Allegra

Allegra information, interactions and side effects, Fexofenadine hydrochloride, the active ingredient of ALLEGRA (fexofenadine hcl) tablets, ALLEGRA (fexofenadine hcl) ODT and ALLEGRA (fexofenadine hcl) oral suspension, is a histamine H1-receptor antagonist with the chemical name (±)-4-[1 nylmethyl)-1-piperidinyl]-butyl]- α, α-dimethylhydroxy-4-benzeneacetic acid hydrochloride. It has the following chemical structure The molecular weight is 538.13 and the empirical formula is C32H39NO4•HCl.

Allegra

ALLEGRA (fexofenadine hydrochloride) is a white to off-white crystalline powder. It is freely soluble in methanol and ethanol, slightly soluble in chloroform and water, and insoluble in hexane. ALLEGRA (fexofenadine hydrochloride) is a racemate and exists as a zwitterion in aqueous media at physiological pH.

ALLEGRA (fexofenadine hcl) is formulated as a tablet for oral administration. Each tablet contains 30, 60, or 180 mg ALLEGRA (fexofenadine hydrochloride) (depending on the dosage strength) and the following excipients: croscarmellose sodium, magnesium stearate, microcrystalline cellulose, and pregelatinized starch. The aqueous tablet film coating is made from hypromellose, iron oxide blends, polyethylene glycol, povidone, silicone dioxide, and titanium dioxide.

ALLEGRA (fexofenadine hcl) ODT is formulated for disintegration in the mouth immediately following administration. Each orally disintegrating tablet contains 30 mg ALLEGRA (fexofenadine hydrochloride) and the following excipients: citric acid anhydrous, crospovidone, magnesium stearate, mannitol, methacrylate copolymer, microcrystalline cellulose, povidone K-30, sodium bicarbonate, sodium starch glycolate, aspartame, natural and artificial orange flavor, artificial cream flavor, and alcohol anhydrous; the alcohol is predominantly removed during the manufacturing process.

ALLEGRA (fexofenadine hcl) oral suspension, a white uniform suspension, contains 6 mg ALLEGRA (fexofenadine hydrochloride) per mL and the following excipients: propylene glycol, edetate disodium, propylparaben, butylparaben, xanthan gum, poloxamer 407, titanium dioxide, sodium phosphate monobasic monohydrate, sodium phosphate dibasic heptahydrate, artificial raspberry cream flavor, sucrose, xylitol and purified water.

INDICATIONS

Seasonal Allergic Rhinitis

ALLEGRA (fexofenadine hcl) is indicated for the relief of symptoms associated with seasonal allergic rhinitis in adults and children 2 years of age and older.

Chronic Idiopathic Urticaria

ALLEGRA (fexofenadine hcl) is indicated for treatment of uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 months of age and older.

DOSAGE AND ADMINISTRATION

ALLEGRA (fexofenadine hcl) tablets

Seasonal Allergic Rhinitis and Chronic Idiopathic Urticaria

Adults and Children 12 Years and Older: The recommended dose of ALLEGRA (fexofenadine hcl) tablets is 60 mg twice daily or 180 mg once daily with water. A dose of 60 mg once daily is recommended as the starting dose in patients with decreased renal function.

Children 6 to 11 Years: The recommended dose of ALLEGRA (fexofenadine hcl) tablets is 30 mg twice daily with water. A dose of 30 mg once daily is recommended as the starting dose in pediatric patients with decreased renal function.

ALLEGRA (fexofenadine hcl) ODT

Seasonal Allergic Rhinitis and Chronic Idiopathic Urticaria

Children 6 to 11 Years: ALLEGRA (fexofenadine hcl) ODT is intended for use only in children 6 to 11 years of age. The recommended dose of ALLEGRA (fexofenadine hcl) ODT is 30 mg twice daily. A dose of 30 mg once daily is recommended as the starting dose in pediatric patients with decreased renal function.

