Razine

375 mg: Add-on therapy for the symptomatic treatment of patients w/ stable angina pectoris who are inadequately controlled or intolerant to 1st-line antianginal therapies (eg, β-blockers &/or Ca antagonists) in adults. 500 mg: Chronic angina. May be used w/ β-blockers, nitrates, Ca channel blockers, anti-platelet & lipid-lowering therapy, ACE inhibitors, & ARBs.

375 mg Initially 375 mg bid. Titrate dose to 500 mg bid after 2-4 wk &, according to patient's response, further titrated to recommended max dose of 750 mg bid. Down-titrate to 500 or 375 mg bid if patient experiences treatment-related adverse events. 500 mg Initially 500 mg bid, increased to 1 g bid as needed. Max daily dose: 1 g bid. Patient on diltiazem, verapamil, other moderate CYP3A4 inhibitors or P-gp inhibitors Max: 500 mg bid.

May be taken with or without food: Swallow whole, do not break/chew/crush.

Hypersensitivity. 375 mg: Concomitant administration of potent CYP3A4 inhibitors (eg, itraconazole, ketoconazole, voriconazole, posaconazole, HIV PIs, clarithromycin, telithromycin, nefazodone); class Ia (eg, quinidine) or class III (eg, dofetilide, sotalol) antiarrhythmics other than amiodarone. Severe renal impairment (CrCl <30 mL/min). Moderate or severe hepatic impairment. 500 mg: Patients taking strong inhibitors & inducers of CYP3A, & w/ clinically significant hepatic impairment.

May cause dizziness, blurred vision, diplopia, confusional state, & abnormal coordination, hallucination, which may affect ability to drive & use machines. Elderly. 375 mg: Exercise caution when prescribing or up-titrating to patients in whom increased exposure is expected; concomitant administration of moderate CYP3A4 & P-gp inhibitors; mild hepatic impairment; mild to moderate renal impairment (CrCl 30-80 mL/min); patients w/ low wt (≤60 kg); moderate to severe CHF (NYHA class III-IV). Risk for increased exposure is higher in patients lacking CYP2D6 activity (poor metabolizers). Patients w/ history of congenital or family history of long QT syndrome, known acquired QT interval prolongation, & treated w/ drugs affecting QTc interval. Not to be used in patients treated w/ CYP3A4 inducers (eg, rifampicin, phenytoin, phenobarb, carbamazepine, St. John's wort). Check renal function at regular intervals during treatment. Not to be used during pregnancy unless clearly necessary & lactation. Not recommended in patients <18 yr. 500 mg: Blocks IKr & prolongs QTc interval. Little experience w/ high doses (>1 g bid) or exposure, other QT-prolonging drugs, or K channel variants resulting in long QT interval. Not to be considered for diabetes. Renal impairment & patients on dialysis. Pregnancy & lactation. Safety & effectiveness have not been established in ped patients.

Dizziness, nausea, asthenia, constipation, & headache. Tinnitus, vertigo; abdominal pain, dry mouth, vomiting; peripheral edema; dyspnea; hypotension. Blurred vision, confusional state, hematuria, hypoesthesia, paresthesia, tremor. 375 mg: Anorexia, decreased appetite, dehydration; anxiety, insomnia, hallucination; lethargy, syncope, somnolence, postural dizziness; visual disturbance, & diplopia; hot flush; cough, epistaxis; dyspepsia, flatulence, stomach discomfort; pruritus, hyperhidrosis; pain in extremity, muscle cramp, joint swelling, muscular weakness; dysuria, chromaturia; fatigue. 500 mg: Bradycardia, palpitations; orthostatic hypotension. Angioedema, renal failure, eosinophilia, pulmonary fibrosis, thrombocytopenia, leukopenia, & pancytopenia.

375 mg: Increased plasma conc w/ inhibitors of CYP3A4; CYP2D6 inhibitors. Increased AUC w/ ketoconazole. Contraindicated w/ potent CYP3A4 inhibitors (eg, itraconazole, ketoconazole, voriconazole, parconazole, HIV PIs, clarithromycin, telithromycin, nefazodone); grapefruit juice. Dose-dependent increases in ave steady-state conc w/ diltiazem & other moderately potent CYP3A4 inhibitors (eg, erythromycin, fluconazole). Increased plasma levels w/ inhibitors of P-gp (eg, ciclosporin, verapamil). Decreased steady-state conc w/ rifampicin. Avoid initiation of treatment during administration of inducers of CYP3A4 (eg, rifampicin, phenytoin, phenobarb, carbamazepine, St. John's wort). Increased steady-state plasma conc w/ potent CYP2D6 inhibitor paroxetine. May increase plasma conc of P-gp or CYP3A4 substrates; sensitive CYP3A4 substrates (eg, simvastatin, lovastatin) & CYP3A4 substrates w/ narrow therapeutic range (eg, ciclosporin, tacrolimus, sirolimus, everolimus). Tissue distribution of drugs which are transported by P-gp may be increased. Increased plasma conc of metoprolol. Exposure to metoprolol or other CYP2D6 substrates (eg, propafenone & flecainide or, TCAs & antipsychotics) may be increased during co-administration. Caution is advised during co-administration w/ CYP2B6 substrates (eg, bupropion, efavirenz, cyclophosphamide). Increased plasma digoxin conc. Increased plasma conc of simvastatin lactone, simvastatin acid; tacrolimus. Increased Cmax & AUC of atorvastatin. Dose limitation of other statins, metabolized by CYP3A4 (eg, lovastatin). Increased plasma exposure of metformin & other OCT2 substrates, including pindolol & varenicline. Concomitant treatment w/ other drugs known to prolong QTc interval including certain antihistamines (eg, terfenadine, astemizole, mizolastine), antiarrhythmics (eg, quinidine, disopyramide, procainamide), erythromycin, & TCAs (eg, imipramine, doxepin, amitriptyline) may give rise to pharmacodynamic interaction & increase the possible risk of ventricular arrhythmias. 500 mg: Do not use w/ strong CYP3A inhibitors including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir & saquinavir. Increased ave steady-state plasma conc of 3.2-fold w/ ketoconazole (200 mg bid). Limit dose to 500 mg bid in patients on moderate CYP3A inhibitors including diltiazem, verapamil, aprepitant, erythromycin, fluconazole, & grapefruit juice or grapefruit-containing products. Increased steady-state plasma conc of about 2-fold w/ diltiazem (180-360 mg daily) & verapamil (120 mg tid). Down-titrate dose in patients concomitantly treated w/ P-gp inhibitors eg, cyclosporine. Avoid co-administration w/ CYP3A inducers eg, rifampin, rifabutin, rifapentin, phenobarb, phenytoin, carbamazepine & St. John's wort. Decreased plasma conc w/ rifampin (600 mg once daily). Increased conc of 1.2-fold w/ paroxetine. Increased plasma levels about 2-fold of simvastatin. Elevated plasma conc about 1.5-fold of digoxin. May require lower doses of CYP2D6 substrates.

Anti-Anginal Drugs

C01EB18 - ranolazine ; Belongs to the class of other cardiac preparations.

Rx