Max Congestion Relief 12.2mg Capsules PL 120630075 · UKPAR Wrafton Laboratories Ltd, Congestion...

PL 12063/0075

UKPAR Wrafton Laboratories Ltd, Congestion Max Relief 12.2mg Capsules

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Public Assessment Report

Paramed/Tesco/Wilko/Morrsions/Superdrug/Sainsbury’s Lloydspharmacy Max Strength Congestion Relief 12.2mg

Capsules

Phenylephrine hydrochloride

PL 12603/0075

Wrafton Laboratories Ltd

Table of Contents Page Lay Summary 2 Scientific Discussion 3 Overall Conclusion And Risk Benefit/Analysis 7 Steps Taken During Assessment 8 Steps Taken After Assessment 9 Summary of Product Characteristics 10 Labels and Leaflet 14

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Lay Summary The MHRA granted Wrafton Laboratories Limited a Marketing Authorisation (licence) for the medicinal products Paramed/Tesco/Wilko/ Morrisons/Superdrug/Sainsbury’s Lloyds Pharmacy Max Congestion Relief 12.2mg Capsules on 24th August 2007. The products contain the active ingredient phenylephrine hydrochloride which has a recognised decongestant activity, by vasoconstriction to reduce oedema of the nasal mucosa. The product was found to be of acceptable quality and no new or unexpected safety concerns arose from this application and it was, therefore, judged that the benefits of Paramed/Tesco/Wilko/ Morrsions/Superdrug/Sainsbury’s Lloyds Pharmacy Max Congestion Relief 12.2mg Capsules outweighed the risks, hence a Marketing Authorisation was granted.


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Scientific Discussion

INTRODUCTION Based on the review of the data on quality, safety and efficacy, the UK granted a Marketing Authorisation for the medicinal products Paramed/Tesco/Wilko/ Morrisons/Superdrug/Sainsbury’s Lloyds Pharmacy Max Congestion Relief 12.2mg Capsules on 24th August 2007. The Market Authorisation was granted under Article 10a of Directive 2001/83 (as amended), a so called bibliographic application. The products contain the active ingredient phenylephrine hydrochloride which is a post-synaptic α-receptor agonist, with low cardioselective β-receptor affinity. It is has a recognised decongestant activity, by vasoconstriction to reduce oedema of the nasal mucosa.

PHARMACEUTICAL ASSESSMENT DRUG SUBSTANCE Phenylephrine hydrochloride

Structure: Description: White or almost white crystalline powder Chemical name: (S)-1-(3-Hydroxyphenyl)-2-methylaminoethanol hydrochloride Molecular formula: C9H13NO2,HCl Relative molecular mass: 203.7 The manufacture of phenylephrine hydrochloride is controlled by current Certificates of Suitability. An appropriate specification based on the European Pharmacopoeia has been provided. Analytical methods have been appropriately validated and are satisfactory for ensuring compliance with the relevant specifications. The specifications and typical analytical test reports are provided and are satisfactory. Batch analysis data are provided and comply with the proposed specification. Satisfactory certificates of analysis have been provided for working standards used by the active substance manufacturer and finished product manufacturer during validation studies.


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Appropriate stability data have been generated supporting a retest period of 3 years if stored at room temperature not exceeding 25°C in a container consisting of two polyethylene bags placed in a fibre drum or in a polyethylene bottle. DRUG PRODUCT The other ingredients of the drug product are listed below Maize Starch Lactose Monohydrate Pregelatinised Starch Magnesium Stearate (E470b) Hard Gelatin Capsule: Quinoline Yellow (E104) Titanium Dioxide (E171) Gelatin Maize starch, lactose monohydrate, pregelatinised starch and magnesium stearate have monographs in the European Pharmacopoeia. Certificates of analysis have been provided for these excipients from the excipient manufacturers. Gelatin and titanium dioxide present in the capsule shell have monographs in the European Pharmacopoeia. The colour quinoline yellow complies with commission directive 95/45/EC. Relevant certification has been provided. Relevant certification has been provided covering the TSE/BSE status and residual solvents for all the materials present in the finished product. The gelatin is covered by the certificates of suitability and a statement from the manufacturer. The magnesium stearate is of vegetable origin. Manufacture A description and flow-chart of the manufacturing method has been provided. In-process controls are appropriate considering the nature of the product and the method of manufacture. Process validation has been carried out on batches. The results are satisfactory. The supplier of the capsules manufactures them under a certificate of suitability. Dissolution and impurity profiles Dissolution and impurity profiles of the drug product were found to be similar to those for the reference product. Finished product specification The finished product specification is satisfactory. Acceptance limits have been justified with respect to conventional pharmaceutical requirements and, where appropriate, safety. Test methods have been described and have been adequately validated, as appropriate. Batch data have been provided and comply with the release specification. Certificates of analysis have been provided for any working standards used.