ALLEGRA (fexofenadine hcl) ODT is designed to disintegrate on the tongue, followed by swallowing with or without water. ALLEGRA (fexofenadine hcl) ODT should be taken on an empty stomach. ALLEGRA (fexofenadine hcl) ODT is not intended to be chewed.

ALLEGRA (fexofenadine hcl) ODT should not be removed from the original blister package until the time of administration.

ALLEGRA (fexofenadine hcl) oral suspension

Seasonal Allergic Rhinitis

Children 2 to 11 Years: The recommended dose of ALLEGRA (fexofenadine hcl) oral suspension is 30 mg twice daily. A dose of 30 mg (5 mL) once daily is recommended as the starting dose in pediatric patients with decreased renal function.

Shake bottle well, before each use.

Chronic Idiopathic Urticaria

Children 6 Months to 11 years: The recommended dose of ALLEGRA (fexofenadine hcl) oral suspension is 30 mg (5 mL) twice daily for patients 2 to 11 years of age and 15 mg (2.5 mL) twice daily for patients 6 months to less than 2 years of age. For pediatric patients with decreased renal function, the recommended starting doses of ALLEGRA (fexofenadine hcl) oral suspension are 30 mg (5 mL) once daily for patients 2 to 11 years of age and 15 mg (2.5 mL) once daily for patients 6 months to less than 2 years of age.

HOW SUPPLIED

Dosage Forms And Strengths

ALLEGRA (fexofenadine hcl) tablets are available in 30 mg, 60 mg, and 180 mg strengths. ALLEGRA (fexofenadine hcl) tablets are coated with a peach colored film coating. Tablets have the following unique shape and identifiers: 30 mg tablets are round, bi-convex and have 03 on one side and a scripted “e” on the other; 60 mg tablets are oval, bi-convex and have 06 on one side and a scripted “e” on the other; and 180 mg tablets are oblong, bi-convex and have 018 on one side and a scripted “e” on the other.

ALLEGRA (fexofenadine hcl) ODT is available as a 30 mg orally disintegrating tablet and is white, flat-faced, 1/2-inch round shaped with beveled edges and debossed with a scripted “e” on side and “311AV” on the other side.

ALLEGRA (fexofenadine hcl) oral suspension is available as 30 mg/ 5 mL (6 mg/mL).

Storage And Handling

ALLEGRA (fexofenadine hcl) tablets

ALLEGRA (fexofenadine hcl) 30 mg tablets are available in: high-density polyethylene (HDPE) bottles of 100 (NDC 0088-1106-47) with a polypropylene screw cap containing a pulp/wax liner with heat-sealed foil inner seal and HDPE bottles of 500 (NDC 0088-1106-55) with a polypropylene screw cap containing a pulp/wax liner with heat-sealed foil inner seal.

ALLEGRA (fexofenadine hcl) 60 mg tablets are available in: HDPE bottles of 100 (NDC 0088-1107-47) with a polypropylene screw cap containing a pulp/wax liner with heat-sealed foil inner seal; HDPE bottles of 500 (NDC 0088-1107-55) with a polypropylene screw cap containing a pulp/wax liner with heat-sealed foil inner seal; and aluminum foil-backed clear blister packs of 100 (NDC 0088-1107-49).

ALLEGRA (fexofenadine hcl) 180 mg tablets are available in: HDPE bottles of 100 (NDC 0088-1109-47) with a polypropylene screw cap containing a pulp/wax liner with heat-sealed foil inner seal and HDPE bottles of 500 (NDC 0088-1109-55) with a polypropylene screw cap containing a pulp/wax liner with heat-sealed foil inner seal.

ALLEGRA (fexofenadine hcl) tablets are coated with a peach colored film coating. Tablets have the following unique shape and identifiers: 30 mg tablets are round, bi-convex and have 03 on one side and a scripted “e” on the other; 60 mg tablets are oval, bi-convex and have 06 on one side and a scripted “e” on the other; and 180 mg tablets are oblong, bi-convex and have 018 on one side and a scripted “e” on the other.

