Macrolides Disopyramide

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

VENLAFAXINE 1. ANTIARRHYTHMICS - amiodarone, disopyramide, procainamide, propafenone 2. ANTIBIOTICS — macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfopristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS -arsenic trioxide 4. ANTIDEPRESSANTS-TCAs 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES-terfenadine, hydroxyzine, mizolastine 8. ANTIMALARIALS -artemetherwith lumefantrine, chloro-quine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS -pentamidine isetionate 10. ANTIPSY-CHOTICS - atypicals, phenothiazines, pimozide 11. BETA-BLOCKERS -sotalol 12. BRONCHODILATORS-parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs cause prolongation of the Q-T interval Avoid co-administration... 

Some of the macrolide antibiotics have been reported to inhibit the clearance of disopyramide (SEDA-21, 200) (SEDA-22, 207), resulting in serious dysrhythmias or hypoglycemia. The mechanism of this interaction is presumed to be inhibition of dealkylation of disopyramide to its major metabolite, mono-A-dealkyldisopyramide. For example, in human liver microsomes the macrolide antibiotic troleandomycin significantly inhibited the mono-A-dealkylation of disopyramide enantiomers by inhibition of CYP3A4 (34). This interaction can result in serious dysrhythmias or other adverse effects of disopyramide. 

Severe cardiac dysrhythmias and major hjrpoglycemia have occurred in patients taking disopyramide with some macrolide antibiotics, especially erythromycin and clarithromycin (153). 

Additive effect these drugs prolong the Q-T interval. Also, macrolides T the levels of disopyramide by inhibiting its metabolism (probably CYP3A mediated)... 

ANTIARRHYTHMICS - amiodarone, disopyramide, procainamide, propafenone 2. ANTIBIOTICS-macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/dalfbpristin... 

I. ANTI ARRHYTHMICS - amiodarone, disopyramide, procainamide, propafenone 2. ANTIBIOTICS -macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfbpristin 3. ANTICANCER AND IMMUNOMODULATING DRUGS-arsenic trioxide 4. ANTIDEPRESSANTS-TCAs, venlafaxine 5. ANTIEMETICS -dolasetron 5. ANTIFUNGALS - fluconazole, posaconazole, voriconazole... 

Not fully established. An in vitro study using human liver microsomes indicated that erythromycin inhibits the metabolism (mono-A-dealkylation) of disopyramide which, in vivo, would be expected to reduce its loss from the body and increase its serum levels. Clarithromycin and azithromycin probably do the same. The increased serum levels of disopyramide can result in adverse effects such as QT prolongation and torsade de pointes, and may result in enhanced insulin secretion and hypoglycaemia. - Both intravenous erythromycin and clarithromycin" alone have been associated with prolongation of the QT interval and torsade de pointes. Therefore, disopyramide and macrolides may have additive effects on the QT interval in addition to the pharmacokinetic interaction. 

Echizen H, Kawasaki H, Qiiba K, Tani M. Ishizaki T. A potent inhibitoiy effect of erythromycin and other macrolide antibiotics on the mono-N-dealkylation metabolism of disopyramide with human liver microsomes. J Pharmacol Exp TTrer (1993) 264,1425-31. 

---