Allegra, Fexofenadine Pill Patient Information Sheet

For the use only of a Registered Medical Practitioner or hospital or a laboratory

This package insert is continually updated: Please read carefully before using a new pack

Fexofenadine Hydrochloride

^Aventis

THERAPEUTIC OR PHARMACOLOGICAL CLASS

Fexofenadine, is a non-sedating

antihistamine with selective peripheral

Hi receptor antagonist activity.

PHARMACEUTICAL FORM

Tablets and Oral Suspension

COMPOSITION

Allegra Suspension

Each 5ml (teaspoonful) contains :

Fexofenadine Hydrochloride U.S.P. 30 mg

Allegra 30mg Tablet

Each tablet contains

Fexofenadine Hydrochloride U.S.P. 30 mg (Fexofenadine 28mg) Allegra 120mg Tablet Each tablet contains

Fexofenadine Hydrochloride U.S.P. 120 mg (Fexofenadine 112mg) Allegra 180mg Tablet

Each tablet contains

Fexofenadine Hydrochloride U.S.P. 180 mg

(Fexofenadine 168mg)

INDICATIONS

1 Allegra is indicated for relief of symptoms associated with allergic rhinitis and chronic idiopathic urticaria.

2. Allegra oral suspension is indicated for relief of symptoms associated with allergic rhinitis in children 2-11 years of age and uncomplicated skin manifestations of chronic idiopathic urticaria in children 6 months to 11 years of age.

DOSAGE AND ADMINISTRATION

Allergic rhinitis: Children 2 to 11 years The recommended dose is 30mg twice daily. A dose of 30mg (5ml in case of Allegra Suspension) once daily is recommended as the starting dose in paediatric patients with decreased renal function. Adults and children aged 12 years and over The recommended dose of Fexofenadine hydrochloride is 120mg once daily or 180mg once daily for patients 12 years of age or older Allergic skin conditions, e.g. chronic urticaria Children 6 months to 11 years The recommended dose is 30mg (5ml in case of Allegra suspension) twice daily for patients

2 to 11 years of age and 15mg (2.5ml) twice daily for patients 6 months to less than 2 years of age.

For paediatric patients with decreased renal function the recommended starting dose is 30mg (5ml) once daily for patients 2 to 11 years of age and 15mg (2.5ml) once daily for patients 6 months to less than 2 years of age. Adults and children aged 12 years and over The recommended dose of Fexofenadine hydrochloride is 180mgonce daily for patients 12 years and over. Special Population

Studies in special risk groups (elderly, renally hepatically impaired patients) indicate that it is not necessary to adjust the dose of Fexofenadine Hydrochloride in these patients.

CONTRAINDICATIONS

The product is contraindicated in patients with known hypersensitivity to any of its ingredients

PRECAUTIONS

Patients should be advised to shake the Allegra Suspension bottle well, before each use. INTERACTIONS

The co administration of Fexofenadine with erythromycin or ketoconazole resulted in no significant increases in QTc. No differences in adverse effects were reported whether these agents were administered alone or in combination.

Administration of an antacid containing

aluminium and magnesium hydroxide gels

15 minutes prior to Fexofenadine hydrochloride

caused a reduction in bioavailability.

It is advisable to leave a gap of 2 hours

between administration of Fexofenadine

hydrochloride and aluminium and

magnesium containing antacids.

No interaction between Fexofenadine and

omeprazole was observed

PREGNANCY

There are no studies of Fexofenadine in pregnant women. Fexofenadine should be used in pregnancy only if the potential benefit outweighs the potential risk to the fetus.

In a comprehensive reproductive toxicity study in mice, Fexofenadine did not impair fertility, was not teratogenic, and did not impair pre- or postnatal development.

LACTATION

There are no studies of Fexofenadine in lactating women. Fexofenadine should be used in nursing women only if the potential benefit outweighs the potential risk to the infant.

ADVERSE REACTIONS

In placebo-controlled trials involving seasonal allergic rhinitis and chronic idiopathic urticaria patients, adverse events were comparable in Fexofenadine- and placebo treated patients.The most frequent adverse events reported with Fexofenadine include:>3%: headache,1-3%: drowsiness, dizziness and nausea. Events that have been reported during controlled trials involving seasonal allergic rhinitis and chronic idiopathic urticaria patients with incidences less than 1% and similar to placebo and have been reported rarely during post marketing surveillance include: fatigue, insomnia, nervousness, and sleep disorders or paroniria. In rare cases, rash, urticaria, pruritus and hypersensitivity reactions with manifestations such as angioedema, chest tightness, dyspnea, flushing and systemic anaphylaxis have been reported. Adverse events reported in placebo-controlled chronic idiopathic urticaria studies were similar to those reported in placebo-controlled seasonal allergic rhinitis studies. In placebo-controlled trials involving pediatric seasonal allergic rhinitis patients (6-11years of age), adverse events were similar to those observed in trials involving seasonal allergic rhinitis patients 12 years and older.

In controlled clinical trials involving pediatric patients 6 months to 5 years of age, there were no unexpected adverse events in patients treated with Fexofenadine hydrochloride.

