Fexofenadine Erythromycin

Abacavir Adinazolam 5-Aminosalicylic acid Atorvastatin Avitriptan Bromazepam Bumetanide Celecoxib CGP 43371 Clodronate Cyclosporin Danazol Didanosine Erythromycin Fexofenadine Furosemide Ganciclovir Halofantrine Inidnavir Itraconazole Levofloxacin Methotrexate Nifedipine Pravastatin Rifabutin Stavudine Tacrine... 

Ms. Jones takes fexofenadine 60 mg twice a day for seasonal allergies. She comes to her physician with a sinus infection and receives a prescription for erythromycin, a drug known to inhibit CYP3A4. As a result of this drug interaction, you would expect Ms. Jones to... 

Milne RW, Jensen RH, Larsen C et al. (1997) Comparison of the disposition of hepatically-generated morphine-3-glucuronide and morphine-6-glucuronide in isolated perfused liver from the guinea pig. Pharm Res 14 1014-1018 Milne RW, Larsen LA, Jorgensen KL et al. (2000) Hepatic disposition of fexofenadine influence of the transport inhibitors erythromycin and dibromosulphothalein. Pharm Resl7 1511—1515... 

Adverse effects. Terfenadine can prolong the QTc interval on the surface ECG. This is especially likely to occur when the recommended dose is exceeded or the drug is administered with substances that block hepatic metabolism. Since this is dependent solely on the 3A4 isoform of cytochrome P450, offending drugs include erythromycin, ketoconazole and even grapefruit juice. Fexofenadine is the active metabolite of terfenadine and appears safe in this respect. 

Transporter absorptive effects predominant Examples. Acyclovir, Amiloride -, Amoxicillin Atenolol Atropine, Bidisomide Bisphosphonates Captoprit, Cefazolin Cetirizine Cimetidine Ciprofloxacin, Cloxacillin Dicloxacillin Erythromycin - -, Famotidine Fexofenadine Folinic acid Furosemide, Ganciclovir Hydrochlorothiazide, Lisinopril Metformin Methotrexate, Nadolol Penicillins Pravastatin Ranitidine Tetracycline Trimethoprim Valsartan Zalcitabine... 

The primary metabolite of terfanidine (/ =OH) was recently (1996) marketed as fexofenadine (Allegra). It may not exhibit the serious drug interactions with ketoconazole and erythromycins. 

Many Hj antihistamines are metabolized by CYPs. Thus, inhibitors of CYP activity such as macrolide antibiotics (e.g., erythromycin) or imidazole antifungals (e.g.,ketoconazole) can increase Hj antihistamine levels, leading to toxicity. Some newer antihistamines, such as cetirizine, fexofenadine, levocabastine, and acrivastine, are not subject to these drug interactions. 

There is a case of torsade de pointes possibly due to spiramycin with the sedating antihistamine mequitazine. The situation with erythromycin and loratadine is unclear as one study found that the combination caused a very slight increase in QT interval. Both azithromycin and erythromycin raise fexofenadine levels, but this had no effect on the QT interval, or on adverse events. Azelastine, cetirizine, desloratadine, and intranasal levocabastine seem to be free of clinically relevant interactions with macrolides. 

The increased levels of fexofenadine with erythromycin may be due to increased absorption and decreased biliary secretion, via an effect on drug transporters. 

Fexofenadine levels are raised by both azithromycin and erythromycin but because this does not result in adverse cardiac effects concurrent use is considered safe. Azelastine, cetirizine (and therefore probably its isomer levocetirizine) desloratadine and levocabastine seem to be free from clinically significant pharmacokinetic interactions, and have no cardiac effects, and so may therefore provide suitable alternatives if a non-sedating antihistamine is needed in a patient taking macrolides. 

Fexofenadine 120 mg twice daily Erythromycin 500 mg three times dally 7 24 healthy subjects 82% 109% No change 7... 

An in vitro study showed that ritonavir markedly reduced the transport of fexofenadine, thought to be via inhibition of P-glycoprotein. This would be predicted to markedly increase the bioavailability of fexofenadine, as occurs with verapamil, see Calcium-channel blockers + Antihistamines , p.861. However, the similar marked increases in fexofenadine levels that occurred with erythromycin , (p.589) and ketoconazole , (p.584) did not increase adverse effects and were not associated with any prolongation of the QT interval. This suggests that a clinically relevant interaction between ritonavir and fexofenadine is not expected. 

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