Drug information of Ranolazine

Ranolazine

Drug group:

Ranolazine is an antianginal medication.

Mechanism of effect

The mechanism of action of ranolazine is unknown. In vitro studies suggest that ranolazine is a P-gp inhibitor. Ranolazine is believed to have its effects via altering the trans-cellular late sodium current. It is by altering the intracellular sodium level that ranolazine affects the sodium-dependent calcium channels during myocardial ischemia. Thus, ranolazine indirectly prevents the calcium overload that causes cardiac ischemia.

Pharmacodynamic

Ranolazine has antianginal and anti-ischemic effects that do not depend upon reductions in heart rate or blood pressure. It is the first new anti-anginal developed in over 20 years.

Pharmacokinetics

Bioavailability: 76%; absorption is highly variable but is unaffected by food

Peak plasma time: 2-5 hr

Protein bound: 62%

Metabolism

Intestine and liver (CYP3A4 and CYP2D6)

Enzymes inhibited: CYP3A4 (weak); CYP2D6 (moderate)

Half-life: 7 hr

Excretion: Urine (75%), feces (25%)

Drug indications

Chronic Angina

Dosage

Adult

Chronic angina

500 mg PO BID initially; may increase to 1,000 mg PO BID, if needed

Pediatric

<18 years: Safety and efficacy not established

Drug contraindications

Hepatic cirrhosis, including Child-Pugh class A (mild), B (moderate), and C (severe)
Strong CYP3A inhibitors (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir)
CYP3A inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, rifabutin, rifapentine, St. John’s wort)

Side effects

Dizziness, Nausea , Constipation , Headache , Syncope

Interactions

Amitriptyline , Amiodarone , Aprepitant , Erythromycin , Ondansetron , Everolimus , Oxecarbazepin , Itraconazole , Isoniazid , Budesonide , Bosentan , Primidone , Posaconazole , Pimozide , Triamcinolone , Topotecan , Topiramate , Thioridazine , Dexamethasone , Disopyramide , Cimetidine , Sotalol , Cisapride , Simvastatin , Cyclosporine , Fludrocortisone , Fluvoxamine , Fluconazole , Phenobarbital , Phenytoin , Griseofulvin , Lapatinib , Metronidazole , Metformin , Methylprednisolone , Modafinil , Nortriptyline , Nifedipine , Nilotinib , Hydrocortisone , Verapamil , Voriconazole , Carbamazepine , Ketoconazole , Clarithromycin , miconazol , Rifabutin , Rifapentine , Atazanavir , Daunorubicin , Rifampin , Zafirlukast , Colchicine , saquinavir , Bepridil , Apalutamide , Edoxaban , Lopinavir and Ritonavir , Nitrendipine , Triphasic , Aminoglutethimide (Oral) , cobicistat , Delavirdine , Oxiconazole , Letermovir , Butabarbital , Betrixaban , Etravirine , Halofantrine , Grepafloxacin , Darifenacin , Mibefradil , Troglitazone , Indapamide , Inotuzumab‎ , Fosinopril , Ramipril , Arsenic trioxide , Efavirenz , nelfinavir , mitotane , Prednisolone , vandetanib , Mesoridazine , Procainamide , Darunavir , Pentamidine , Quinidine , Grapefruit , Pentobarbital , Amobarbital , Ethinyl Estradiol , Nefazodone , Eucalyptus , prednisone , cortisone , dronedarone , ritonavir , nevirapine , marijuana , Arsenic , Fosamprenavir , Afatinib , pomalidomide , Indinavir , Panobinostat , Ibutilide , Eribulin , Armodafinil , Butalbital and Acetaminophen , Fosphenytoin , Idelalisib , Lumefantrine / artemether , Terfenadine , Secobarbital , ivosidenib , glasdegib , Eliglustat , riociguat , conivaptan , bosutinib , nafcillin , vemurafenib , Fluticasone and Vilanterol , macimorelin , Venetoclax

Alerts

Not for acute anginal episodes

While ACS patients appear not to be at increased risk for proarrhythmia or sudden death, ranolazine has been shown to block I-Kr and cause dose-related QTc-interval prolongation

Little data available on high doses (ie, >1000 mg BID), long exposure, concomitant use with QT interval-prolonging drugs, or potassium channel variants causing prolonged QT interval

Increased risk of QTc prolongation in patients with mild or moderate hepatic impairment

Acute renal failure reported in some patients with severe renal impairment (CrCl <30 mL/min); discontinue if marked increase in creatinine occurs with increased BUN

Individuals >75 years have higher incidence of adverse effects

Causes small reductions in HbA1c in patients with diabetes; must not be considered a treatment for diabetes

Avoid grapefruit products

Points of recommendation

  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how ranolazine affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Check blood pressure and heart rate as the doctor has told you. Talk with the doctor.
  • If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
  • Do not use ranolazine to treat sudden chest pain. It will not help. Talk with your doctor.
  • Kidney failure has happened with ranolazine in people who already had kidney problems. Talk with the doctor.
  • Talk with your doctor before you drink alcohol.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using ranolazine while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • Take with or without food.
  • Keep taking ranolazine as you have been told by your doctor or other health care provider, even if you feel well.
  • To gain the most benefit, do not miss doses.
  • Swallow whole. Do not chew, break, or crush.
  • Skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Pregnancy level

C


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