8.1 Pregnancy

8.3 Nursing Mothers

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.

8.4 Pediatric Use

The recommended doses of fexofenadine hydrochloride in pediatric patients 6 months to 11 years of age are based on cross-study comparison of the pharmacokinetics of fexofenadine 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 and effectiveness of fexofenadine hydrochloride in pediatric patients under 6 months of age have not been established.

The safety of fexofenadine hydrochloride is based on the administration of fexofenadine hydrochloride tablets at a dose of 30 mg twice daily demonstrated in 438 pediatric subjects 6 years to 11 years of age in 2 placebo-controlled 2-week seasonal allergic rhinitis trials. The safety of fexofenadine hydrochloride at doses of 15 mg and 30 mg given once and twice a day has been demonstrated in 969 pediatric subjects (6 months to 5 years of age) with allergic rhinitis in 3 pharmacokinetic studies and 3 safety studies. The safety of fexofenadine hydrochloride for the treatment of chronic idiopathic urticaria in subjects 6 months 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 30 mg twice daily for the treatment of seasonal allergic rhinitis in patients 2 to 5 years of age is based on the pharmacokinetic comparisons in adult and pediatric subjects and an extrapolation of the demonstrated efficacy of fexofenadine hydrochloride in adult subjects with this condition and the likelihood that the disease course, pathophysiology, and the drug's effect are substantially similar in pediatric patients to those in adult patients. The effectiveness of fexofenadine hydrochloride for the treatment of chronic idiopathic urticaria in patients 6 months to 11 years of age is based on the pharmacokinetic comparisons in adults and children and 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. Administration of a 15 mg dose of fexofenadine hydrochloride to pediatric subjects 6 months to less than 2 years of age and a 30 mg dose to pediatric subjects 2 to 11 years of age produced exposures comparable to those seen with a dose of 60 mg administered to adults.

8.5 Geriatric Use

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 (12.3)

12.1 Mechanism of Action

Fexofenadine hydrochloride, the major active metabolite of terfenadine, is an antihistamine with selective H -receptor antagonist activity. Both enantiomers of fexofenadine hydrochloride displayed approximately equipotent antihistaminic effects. Fexofenadine hydrochloride inhibited antigen-induced bronchospasm in sensitized guinea pigs and histamine release from peritoneal mast cells in rats. The clinical significance of these findings is unknown. In laboratory animals, no anticholinergic or alpha -adrenergic blocking effects were observed. Moreover, no sedative or other central nervous system effects were observed. Radiolabeled tissue distribution studies in rats indicated that fexofenadine does not cross the blood-brain barrier. 11

12.2 Pharmacodynamics

12.3 Pharmacokinetics

The pharmacokinetics of fexofenadine hydrochloride in subjects with seasonal allergic rhinitis and subjects with chronic urticaria were similar to those in healthy subjects.

13. 1 Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenic potential of fexofenadine was assessed using terfenadine studies with adequate fexofenadine 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 at the maximum recommended daily oral dose of fexofenadine hydrochloride in adults [180 mg] and children [60 mg] respectively).

In (Bacterial Reverse Mutation, CHO/HGPRT Forward Mutation, and Rat Lymphocyte Chromosomal Aberration assays) and (Mouse Bone Marrow Micronucleus assay) tests, fexofenadine hydrochloride revealed no evidence of mutagenicity. in vitroin vivo

In rat 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 exposures that were approximately 3 times the exposure at the maximum recommended human daily oral dose of 180 mg of fexofenadine hydrochloride based on comparison of AUCs). In mice, fexofenadine hydrochloride produced no effect on male or female fertility at average oral doses up to 4438 mg/kg (which led to fexofenadine exposures that were approximately 13 times the exposure at the maximum recommended human daily oral dose of 180 mg of fexofenadine hydrochloride based on comparison of AUCs).