Bicalutamide 50mg Film-coated Tablets PL 20075 .Module 3: Product Information Leaflet Page 12 Module

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  • MHRA PAR; BICALUTAMIDE 50MG FILM-COATED TABLETS, PL 20075/0074

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    Public Assessment Report

    Decentralised Procedure

    Bicalutamide 50mg Film-coated Tablets

    PL 20075/0074

    UK/H/1154/001/DC

    Accord Healthcare Limited

  • MHRA PAR; BICALUTAMIDE 50MG FILM-COATED TABLETS, PL 20075/0074

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    Lay summary

    The Medicines and Healthcare products Regulatory Agency (MHRA) granted Accord Healthcare Limited a Marketing Authorisation (licence) for the medicinal product Bicalutamide 50mg Film-coated Tablets (PL 20075/0074). Bicalutamide belongs to a group of medicines known as the non-steroidal antiandrogens and is used for the treatment of advanced prostate cancer. It is taken together with a drug known as luteinising hormone-releasing hormone analogue or with accompanying surgical removal of the testicles. The active substance, bicalutamide, blocks the undesired effect of the male sex hormones (androgens) and inhibits cell growth in the prostate in this way. The data submitted in support of the application for Bicalutamide 50mg Film-coated Tablets raised no clinically significant safety concerns and it was, therefore, judged that the benefits of using this product outweigh the risks; hence a Marketing Authorisation has been granted.

  • MHRA PAR; BICALUTAMIDE 50MG FILM-COATED TABLETS, PL 20075/0074

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    TABLE OF CONTENTS

    Module 1: Information about decentralised procedure Page 4 Module 2: Summary of Product Characteristics Page 5 Module 3: Product Information Leaflet Page 12 Module 4: Labelling Page 14 Module 5: Scientific Discussion Page 16 1 Introduction 2 Quality aspects 3 Non-clinical aspects 4 Clinical aspects 5 Overall conclusions

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    Module 1

    Information about decentralised procedure

    Name of the product in the Reference Member State

    Bicalutamide 50mg Film-coated Tablets

    Name of the active substance (INN)

    Bicalutamide

    Pharmacotherapeutic classification (ATC code)

    L02BB03 Non-steroidal anti-androgens

    Pharmaceutical form and strength

    Film-coated tablet 50 mg

    Reference numbers for the Decentralised Procedure

    UK/H/1154/001/DC

    Reference Member State

    UK

    Member States concerned

    Belgium, Germany, Estonia, Spain, Ireland, Italy, Latvia, Malta, The Netherlands, Portugal, Slovenia and Slovakia

    Date of start of the procedure 9 July 2007 End date of decentralised procedure

    29 September2008

    Marketing Authorisation Number

    PL 20075/0074

    Name and address of the authorisation holder

    Accord Healthcare Limited Sage House, 319 Pinner Road, North Harrow Middlesex, HA1 4HF, UK

  • MHRA PAR; BICALUTAMIDE 50MG FILM-COATED TABLETS, PL 20075/0074

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    Module 2

    Summary of Product Characteristics 1 NAME OF THE MEDICINAL PRODUCT

    Bicalutamide 50mg Film-coated Tablets

    2 QUALITATIVE AND QUANTITATIVE COMPOSITION

    Each film-coated tablet contains 50 mg Bicalutamide. Excipients: Each tablet contains 56mg of Lactose monohydrate. For a full list of excipients, see section 6.1

    3 PHARMACEUTICAL FORM Film-coated tablet. White to off white, round biconvex, film-coated tablet debossed B 50 on one side and plain on other side.

    4 CLINICAL PARTICULARS 4.1 Therapeutic indications

    Treatment of advanced prostate cancer in combination with LHRH analogue therapy or surgical castration.

    4.2 Posology and method of administration Adult males including the elderly: one tablet (50mg) once a day. Treatment with Bicalutamide Tablets 50mg should be started at least 3 days before commencing treatment with an LHRH analogue, or at the same time as surgical castration. Children and adolescents: Bicalutamide is not indicated in children and adolescents. Renal impairment: no dosage adjustment is necessary for patients with renal impairment. There is no experience with the use of bicalutamide in patients with severe renal impairment (creatinine clearance < 30ml/min) (see section 4.4). Hepatic impairment: no dosage adjustment is necessary for patients with mild hepatic impairment. Increased accumulation may occur in patients with moderate to severe hepatic impairment (see Section 4.4).