OVERDOSE

Human Experience:

Most reports of Fexofenadine hydrochloride overdose contain limited information. However, dizziness, drowsiness and dry mouth have been reported. Single doses up to 800 mg and doses up to 690 mg BID for 1 month or 240 mg QD for 1 year were studied in healthy subjects without the development of clinically significant adverse events as compared to placebo The maximum tolerated dose of Fexofenadine was not established

Management:

Consider standard measures to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. Hemodialysis did not effectively remove Fexofenadine from blood.

PHARMACODYNAMICS

Fexofenadine is an antihistamine with selective peripheral H-j -receptor antagonist activity.Fexofenadine inhibited antigen-induced bronchospasm in sensitized guinea pigs and histamine release from peritoneal mast cells in rats. In laboratory animals, no anticholinergic or alphal-adrenergic-receptor blocking effects were observed. Moreover, no sedative or other central nervous system effects were observed. Radio labeled tissue distribution studies in rats indicated that Fexofenadine does not cross the blood-brain barrier. Fexofenadine hydrochloride inhibits skin wheal and flare responses produced by histamine injection. Following single and twice daily oral dose administration, antihistaminic effects occurred within 1 hour, achieved a maximum of 2-3 hours, and lasted a minimum of 12 hours. Maximum inhibition in skin wheal and flare areas were greater than 80%. There is no evidence of tolerance to these effects after 28 days of dosing. Using reflective total symptom score assessments as the primary endpoint, clinical studies conducted in seasonal allergic rhinitis have shown that a dose of 120 mg is sufficient for 24 hour efficacy. In children aged 6 to 11 years, the suppressive effects of Fexofenadine on histamine - induced wheal and flare were comparable to that in adults at similar exposure.ln an integrated analysis of placebo-controlled double-blind phase III studies, involving 1369 children with seasonal allergic rhinitis aged 6 to 11 years, Fexofenadine hydrochloride at 30 mg twice daily was significantly better than placebo in reducing total symptom score (p=0.0001). All individual component symptoms including rhinorrhea, sneezing, itchy/ watery/red eyes, itchy nose/ palate and throat, and nasal congestion were significantly (p=0.0334 to p=0.0001) improved by Fexofenadine hydrochloride 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 and older pediatric 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 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 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 mgdose 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.

The onset of action for the reduction in total symptom scores was observed at 60 minutes compared to placebo following a single 60 mg dose administered to seasonal allergic rhinitis patients who were exposed to ragweed pollen in an environmental exposure unit.

No effect on OJc intervals was observed in seasonal allergic rhinitis patients given Fexofenadine hydrochloride up to 240 mg twice daily for 2 weeks when compared to placebo. Also, no effect on OJc intervals was observed in healthy subjects given Fexofenadine hydrochloride up to 400 mg twice daily for 6.5 days and 240 mg once daily for 1 year when compared to placebo. In children aged 6 to 11 years, no significant differences in QTc were observed following up to 60mg Fexofenadine hydrochloride twice daily compare to placebo for two weeks. Fexofenadine at concentrations 32 times greater than the therapeutic concentration in man had no effect on the delayed potassium rectifier K+ channel cloned from human heart. PHARMACOKINETICS Fexofenadine hydrochloride is rapidly

absorbed following oral administration Tmax occurred approximately 1-3 hours post dose The mean Cmax was approximately 142 ng/ml following the administration of a single 60 mg dose, approximately 289 ng/mLfollowing a single 120 mg dose and approximately 494 ng/mL following a single 180 mg dose. The plasma exposures produced by single doses of 15, 30, and 60 mg in children aged 2-11 years are dose proportional and comparable to those produced by corresponding single doses of 30, 60, and 120 mg in adults, respectively. A dose of 30 mg BID was determined to provide plasma exposures (AUC) in pediatric patients which were comparable to plasma exposures achieved in adults following a total daily dose of 120 mg . A 5ml dose of suspension containing 30mg of Fexofenadine Hydrochloride is bio-equivalent to a 30mg dose of Fexofenadine Hydrochloride tablets Fexofenadine is 60% to 70% bound to plasma proteins. Fexofenadine undergoes negligible metabolism. Following a single 60 mg oral dose, 80% of the total Fexofenadine hydrochloride dose was recovered in the feces and 11% was recovered in the urine. Following multiple dosing, Fexofenadine has a mean terminal elimination half-life of 11 to 16 hours. The major route of elimination is believed to be biliary excretion while up to 10% of ingested dose is excreted unchanged through the urine. The single and multiple dose pharmacokinetics of Fexofenadine hydrochloride are linear from 20 mg to 120 mg doses. A dose of 240mg BID produced slightly greater than proportional increase (8.8%) in steady state area under the curve.

EXPIRY DATE

Do not use later than the date of expiry. Keep Medicine out of reach of children. AVENTIS PHARMA LIMITED

54-A, Sir Mathuradas Vasanji Road, Chakala, Andheri(E), Mumbai-400 093 India.

TM - Trademark Date : FEB 2007

Source : CDS NOV 2006; USPI 2006