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Container Closure System The packaging consists of opaque white 250µm PVC blisters lidded with 20µm aluminium foil. Relevant specifications have been supplied accompanied by certificates of conformity from the packaging material manufacturers. Relevant certification has been provided for the PVC stating compliance to the EU requirements on food contact materials. Relevant certification has been provided for the aluminium foil. The PVC film conforms to the requirements of the European Pharmacopoeia, relevant certification has been provided. Stability Finished product stability studies have been conducted in accordance with current guidelines. The data presented supported a product shelf life of 30 months with a storage condition of: ‘Do not store above 25°C. Store in original package to protect from moisture.’

ASSESSOR’S OVERALL CONCLUSIONS ON QUALITY AND ADVICE A Marketing Authorisation was granted.


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MEDICAL ASSESSMENT

CLINICAL PHARMACOLOGY Pharmacokinetics Phenylephrine has reduced bioavailability from the gastrointestinal tract owing to first-pass metabolism, but is active as a decongestant by the oral route, the drug distributing through the systemic circulation to the vascular bed of the nasal mucosa. The applicant has provided an adequate justification for the absence of a bioequivalence study, in line with current guidelines. Pharmacodynamics Phenylephrine hydrochloride is a post-synaptic α-receptor agonist, with low cardioselective β-receptor affinity. It is has a recognised decongestant activity, by vasoconstriction to reduce oedema of the nasal mucosa. CLINICAL EFFICACY No new clinical data have been provided. Phenylephrine hydrochloride is a decongestant which acts by vasoconstriction to reduce oedema and swelling of the nasal mucosa. By this means nasal discharge may be reduced and obstruction associated with colds and influenza may be relieved. CLINICAL SAFETY Phenylephrine, at doses large enough to result in nasal decongestion, has the potential to affect other vascular beds and exert a vasoconstrictor effect, therefore resulting in hypertension and bradycardia. EXPERT REPORTS The clinical overview was provided by an appropriately qualified physician and is of acceptable quality.

SUMMARY OF PRODUCT CHARACTERISTICS AND PRODUCT LITERATURE After minor amendments was satisfactory.

OVERALL CONCLUSION A marketing authorisation can be granted.


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Overall Conclusion and Risk/Benefit Analysis

Quality The important quality characteristics of Paramed/Tesco/Wilko/ Morrisons/Superdrug/ Sainsbury’s Lloyds Pharmacy Max Congestion Relief 12.2mg Capsules are well-defined and controlled. There are no outstanding quality issues that would have negative impact on the benefit/risk balance. Pre-Clinical No pre-clinical data were submitted and none are required for applications of this type.

Clinical No bioequivalence studies have been conducted as the proposed products are indicated for the relief of symptoms in non-serious, self-limiting conditions and it is associated with a low incidence of serious adverse events at the dose proposed. The SPC, PIL and labelling are satisfactory and consistent with that for the reference product.

Risk/Benefit Analysis The quality of the products are acceptable and no new preclinical or clinical safety concerns have been identified. The risk benefit is therefore considered positive.


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Steps Taken During Assessment 1

The MHRA received the application on 10th October 2005.

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Following standard checks and communication with the applicant the MHRA considered the application valid on 28th November 2005.

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Following assessment of the application the MHRA requested further information from the applicant regarding the quality assessment on 4th November 2005, 14th August 2006, 1st February 2007 and 30th May 2007 and on the medical assessment on 29th January 2007.

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The applicant provided further information in regard to the quality assessment on 8th August 2006, 28th November 2006, 19th April 2007 and 22nd August 2007 and on the medical assessment on 23rd February 2007.

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The application was determined on 24th August 2007.


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Steps Taken after Assessment None


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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT Paramed Max Strength Congestion Relief 12.2 mg Capsules

Tesco Max Strength Congestion Relief 12.2 mg Capsules

Wilko Max Strength Congestion Relief 12.2 mg Capsules

Morrisons Max Strength Congestion Relief 12.2 mg Capsules

Superdrug Max Strength Congestion Relief 12.2 mg Capsules

Sainsbury’s Max Strength Congestion Relief 12.2 mg Capsules

Lloydspharmacy Max Strength Congestion Relief 12.2 mg Capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Active Ingredient mg/capsule Phenylephrine Hydrochloride 12.2 Also contains lactose, see 4.4 For a full list of excipients, see 6.1.

3 PHARMACEUTICAL FORM Capsule, Hard Capsule with opaque yellow body and cap.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications For the relief of nasal congestion, particularly when associated with colds and flu or hayfever.