    4.3 Contraindications Hypersensitivity to bicalutamide or to any of the excipients:

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    Use in females, children and adolescents is contraindicated. Co-administration of terfenadine, astemizole or cisapride with Bicalutamide is contra-indicated.

    4.4 Special warnings and precautions for use As there is no experience with the use of bicalutamide in patients with severe renal impairment (creatinine clearance < 30/min), bicalutamide should only be used with caution in these patients. Bicalutamide is extensively metabolized in the liver. Data suggests that its elimination may be slower in subjects with severe hepatic impairment and this could lead to increased accumulation of Bicalutamide. Therefore, Bicalutamide should be used with caution in patients with moderate to severe hepatic impairment. Periodic liver function testing should be considered due to the possibility of hepatic changes. The majority of changes are expected to occur within the first 6 months of Bicalutamide therapy. Severe hepatic changes have been observed rarely with Bicalutamide (see Section 4.8). Bicalutamide therapy should be discontinued if changes are severe. Bicalutamide has been shown to inhibit Cytochrome P450 (CYP 3A4), as such caution should be exercised when co-administered with drugs metabolised predominantly by CYP 3A4, see Sections 4.3 and 4.5. Lactose: This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

    4.5 Interaction with other medicinal products and other forms of interaction There is no evidence of any Pharmacodynamic or pharmacokinetic interactions between Bicalutamide and LHRH analogues. In vitro studies have shown that R-bicalutamide is an inhibitor of CYP 3A4, with lesser inhibitory effects on CYP 2C9, 2C19 and 2D6 activity. Although clinical studies using antipyrine as a marker of cytochrome P450 (CYP) activity showed no evidence of a drug interaction potential with ' Bicalutamide, mean midazolam exposure (AUC) was increased by up to 80%, after co-administration of Bicalutamide for 28 days. For drugs with a narrow therapeutic index such an increase could be of relevance. As such, concomitant use of terfenadine, astemizole and cisapride is contra-indicated and caution should be exercised with the co-administration of Bicalutamide with compounds such as cyclosporin and calcium channel blockers. Dosage reduction may be required for these drugs particularly if there is evidence of enhanced or adverse drug effect. For cyclosporin, it is recommended that plasma concentrations and clinical condition are closely monitored following initiation or cessation of Bicalutamide therapy. Caution should be exercised when prescribing Bicalutamide with other drugs which may inhibit drug oxidation e.g. cimetidine and ketoconazole. In theory, this could result in increased plasma concentrations of Bicalutamide, which theoretically could lead to an increase in side effects.

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    In vitro studies have shown that Bicalutamide can displace the coumarin anticoagulant, warfarin, from its protein binding sites. It is therefore recommended that if Bicalutamide is started in patients who are already receiving coumarin anticoagulants, prothrombin time should be closely monitored.

    4.6 Pregnancy and lactation Bicalutamide Tablets 50mg are contra-indicated in females and must not be given to pregnant women or breast-feeding mothers.

    4.7 Effects on ability to drive and use machines No studies on the effect on the ability to drive and use machines have been performed. However, it should be noted that occasionally dizziness or somnolence may occur (see section 4.8). Any affected patients should exercise caution.

    4.8 Undesirable effects The frequencies of adverse events are ranked according to the following: very common (1/10); common (1/100, < 1/10); uncommon (1/1,000, < 1/100); rare (1/10,000, < 1/1,000); very rare (< 1/10,000). Table 1 Frequency of Adverse Reactions

    System organ class Frequency Event

    Cardiac disorders Very rare (< 1/10,000) Angina, heart failure, conduction defects including PR and QT interval prolongations, arrhythmias and non-specific ECG changes.

    Common (1/100, < 1/10)

    Anaemia Blood and lymphatic system disorders

    Very rare (< 1/10,000) Thrombocytopenia

    Common (1/100, < 1/10)

    Dizziness, insomnia. Nervous system disorders

    Uncommon (1/1,000, < 1/100)

    Somnolence

    Respiratory, thoracic and mediastinal disorders

    Uncommon (1/1,000, < 1/100)

    Interstitial lung disease, dyspnoea

    Common (1/100, < 1/10)

    Diarrhoea, nausea, constipation

    Gastrointestinal disorders

    Uncommon (1/1,000, < 1/100)

    Dry mouth, dyspepsia, flatulence.

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    Rare (1/10,000, < 1/1,000)

    Vomiting

    Renal and urinary disorders

    Uncommon (1/1,000, < 1/100)

    Nocturia

    Common (1/100, < 1/10)

    Rash, sweating, hirsutism

    Uncommon (1/1,000, < 1/100)

    Alopecia