Erythromycin arrhythmia with

MACROLIDES IVABRADINE 1. Risk of arrhythmias with erythromycin 2. Possible t levels with clarithromycin and telithromycin 1. Additive effect 2. Uncertain Avoid co-administration... 

Non-sedating antihistamines (e.g. loratidine, e.g. Clarityn cetirizine, e.g. Benadryl, Piriteze, Zirtek clemastine), which can cause dangerous arrhythmias with antifungal agents (itraconazole, ketoconazole), antibiotics (erythromycin, clarithromycin) and drugs used to counteract acidity... 

Some macrolides (particularly erythromycin and clarithromycin) appear to reduce the metabolism of terfenadine and astemizole by inhibition of the cytochrome P450 isoenzyme CYP3A. High serum levels of astemizole and terfenadine cause a prolongation of the QT interval and may precipitate the development of torsade de pointes arrhythmia, see Table 15.2 , (p.583). The risk of cardiac arrhythmias with other non-sedating antihistamines appears to be non-existent or very much lower (see Table... 

Concomitant administration of clarithromycin with cisapride, pimozide, astemizole, or terfenadine is contraindicated. There have been postmarketing reports of drug interactions when clarithromycin and/ or erythromycin are coadministered with cisapride, pimozide, astemizole, or terfenadine resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes). 

PROPAFENONE I. ANTIARRHYTHMICS - disopyra-mide, procainamide 2. ANTIBIOTICS - macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafaxine 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine 8. ANTI-M ALARIALS - artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS - pentamidine isetionate 10. ANTIPSYCHOTICS-atypicals, phenothiazines, pimozide II. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS -parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs prolong the Q-T interval. Also, amitriptyline, clomipramine and desipramine levels may be t by propafenone. Amitriptyline and clomipramine may t propafenone levels. Propafenone and these TCAs inhibit CYP2D6-mediated metabolism of each other Avoid co-administration... 

Interactions. Erythromycin and the other macro-lides are enzyme inhibitors and interfere with the metabolic inactivation of some drugs, e.g. warfarin, carbamazepine, theophylline, disopyramide, increasing their effects. Reduced inactivation of terfena-dine may lead to serious cardiac arrhythmias, and of ergot alkaloids may cause ergotism. 

Wyim RL. Erythromycin and ketoconazole (Nizoral) associated with terfenadine (Seldane)-induced ventricular arrhythmias. Gen Dent 1993 41(l) 27-9. 

Patients presenting with acute erythromycin overdose are usually asymptomatic or experiencing minor to moderate gastrointestinal side effects/ discomfort. Serious cardiac effects, including prolongation of the QT interval, arrhythmias (i.e., ventricular tachycardia. Torsades de Pointes, ventricular fibrillation, and heart block), may be observed after rapid intravenous administration and coincident with high, peak erythromycin plasma concentrations. The occurrences of these QT prolongation-associated arrhythmias are rare. 

Potentially harmful drug interactions may not be identified during controlled clinical trials, due to the exclusion of patients taking concomitant medications, which are not allowed to be taken during a study. For example, terfenadine, a novel nonsedating antihistamine which was found to cause a serious and potentially fatal cardiac arrhythmia, torsades de pointes, when administered with keto-conazole or erythromycin, and this could not realistically have been expected to be identified in the clinical trial setting. The mechanism of this adverse drug interaction was found to be due to cumulation of unmetabolized terfenadine, due to inhibition of cytochrome P-450 (CYP) by ketoconazole or erythromycin the parent terfenadine molecule is usually cleared very rapidly when there is no concomitant CYP inhibitor. 

Erythromycin and propably clarithromycin inhibit this metabolism, and the increased terfenadine serum concentration can result in cardiac arrhythmias (e.g., torsades de pointes). Early evidence suggests that astemizole can produce the same result if combined with erythromycin. Erythromycin also inhibits the metabolism of loratadine however, loratadine does not appear to be cardiotoxic. 

Factors that commonly precipitate cardiac arrhythmias include hypoxia, electrolyte disturbances (especially hypokalemia), myocardial ischemia, and certain drugs (Table 34-1). For example, theophylline can cause multifocal atrial tachycardia, while torsades de pointes can arise not only during therapy with action potential-prolonging antiarrhythmics but also with other drugs, including erythromycin (see Chapter 46) pentamidine (see Chapter 40) and some antipsy-chotics, notably thioridazine (see Chapter 18). 

Erythromycin can cause cardiac arrhythmias, including QT prolongation with polymorphic ventricular tachycardia. Most patients have had underlying cardiac disease, or the arrhythmias were seen in combination with other drugs ("see Chapter 34). 

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