4.2 Posology and method of administration Adults and children over 12 years: For oral use, one capsule, if necessary, up to four times daily. Children under 12 years: Not recommended. The Elderly: Normal adult dosage is appropriate.

4.3 Contraindications Hypersensitivity to any of the ingredients. Avoid in patients with cardiovascular disease, hypertension, diabetes mellitus, closed angle glaucoma, hyperthyroidism, prostatic enlargement and phaeochromocytoma. Patients being treated with monoamine oxidase inhibitors or within 14 days of ceasing such treatment (see section 4.5).


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4.4 Special warnings and precautions for use This medicine should be used with caution in patients with occlusive vascular disease including Raynaud's Phenomenon. Do not take for longer than 7 days, unless your doctor agrees. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. If symptoms do not go away seek a doctors advice.

4.5 Interaction with other medicinal products and other forms of interaction

Should not be given to patients being treated with monoamine oxidase inhibitors or within 14 days of stopping such treatment. May enhance the effects of anticholinergic drugs such as tricyclic antidepressants. May increase the possibility of arrhythmias in digitalised patients. May enhance the cardiovascular effects of other sympathomimetic amines (e.g. decongestants). This medicine should not be taken together with vasodilators, Beta-blockers or enzyme inducers such as alcohol.

4.6 Pregnancy and lactation The safety of this medicine during pregnancy and lactation has not been established but in view of a possible association of foetal abnormalities with first trimester exposure to phenylephrine, the use of the product during pregnancy should be avoided. In addition, because phenylephrine may reduce placental perfusion, the product should not be used in patients with a history of pre-eclampsia. In view of the lack of data on the use of phenylephrine during lactation, this medicine should not be used during breast feeding

4.7 Effects on ability to drive and use machines No adverse effects known.

4.8 Undesirable effects Adverse effects may include tachycardia, cardiac arrhythmias, palpitations, hypertension, nausea, vomiting, headache and occasionally urinary retention in males.

4.9 Overdose Symptoms of overdosage include irritability, restlessness, palpitations, hypertension, difficulty in micturition, nausea, vomiting, thirst and convulsions. In severe overdosage gastric lavage and aspiration should be


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performed. Symptomatic and supportive measures should be undertaken, particularly with regard to cardiovascular and respiratory systems. Convulsions should be controlled with intravenous diazepam. Chlorpromazine may be used to control marked excitement and hallucinations. Severe hypertension may need to be treated with an alpha-adrenoreceptor blocking drug, such as phentolamine. A beta blocker may be required to control cardiac arrhythmias.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties Pharmacotherapeutic Group (ATC classification)

R01BA03 Phenylephrine is a sympathomimetic agent with mainly direct effects on adrenergic receptors. It has predominantly alpha adrenergic activity and is without stimulating effects on the central nervous system. The sympathomimetic effect of phenylephrine produces vasoconstriction, which in turn relieves nasal congestion.

5.2 Pharmacokinetic properties Phenylephrine is readily absorbed after oral administration but is subject to extensive presystemic metabolism, much of which occurs in the enterocytes. As a consequence, systemic bioavailability is only about 40%. Following oral administration, peak plasma concentrations are achieved in 1-2 hours. The mean plasma half life is in the range 2-3 hours. Penetration into the brain appears to be minimal. Following absorption, the drug is extensively metabolised in the liver. Both phenylephrine and its metabolites are excreted in the urine. The volume of distribution is between 200 and 500 litres, but there are no data on the extent of plasma protein binding.

5.3 Preclinical safety data There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients Maize Starch Lactose Monohydrate Pregelatinised Starch Magnesium Stearate (E470b) Hard Gelatin Capsule: Quinoline Yellow (E104) Titanium Dioxide (E171) Gelatin


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6.2 Incompatibilities None known.

6.3 Shelf life 30 months.

6.4 Special precautions for storage Do not store above 25° C. Store in the original packaging to protect from moisture.

6.5 Nature and contents of container 250 µm white opaque PVC blisters lidded with 20 µm hard temper Aluminium foil. Each pack contains 12 capsules.

6.6 Special precautions for disposal Not applicable.

7 MARKETING AUTHORISATION HOLDER Wrafton Laboratories Limited Wrafton Braunton North Devon EX33 2DL.

8 MARKETING AUTHORISATION NUMBER(S) PL 12063/0075

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION 24/08/2007 10 DATE OF REVISION OF THE TEXT

24/08/2007


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Leaflet and Labels


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Max Congestion Relief 12.2mg Capsules PL 120630075 · UKPAR Wrafton Laboratories Ltd, Congestion...

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