Quinine Astemizole

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

Quinine causes a marked but transient increase in plasma astemizole levels, and to avoid the possible risk of cardiac arrhythmias the manufacturers contraindicate this combination. Three case reports confirm that this is a clinically important interaction. 

Astemizole 30 mg daily for 4 days followed by 10 mg daily for the next 20 days, was given to 12 healthy subjects. The steady-state pharmacokinetics of the astemizole were then examined after the subjects took quinine 20 mg every 4 hours for 12 hours (a total of 80 mg quinine), and after a single 430-mg dose of quinine. The smaller dose of quinine caused only a slight increase in the maximum plasma astemizole levels and AUC, but the larger single dose of quinine resulted in a transient threefold increase in both maximum plasma levels and AUC, especially of desmethylastem-izole, the metabolite of astemizole. ... 

A patient who had been taking astemizole 10 mg daily for 10 months with fluoxetine, alprazolam, isradipine, and diuretics with potassium had a syncopal episode one hour after taking the first dose of quinine sulphate 260 mg for leg cramp. The ECG showed recurrent episodes of torsade de pointes with a QT interval of greater than 680 milliseconds. The only electrolyte abnormality was slight hypomagnesaemia. Intravenous magnesium was given and the patient s QT interval shortened to 420 milliseconds over 3 days. The manufacturers have on record two other case reports of cardiac arrhythmias possibly attributable to an interaction between astemizole and quinine. 

Uncertain. One suggestion is that the interaction is not primarily due to inhibition of the metabolism of astemizole by the quinine, but rather to a... 

Information is very limited, but on the basis of the evidence cited above the manufacturers of astemizole contraindicate the concurrent use of quinine in order to avoid the risk of cardiac arrhythmias. The case report that is cited here confirms that this is a potentially clinically hazardous drug combination. ... 

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