Drug Interactions Caution should be exercised when Inderal LA is administered with drugs that have an affect on CYP2D6, 1A2, or 2C19 metabolic pathways. Co-administration of such drugs with propranolol may lead to clinically relevant drug interactions and changes on its efficacy and/or toxicity (see Drug Interactions in PHARMACOKINETICS AND DRUG METABOLISM ). Alcohol when used concomitantly with propranolol, may increase plasma levels of propranolol.
Cardiovascular Drugs Antiarrhythmics Propafenone has negative inotropic and beta-blocking properties that can be additive to those of propranolol. Quinidine increases the concentration of propranolol and produces greater degrees of clinical beta-blockade and may cause postural hypotension. Amiodarone is an antiarrhythmic agent with negative chronotropic properties that may be additive to those seen with β-blockers such as propranolol.
The clearance of lidocaine is reduced with administration of propranolol. Lidocaine toxicity has been reported following co-administration with propranolol. Caution should be exercised when administering Inderal LA with drugs that slow A-V nodal conduction, e.g., lidocaine and calcium channel blockers. Digitalis Glycosides Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate.
Concomitant use can increase the risk of bradycardia. Calcium Channel Blockers Caution should be exercised when patients receiving a beta-blocker are administered a calcium-channel-blocking drug with negative inotropic and/or chronotropic effects. Both agents may depress myocardial contractility or atrioventricular conduction. There have been reports of significant bradycardia, heart failure, and cardiovascular collapse with concurrent use of verapamil and beta-blockers.
Co-administration of propranolol and diltiazem in patients with cardiac disease has been associated with bradycardia, hypotension, high degree heart block, and heart failure. ACE Inhibitors When combined with beta-blockers, ACE inhibitors can cause hypotension, particularly in the setting of acute myocardial infarction. The antihypertensive effects of clonidine may be antagonized by beta-blockers. Inderal LA should be administered cautiously to patients withdrawing from clonidine.
Alpha Blockers Prazosin has been associated with prolongation of first dose hypotension in the presence of beta-blockers. Postural hypotension has been reported in patients taking both beta-blockers and terazosin or doxazosin. Reserpine Patients receiving catecholamine-depleting drugs, such as reserpine should be closely observed for excessive reduction of resting sympathetic nervous activity, which may result in hypotension, marked bradycardia, vertigo, syncopal attacks, or orthostatic hypotension.
Inotropic Agents Patients on long-term therapy with propranolol may experience uncontrolled hypertension if administered epinephrine as a consequence of unopposed alpha-receptor stimulation. Epinephrine is therefore not indicated in the treatment of propranolol overdose (see OVERDOSAGE ). Isoproterenol and Dobutamine Propranolol is a competitive inhibitor of beta-receptor agonists, and its effects can be reversed by administration of such agents, e.g., dobutamine or isoproterenol.
Also, propranolol may reduce sensitivity to dobutamine stress echocardiography in patients undergoing evaluation for myocardial ischemia. Non-Cardiovascular Drugs Nonsteroidal Anti-Inflammatory Drugs Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to blunt the antihypertensive effect of beta-adrenoreceptor blocking agents. Administration of indomethacin with propranolol may reduce the efficacy of propranolol in reducing blood pressure and heart rate.
Antidepressants The hypotensive effects of MAO inhibitors or tricyclic antidepressants may be exacerbated when administered with beta-blockers by interfering with the beta-blocking activity of propranolol. Anesthetic Agents Methoxyflurane and trichloroethylene may depress myocardial contractility when administered with propranolol. Warfarin Propranolol when administered with warfarin increases the concentration of warfarin.
Prothrombin time, therefore, should be monitored. Neuroleptic Drugs Hypotension and cardiac arrest have been reported with the concomitant use of propranolol and haloperidol. Thyroxine Thyroxine may result in a lower than expected T 3 concentration when used concomitantly with propranolol.