Store ALLEGRA (fexofenadine hcl) tablets at controlled room temperature 20-25°C (68-77°F). (See USP Controlled Room Temperature). Foil-backed blister packs containing ALLEGRA (fexofenadine hcl) tablets should be protected from excessive moisture.

ALLEGRA (fexofenadine hcl) ODT

ALLEGRA (fexofenadine hcl) ODT 30 mg orally disintegrating tablets are available in aluminum-foil blister packs of 60 (NDC 0088-1113-30).

Each ALLEGRA (fexofenadine hcl) ODT is white, flat-faced, ½-inch round shaped with beveled edges and debossed with a scripted “e” on one side and “311AV” on the other side.

Store ALLEGRA (fexofenadine hcl) ODT at controlled room temperature 20-25°C (68-77°F). (See USP Controlled Room Temperature). Foil-backed blister packs containing ALLEGRA (fexofenadine hcl) ODT should be protected from moisture. ALLEGRA (fexofenadine hcl) ODT should not be removed from the original blister package until the time of administration.

ALLEGRA (fexofenadine hcl) oral suspension

ALLEGRA oral suspension (fexofenadine hydrochloride, 30 mg/5 mL (6 mg/mL)) is available in an amber PET bottle containing 300 mL (NDC 0088-1097-20) of suspension.

Store ALLEGRA (fexofenadine hcl) oral suspension at controlled room temperature 20-25°C (68-77°F). (See USP Controlled Room Temperature).

Shake bottle well, before each use.

SIDE EFFECTS

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety data described below reflect exposure to ALLEGRA (fexofenadine hydrochloride) in 5083 patients in trials for allergic rhinitis and chronic idiopathic urticaria. In these trials, 3010 patients 12 years of age and older with seasonal allergic rhinitis were exposed to ALLEGRA (fexofenadine hydrochloride) at doses of 20 to 240 mg twice daily or 120 to 180 mg once daily. A total of 646 patients 6 to 11 years of age with seasonal allergic rhinitis were exposed to ALLEGRA (fexofenadine hydrochloride) at doses of 15 to 60 mg twice daily. The duration of treatment in these trials was 2 weeks. A total of 534 patients 6 months to 5 years of age with allergic rhinitis were exposed to ALLEGRA (fexofenadine hydrochloride) at doses of 15 to 30 mg twice daily. The duration of treatment in these trials ranged from 1 day to 2 weeks. There were 893 patients 12 years of age and older with chronic idiopathic urticaria exposed to ALLEGRA (fexofenadine hydrochloride) at doses of 20 to 240 mg twice daily or 180 mg once daily. The duration of treatment in these trials was 4 weeks.

Seasonal Allergic Rhinitis

Adults and Adolescents: In placebo-controlled seasonal allergic rhinitis clinical trials in subjects 12 years of age and older, 2439 subjects received ALLEGRA (fexofenadine hydrochloride) capsules at doses of 20 mg to 240 mg twice daily. All adverse reactions that were reported by greater than 1% of subjects who received the recommended daily dose of ALLEGRA (fexofenadine hydrochloride) (60 mg capsules twice daily) are listed in Table 1.

In another placebo-controlled clinical study in the United States, 571 subjects aged 12 years and older received ALLEGRA (fexofenadine hydrochloride) tablets at doses of 120 or 180 mg once daily. Table 1 also lists adverse reactions that were reported by greater than 2% of subjects treated with ALLEGRA (fexofenadine hydrochloride) tablets at doses of 180 mg once daily.

The incidence of adverse reactions, including somnolence/fatigue, was not dose-related and was similar across subgroups defined by age, gender, and race.

