0.5 mg film‑coated tablets
Each tablet contains 0.5 mg or 1 mg entecavir (as monohydrate).
Excipients: each 0.5 mg tablet contains 120.5 mg lactose.
1.0 mg film‑coated tablets
Each tablet contains 1 mg entecavir (as monohydrate).
Excipients: and each 1 mg tablet contains 241 mg lactose.
0.05 mg/ml oral solution
Each ml oral solution contains 0.05 mg entecavir (as monohydrate).
Excipient: 650380 mg maltitol liquid/ml
21.5 mg methylhydroxybenzoate/ml
0.2818 mg propylhydroxybenzoate/ml
4.2 Posology and method of administration
Lamivudine-refractory patients (i.e. with evidence of viraemia while on lamivudine or the presence of lamivudine resistance [LVDr] mutations) (see sections 4.4 and 5.1): the recommended dose is 1 mg once daily, which must be taken on an empty stomach (more than 2 hours before or more than 2 hours after a meal) (see sections 4.4, 5.1 and 5.2).
4.4 Special warnings and precautions for use
Oral Solution
Maltitol: Baraclude oral solution contains maltitol (13 g maltitol liquid per 20 ml dose). Baraclude may have a mild laxative effect. Calorific value 2.3 kcal/g maltitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine. Baraclude tablets do not contain maltitol and can be taken by patients with fructose intolerance.
Parahydroxybenzoates: Baraclude oral solution contains the preservatives methylhydroxybenzoate and propylhydroxybenzoate, that may cause allergic reactions (possibly delayed).
4.8 Undesirable effects
Postmarketing experience: in addition to the adverse drug reactions identified from clinical trials, the following adverse reaction hasreactions have been identified during post-approval use of entecavir.
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Skin and subcutaneous tissueImmune system disorders:
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frequency not known: rashanaphylactoid reaction
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Skin and subcutaneous tissue disorders:
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frequency not known: rash, alopecia
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4.9 Overdose
No caseThere is limited experience of entecavir overdose has been reported in patients. Healthy subjects who received up to 20 mg/day for up to 14 days, and single doses up to 40 mg had no unexpected adverse reactions. If overdose occurs, the patient must be monitored for evidence of toxicity and given standard supportive treatment as necessary.
5.1 Pharmacodynamic properties
(.)
In HBV combination assays in cell culture, abacavir, didanosine, lamivudine, stavudine, tenofovir or zidovudine were not antagonistic to the anti-HBV activity of entecavir over a wide range of concentrations. In HIV antiviral assays, entecavir at micromolar concentrations was not antagonistic to the anti-HIV activity in cell culture of these six NRTIs at > 4 times the Cmax of entecavir.or emtricitabine.
(....)
Liver biopsy results: 57 patients from the pivotal nucleoside-naive studies 022 (HBeAg positive) and 027 (HBeAg negative) who enrolled in a long-term rollover study were evaluated for long-term liver histology outcomes. The entecavir dosage was 0.5 mg daily in the pivotal studies (mean exposure 85 weeks) and 1 mg daily in the rollover study (mean exposure 177 weeks), and 51 patients in the rollover study initially also received lamivudine (median duration 29 weeks). Of these patients, 55/57 (96%) had histological improvement as previously defined (see above), and 50/57 (88%) had a ≥ 1‑point decrease in Ishak fibrosis score. For patients with baseline Ishak fibrosis score ≥ 2, 25/43 (58%) had a ≥ 2‑point decrease. All (10/10) patients with advanced fibrosis or cirrhosis at baseline (Ishak fibrosis score of 4, 5 or 6) had a ≥ 1 point decrease (median decrease from baseline was 1.5 points). At the time of the long-term biopsy, all patients had HBV DNA < 300 copies/ml and 49/57 (86%) had serum ALT ≤ 1 x ULN. All 57 patients remained positive for HBsAg.
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
26th26 June 2006
10. DATE OF REVISION OF THE TEXT
10 February04 August 2009
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http://www.emea.europa.eu//.
http://www.emea.europa.eu/.