Telfast 30 mg film-coated tablets

Each tablet contains 30 mg of fexofenadine hydrochloride, which is equivalent to 28 mg of fexofenadine.

For a full list of excipients, see section 6.1.

Film-coated tablet.

Peach round film-coated tablet debossed with “03” on one side and a scripted “e” on the other side.

Relief of symptoms associated with seasonal allergic rhinitis.

Paediatric population

The recommended dose of Fexofenadine hydrochloride in children aged 6 to 11 years is 30 mg twice daily.

• Children under 6 years of age

The efficacy of Fexofenadine hydrochloride has not been established in children under 6 years of age.

Special population

The safety and efficacy of Fexofenadine hydrochloride in renally or hepatically impaired children have not been established (see section 4.4). Studies conducted in adults in special risk groups (renally or hepatically impaired patients) indicate that it is not necessary to adjust the dose of Fexofenadine hydrochloride in adults.

Hypersensitivity to the active substance or to any of the excipients.

The safety and efficacy of fexofenadine hydrochloride in renally or hepatically impaired children have not been established (see section 4.2). Fexofenadine hydrochloride should be administered with caution in these patients.

Patients with a history of or ongoing cardiovascular disease should be warned that, antihistamines as a drug class, have been associated with the adverse events, tachycardia and palpitations (see section 4.8).

Interaction studies have only been performed in adults.

Fexofenadine does not undergo hepatic biotransformation and therefore will not interact with other medicinal products through hepatic mechanisms.

Co administration of Fexofenadine hydrochloride with erythromycin or ketoconazole has been found to result in a 2-3 times increase in the level of Fexofenadine in plasma. The changes were not accompanied by any effects on the QT interval and were not associated with any increase in adverse reactions compared to the medicinal products given singly.

Animal studies have shown that the increase in plasma levels of Fexofenadine observed after co administration of erythromycin or ketoconazole, appears to be due to an increase in gastrointestinal absorption and either a decrease in biliary excretion or gastrointestinal secretion, respectively.

No interaction between Fexofenadine hydrochloride and omeprazole was observed. However, the administration of an antacid containing aluminium and magnesium hydroxide gels 15 minutes prior to Fexofenadine hydrochloride caused a reduction in bioavailability, most likely due to binding in the gastrointestinal tract. It is advisable to leave 2 hours between administration of Fexofenadine hydrochloride and aluminium and magnesium hydroxide containing antacids.

Pregnancy

There are no adequate data from the use of Fexofenadine hydrochloride in pregnant women. Limited animal studies do not indicate direct or indirect harmful effects with respect to effects on pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). Fexofenadine hydrochloride should not be used during pregnancy unless clearly necessary.

Breastfeeding

There are no data on the content of human milk after administering Fexofenadine hydrochloride. However, when terfenadine was administered to nursing mothers Fexofenadine was found to cross into human breast milk. Therefore Fexofenadine hydrochloride is not recommended for mothers breast-feeding their babies.

On the basis of the pharmacodynamic profile and reported adverse reactions it is unlikely that Fexofenadine hydrochloride tablets will produce an effect on the ability to drive or use machines.

In objective tests, Telfast has been shown to have no significant effects on central nervous system function. This means that patients may drive or perform tasks that require concentration. However, in order to identify sensitive people who have an unusual reaction to medicinal products, it is advisable to check the individual response before driving or performing complicated tasks.

In controlled clinical trials in children aged 6 to 11 years, the most commonly reported adverse reaction considered at least possibly related to fexofenadine hydrochloride by the investigator was headache. The incidence of headache in pooled data from clinical trials was 1.0% for patients taking fexofenadine hydrochloride 30 mg (673 children) and for patients taking placebo (700 children). There are no clinical safety data in children treated with fexofenadine hydrochloride for periods longer than two weeks

In controlled clinical trials in 845 children aged 6 months to 5 years with allergic rhinitis, 415 children were administered 15 mg or 30 mg of fexofenadine hydrochloride (capsule content sprinkled onto dosing vehicle) and 430 children were administered placebo. There were no unexpected adverse events in the children treated with fexofenadine and the adverse event profile was similar to that of older children and adults (see section 4.2).

