Hydrochlorothiazideinteractions

Catecholamine-depleting drugs (e.g., MAO inhibitors): Hypotension, bradycardia.

CYP2D6 inhibitors: Increased metoprolol concentration. Digitalis glycosides, clonidine, diltiazem and verapamil: Bradycardia.

Clonidine: Rebound hypertension following clonidine withdrawal.

Antidiabetic drugs: Dosage adjustment may be required.

Cholestyramine and colestipol: Reduced absorption of thiazides.

Lithium: Risk of lithium toxicity. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Reduced diuretic, natriuretic, and antihypertensive effects of diuretics.

7.1 Drug Interactions with

Metoprolol Catecholamine Depleting Drugs: The concomitant use of catecholamine-depleting drugs (e.g., reserpine, monoamine oxidase (MAO) inhibitors) with beta adrenergic blockers may have an additive affect and increase the risk of hypotension or bradycardia.

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. Monitor patients closely when the combination cannot be avoided. Digitalis, Clonidine, and Calcium Channel Blockers: 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.

7.2 Drug Interactions with

Hydrochlorothiazide Antidiabetic drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be required.

Ion exchange resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively. Stagger the dosage of hydrochlorothiazide and ion exchange resins ( e.g., cholestyramine and colestipol resins ) such that hydrochlorothiazide is administered at least 4 hours before or 4 to 6 hours after the administration of resins to minimize the interaction.

Lithium: Diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity. Monitor serum lithium concentrations during concurrent use.

Non-Steroidal Anti-Inflammatory Drugs: NSAIDs can reduce the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics.