Allegra® Information Page

Seasonal allergies can make it difficult for you to enjoy what you're doing. Allegra can help you feel better by relieving allergy symptoms in patients 12 and over, so you can more fully enjoy the world around you. Allegra was made to give you nondrowsy relief. In tests, drowsiness in people who took Allegra was similar to placebo (sugar pill), 1.3% vs 0.9%.

The most commonly reported adverse events with Allegra and placebo are cold or flu (2.5% vs 1.5%), nausea (1.6% vs 1.5%), and menstrual pain (1.5% vs 0.3%).

Allegra-D for Stuffy Noses Allegra works on your seasonal allergy symptoms: your itchy, watery eyes, plus sneezing and runny nose. But if you find your nose is stuffed up too, you should ask your doctor about Allegra-D. Allegra-D has the same antihistamine as Allegra with the added relief of a decongestant.

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CONTRAINDICATIONS
ALLEGRA-D is contraindicated in patients with known hypersensitivity to any of its ingredients.

Due to its pseudoephedrine component, ALLEGRA-D is contraindicated in patients with narrow-angle glaucoma or urinary retention, and in patients receiving monoamine oxidase (MAO) inhibitor therapy or within fourteen (14) days of stopping such treatment. It is also contraindicated in patients with severe hypertension, or severe coronary artery disease, and in those who have shown hypersensitivity or idiosyncrasy to its components, to adrenergic agents, or to other drugs of similar chemical structures. Manifestations of patient idiosyncrasy to adrenergic agents include: insomnia, dizziness, weakness, tremor, or arrhythmias.

WARNINGS
Sympathomimetic amines should be used judiciously and sparingly in patients with hypertension, diabetes mellitus, ischemic heart disease, increased intraocular pressure, hyperthyroidism, renal impairment, or prostatic hypertrophy. Sympathomimetic amines may produce central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension.

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PRECAUTIONS
Due to its pseudoephedrine component, ALLEGRA-D should be used with caution in patients with hypertension, diabetes mellitus, ischemic heart disease, increased intraocular pressure, hyperthyroidism, renal impairment, or prostatic hypertrophy. Patients with decreased renal function should be given a lower initial dose (one tablet per day) because they have reduced elimination of fexofenadine and pseudoephedrine.

Information for Patients
Patients taking ALLEGRA-D tablets should receive the following information: ALLEGRA-D tablets are prescribed for the relief of symptoms of seasonal allergic rhinitis. Patients should be instructed to take ALLEGRA-D tablets only as prescribed. Do not exceed the recommended dose. If nervousness, dizziness, or sleeplessness occur, discontinue use and consult the doctor. Patients should also be advised against the concurrent use of ALLEGRA-D tablets with over-the-counter antihistamines and decongestants.

The product should not be used by patients who are hypersensitive to it or to any of its ingredients. Due to its pseudoephedrine component, this product should not be used by patients with narrow-angle glaucoma, urinary retention, or by patients receiving a monoamine oxidase (MAO) inhibitor or within 14 days of stopping use of MAO inhibitor. It also should not be used by patients with severe hypertension or severe coronary artery disease.

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 cautioned not to break or chew the tablet. Patients should be directed to swallow the tablet whole. Patients should be instructed not to take the tablet with food. Patients should also be instructed to store the medication in a tightly closed container in a cool, dry place, away from children.

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Clinical Studies

Seasonal Allergic Rhinitis:

Adults.
 In three, 2-week, multicenter, randomized, double-blind, placebo-controlled trials in patients 12 to 68 years of age with seasonal allergic rhinitis (n=1634), fexofenadine hydrochloride 60 mg twice daily significantly reduced total symptom scores (the sum of the individual scores for sneezing, rhinorrhea, itchy nose/palate/throat, itchy/watery/red eyes) compared to placebo. Statistically significant reductions in symptom scores were observed following the first 60 mg dose, with the effect maintained throughout the 12-hour interval. In these studies, there was no additional reduction in total symptom scores with higher doses of fexofenadine hydrochloride up to 240 mg twice daily.

In one 2-week, multicenter, randomized, double-blind clinical trial in patients 12 to 65 years of age with seasonal allergic rhinitis (n=863), fexofenadine hydrochloride 180 mg once daily significantly reduced total symptom scores (the sum of the individual scores for sneezing, rhinorrhea, itchy nose/palate/throat, itchy/watery/red eyes) compared to placebo. Although the number of patients in some of the subgroups was small, there were no significant differences in the effect of fexofenadine hydrochloride across subgroups of patients defined by gender, age, and race. Onset of action for reduction in total symptom scores, excluding nasal congestion, was observed at 60 minutes compared to placebo following a single 60 mg fexofenadine hydrochloride dose administered to patients with seasonal allergic rhinitis who were exposed to ragweed pollen in an environmental exposure unit. In one clinical trial conducted with ALLEGRA 60 mg capsules, and in one clinical trial conducted with ALLEGRA-D extended release tablets, onset of action was seen within 1 to 3 hours.

