Implicor

Per 25 mg/5 mg tab Metoprolol tartrate 25 mg, ivabradine 5 mg. Per 50 mg/5 mg tab Metoprolol tartrate 50 mg, ivabradine 5 mg

Symptomatic treatment of chronic stable angina pectoris as substitution therapy in adults w/ normal sinus rhythm already controlled by metoprolol & ivabradine taken concomitantly at the same dose level.

1 tab bid once in the morning & once in the evening. Should only be used in patients controlled on stable doses of the monocomponents given concurrently when metoprolol is at the optimal dose. Up-titration: Depends on serial heart measurements, ECG or ambulatory 24-hr monitoring; should be done w/ the individual components, ensure to maintain patient at an optimal dose of metoprolol & ivabradine. Down-titration: Heart rate <50 bpm at rest or symptoms of bradycardia; should be done w/ individual components, ensuring optimal dose of metoprolol; discontinue if heart rate remains <50 bpm or symptoms of bradycardia persist despite dose reduction.

Should be taken with food.

Hypersensitivity. Symptomatic bradycardia; cardiogenic shock, sick sinus syndrome (including SA block); AV-block of 2nd & 3rd degree; acute MI or patients w/ suspected acute MI complicated by significant bradycardia, 1st degree heart block, systolic hypotension &/or severe heart failure; severe or symptomatic hypotension; unstable or acute heart failure; patients undergoing intermittent inotropic therapy w/ β-receptor agonist; pacemaker dependent; unstable angina; severe peripheral vascular disease; untreated pheochromocytoma; severe hepatic insufficiency; metabolic acidosis; combination w/ strong cytochrome P450 3A4 inhibitors eg, azole antifungals, macrolide antibiotics, HIV PIs & nefazodone; combination w/ verapamil or diltiazem. Women of child-bearing potential. Pregnancy & lactation.

Hypersensitivity. CrCl <15 mL/min. Moderate hepatic impairment. Monitor serial heart rate, ECG. Atrial fibrillation or other cardiac arrhythmias that interfere w/ sinus node function. Chronic heart failure w/ intraventricular conduction defects & ventricular dyssynchrony should be monitored closely. Low heart rate. Heart failure patients w/ NYHA IV. Stroke. Retinitis pigmentosa. Avoid abrupt cessation of therapy w/ β-blocker especially in patients w/ ischemic heart disease. Mild to moderate hypotension. Avoid in patients w/ congenital QT syndrome or treated w/ QT prolonging drugs, otherwise, close cardiac monitoring. Peripheral arterial disorders. DM especially those who are using insulin or oral antidiabetics. Thyrotoxicosis. May impair ability to drive or use machinery. Elderly. Metoprolol: Bronchial asthma & COPD. Pheochromocytoma. Prinzmetal angina. Exacerbation of psoriasis. General anesth. Consider patients taking metoprolol in fasting state & switch to Implicor; exposure of metoprolol is increased when administered w/ food. Ivabradine: Hypertensive patients requiring BP treatment modifications.

Ivabradine: Headache, dizziness, luminous phenomena (phosphenes), blurred vision, bradycardia, AV 1st degree block (ECG prolonged PQ interval), ventricular extrasystoles, atrial fibrillation, uncontrolled BP. Metoprolol: Bradycardia, nightmares, headache, somnolence, insomnia, dizziness, palpitations, orthostatic hypotension, peripheral coldness, Raynaud's disease, dyspnea exertional, nausea, constipation, diarrhea, abdominal pain, vomiting, fatigue & libido disorder.

Contraindications: Potent CYP3A4 inhibitors eg, azole antifungals, macrolide antibiotics, HIV PIs & nefazodone. Increased ivabradine exposure & additional heart rate reduction of 5 bpm w/ moderate CYP3A4 inhibitors. Enhanced depressant effect on BP, heart rate, myocardial contractility & AV conduction w/ IV Ca channel blockers eg, verapamil or diltiazem. Not recommended: Ivabradine: QT prolongation may be exacerbated by heart rate reduction w/ cardiovascular QT prolonging drugs (eg, quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone), non-cardiovascular QT prolonging drugs (eg, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, IV erythromycin). Increased exposure w/ grapefruit juice. Metoprolol: Decreased plasma conc w/ barbituric acid derivatives. May increase risk of rebound HTN w/ centrally-acting antihypertensive agents (eg, clonidine). May increase -ve inotropic effect & atrial conduction time w/ class 1 antiarrhythmics (eg, quinidine, tocainide, procainamide, aimaline, amiodarone, flecainide & disopyramide). Precautions: Ivabradine: Increased risk of arrhythmia w/ K-depleting diuretics; fluconazole; decreased exposure w/ CYP3A4 inducers (eg, rifampicin, barbiturates, phenytoin, St. John's wort). Metoprolol: Plasma conc lowering w/ rifampicin; increased plasma conc w/ cimetidine, alcohol & hydralazine. Plasma conc increase w/ SSRI (eg, paroxetine, fluoxetine & sertraline), diphenhydramine, hydroxychloroquine, celecoxib, terbinafine, neuroleptics, propafenone. Inhibitory effect on CYP2D6 w/ amiodarone & quinidine. Reduced elimination of lidocaine. Enhanced bradycardic effect w/ inhalation anesth. May enhance hypotensive effect w/ nitrates, digoxin. May result in bradycardia & enhanced hypotensive effect w/ β-receptor blockers or MAOIs. Adrenaline; parasympathomimetics; reduced antihypertensive effects w/ NSAIDs; increased hypoglycemic effects w/ insulin & oral antidiabetics. To be taken into consideration: Ivabradine: Increased plasma conc w/ CYP3A4 inhibitors. Decreased plasma conc w/ CYP3A4 inducers. Metoprolol: Additive effects w/ TCA & neuroleptics; additive bradycardiac effects w/ mefloquine; increased antihypertensive effects w/ IV dipyridamole. Increased hypotensive effects w/ urology α-blockers; increased vasoconstrictive effects w/ ergotamine; enhancement of neuromuscular block w/ skeletal muscle relaxant; may impede compensatory CV reactions associated w/ hypotension or shock w/ floctafenine; increased plasma conc w/ antacid.

Anti-Anginal Drugs / Beta-Blockers

C07FX05 - metoprolol and ivabradine ; Belongs to the class of beta-blocking agents in combination with other cardiac drugs. Used in the treatment of cardiovascular diseases.

Rx