FEXOFENADINE HYDROCHLORIDE 180 MG FILM-COATED TABLETS

FEXOFENADINE HYDROCHLORIDE 180 MG FILM-COATED TABLETS

Each tablet contains 180 mg of fexofenadine hydrochloride, which is equivalent to 168 mg of fexofenadine.

For a full list of excipients, see section 6.1.

Film-coated tablet

Yellow coloured, oblong, bi-convex film coated tablet with dimensions of 16.9-17.3 mm x 7.9-8.3 mm; plain on one side with a central breakline on the other. The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

FEXOFENADINE HYDROCHLORIDE 180 mg is indicated in adults and children 12 years and older for the relief of symptoms associated with chronic idiopathic urticaria.

Posology

Adults

The recommended dose of fexofenadine hydrochloride to for adults is 180 mg once daily taken before meals.

Fexofenadine is a pharmacologically active metabolite of terfenadine.

Paediatric population

• Children aged 12 years and over

The recommended dose of fexofenadine hydrochloride to children aged 12 years and over is 180 mg once daily taken before a meal.

• Children under 12 years of age

The efficacy and safety of fexofenadine hydrochloride 180 mg has not been studied in children under 12.

Special populations

Studies in special risk groups (older people renally or hepatically impaired patients) indicate that it is not necessary to adjust the dose of fexofenadine hydrochloride in these patients.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

As with most new medicinal products there is only limited data in the older people and renally or hepatically impaired patients. Fexofenadine hydrochloride should be administered with care in these special groups.

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

This medicine contains less than 1 mmol sodium (23 mg) per 180 mg of fexofenadine hydrochloride film-coated tablet, that is to say essentially 'sodium-free'.

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 coadministration 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 interactions between fexofenadine 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 the 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 necessary.

Breast-feeding

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

Fertility

No human data on the effect of fexofenadine hydrochloride on fertility are available. In mice, there was no effect on fertility with fexofenadine hydrochloride treatment (see section 5.3).

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 to use machines. In objective tests, Fexofenadine hydrochloride 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.

The following frequency rating has been used, when applicable:

Very common ≥ 1/10; Common ≥ 1/100 and <1/10; Uncommon ≥ 1/1.000 and <1/100; Rare ≥ 1/10,000 and <1/1,000; Very rare <1/10.000 and not known (frequency cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

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: headache, drowsiness, dizziness.

Gastrointestinal disorders

Common: nausea.

General disorders and administration site conditions

Uncommon: fatigue

In adults, the following undesirable effects have been reported in post-marketing surveillance. The frequency with which they occur is not known (cannot be estimated from available data):

Immune system disorders

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

Psychiatric disorders

insomnia, nervousness, sleep disorders or nightmares/excessive dreaming (paroniria)

Cardiac disorders

tachycardia, palpitations

Gastrointestinal disorders

diarrhea

Skin and subcutaneous tissue disorders

rash, urticaria, pruritus

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

Dizziness, drowsiness, fatigue and dry mouth have been reported with overdose of fexofenadine hydrochloride. 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

Mechanism of action

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

Clinical efficacy and safety

Human histamine wheal and flare studies following single and twice daily doses of fexofenadine hydrochloride demonstrate that the medicinal product exhibits an antihistaminic effect beginning within one hour, achieving maximum at 6 hours and lasting 24 hours. There was no evidence of tolerance to these effects after 28 days of dosing. A positive dose-response relationship between doses of 10 mg to 130 mg taken orally was found to exist. In this model of antihistaminic activity, it was found that doses of at least 130 mg were required to achieve a consistent effect that was maintained over a 24 hour period. Maximum inhibition in skin wheal and flare areas were greater than 80%.

No significant differences in QT_c intervals were observed in seasonal allergic rhinitis patients given fexofenadine hydrochloride up to 240 mg twice daily for 2 weeks when compared to placebo. Also, no significant change in QT_c intervals was observed in healthy 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 to pacebo Fexofenadine at concentrations 32 times greater than the therapeutical concentration in man had no effect on the delayed rectifier K⁺ channel cloned from human heart.

Fexofenadine hydrochloride (5-10 mg/kg po) inhibited antigen induced bronchospasm in sensitised guinea pigs and inhibited histamine release at supratherapeutic concentrations (10-100 μM) from peritoneal mast cells.

Absorption

Fexofenadine hydrochloride is rapidly absorbed into the body following oral administration with T_max occurring approximately 1-3 hours post-dose. The mean C_max value was approximately 494 ng/ml following the administration of a180 mg dose once daily.

Distribution

Fexofenadine is 60 - 70% to plasma protein bound.

Biotransformation and elimination

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 to15 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, which could indicating that the fexofenadine pharmacokinetics are practically linear at 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

Croscarmellose sodium

Maize starch

Povidone

Magnesium stearate

Film Coat:

Hypromellose (E464)

Titanium dioxide (E 171)

Macrogol 400

Macrogol 4000

Iron oxide, yellow (E 172)

Not applicable.

3 years.

This medicinal product does not require any special storage conditions.

Blister package. PVC/PVDC/Al blister packed in carton. 2, 7, 10, 15, 20, 30, 50, 100 or 200 (10 x 20) tablets per package.

Not all package sizes may be marketed.

Any unused product or waste material should be disposed of in accordance with local requirements.

Chanelle Medical,

Loughrea,

Co Galway,

Ireland

PL 13931/0040

07/12/2007

05.04.2020