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 fllm-coated tablet contains 120 mg of fexofenadine hydrochloride equivalent to 112 mg of fexofenadine
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablet
Peach coloured oblong, bi-convex film-coated tablet; plain on both sides.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Symptomatic relief of seasonal allergic rhinitis
4.2 Posology and method of administration
Adults and children 12 years and older:
The recommended dose of fexofenadine hydrochloride to adults and children 12 years and older is 120 mg once daily.
The tablet should be swallowed with a sufficient amount of water.
Children under 12 years:
Fexofenadine hydrochloride is not recommended for use in children below age 12 due to a lack of data on safety and efficacy.
Special populations at risk:
Only limited data is available regarding the administration in elderly and in patients with renal or hepatic impairment. It is not necessary to adjust the dose of fexofenadine hydrochloride in these patient groups, however, it should be used with caution in these patient groups.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
4.4. Special warnings and precautions for use
Patients with a history of 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).
Only limited data is available regarding the administration in elderly and in patients with renal or hepatic impairment. Fexofenadine hydrochloride should be used with caution in these patient groups.
4.5. Interaction with other medicinal products and other forms of interaction
Fexofenadine is only metabolised to a limited degree (hepatic or non-hepatic), and on this basis no interaction is likely with medicines metabolised through hepatic mechanisms.
Fexofenadine is a P-gp and OATP substrate. Co-administration of fexofenadine and erythromycin or ketoconazole has been found to result in 2-3 fold increase in plasma concentrations of fexofenadine. 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 medicinal products given singly. Animal studies have shown this increase appears to be due to an increase in gastrointestinal absorption and either a decrease in biliary excretion or gastrointestinal secretion, respectively.
Also single dose of lopinavir and ritonavir combination (400 mg/100 mg) has been found to increase the AUC of fexofenadine 4.0-fold, while the steady-state lopinavir/ritonavir increased the fexofenadine AUC by 2.9-fold. Thus the adverse effects of fexofenadine may increase. No pharmacodynamic interaction is known.
No interactions have been observed between fexofenadine and omeprazole. Administration of antacids containing aluminium and magnesium hydroxide 15 min. before fexofenadine caused a reduction in the bioavailability of fexofenadine, most likely due to binding in the gastrointestinal tract. It is advisable to wait 2 hours after taking antacids containing aluminium and magnesium hydroxide before fexofenadine administration.
Allergy tests: Use of fexofenadine hydrochloride must be discontinued three days before allergy tests (s.c. pricktest).
4.6 Pregnancy and lactation
Pregnancy
There is no experience with the use of fexofenadine for 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 should be used during pregnancy only if strictly necessary.
Lactation
Data for content in human milk after administration of fexofenadine is not available. However, when terfenadine was administered to nursing mothers, fexofenadine was found to cross into human breast milk. Therefore, it is not recommended to administer fexofenadine to breast-feeding mothers.
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 to use machines.
In objective tests, Fexofenadine hydrochloride has been shown to have no significant effect on the 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 drugs, it is advisable to check the individual response before driving or performing complicated tasks.
4.8. Undesirable effects
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 to <1/10): headache drowsiness, dizziness.
Gastrointestinal disorders
Common (>1/100 to <1/10): nausea, dry mouth.
General disorders and administration site conditions Uncommon (>1/1000, <1/100): 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 angio-oedema, chest tightness, dyspnoea, flushing and systemic anaphylaxis
Psychiatric disorders
insomnia, nervousness, sleep disorders or nightmares/excessive dreaming (paroniria)
Cardiac disorders tachycardia, palpitations
Gastrointestinal disorders diarrhoea
Skin and subcutaneous tissue disorders rash, urticaria, pruritus
4.9. Overdose
Dizziness, drowsiness, fatigue and dry mouth have been reported with an overdose of fexofenadine. 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 a month, or 240 mg once daily for a year, were administered to healthy adult subjects without the development of clinically significant adverse events as compared with placebo. The maximum tolerated dose of fexofenadine has not been established.
Standard measures should be considered to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. Haemodialysis does not effectively remove Fexofenadine from blood.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other antihistamines for systemic use
ATC-code: R 06 AX 26
Mechanism of action: Fexofenadine hydrochloride is a non-sedating H1-antihistamine. Fexofenadine is a pharmacologically active metabolite of terfenadine.
Clinical trials for treatment of seasonal allergic rhinitis have shown that a dose of 120 mg was adequate to obtain efficacy for 24 hours.
No changes in the QTc interval were observed in patients with seasonal allergic rhinitis, who were treated with fexofenadine hydrochloride 240 mg twice daily for two weeks, compared with placebo. Also, no significant changes in the QTc interval compared to placebo were observed in healthy volunteers, who received up to 60 mg fexofenadine hydrochloride twice daily for 6 months, 400 mg twice daily for 6.5 days and 240 mg once daily for a year.
Fexofenadine concentrations 32 times higher than the therapeutical level in humans did not affect the delayed-rectifier K+-channel cloned from a human heart.
5.2 Pharmacokinetic properties
Fexofenadine hydrochloride is rapidly absorbed following oral administration. Tmax is reached approx. 1-3 hours post-dose. Mean value for Cmax was approx. 427 ng/ml after administration of 120 mg once daily.
Fexofenadine is 60% to 70% bound to plasma proteins. Fexofenadine is only metabolised to a limited degree (hepatic or non-hepatic) and was the only major compound found in urine and faeces in animals and humans. The profile for the plasma concentration of fexofenadine follows a bi-exponential decline with a terminal half-life of 11-15 hours after multiple dosing. Single or multiple dose pharmacokinetics for fexofenadine are linear for oral doses of up to 120 mg twice daily. At a dose of 240 mg given twice daily a slightly larger increase was observed (8.8 %) than the proportional increase for the steady state area under the curve, which could indicate that the pharmacokinetics for fexofenadine is linear at doses of 40-240 mg daily. The major route of elimination is presumed to be through biliary excretion, while up to 10% of the administered dose is excreted unchanged through the urine.
5.3 Preclinical safety data
Dogs tolerated doses of 450 mg/kg given twice daily for 6 months and did not exhibit signs of toxicity except for occasional vomiting. No evident treatment related findings in dogs and rodents 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 revealed no evidence of mutagenicity in various in vitro and in vivo tests.
The carcinogenic potential of fexofenadine was assessed in terfenadine trials by the use of pharmacokinetic tests, which determined the fexofenadine exposure (based on plasma AUC-values). No evidence of carcinogenicity in rats and mice treated with terfenadine (up to 150 mg/kg/day) were observed.
In a reproduction toxicity trial with mice fexofenadine did not impair fertility, was not teratogenic and did not impair the pre- or postnatal development.
6.1 List of excipients
Tablet core:
Microcrystalline cellulose Croscarmellose sodium Maize starch Povidone
Magnesium stearate
Coating:
Hypromellose (E464) Titanium dioxide (E 171) Macrogol 400 Macrogol 4000 Iron oxide, yellow (E 172) Iron oxide, red (E 172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
4 years
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
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.
Special precautions for disposal
6.6
7
Any unused product or waste material should be disposed of in accordance with local requirements.
MARKETING AUTHORISATION HOLDER
Chanelle Medical,
Loughrea,
Co Galway,
Ireland.
8
9
MARKETING AUTHORISATION NUMBER(S)
PL 13931/0039
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
04/03/2012
DATE OF REVISION OF THE TEXT
28/03/2012