Terfenadine Paracetamol

Cyt 3A3/4 metabolizes clozapine, sertindole, quetiapine common substrates -tricyclic antidepressants, nefazodone, sertraline, carbamazepine, ethosuximide, terfenadine, benzodiazepines, diltiazem, nifedipine, verapamil, erythromycin, cyclosporine, lidocaine, quinidine, cisapride, paracetamol. Common inhibitors -nefazodone, fluvoxamine, fluoxetine, ketoconazole. 

Cimetidine 1.2 g daily for 5 days had no effect on the pharmacokinetics of a single 120-mg dose of terfenadine in 12 healthy subjects. Another study in two groups of 6 healthy subjects confirmed that cimetidine 600 mg every 12 hours or ranitidine 150 mg every 12 hours had no effect on the pharmacokinetics of terfenadine 60 mg every 12 hours. No adverse ECG changes were seen. However, an isolated case report describes a 63-year-old woman who had 8 episodes of syncope (later identiiied as being due to torsade de pointes) and a convulsion 2 days after starting terfenadine 60 mg twice daily and cimetidine 400 mg twice daily. She was also taking chiorphenamine and co-proxamol (paracetamol (acetaminophen) and dextropropoxyphene (propoxyphene)). ... 

An isolated report describes the development of torsade de pointes arrhythmia in an elderly man on very large doses of paracetamol (acetaminophen) and amitriptyline when he began to take terfenadine. 

This is an isolated case and unlikely to be of general importance. There would seem to be little reason on the basis of this report for patients on terfenadine to avoid normal therapeutic doses of paracetamol (acetaminophen). There appear to be no other reports of this interaction. 

Matsis PP, Eastiiope RN. Torsades de pointes ventricular tachycardia associated with terfenadine and paracetamol self medication. NZh4cdJ 99A) 107,402-403. 

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