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 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.
3 years
Not applicable
Tablet core:
Microcrystalline Cellulose
Pregelatinised Maize Starch
Croscarmellose Sodium
Magnesium Stearate
Film coat:
Hypromellose
Povidone K30
Titanium Dioxide (E171)
Colloidal Anhydrous Silica
Macrogol 400
Red Iron oxide (E172)
Yellow Iron oxide (E172)
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.
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%. Clinical studies conducted in seasonal allergic rhinitis have shown that a dose of 120 mg is sufficient for 24 hour efficacy.
No significant differences in QTc 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 QTc 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 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 (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 Tmax occurring at approximately 1-3 hours post dose. The mean Cmax value was approximately 427 ng/ml following the administration of a 120 mg dose once daily.
Distribution
Fexofenadine is 60-70% 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 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.
07 January 2016
Aventis Pharma Limited
One Onslow Street
Guildford
Surrey
GU1 4YS
United Kingdom
Or trading as
Sanofi-aventis or Sanofi
One Onslow Street
Guildford
Surrey
GU1 4YS
United Kingdom
This medicinal product does not require any special storage conditions.
PVC/PE/PVDC/Al or PVC/PVDC/Al blisters, packaged into cardboard boxes. 2(sample only), 7, 10, 15, 20, 30, 50, 100 and 200 (as 10x20) tablets per package.
Not all packs sizes may be marketed
PL 4425/0157
No special requirements.
28/06/2006
