Terfenadine Azithromycin

Honig PK, Wortham DC, Zamani K, et al. Comparison of the effect of macrolide antibiotics erythromycin, clarithromycin and azithromycin on terfenadine steady-state pharmacokinetics and electrocardiographic parameters. Drug Invest 1994 7 148-156. 

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... 

ANTIBIOTICS-macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/ dalfbpristin 3. ANTIDEPRESSANTS - TCAs, venlafaxine 4. ANTI EMETICS -dolasetron 5. ANTIFUNGALS-fluconazole, posaconazole, voriconazole 6. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine... 

The potential interaction of azithromycin with terfenadine has been evaluated in a randomized, placebo-controlled study in 24 patients who took terfenadine plus azithromycin or terfenadine plus placebo (52). Azithromycin did not alter the pharmacokinetics of the active carboxylate metabolite of terfenadine or the effect of terfenadine on the QT interval. 

Harris S, Hilligoss DM, Colangelo PM, Eller M, Okerholm R. Azithromycin and terfenadine lack of drug interaction. Clin Pharmacol Ther 1995 58(3) 310-15. 

Clinically important, potentially hazardous interactions with amiodarone, azithromycin, bepredil, bosentan, bretylium, cisapride, clarithromycin, disopyramide, erythromycin, erythromycin fluconazole, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ketoconazole, metronidazole, miconazole, nefazodone, nilotinib, paroxetine, pimozide, probucol, procainamide, quinidine, quinine, ritonavir, saquinavir, sertraline, sotalol, SSRIs, terfenadine, troleandomycin, voriconazole, zileuton, ziprasidone... 

Azithromycin Early evidence suggests that azithromycin does not inhibit hepatic drug metabolism. It does not appear to interact with carbamazepine, theophylline, or terfenadine. 

Studies of the concomitant use of azithromycin with carbamazepine, terfenadine, and zidovudine have not reported drug interactions [131-133]. With the potential exception of antacids, no drug interactions have been reported with azithromycin, which does not appear to be metabolized by the cytochrome P-450 system [4, 134], Both azithromycin and clarithromycin have been associated with digoxin toxicity. The postulated mechanism is by eradication of Eubacterium lentum, an anaerobic gram-positive bacteria responsible for the metabolism of digoxin in some patients [43]. 

Erythromycin causes terfenadine and astemizole to accumulate in a few individuals, which can prolong the QT interval and lead to life-threatening torsade de pointes arrhythmias. Cases of torsade de pointes have been reported for astemizole with erythromycin, and terfenadine with erythromycin or troleandomycin. Other macrolides are believed to interact similarly, with the exception of azithromycin and possibly dirithromycin. 

The interactions of terfenadine with erythromycin, clarithromycin, and troieandomycin and astemizole with erythromycin are established, clinically important and potentially hazardous. From the reports above it does seem that only a very few individuals develop a clinically important adverse interaction with these macrolides, but identifying them in advance is not often practical or possible. Because of the unpredictability and potential severity of this interaction, the FDA, the CSM" in the UK and the manufacturers of terfenadine and astemizole now contraindicate macrolides in anyone taking terfenadine or astemizole. The only exception to this is azithromycin with astemizole. The manufacturer of terfenadine extends this contraindication to the concurrent use of topical macrolides. ... 

Terfenadine 60 mg twice daily Azithromycin 500 mg then 250 mg daily 5 Healthy subjects Terfenadine undetectable No change in terfenadine acid metabolite No change in terfenadine acid metabolite No change 12. 13... 

Class 2 (High PermeabiUty, Low Solrrbility) Azathioprine, Azithromycin, Alprazolam, Warfarin, Haloperidol, Glipizide, Griseofulvinum, Danazol, Dapsone, Diclofenac, Indometacin, Itraconzol, Carbamazepine, Carvedilol, Ketoconazole, Lansoprazol, Mebendazole, Mefloqrrine, Nalidixic acid. Nevirapine, Piroxicam, Praziquantel, Ritonavir, Rifampicinirm, Spironolactone, Tamoxifen, Terfenadine, Trimethoprim, Ibnprofen, lopanoic add, Lovastatin, Naproxen, Oxaprozin, Flubiprofen, Cisapride. ... 

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