In adults, the following undesirable effects have been reported in clinical trials, with an incidence similar to that observed with placebo:

Nervous system disorders

Common (1/100, <1/10): headache, drowsiness, dizziness

Gastrointestinal disorders

Common (1/100, <1/10): nausea

General disorders and administration site conditions

Uncommon (1/1000, <1/100): fatigue

In adults, the following undesirable effects have been rarely (1/10 000, <1/1 000) reported in post-marketing surveillance:

Immune system disorders

hypersensitivity reactions with manifestations such as angioedema, chest tightness, dyspnoea, flushing and systemic anaphylaxis

Psychiatric disorders

insomnia, nervousness, sleep disorders or paroniria, such as nightmares

Cardiac disorders

tachycardia, palpitations

Gastrointestinal disorders

diarrhoea

Skin and subcutaneous tissue disorders

rash, urticaria, pruritus

Dizziness, drowsiness, fatigue and dry mouth have been reported with overdose of Fexofenadine hydrochloride. Doses up to 60 mg twice daily for two weeks have been administered to children, and single doses up to 800 mg and doses up to 690 mg twice daily for 1 month or 240 mg once daily for 1 year have been administered to healthy adult subjects without the development of clinically significant adverse reactions as compared with placebo. The maximum tolerated dose of Fexofenadine hydrochloride has not been established.

Standard measures should be considered to remove any unabsorbed medicinal product. Symptomatic and supportive treatment is recommended. Haemodialysis does not effectively remove Fexofenadine hydrochloride from blood.

Pharmacotherapeutic group: Antihistamines for systemic use, ATC code: R06A X26

Fexofenadine hydrochloride is a non-sedating H₁ antihistamine. Fexofenadine is a pharmacologically active metabolite of terfenadine.

In children aged 6 to 11 years, the suppressive effects of Fexofenadine hydrochloride on histamine – induced wheal and flare were comparable to that in adults at similar exposure. Inhibition of histamine-induced wheal and flare was observed at one hour post dose following single doses of 30 and 60 mg Fexofenadine hydrochloride. Peak inhibitory effects of Fexofenadine generally occurred at 3-6 hours post dose.

In a pooled analysis of three 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 (p=0.0058), sneezing (p=0.0001), itchy/ watery/red eyes (p=0.0001), itchy nose/ palate and throat (p=0.0001), and nasal congestion (p=0.0334) were significantly improved by fexofenadine hydrochloride.

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

Fexofenadine hydrochloride is rapidly absorbed into the body following oral administration, with T_max occurring at approximately 1-3 hours post dose. In children, the mean C_max value was approximately 128 ng/ml following a single dose oral administration of 30 mg Fexofenadine hydrochloride.

A dose of 30 mg BID was determined to provide plasma levels (AUC) in paediatric patients which are comparable to those achieved in adults with the approved adult regimen of 120 mg once daily.

After oral administration in adults, Fexofenadine is 60-70% plasma protein bound. Fexofenadine undergoes negligible metabolism (hepatic or non-hepatic), as it was the only major compound identified in urine and faeces of animals and man. The plasma concentration profiles of Fexofenadine follow a bi-exponential decline with a terminal elimination half-life ranging from 11 to 15 hours after multiple dosing. The single and multiple dose pharmacokinetics of Fexofenadine are linear for oral doses up to 120 mg BID. A dose of 240 mg BID produced slightly greater than proportional increase (8.8%) in steady state area under the curve, indicating that Fexofenadine pharmacokinetics are practically linear at these doses between 40 mg and 240 mg taken daily. The major route of elimination is believed to be via biliary excretion while up to 10% of ingested dose is excreted unchanged through the urine.

Dogs tolerated 450 mg/kg administered twice daily for 6 months and showed no toxicity other than occasional emesis. Also, in single dose dog and rodent studies, no treatment-related gross findings were observed following necropsy.

Radiolabelled Fexofenadine hydrochloride in tissue distribution studies of the rat indicated that Fexofenadine did not cross the blood brain barrier.

Fexofenadine hydrochloride was found to be non-mutagenic in various in vitro and in vivo mutagenicity tests.

The carcinogenic potential of Fexofenadine hydrochloride was assessed using terfenadine studies with supporting pharmacokinetic studies showing Fexofenadine hydrochloride exposure (via plasma AUC values). No evidence of carcinogenicity was observed in rats and mice given terfenadine (up to 150 mg/kg/day).

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

Tablet core :

Microcrystalline Cellulose

Pregelatinised Starch

Croscarmellose Sodium

Magnesium Stearate

Film coat:

Hypromellose

Povidone

Titanium Dioxide (E171)

Colloidal Anhydrous Silica

Macrogol

Pink Iron oxide (E172) blend

Yellow Iron oxide (E172) blend

Not applicable.

3 years

This medicinal product does not require any special storage condition

PVC/PE/PVDC/Al blisters, packaged into cardboard boxes. 1, 2, 4, 8, 10 or 15 (sample only); 20, 30, 40, 50, 60 and 100 tablets per package.

Not all pack sizes may be marketed.

No special requirements

Aventis Pharma Ltd

50 Kings Hill

West Malling

Kent

ME19 4AH

Or trading as

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

PL 04425/0162

1^st April 2003

22 November 2011