Metoprolol

7 DRUG INTERACTIONS • Catecholamine-depleting drugs may have an additive effect when given with beta-blocking agents. ( 7.1 ) • Patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction. ( 7.2 ) • CYP2D6 Inhibitors are likely to increase metoprolol concentration. ( 7.3 ) • Concomitant use of glycosides, clonidine, and diltiazem and verapamil with beta-blockers can increase the risk of bradycardia. ( 7.4 ) • Beta-blockers including metoprolol, may exacerbate the rebound hypertension that can follow the withdrawal of clonidine. ( 7.4 ) 7.1 Catecholamine Depleting Drugs Catecholamine depleting drugs (e.g., reserpine, monoamine oxidase (MAO) inhibitors) may have an additive effect when given with beta-blocking agents. Observe patients treated with metoprolol tartrate plus a catecholamine depletor for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension. 7.2 Epinephrine While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated challenge and may be unresponsive to the usual doses of epinephrine used to treat an allergic reaction. 7.3 CYP2D6 Inhibitors Drugs that are strong inhibitors of CYP2D6 such as quinidine, fluoxetine, paroxetine, and propafenone were shown to double metoprolol concentrations. While there is no information about moderate or weak inhibitors, these too are likely to increase metoprolol concentration. Increases in plasma concentration decrease the cardioselectivity of metoprolol [see Clinical Pharmacology (12.3)]. Monitor patients closely, when the combination cannot be avoided. 7.4 Negative Chronotropes Digitalis glycosides, clonidine, diltiazem and verapamil slow atrioventricular conduction and decrease heart rate. Concomitant use with beta-blockers can increase the risk of bradycardia. If clonidine and a beta-blocker, such as metoprolol are coadministered, withdraw the beta-blocker several days before the gradual withdrawal of clonidine because beta-blockers may exacerbate the rebound hypertension that can follow the withdrawal of clonidine. If replacing clonidine by beta-blocker therapy, delay the introduction of beta-blockers for several days after clonidine administration has stopped .

Metoprolol tartrate tablets are indicated for three conditions: - Hypertension: "treatment of hypertension. They may be used alone or in combination with other antihypertensive agents." - Angina Pectoris: "long-term treatment of angina pectoris" - Myocardial Infarction: "treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality"

2 DOSAGE AND ADMINISTRATION • Administer once daily with food or after a meal. Titrate at weekly or longer intervals as needed and tolerated. ( 2 ) • Hypertension: Recommended starting dosage is 100 mg daily, in single or divided doses. ( 2.1 ) • Angina Pectoris: Recommended starting dosage is 100 mg daily, given as two divided doses. ( 2.2 ) • Myocardial Infarction: The starting dosage depends upon tolerance of intravenous metoprolol, see full prescribing information. ( 2.3 ) 2.1 Hypertension Individualize the dosage of metoprolol tartrate tablets. Metoprolol tartrate tablets should be taken with or immediately following meals. The usual initial dosage is 100 mg daily in single or divided doses. Adjust dosage at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after 1 week of therapy. The effective dosage range of metoprolol tartrate tablets is 100 mg to 450 mg per day. Dosages above 450 mg per day have not been studied. While once-daily dosing can maintain a reduction in blood pressure throughout the day, lower doses (especially 100 mg) may not maintain a full effect at the end of the 24-hour period. Larger or more frequent daily doses may be required. Measure blood pressure near the end of the dosing interval to determine whether satisfactory control is being maintained throughout the day. 2.2 Angina Pectoris The dosage of metoprolol tartrate tablets should be individualized. Metoprolol tartrate tablets should be taken with or immediately following meals. The usual initial dosage is 100 mg daily, given in two divided doses. Gradually increase the dosage at weekly intervals until optimum clinical response has been obtained or there is a pronounced slowing of the heart rate. The effective dosage range of metoprolol tartrate tablets is 100 to 400 mg per day. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, reduce the dosage gradually over a period of 1 to 2 weeks [see Warnings and Precautions (5.1)]. 2.3 Myocardial Infarction See prescribing information of intravenous metoprolol for dosage instructions for intravenous therapy. In patients who tolerate the full intravenous dose, initiate metoprolol tartrate tablets, 50 mg every 6 hours, 15 minutes after the last intravenous dose of metoprolol and continue for 48 hours. In the case of intolerance, reduce dose to 25 mg and administer for 48 hours. Titrate, based on tolerability, to a maintenance dosage of 100 mg twice daily. Continue therapy for at least 3 months. Although the efficacy of metoprolol tartrate beyond 3 months has not been conclusively established, data from studies with other beta-blockers suggest that treatment should be continued for 1 to 3 years.

For hypertension and angina: - Tiredness and dizziness (approximately 10%) - Depression (approximately 5%) - Diarrhea (approximately 5%) - Shortness of breath and bradycardia (approximately 3%)