Information for Patients
Patients taking Fexofenadine Hydrochloride Tablets should receive the following information:
Fexofenadine Hydrochloride Tablets are prescribed for the relief of symptoms of seasonal allergic rhinitis or for the relief of symptoms of chronic idiopathic urticaria (hives). Patients should be instructed to take Fexofenadine Hydrochloride Tablets only as prescribed. Do not exceed the recommended dose. If any untoward effects occur while taking Fexofenadine Hydrochloride Tablets, discontinue use and consult the doctor.
The product should not be used by patients who are hypersensitive to it or to any of its ingredients.
Patients should be told that this product should be used in pregnancy or lactation only if the potential benefit justifies the potential risk to the fetus or nursing infant.
Patients should be advised to take the tablet with water. Patients should also be advised to store the medication in a tightly closed container in a cool, dry place, away from children.
Drug Interaction with Erythromycin and Ketoconazole
Fexofenadine has been shown to exhibit minimal (ca. 5%) metabolism. However, co-administration of fexofenadine hydrochloride with either ketoconazole or erythromycin led to increased plasma concentrations of fexofenadine. Fexofenadine had no effect on the pharmacokinetics of either erythromycin or ketoconazole. In 2 separate studies, fexofenadine hydrochloride 120 mg twice daily (240 mg total daily dose) was co-administered with either erythromycin 500 mg every 8 hours or ketoconazole 400 mg once daily under steady-state conditions to healthy volunteers (n=24, each study). No differences in adverse events or QTc interval were observed when subjects were administered fexofenadine hydrochloride alone or in combination with either erythromycin or ketoconazole. The findings of these studies are summarized in the following table:
Effects on steady-state fexofenadine pharmacokinetics after 7 days of co-administration with fexofenadine hydrochloride 120 mg every 12 hours (two times the recommended twice daily dose) in healthy volunteers (n=24)
| Concomitant Drug || CmaxSS |
(Peak plasma concentration)
| AUCss(0–12h) |
(Extent of systemic exposure)
|Erythromycin ||+82% ||+109% |
|(500 mg every 8 hrs) |
|Ketoconazole ||+135% ||+164% |
|(400 mg once daily) |
The changes in plasma levels were within the range of plasma levels achieved in adequate and well-controlled clinical trials.
The mechanism of these interactions has been evaluated in in vitro, in situ, and in vivo animal models. These studies indicate that ketoconazole or erythromycin co-administration enhances fexofenadine gastrointestinal absorption. This observed increase in the bioavailability of fexofenadine may be due to transport-related effects, such as p-glycoprotein. In vivo animal studies also suggest that in addition to enhancing absorption, ketoconazole decreases fexofenadine gastrointestinal secretion, while erythromycin may also decrease biliary excretion.
Drug Interactions with Antacids
Administration of 120 mg of fexofenadine hydrochloride (2 × 60 mg capsule) within 15 minutes of an aluminum and magnesium containing antacid (Maalox®) decreased fexofenadine AUC by 41% and Cmax by 43%. Fexofenadine hydrochloride should not be taken closely in time with aluminum and magnesium containing antacids.
Interactions with Fruit Juices
Fruit juices such as grapefruit, orange and apple may reduce the bioavailability and exposure of fexofenadine. This is based on the results from 3 clinical studies using histamine induced skin wheals and flares coupled with population pharmacokinetic analysis. The size of wheal and flare were significantly larger when fexofenadine hydrochloride was administered with either grapefruit or orange juices compared to water. Based on the literature reports, the same effects may be extrapolated to other fruit juices such as apple juice. The clinical significance of these observations is unknown. In addition, based on the population pharmacokinetics analysis of the combined data from grapefruit and orange juices studies with the data from a bioequivalence study, the bioavailability of fexofenadine was reduced by 36%. Therefore, to maximize the effects of fexofenadine, it is recommended that Fexofenadine hydrochloride should be taken with water (see Dosage and Administration).
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
The carcinogenic potential and reproductive toxicity of fexofenadine hydrochloride were assessed using terfenadine studies with adequate fexofenadine hydrochloride exposure (based on plasma area-under-the-concentration vs. time [AUC] values). No evidence of carcinogenicity was observed in an 18-month study in mice and in a 24-month study in rats at oral doses up to 150 mg/kg of terfenadine (which led to fexofenadine exposures that were approximately 3 and 5 times the exposure from the maximum recommended human daily oral dose of fexofenadine hydrochloride in adults [180 mg] and children [60 mg] respectively.