Table 1: Adverse reactions in subjects aged 12 years and older reported in placebo-controlled seasonal allergic rhinitis clinical trials in the United States

 

Twice-daily dosing with fexofenadine capsules at rates of greater than 1%
Adverse reaction Fexofenadine 60 mg Twice Daily
(n=680)
Frequency
Placebo Twice Daily
(n=674)
Frequency
Dysmenorrhea 1.5% 0.3%
Once-daily dosing with ALLEGRA (fexofenadine hydrochloride) tablets at rates of greater than 2%
Adverse reaction Fexofenadine 180 mg Once Daily
(n=283)
Frequency
Placebo
(n=293)
Frequency
Headache 10.3% 7.2%
Back Pain 2.5% 1.4%

The frequency and magnitude of laboratory abnormalities were similar in ALLEGRA (fexofenadine hydrochloride)- and placebo-treated subjects.

Pediatrics: Table 2 lists adverse reactions in subjects aged 6 years to 11 years of age which were reported by greater than 2% of subjects treated with ALLEGRA (fexofenadine hydrochloride) tablets at a dose of 30 mg twice daily in placebo-controlled seasonal allergic rhinitis studies in the United States and Canada.

Table 2: Adverse reactions reported in placebo-controlled seasonal allergic rhinitis studies in pediatric subjects aged 6 years to 11 years in the United States and Canada at rates of greater than 2%

 

Adverse reaction Fexofenadine 30 mg Twice Daily
(n=209)
Frequency
Placebo
(n=229)
Frequency
Cough 3.8% 1.3%
Upper Respiratory Tract Infection 2.9% 0.9%
Pyrexia 2.4% 0.9%
Otitis Media 2.4% 0.0%

Table 3 lists adverse reactions in subjects 6 months to 5 years of age which were reported by greater than 2% of subjects treated with ALLEGRA (fexofenadine hydrochloride) in 3 open single- and multiple-dose pharmacokinetic studies and 3 placebo-controlled safety studies with ALLEGRA (fexofenadine hydrochloride) capsule content (484 subjects) and suspension (50 subjects) at doses of 15 mg (108 subjects) and 30 mg (426 subjects) given twice a day.

Table 3: Adverse reactions reported in placebo-controlled studies in pediatric subjects with allergic rhinitis aged 6 months to 5 years of age at rates greater than 2%

 

Adverse reaction Fexofenadine 15 mg Twice Daily
(n=108)
Frequency
Fexofenadine 30 mg Twice Daily
(n=426)
Frequency
Fexofenadine Total
Twice Daily
(n=534)
Frequency
Placebo
(n=430)
Frequency
Vomiting 12.0% 4.2% 5.8% 8.6%
Diarrhea 3.7% 2.8% 3.0% 2.6%
Somnolence/Fatigue 2.8% 0.9% 1.3% 0.2%
Rhinorrhea 0.9% 2.1% 1.9% 0.9%

 

Chronic Idiopathic Urticaria

Adverse reactions reported by subjects 12 years of age and older in placebo-controlled chronic idiopathic urticaria studies were similar to those reported in placebo-controlled seasonal allergic rhinitis studies.

In placebo-controlled chronic idiopathic urticaria clinical trials, 726 subjects 12 years of age and older received ALLEGRA (fexofenadine hydrochloride) tablets at doses of 20 to 240 mg twice daily. Table 4 lists adverse reactions in subjects aged 12 years and older which were reported by greater than 2% of subjects treated with ALLEGRA (fexofenadine hydrochloride) 60 mg tablets twice daily in controlled clinical studies in the United States and Canada.

In a placebo-controlled clinical study in the United States, 167 subjects aged 12 years and older received ALLEGRA (fexofenadine hydrochloride) 180 mg tablets. Table 4 also lists adverse reactions that were reported by greater than 2% of subjects treated with ALLEGRA (fexofenadine hydrochloride) tablets at doses of 180 mg once daily.

