Fexofenadine

Increased concentrations of fexofenadine have been reported in 2 controlled drug interaction studies in healthy individuals receiving 120 mg of fexofenadine hydrochloride twice daily concomitantly with erythromycin dosages of 500 mg every 8 hours or ketoconazole 400 mg once daily. In these studies, area under the plasma-concentration time curve (AUC) of fexofenadine increased by 109 or 164% following concomitant administration with erythromycin or ketoconazole, respectively, while peak plasma concentrations of fexofenadine increased by 82 or 135%, respectively. However, no clinically important adverse effects or changes in the QT interval corrected for rate (QTc) were reported after concomitant administration of erythromycin or ketoconazole with fexofenadine.

Administration of a single 120-mg dose (2 capsules of 60 mg) of fexofenadine hydrochloride within 15 minutes of administration of an aluminum and magnesium hydroxides antacid (Maalox) decreased the AUC and peak plasma concentration of fexofenadine by 41 and 43%, respectively. Therefore, the manufacturer states that fexofenadine (alone or in fixed combination with pseudoephedrine hydrochloride) should not be taken closely in time with antacids containing aluminum and magnesium.

Fruit (grapefruit, orange, apple) juices may reduce bioavailability and systemic exposure of fexofenadine. In clinical studies, the size of wheal and flare was substantially larger when fexofenadine hydrochloride was administered with grapefruit juice or orange juice compared with water; based on literature reports, the same effects may be extrapolated to other fruit juices such as apple juice. The clinical importance of these observations is unknown. Based on a population pharmacokinetic analysis of combined data from the studies using concomitant grapefruit juice or orange juice with data from a bioequivalence study, bioavailability of fexofenadine was reduced by 36%. Therefore, to maximize the effects of fexofenadine, the manufacturer recommends that the drug be administered with water.

Fexofenadine use is not generally associated with liver enzyme elevations but terfenadine, a second generation antihistamine that is metabolized in part to fexofenadine, was the attributed cause of several reported cases of clinically apparent liver injury. Terfenadine was also linked to cardiac arrhythmias and prolongation of the QTc interval for which reason it was withdrawn from use in 1997, just as fexofenadine was introduced. Liver injury from terfenadine typically arose after 1 to 5 months and was associated with a hepatocellular pattern of liver enzyme abnormalities without immunoallergic or autoimmune features. Fexofenadine has not been linked to similar cases of cardiac arrhythmias or liver injury.

The most common dose-dependent adverse drug reactions associated with fexofenadine include drowsiness, fatigue, and dry mouth. In addition, post-marketing surveillance has reported rare occurrences of Stevens-Johnson syndrome or toxic epidermal necrolysis induced by fexofenadine.

Signs and Symptoms of Overdose

Like other H1-blockers, Fexofenadine competes with free histamine for binding at H1-receptors in the GI tract, large blood vessels, and bronchial smooth muscle. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms (eg. nasal congestion, watery eyes) brought on by histamine. Fexofenadine exhibits no anticholinergic, antidopaminergic, alpha1-adrenergic or beta-adrenergic-receptor blocking effects.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

fexofenadine

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ No evidence of carcinogenesis was seen in mice and rats receiving oral terfenadine (the parent drug of fexofenadine; no longer commercially available in the US) dosages up to 150 mg/kg daily for 18 and 24 months, respectively, resulting in fexofenadine exposure levels calculated to be of 2-3 times the maximum recommended daily oral human dosage.[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 34]

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproduction studies in rats and rabbits using oral terfenadine dosages up to 300 mg/kg resulting in fexofenadine exposure levels calculated to be about 3-4 and 25-31 times, respectively, those resulting from the maximum recommended daily oral human dosage of fexofenadine hydrochloride in adults have not revealed evidence of teratogenicity.[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 34]

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproduction studies in mice receiving fexofenadine doses up to 3730 mg/kg (approximately 10-15 times the maximum recommended daily oral human dosage of fexofenadine hydrochloride in adults) have not revealed evidence of adverse or teratogenic effects during gestation.[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 34]

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproduction studies in male and female mice receiving fexofenadine doses up to 4438 mg/kg (approximately 10-15 times the maximum recommended daily oral human dosage of fexofenadine hydrochloride in adults) have not revealed evidence of impaired fertility. Reproduction studies in rats using terfenadine dosages of 150 mg/kg (resulting in fexofenadine exposure levels calculated to be about 3-4 times those resulting from the maximum recommended daily oral human dosage of fexofenadine hydrochloride), revealed dose-related decreases in implantation and an increased incidence of postimplantation losses.[McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2006., p. 34]

For more Non-Human Toxicity Excerpts (Complete) data for FEXOFENADINE (6 total), please visit the HSDB record page.