Fexofenadine adverse effects

Fexofenadine is indicated for the relief of the symptoms of allergic rhinitis in adults and children 12 years of age and older. Fexofenadine is a selective antagonist of the Hi histamine receptor in the periphery of the body. Experimental studies demonstrated that the drug does not cross the blood-brain barrier. Fexofenadine is rapidly absorbed following oral administration. Very little of the drug is metabolized, with 80 percent excreted in the feces, and 11 percent in the urine. Its half-life is about 15 hours. In patients older than 65 years, the peak concentration was twice that of normal volunteers less than 65 years old. Renal impairment also results in increased plasma levels. Adverse effects are mild and infrequent, and include drowsiness, dyspepsia and fatigue. 

The serious effects of terfenadine on K+-H ERG (human ether-a-go-go related gene) channels leading to cardiac arrhythmia are not seen with fexofenadine, and this is why terfenadine - despite widespread use - was subsequently replaced by fexofenadine. This serious adverse effect is also seen for astemizole, another second-generation antihistamine. This problem is not confined to second-generation antihistamines, as some older first-generation antihistamines produce similar effects [21]. 

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. 

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. 

An isolated report describes increased adverse effects in two patients when terfenadine was given to patients taking nifedipine or verapamil. Verapamil markedly increased the AUC of a singie dose of fexofenadine in one study, but another study found a much more modest effect. However, even a marked increase may not be clinically important. 

Comparative studies Pranlukast versus fexofenadine No clinically important adverse effects were seen in a comparison of pranlukast 60 mg bd and fexofenadine 120 mg bd (-1- mequitazine in both groups) in non-asthmatic patients with Japanese cedar pollinosis, but the numbers were small [110 ]. Pranlukast appeared to inhibit airway hyper-responsiveness whereas fexofenadine did not. 

Fexofenadine is the active metabolite of terfenadine. Its adverse effect profile is improved compared to the parent compound terfenadine, i.e., fexofenadine has not been associated with QT interval prolongation or cardiac arrhythmias... 

Ketoconazole raises the levels of desloratadine, emedastine, fexofenadine but as no adverse cardiac effects were seen these combinations are considered safe. No interaction occurs between ketoconazole and azelastine, cetirizine, intranasal levocabastine, and none is expected with levocetirizine. 

Etesloratadine, emedastine and fexofenadine levels are raised by ketoconazole but because this does not result in adverse cardiac effects concurrent use is considered safe. Azelastine, cetirizine (and therefore probably... 

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. 

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. 

It is clinically effective in the treatment of seasonal allergic rhinitis and chronic idiophatic urticaria and is not associated with adverse cardiac or cognitive/psycho-motor effects. These qualities have led to the ranking of fexofenadine in eighth place among the 200 best marketed drugs, and in 2007, it led to approximately 0.9 billion in sales. 

---