Table 4: Adverse reactions reported in subjects 12 years of age and older in placebo-controlled chronic idiopathic urticaria studies

 

Twice-daily dosing with ALLEGRA (fexofenadine hydrochloride) in studies in the UnitedStates and Canada at rates of greater than 2%
Adverse reaction Fexofenadine 60 mg Twice Daily
(n=191)
Frequency
Placebo
(n=183)
Frequency
Dizziness 2.1% 1.1%
Back Pain 2.1% 1.1%
Stomach discomfort 2.1% 0.6%
Pain in extremity 2.1% 0.0%
Once-daily dosing with ALLEGRA (fexofenadine hydrochloride) in a study in the United States at rates of greater than 2%
Adverse reaction Fexofenadine 180 mg Once Daily
(n=167)
Frequency
Placebo
(n=92)
Frequency
Headache 4.8% 3.3%

The safety of ALLEGRA (fexofenadine hydrochloride) in the treatment of chronic idiopathic urticaria in pediatric patients 6 months to 11 years of age is based on the safety profile of ALLEGRA (fexofenadine hydrochloride) in adults and pediatric patients at doses equal to or higher than the recommended dose.

Postmarketing Experience

In addition to the adverse reactions reported during clinical studies and listed above, the following adverse events have been identified during post-approval use of ALLEGRA (fexofenadine hcl). Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Events that have been reported rarely during postmarketing experience include: insomnia, nervousness, sleep disorders or paroniria, and hypersensitivity reactions (including anaphylaxis, urticaria, angioedema, chest tightness, dyspnea, flushing, pruritus, and rash).

DRUG INTERACTIONS

Antacids

ALLEGRA (fexofenadine hydrochloride) should not be taken closely in time with aluminum and magnesium containing antacids. In healthy adult subjects, administration of 120 mg of ALLEGRA (fexofenadine hydrochloride) (2 x 60 mg capsule) within 15 minutes of an aluminum and magnesium containing antacid (Maalox® ) decreased fexofenadine AUC by 41% and Cmax by 43%.

Erythromycin and Ketoconazole

Fexofenadine has been shown to exhibit minimal (ca. 5%) metabolism. However, co- administration of ALLEGRA (fexofenadine hydrochloride) with either ketoconazole or erythromycin led to increased plasma concentrations of fexofenadine in healthy adult subjects. Fexofenadine had no effect on the pharmacokinetics of either erythromycin or ketoconazole. In 2 separate studies in healthy adult subjects, ALLEGRA (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 adult subjects (n=24, each study). No differences in adverse events or QTc interval were observed when subjects were administered ALLEGRA (fexofenadine hydrochloride) alone or in combination with either erythromycin or ketoconazole. The findings of these studies are summarized in the following table:

Table 5: Effects on steady-state fexofenadine pharmacokinetics after 7 days of co-administration with ALLEGRA (fexofenadine hydrochloride) 120 mg every 12 hours in healthy adult subjects (n=24)

 

Concomitant Drug CmaxSS
(Peak plasma concentration)
AUCss(0-12h)
(Extent of systemic exposure)
Erythromycin (500 mg every 8 hrs) +82% +109%
Ketoconazole (400 mg once daily) +135% +164%

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.

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 ALLEGRA (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 ALLEGRA (fexofenadine hcl) tablets should be taken with water.

ALLEGRA (fexofenadine hcl) ODT can be taken with or without water.

PRECAUTIONS

Phenylketonurics

ALLEGRA (fexofenadine hcl) ODT contains phenylalanine, a component of aspartame. Each 30 mg ALLEGRA (fexofenadine hcl) ODT contains 5.3 mg phenylalanine. ALLEGRA (fexofenadine hcl) products other than ALLEGRA (fexofenadine hcl) ODT do not contain phenylalanine.

Nonclinical Toxicology

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 ALLEGRA (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, ALLEGRA (fexofenadine hydrochloride) revealed no evidence of mutagenicity.

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 ALLEGRA (fexofenadine hydrochloride) based on comparison of AUCs). In mice, ALLEGRA (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 ALLEGRA (fexofenadine hydrochloride) based on comparison of AUCs).

Use In Specific Populations

Pregnancy

Teratogenic Effects: Pregnancy Category C. 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 4 and 30 times, respectively, the exposure at the maximum recommended human daily oral dose of 180 mg of ALLEGRA (fexofenadine hydrochloride) based on comparison of AUCs).