In in vitro (Bacterial Reverse Mutation, CHO/HGPRT Forward Mutation, and Rat Lymphocyte Chromosomal Aberration assays) and in vivo (Mouse Bone Marrow Micronucleus assay) tests, fexofenadine hydrochloride revealed no evidence of mutagenicity.
In rat dietary fertility studies, dose-related reductions in implants and increases in postimplantation losses were observed at an oral dose of 150 mg/kg of terfenadine (which led to fexofenadine hydrochloride exposures that were approximately 3 times the exposure of the maximum recommended human daily oral dose of 180 mg fexofenadine hydrochloride). In mice, fexofenadine hydrochloride produced no effect on male or female fertility at average dietary doses up to 4438 mg/kg (approximately 10 times the maximum recommended human daily oral dose of fexofenadine hydrochloride 180 mg based on comparison of AUCs).
There was no evidence of teratogenicity in rats or rabbits at oral doses of terfenadine up to 300 mg/kg (which led to fexofenadine exposures that were approximately 3 and 30 times, respectively, the exposure from the maximum recommended human daily oral dose of fexofenadine hydrochloride of 180 mg based on comparison of AUCs).
In mice, no adverse effects and no teratogenic effects during gestation were observed with fexofenadine at dietary doses up to 3730 mg/kg (approximately 15 times the maximum recommended human daily oral dose of fexofenadine hydrochloride 180 mg based on comparison of AUCs).
There are no adequate and well controlled studies in pregnant women. Fexofenadine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Dose-related decreases in pup weight gain and survival were observed in rats exposed to an oral dose of 150 mg/kg of terfenadine (approximately 3 times the maximum recommended human daily oral dose of fexofenadine hydrochloride of 180 mg in adults based on comparison of fexofenadine hydrochloride AUCs).
It is not known if fexofenadine is excreted in human milk. There are no adequate and well-controlled studies in women during lactation. Because many drugs are excreted in human milk, caution should be exercised when fexofenadine hydrochloride is administered to a nursing woman.
The recommended dose in patients 6 to 11 years of age is based on cross-study comparison of the pharmacokinetics of fexofenadine hydrochloride in adults and pediatric subjects and on the safety profile of fexofenadine hydrochloride in both adult and pediatric subjects at doses equal to or higher than the recommended doses.
The safety of fexofenadine hydrochloride tablets at a dose of 30 mg twice daily has been demonstrated in 438 pediatric subjects 6 to 11 years of age in two placebo-controlled 2-week seasonal allergic rhinitis trials. The safety of fexofenadine hydrochloride for the treatment of chronic idiopathic urticaria in subjects 6 to 11 years of age is based on cross-study comparison of the pharmacokinetics of fexofenadine hydrochloride in adult and pediatric subjects and on the safety profile of fexofenadine in both adult and pediatric subjects at doses equal to or higher than the recommended dose.
The effectiveness of fexofenadine hydrochloride for the treatment of seasonal allergic rhinitis in subjects 6 to 11 years of age was demonstrated in 1 trial (n=411) in which fexofenadine hydrochloride tablets 30 mg twice daily significantly reduced total symptom scores compared to placebo, along with extrapolation of demonstrated efficacy in subjects aged 12 years and above, and the pharmacokinetic comparisons in adults and children. The effectiveness of fexofenadine hydrochloride for the treatment of chronic idiopathic urticaria in patients 6 to 11 years of age is based on an extrapolation of the demonstrated efficacy of fexofenadine hydrochloride in adults with this condition and the likelihood that the disease course, pathophysiology and the drug's effect are substantially similar in children to that of adult patients.
Three clinical safety studies comparing 15 mg twice daily (n=85) and 30 mg twice daily (n=330) of an experimental formulation of fexofenadine to placebo (n=430) have been conducted in pediatric subjects aged 6 months to 5 years. In general, fexofenadine hydrochloride was well tolerated in these studies. No unexpected adverse events were seen given the known safety profile of fexofenadine and likely adverse reactions for this patient population. (See ADVERSE REACTIONS and CLINICAL PHARMACOLOGY.)
The safety and effectiveness of fexofenadine hydrochloride in pediatric patients under 6 years of age have not been established.
Clinical studies of fexofenadine hydrochloride tablets and capsules did not include sufficient numbers of subjects aged 65 years and over to determine whether this population responds differently from younger subjects. Other reported clinical experience has not identified differences in responses between the geriatric and younger subjects. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See CLINICAL PHARMACOLOGY).