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 tablet contains 120 mg of fexofenadine hydrochloride, which is 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, biconvex and film-coated tablets; plain on both sides.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Relief of symptoms associated with 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 aged 12 years and older is 120 mg once daily taken before a meal.
Fexofenadine is a pharmacologically active metabolite of terfenadine.
Children under 12 years of age:
The efficacy and safety of fexofenadine hydrochloride 120 mg has not been studied in children under 12 years of age. In children from 6 to 11 years of age: fexofenadine hydrochloride 30 mg tablets are the appropriate formulation for administration and dosing in this population. Fexofenadine hydrochloride is not available in 30 mg tablets. Please refer to other medicinal products with this strength available.
Special populations at risk:
Studies of patients belonging to special risk groups (elderly, patients with renal or hepatic impairment) show, that it is not necessary to adjust the dose of fexofenadine hydrochloride 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
As with most new drugs, there are only limited data for use in elderly and in patients with renal or hepatic impairment. Fexofenadine should be used with caution in these patient 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 hydrochloride 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 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 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 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.
Allergy tests: Use of fexofenadine hydrochloride must be discontinued three days before allergy tests (s.c. pricktest).
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 breast-feeding mothers.
4.7 Effects on ability to drive and use machines
Based on the pharmacodynamic profile and reported adverse events it is unlikely that fexofenadine hydrochloride will affect the ability to drive or use machines. In objective tests fexofenadine has been shown to have no significant effects on the central nervous system function. This means that patients may drive or perform tasks that require concentration. However, in order to identify particularly sensitive people who have an unusual reaction to the medicine, it is advisable to check the patient’s response to the medicine 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, <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 reported in postmarketing 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 diarrhoea
Skin and subcutaneous tissue disorders rash, urticaria, pruritus
In controlled clinical trials, the incidence of the common adverse events was similar to that observed with placebo.
Adverse events, which have been reported with an incidence of less than 1% and equal to placebo in controlled trials, have also been reported rarely during post marketing surveillance.
4.9 Overdose
Dizziness, drowsiness, fatigue and dry mouth have been reported with an 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 events, compared with placebo. The maximum tolerated dose of fexofenadine hydrochloride 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 hydrochloride from blood.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antihistamines for systemic use, ATC code: R06A X26
Fexofenadine is a non-sedating Hi antihistamine. Fexofenadine is a pharmacologically active metabolite of terfenadine.
Histamine provocation tests in humans, in which fexofenadine was administered once and twice daily, demonstrate that the drug exhibits an antihistamine effect beginning within 1 hour, reaching maximum at 6 hours and lasting at least 24 hours. There was no evidence of tolerance after 28 days of treatment. There was a positive dose-response relationship with oral doses of 10 mg-130 mg. In this model of antihistamine activity it was found that doses of at least 130 mg were required to achieve a constant effect over a 24-hour period. Maximum inhibition in the provoked skin area exceeded 80%. Clinical studies for treatment of seasonal allergic rhinitis have shown that a dose of 120 mg is sufficient for 24-hour efficacy.
No changes in QTc intervals were observed in patients with seasonal allergic rhinitis who were treated with doses up to 240 mg of fexofenadine hydrochloride twice daily for 2 weeks, compared with placebo. Also, no significant changes in QTc intervals were observed in healthy volunteers, who received up to 60 mg fexofenadine twice daily for six months, 400 mg twice daily for 6.5 days and 240 mg once daily for 1 year, compared with placebo.
Fexofenadine at concentrations 32 times greater than the therapeutic concentrations in humans had no effect on the delayed rectifier K+ channel cloned from human heart.
Fexofenadine (5-10 mg/kg po) inhibited antigen-induced bronchospasm in sensitised guinea pigs and inhibited histamine release from peritoneal mast cells at supratherapeutic concentrations (10-100 pM).
5.2 Pharmacokinetic properties
Following oral administration fexofenadine is rapidly absorbed. Tmax is reached approx. 1-3 hours after administration. The mean Cmax value was approx. 427 ng/ml after administration of 120 mg once daily.
Fexofenadine is 60% to 70% bound to plasma proteins. Fexofenadine undergoes insignificant metabolism (hepatic or non-hepatic) and was the only major substance identified in urine and faeces in animals and humans. 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 twice daily. At a dose of 240 mg twice daily, an increase slightly greater (8.8%) than the proportional increase for steady state area under the curve was observed. This indicates that the pharmacokinetics of fexofenadine is practically linear at daily doses between 40 mg and 240 mg. The major route of elimination is presumed to be via biliary excretion; while up to 10% of the administrated dose is excreted unchanged through the urine.
5.3 Preclinical safety data
Dogs tolerated 450 mg/kg given twice daily for 6 months and did not exhibit any signs of toxicity other than occasional vomiting. Also, no treatment-related gross findings were observed in dogs and rodents following necropsy.
Radiolabelled fexofenadine hydrochloride in tissue studies in rats 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 carcinogenicity of fexofenadine was assessed using terfenadine studies with supporting pharmacokinetic studies showing fexofenadine 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.
6.1 List of excipients
Tablet core:
Cellulose, microcrystalline Croscarmellose sodium Maize starch Povidone K30 Magnesium stearate
Film coat:
Opadry 03C54667:
Hypromellose 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
3 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 packs (PVC/PVDC/Aluminium) with 7, 10, 15, 20, 30, 50, 100, 200 and 250 tablets per package.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Generics [UK] Limited t/a Mylan
Station Close
Potters Bar
Hertfordshire
EN6 1TL
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 04569/0821
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
13/07/2010
10 DATE OF REVISION OF THE TEXT
14/01/2016