VA CLASSIFICATION
Primary: AH102
Commonly used brand name(s): Allegra.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Antihistaminic (H 1 -receptor)&mdash,
Indications
Accepted
Rhinitis, seasonal allergic (treatment)&mdash,Fexofenadine is indicated to relieve symptoms that are associated with seasonal allergic rhinitis, such as sneezing, rhinorrhea, itchy eyes, nose, and throat, and red, watery eyes <01> .
Urticaria (treatment) 1 &mdash,Fexofenadine is indicated for the treatment of uncomplicated skin manifestations of chronic idiopathic urticaria. It significantly reduces pruritus and the number of wheals. <04>
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Chemical group&mdash,
Metabolite of terfenadine <01> .
Molecular weight&mdash,
538.13 <04>
Solubility
&mdash,Freely soluble in methanol and ethanol, slightly soluble in chloroform and water, and insoluble in hexane <04>
Mechanism of action/Effect:
Fexofenadine is an antihistamine with selective peripheral H 1 -receptor antagonist activity. It inhibits antigen-induced bronchospasm in sensitized guinea pigs and histamine release from peritoneal mast cells in rats. <01> <06>
Absorption:
Rapid following oral administration <01>. The bioavailabilities of fexofenadine capsule and tablet formulations are equivalent when administered in equal doses <04>
The pharmacokinetics of fexofenadine are linear for oral doses up to 240 mg a day (120 mg twice a day). <04>
Distribution:
Volume of distribution (V d ) &mdash,5.4 to 5.8 liters/kilogram <05>
Tissue distribution studies in rats using radiolabeled fexofenadine show that it does not cross the blood-brain barrier <01> <04> .
Protein binding:
High (60 to 70%)&mdash,predominantly to albumin and alpha 1 -acid glycoprotein <01> <04> <06> .
Biotransformation:
About 5% of the total dose is metabolized <01> <04> , approximately 0.5 to 1.5% by cytochrome P450 3A4 isoenzyme metabolism and 3.5% transformed to a methyl ester metabolite by intestinal microflora. <02>
Elimination
14.4 hours in healthy subjects, in patients with mild renal impairment (creatinine clearance of 41 to 80 mL per minute) and severe renal impairment (creatinine clearance of 11 to 40 mL per minute), the mean elimination half-life was 59% and 72% longer, respectively, than in healthy subjects. In patients on dialysis, half-life was 31% longer than in healthy subjects <01> .
Onset of action:
Within 1 hour, as determined by a reduction in rhinitis symptoms following administration of a single 60-mg dose to patients exposed to ragweed pollen and by human histamine skin wheal and flare studies following administration of single and twice-daily doses of 20 and 40 mg of fexofenadine <01> .
Peak serum concentration:
209 ng/mL&mdash,after a single 60-mg dose as an oral solution in healthy volunteers <01> .
142 ng/mL&mdash,after a single 60&ndash,mg tablet in healthy volunteers. <04>
494 ng/mL&mdash, after a single 180&ndash,mg oral tablet in healthy volunteers. <04>
286 ng/mL&mdash,after 10 doses of 60-mg as an oral solution every 12 hours in healthy volunteers. <01>
Time to peak effect:
2 to 3 hours, as determined by human histamine skin wheal and flare studies following administration of single and twice-daily doses of 20 and 40 mg of fexofenadine <01> .
Duration of action:
Effect evident 12 hours after administration, as determined by clinical studies in patients with seasonal allergic rhinitis given a single 60-mg dose, and by human histamine skin wheal and flare studies in patients given single and twice-daily doses of 20 and 40 mg of fexofenadine <01> <04> <06> .
Note: Tolerance to the antihistamine effect of fexofenadine was not demonstrated following 28 days of dosing <01> .
Elimination:
Renal&mdash,
Renal clearance: 3 to 4 L per hour <03> <06> , approximately 11% of a radioactive fexofenadine dose is excreted in the urine <01> <04>
Fecal &mdash,
Approximately 80% of a radioactive fexofenadine dose is excreted in the feces, however, it is unclear whether this represents unabsorbed drug or is the result of biliary excretion <01> <04> .
Precautions to Consider
Carcinogenicity
Fexofenadine showed no carcinogenic potential in 18- and 24-month studies in mice and rats given oral terfenadine doses of 50 and 150 mg per kg of body weight (mg/kg) per day, respectively. These doses resulted in area under the plasma concentration&ndash,time curve (AUC) values for fexofenadine of up to four times the human therapeutic value based on the recommended dosage <01> .
Mutagenicity
Fexofenadine was not mutagenic in in vitro bacterial or animal studies and in vivo animal studies <01> .
Pregnancy/Reproduction
Fertility&mdash,
Dose-related reductions in implants and increases in postimplantation losses were seen in rats given oral doses of terfenadine ³, 150 mg/kg. These doses resulted in AUC values for fexofenadine of ³, three times the human therapeutic value based on the recommended dosage <01> .
Pregnancy&mdash,
Adequate and well-controlled studies in humans have not been done <01> .
Fexofenadine was not teratogenic in studies in which rats or rabbits were given oral doses of terfenadine of up to 300 mg/kg per day. These doses resulted in AUC values for fexofenadine of up to 4 and 37 times the human therapeutic value based on the recommended dosage, respectively. <01>
In rats given oral doses of terfenadine ³, 150 mg/kg, dose-related decreases in pup weight and survival were observed. These doses resulted in AUC values for fexofenadine of three or more times the human therapeutic value based on the recommended dosage, respectively <01> .
FDA Pregnancy Category C <01> .
Breast-feeding
It is not known whether fexofenadine is distributed into breast milk <01> .
Pediatrics
In clinical trials, 438 children 6 to 11 years of age were safely treated for seasonal allergic rhinitis with fexofenadine 30 mg twice daily, for up to 2 weeks. However, the safety and efficacy of fexofenadine in children up to6 years of age has not been established. <04>
Geriatrics
In patients 65 years of age and older, peak plasma concentrations of fexofenadine were 99% greater than those in healthy subjects younger than 65 years of age. Mean elimination half-lives were similar in the two groups. Adverse effects were similar to those occurring in patients up to 60 years of age. <01>
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)&mdash,not necessarily inclusive (», = major clinical significance):
Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Erythromycin <01> or
Ketoconazole <01> (concurrent administration with fexofenadine has been found to increase plasma fexofenadine concentrations, however, no differences in adverse effects or increased QT c intervals were seen <01> <04> )
», Antacids, aluminum and magnesium hydroxide-containing (administration of fexofenadine within 15 minutes of dosing with an aluminum and magnesium hydroxide-containing antacid has decreased the fexofenadine area under the time-concentration curve by 41% and C max by 43% <04> )
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)&mdash, not necessarily inclusive (», = major clinical significance).
Risk-benefit should be considered when the following medical problems exist
», Renal function impairment (based upon increases in the bioavailability and half-life of fexofenadine, once-daily administration is recommended initially in patients with impaired renal function)
Hypersensitivity to fexofenadine
Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)&mdash,not necessarily inclusive:
Those indicating need for medical attention
Incidence rare
&mdash,Observed during clinical practice
Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
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