Fexofenadine Hydrochloride 120 Mg Film-Coated Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Fexofenadine Hydrochloride 120 mg Film-coated Tablets.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 120mg of fexofenadine hydrochloride, which is equivalent to 112mg of fexofenadine.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablet.
Peach coloured, oblong, biconvex, film coated tablets.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Relief of symptoms associated with seasonal allergic rhinitis.
4.2 Posology and method of administration Adults
The recommended dose of fexofenadine hydrochloride for adults is 120 mg once daily taken before a meal.
Fexofenadine is a pharmacologically active metabolite of terfenadine.
Paediatric population Children aged 12 years and over
The recommended dose of fexofenadine hydrochloride for children aged 12 years and over is 120 mg once daily taken before a meal.
Children under 12 years of age
The efficacy and safety of fexofenadine hydrochloride 120mg has not been studied in children under 12. In children from 6 to 11 years of age: fexofenadine hydrochloride 30mg tablet is the appropriate formulation for administration and dosing in this population.
Special risk groups
Studies in special risk groups (elderly, renally or hepatically impaired patients) indicate that it is not necessary to adjust the dose of fexofenadine hydrochloride in these patients.
4.3 Contraindications
In patients with known hypersensitivity to the active substance or to any of the excipients.
4.4 Special warnings and precautions for use
As with most new drugs there is only limited data in the elderly and renally or hepatically impaired patients.
Fexofenadine hydrochloride should be administered with care in these special groups.
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).
4.5 Interaction with other medicinal products and other forms of interaction
Fexofenadine does not undergo hepatic biofransforrnation and therefore will not interact with other drugs through hepatic mechanisms. Coadministration 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 events compared to the drugs 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 interaction between fexofenadine and omeprazole has been 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.
4.6 Fertility, pregnancy and lactation 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.
Lactation
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.
4.7 Effects on ability to drive and use machines
On the basis of the pharmacodynamic profile and reported adverse events it is unlikely that fexofenadine hydrochloride tablets will produce an effect on the ability to drive or use machines. In objective tests, Fexofenadine has been shown to have no significant effects on central nervous system function. This means that patients may drive or perform tasks thatrequire concentration. However, in order to identify sensitive people who have an unusual reaction to drugs, it is advisable to check the individual response before driving or performing complicated tasks.
4.8 Undesirable effects
In controlled clinical trials in adults the most commonly reported adverse events related to treatment were headache (7.3%), drowsiness (2.3%), nausea (1.5%) and dizziness (1.5%). The incidence of these events observed with fexofenadine was similar to that observed with placebo.
Events related to treatment that have been reported with an incidence of less than 1% include: fatigue, insomnia, nervousness and sleep disorders or paroniria, such as nightmares and tachycardia, palpitations and diarrhoea. In rare cases, rash, urticaria, pruritus, and hypersensitivity reactions with manifestations such as angioedema, chest tightness, dyspnoea, flushing and systemic anaphylaxis have also been reported.
4.9 Overdose
Symptoms of 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 events. The maximum tolerated dose of fexofenadine hydrochloride has not been established. Standard measures should be considered to remove any unabsorbed fexofenadine. Symptomatic and supportive treatment is recommended. Haemodialysis does not effectively remove fexofenadine hydrochloride from blood.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic Group: Antihistamines for systemic use, ATC code: RO6A X26.
Fexofenadine hydrochloride is a non-sedating H1antihistamine. Fexofenadine is a pharmacologically active metabolite of terfenadine.
Human histamine wheal and flare studies following single and twice daily doses of fexofenadine hydrochloride demonstrate that the drug exhibits an antihistaminic effect beginning within one hour, achieving maximum at 6 hours and lasting 24 hours. There is no evidence of tolerance to these effects after 28 days of dosing. A positive dose-response relationship between doses of 10mg to 130mg taken orally was found to exist. In this model of antihistaminic activity, it was found that doses of at least 130mg were required to achieve a consistent effect that was maintained over a 24 hour period. Maximum inhibition in skin wheal and flare areas was greater than 80%. Clinical studies conducted in seasonal allergic rhinitis have shown that a dose of 120mg is sufficient for 24 hour efficacy.
No significant differences in QTc, 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 to placebo. Also, no significant change in QTc 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 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 (5-10mg/kg per orally) inhibited antigen induced bronchospasm in sensitised guinea pigs and inhibited histamine release at supratherapeutic concentrations (10- 100pM) from peritoneal mast cells.
5.2 Pharmacokinetic properties
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 427ng/rnl following the administration of a 120mg dose once daily.
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 120mg BID. A dose of 240mg 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 240mg 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.
5.3 Preclinical safety data
Dogs tolerated 450mg/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 150mg/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.
6 PHARMACEUTICAL PARTICULARS
6.1
List of excipients
Tablet core:
Microcrystalline Cellulose Maize Starch Magnesium Stearate Croscarmellose Sodium Povidone
Film-coating: Hypromellose (E464) Macrogol (PEG 400) Macrogol (PEG 4000) Titanium Dioxide (E171) Iron Oxide Yellow (El72) Iron Oxide Red (E172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
6.4 Special precautions for storage
Store the tablets in the original package. This medicinal product does not require any special temperature storage conditions.
6.5 Nature and contents of container
PVC/PVDC foil blister packs of 7, 10, 15, 20, 30, 50, 100 or 500 tablets.
Not all pack sizes may be marketed.
6.6
Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Fannin (UK) Limited 42-46 Booth Drive Park Farm South Wellingborough Northamptonshire NN8 6GT UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 20417/0041
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
25/03/2011
10 DATE OF REVISION OF THE TEXT
07/10/2015