In mice, no adverse effects and no teratogenic effects during gestation were observed with ALLEGRA (fexofenadine hydrochloride) at oral doses up to 3730 mg/kg (which led to fexofenadine exposures that were approximately 15 times the exposure at the maximum recommended human daily oral dose of 180 mg of ALLEGRA (fexofenadine hydrochloride) based on comparison of AUCs).

There are no adequate and well controlled studies in pregnant women. ALLEGRA (fexofenadine hydrochloride) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects: Dose-related decreases in pup weight gain and survival were observed in rats exposed to 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 ALLEGRA (fexofenadine hydrochloride) based on comparison of AUCs).

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 ALLEGRA (fexofenadine hydrochloride) is administered to a nursing woman.

Pediatric Use

The recommended doses of ALLEGRA (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 ALLEGRA (fexofenadine hydrochloride) in both adult and pediatric subjects at doses equal to or higher than the recommended doses. The safety and effectiveness of ALLEGRA (fexofenadine hydrochloride) in pediatric patients under 6 months of age have not been established.

The safety of ALLEGRA (fexofenadine hydrochloride) is based on the administration of ALLEGRA (fexofenadine hcl) 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 ALLEGRA (fexofenadine hydrochloride) at doses of 15mg 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 ALLEGRA (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 ALLEGRA (fexofenadine hcl) 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 ALLEGRA (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 ALLEGRA (fexofenadine hcl) 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 ALLEGRA (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 ALLEGRA (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 ALLEGRA (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 ALLEGRA (fexofenadine hcl) 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 ALLEGRA (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.

Geriatric Use

Clinical studies of ALLEGRA (fexofenadine hcl) 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.

Renal Impairment

Based on increases in bioavailability and half-life, a dose of 60 mg once daily is recommended as the starting dose in adult patients with decreased renal function (mild, moderate or severe renal impairment). For pediatric patients with decreased renal function (mild, moderate or severe renal impairment), the recommended starting dose of fexofenadine is 30 mg once daily for patients 2 to 11 years of age and 15 mg once daily for patients 6 months to less than 2 years of age.

Hepatic Impairment

The pharmacokinetics of ALLEGRA (fexofenadine hydrochloride) in subjects with hepatic impairment did not differ substantially from that observed in healthy subjects.

OVERDOSE

Dizziness, drowsiness, and dry mouth have been reported with ALLEGRA (fexofenadine hydrochloride) overdose. Single doses of ALLEGRA (fexofenadine hydrochloride) up to 800 mg (6 healthy subjects at this dose level), and doses up to 690 mg twice daily for 1 month (3 healthy subjects at this dose level) or 240 mg once daily for 1 year (234 healthy subjects at this dose level) were administered without the development of clinically significant adverse events as compared to placebo.

In the event of overdose, consider standard measures to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. Following administration of terfenadine, hemodialysis did not effectively remove fexofenadine, the major active metabolite of terfenadine, from blood (up to 1.7% removed).

No deaths occurred at oral doses of ALLEGRA (fexofenadine hydrochloride) up to 5000 mg/kg in mice (110 times the maximum recommended daily oral dose in adults and children based on mg/m2) and up to 5000 mg/kg in rats (230 times the maximum recommended daily oral dose in adults and 210 times the maximum recommended daily oral dose in children based on mg/m2). Additionally, no clinical signs of toxicity or gross pathological findings were observed. In dogs, no evidence of toxicity was observed at oral doses up to 2000 mg/kg (300 times the maximum recommended daily oral dose in adults and 280 times the maximum recommended daily oral dose in children based on mg/m2).

CONTRAINDICATIONS

ALLEGRA (fexofenadine hcl) tablets, ALLEGRA (fexofenadine hcl) ODT and ALLEGRA (fexofenadine hcl) oral suspension are contraindicated in patients with known hypersensitivity to fexofenadine and any of the ingredients of ALLEGRA (fexofenadine hcl) . Rare cases of hypersensitivity reactions with manifestations such as angioedema, chest tightness, dyspnea, flushing and systemic anaphylaxis have been reported.

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