Pediatrics.
Two 2-week multicenter, randomized, placebo-controlled, double-blind trials in 877 pediatric patients 6 to 11 years of age with seasonal allergic rhinitis were conducted at doses of 15, 30, and 60 mg twice daily. In one of these two studies, conducted in 411 pediatric patients, all three doses of fexofenadine hydrochloride significantly reduced total symptom scores (the sum of the individual scores for sneezing, rhinorrhea, itchy nose/palate/throat, itchy/watery/red eyes) compared to placebo, however a dose response relationship was not seen. The 60 mg twice daily dose did not provide any additional benefit over the 30 mg twice daily dose. Furthermore, exposure in pediatric patients given 30 mg fexofenadine hydrochloride is comparable to adults given 60 mg.

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Chronic Idiopathic Urticaria:
Two 4-week multicenter, randomized, double-blind, placebo-controlled clinical trials compared four different doses of fexofenadine hydrochloride tablet (20, 60, 120, and 240 mg twice daily) to placebo in patients aged 12 to 70 years with chronic idiopathic urticaria (n=726). Efficacy was demonstrated by a significant reduction in mean pruritus scores (MPS), mean number of wheals (MNW), and mean total symptom scores (MTSS, the sum of the MPS and MNW score). Although all four doses were significantly superior to placebo, symptom reduction was greater and efficacy was maintained over the entire 4-week treatment period with fexofenadine hydrochloride doses of >60 mg twice daily. However, no additional benefit of the 120 or 240 mg fexofenadine hydrochloride twice daily dose was seen over the 60 mg twice daily dose in reducing symptom scores. There were no significant differences in the effect of fexofenadine hydrochloride across subgroups of patients defined by gender, age, weight, and race.

Drug Interactions with Antacids

Administration of 120 mg of fexofenadine hydrochloride (2 x 60 mg capsule) within 15 minutes of an aluminum and magnesium containing antacid (Maalox^®) decreased fexofenadine AUC by 41% and C_max by 43%. ALLEGRA should not be taken closely in time with aluminum and magnesium containing antacids.

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Drug Interaction with Erythromycin and Ketoconazole

Fexofenadine hydrochloride has been shown to exhibit minimal (ca. 5%) metabolism. However, co-administration of fexofenadine hydrochloride with ketoconazole and erythromycin led to increased plasma levels of fexofenadine hydrochloride. Fexofenadine hydrochloride had no effect on the pharmacokinetics of erythromycin and ketoconazole. In two separate studies, fexofenadine hydrochloride 120 mg twice daily (two times the recommended twice daily dose) was co-administered with erythromycin 500 mg every 8 hours or ketoconazole 400 mg once daily under steady-state conditions to normal, healthy volunteers (n=24, each study). No differences in adverse events or QT_c interval were observed when patients were administered fexofenadine hydrochloride alone or in combination with erythromycin or ketoconazole. The findings of these studies are summarized in the following table:

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. In vivo animal studies also suggest that in addition to increasing absorption, ketoconazole decreases fexofenadine hydrochloride gastrointestinal secretion, while erythromycin may also decrease biliary excretion.

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Pregnancy

Teratogenic Effects: 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 31 times, respectively, the exposure from the maximum recommended daily oral dose of fexofenadine in adults).

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.

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 (approximately 3 times the maximum recommended daily oral dose of fexofenadine hydrochloride in adults based on comparison of fexofenadine hydrochloride AUCs).

Nursing Mothers

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.

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Pediatric Use

The recommended dose in patients 6 to 11 years of age is based on cross-study comparison of the pharmacokinetics of ALLEGRA in adults and pediatric patients and on the safety profile of fexofenadine hydrochloride in both adult and pediatric patients at doses equal to or higher than the recommended doses.

The safety of ALLEGRA tablets at a dose of 30 mg twice daily has been demonstrated in 438 pediatric patients 6 to 11 years of age in two placebo-controlled 2-week seasonal allergic rhinitis trials. The safety of ALLEGRA for the treatment of chronic idiopathic urticaria in patients 6 to 11 years of age is based on cross-study comparison of the pharmacokinetics of ALLEGRA in adult and pediatric patients and on the safety profile of fexofenadine in both adult and pediatric patients at doses equal to or higher than the recommended dose.

The effectiveness of ALLEGRA for the treatment of seasonal allergic rhinitis in patients 6 to 11 years of age was demonstrated in one trial (n=411) in which ALLEGRA tablets 30 mg twice daily significantly reduced total symptom scores compared to placebo, along with extrapolation of demonstrated efficacy in patients ages 12 years and above, and the pharmacokinetic comparisons in adults and children. The effectiveness of ALLEGRA 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 ALLEGRA 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.

The safety and effectiveness of ALLEGRA in pediatric patients under 6 years of age have not been established.

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Geriatric Use

Clinical studies of ALLEGRA tablets and capsules did not include sufficient numbers of subjects aged 65 years and over to determine whether this population responds differently from younger patients. Other reported clinical experience has not identified differences in responses between the geriatric and younger patients. 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 may be useful to monitor renal function.

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DOSAGE AND ADMINISTRATION

Seasonal Allergic Rhinitis

Adults and Children 12 Years and Older. The recommended dose of ALLEGRA is 60 mg twice daily, or 180 mg once daily. 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 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.

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Chronic Idiopathic Urticaria

Adults and Children 12 Years and Older. The recommended dose of ALLEGRA is 60 mg twice daily. 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 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.