Macrolides Astemizole

A4 Acetaminophen, alfentanil, amiodarone, astemizole, cocaine, cortisol, cyclosporine, dapsone, diazepam, dihydroergotamine, dihydropyridines, diltiazem, ethinyl estradiol, gestodene, indinavir, lidocaine, lovastatin, macrolides, methadone, miconazole, midazolam, mifepristone (RU 486), paclitaxel, progesterone, quinidine, rapamycin, ritonavir, saquinavir, spironolactone, sulfamethoxazole, sufentanil, tacrolimus, tamoxifen, terfenadine, testosterone, tetrahydro-cannabinol, triazolam, troleandomycin, verapamil Barbiturates, carbamazepine, macrolides, glucocorticoids, pioglitazone, phenytoin, rifampin Erythromycin, 613-hydroxy cortisol... 

P155) (114) arrhythmias. Induced by drugs including antiarrhythmics (quinidine), antipsychotics (chlorpromazine), psychotropics (tricylic antidepressants), macrolide antibiotics (clathromycin), HI antihistamines (terfenadine, astemizole) (113) deletions mutations create defective ion channel receptors (115)... 

Macrolide antibiotics are contraindicated in patients with known hypersensitivity or intolerance to any macrolide. Because clarithromycin can have adverse effects on embryo-fetal development in animals, this drug should be avoided in pregnant women unless no other therapy is appropriate. Concurrent administration of the macrolides and astemizole or terfenadine can cause elected antihistamine levels, resulting in life-threatening cardiac arrhythmias, and should be avoided. 

Toxic effects of terfenadine and astemizole have been reported in patients taking concomitant macrolides, especially clarithromycin (48-51), typically resulting in prolongation of the QT interval and cardiac dysrhythmias (torsade de pointes) (52). 

Terfenadine (Seldane) or astemizole (Hismanal) given with macrolides might cause toxicity to the heart. The patient is also at risk for hemorrhage if the patient takes both warfarin (Coumadin) and marolides within the same time period. The patient may also experience increased theophylline levels which can lead to toxicity when theophylline is given along with zanthines such as aminophylline and caffeine. 

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. 

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... 

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. ... 

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