].
In a prospective randomized pilot study, addition of a single dose of ranolazine, an antianginal and anti-ischemic agent with atrial-selective inhibition of late sodium channel current, substantially increased AF conversion rate at 24 hours by 23%, in addition to significantly accelerating SR restoration by >4 hours compared with amiodarone treatment [23].
Doses of simvastatin should not exceed 10 mg/d when combined with diltiazem, dronedarone, or verapamil, and doses should not exceed 20 mg/d when used with amiodarone, amlodipine, or ranolazine. (6) These recommendations are in response to results from the SEARCH (Study of the Effectiveness of Additional Reductions in cholesterol and homocysteine) trial, which found a higher incidence of myopathies and rhabdomyolysis in patients taking 80 mg of simvastatin compared with those taking 20-mg doses.
Those ACC/American Heart Association guidelines recommend a stepwise approach beginning with a beta-blocker and sublingual nitroglycerin, adding a calcium channel blocker if the beta-blocker isn't tolerated or effective, further adding a long-acting nitrate if symptoms persist, incorporating ranolazine (Ranexa) as needed, and finally turning to revascularization for symptomatic relief if multidrug therapy proves inadequate (J Am Coll Cardiol.
Modulation of the late sodium current by ATX-II and ranolazine affects the reverse use-dependence and proarrhythmic liability of IKr blockade.
In contrast, LQT3 (caused by gain of function variants in SCN5A) may be treated with sodium channel blockers such as mexilitine, flecainide, or ranolazine (24).