Tubilux Infected Eyes Eye Ointment PL 17918/0011 UKPAR ... · PDF fileTubilux Infected Eyes...

Tubilux Infected Eyes Eye Ointment PL 17918/0011

UKPAR TABLE OF CONTENTS Lay Summary

Page 2

Scientific discussion

Page 3

Steps taken for assessment

1

Steps taken after authorisation – summary

Page 12

Summary of Product Characteristics Page 13

Product Information Leaflet

Page 16

Labelling

Page 18

MHRA PAR – Tubilux Infected Eyes Eye Ointment (PL 17918/0011) - 1 -

TUBILUX INFECTED EYES EYE OINTMENT PL 17918/0011

LAY SUMMARY The MHRA granted Tubilux Pharma SpA a Marketing Authorisation (licence) for the medicinal product Tubilux Infected Eyes Eye Ointment on 29 July 2010. This is a prescription only medicine (POM) for the treatment of bacterial conjunctivitis caused by chloramphenicol susceptible organisms. Tubilux Infected Eyes Eye Ointment contains the active ingredient chloramphenicol, which is an antibiotic. It is used to treat acute bacterial conjunctivitis, which is an infection of the outer surface the eye that causes redness, discomfort and discharge from the affected eye. This application is a duplicate of a previously granted application for Chloramphenicol 1.0% w/w Eye Ointment (PL 17918/0004), for which the Marketing Authorisation Holder is Tubilux Pharma SpA and which was granted on 01 March 2007. No new or unexpected safety concerns arose from this simple application and it was, therefore, judged that the benefits of taking Tubilux Infected Eyes Eye Ointment outweigh the risks, hence a Marketing Authorisation has been granted.



SCIENTIFIC DISCUSSION TABLE OF CONTENTS Introduction

Page 4

Pharmaceutical assessment

Page 5

Preclinical assessment

Page 8

Clinical assessment

Page 9

Overall conclusions and risk benefit assessment Page 10


INTRODUCTION The UK granted a Marketing Authorisation for the medicinal product Tubilux Infected Eyes Eye Ointment (PL 17918/0011) to Tubilux Pharma SpA on 29 July 2010. The product is available as a prescription only medicine (POM) and is used for the treatment bacterial conjunctivitis caused by chloramphenicol susceptible organisms. The application was submitted as a simple abridged application according to Article 10c (formerly Article 10.1(a)(i)) of Directive 2001/83/EC, cross-referring to Chloramphenicol 1.0% w/w Eye Ointment (PL 17918/0004), approved on 01 March 2007 to the same Marketing Authorisation Holder, Tubilux Pharma SpA. No new data was submitted nor was it necessary for this simple application, as the data are identical to that of the previously granted cross-reference product. The product contains the active ingredient chloramphenicol which is a bacteriostatic antibiotic with a broad spectrum of action against both Gram-positive and Gram-negative bacteria, as well as some other organisms. Chloramphenicol is thought to enter sensitive cells by an active transport process. Within the cell it binds to the 50S subunit of the bacterial ribosome at a site adjacent to the site of action of the macrolides and clindamycin, and inhibits bacterial protein synthesis by preventing attachment of aminoacyl transfer RNA to its acceptor site on the ribosome, thus preventing peptide bond formation by peptidyl transferase. Chloramphenicol is extensively used in the topical treatment of eye infections and also to treat infections of the ear.


PHARMACEUTICAL ASSESSMENT LICENCE NO: PL 17918/0011 PROPRIETARY NAME: Tubilux Infected Eyes Eye Ointment ACTIVE(S): Chloramphenicol COMPANY NAME: Tubilux Pharma SpA E.C. ARTICLE: Article 10c (formerly Article 10.1(a)(i)) of Directive

2001/83/EC LEGAL STATUS: POM 1. INTRODUCTION This is a simple, ‘piggy back’ application for Tubilux Infected Eyes Eye Ointment submitted under Article 10c of Directive 2001/83/EC. The proposed Marketing Authorisation Holder is Tubilux Pharma SpA, via Costarica, 20/22–00040 Pomezia, Rome, Italy. The application cross-refers to Chloramphenicol 1.0% w/w Eye Ointment (PL 17918/0004), approved on 01 March 2007 to the same Marketing Authorisation Holder, Tubilux Pharma SpA. The current application is considered valid. 2. MARKETING AUTHORISATION APPLICATION FORM 2.1 Name(s) The proposed name of the product is Tubilux Infected Eyes Eye Ointment. The name is in line with current requirements. 2.2 Strength, pharmaceutical form, route of administration, container and pack sizes Each gram of ointment contains chloramphenicol 1.0% w/w. The product is packaged in an aluminium tube with epoxy-phenolic-ureic resin internal coating with a polyethylene screw cap and nozzle and is available in a pack size of 4g. The proposed shelf-life (2 years unopened and 28 days after opening) and storage conditions (Do not store above 25°C) are consistent with the details registered for the cross-reference product. 2.3 Legal status On approval, the product will be available as a prescription-only medicine (POM). 2.4 Marketing Authorisation Holder/Contact Persons/Company Tubilux Pharma SpA, via Costarica, 20/22–00040 Pomezia, Rome, Italy. The QP responsible for pharmacovigilance is stated and his CV is included. 2.5 Manufacturers The proposed manufacturing sites are consistent with those registered for the cross-reference product and evidence of GMP compliance has been provided. 2.6 Qualitative and quantitative composition The proposed composition is consistent with the details registered for the cross-reference product.


2.7 Manufacturing process The proposed manufacturing process is consistent with the details registered for the cross-reference product and the maximum batch size is stated. 2.8 Finished product/shelf-life specification The proposed finished product specification is in line with the details registered for the cross-reference product. 2.9 Drug substance specification The proposed drug substance specification is consistent with the details registered for the cross-reference product. 2.10 TSE Compliance No materials of animal or human origin are included in the product. This is consistent with the cross reference product. 2.11 Bioequivalence No bioequivalence data are required to support this informed consent application, as the proposed product is manufactured to the same formula utilising the same process as the reference product Chloramphenicol 1.0% w/w Eye Ointment (PL 17918/0004). 3. EXPERT REPORTS The applicant cross-refers to the data for Chloramphenicol 1.0% w/w Eye Ointment (PL 17918/0004), to which it claims identicality. This is acceptable. 4. PRODUCT NAME & APPEARANCE See 2.1 for details of the proposed product name. The appearance of the product is identical to the cross-reference product. 5. SUMMARY OF PRODUCT CHARACTERISTICS The proposed Summary of Product Characteristics is consistent with the details registered for the cross-reference product. 6. PATIENT INFORMATION LEAFLET/CARTON PIL The patient information leaflet has been prepared in-line with the details registered for the cross-reference product. The applicant has previously submitted results of PIL user testing for the reference product Chloramphenicol 1.0% w/w Eye Ointment (PL 17918/0004). The results indicate that the PIL is well-structured and organised, easy to understand and written in a comprehensive manner. The test shows that the patients/users are able to act upon the information that it contains. As the leaflet for Chloramphenicol 1.0% w/w Eye Ointment (PL 17918/0004) and this product is considered the same, no further user testing of the leaflet for this product is necessary.


Carton and blister The proposed artwork is comparable to the artwork registered for the cross-reference product and complies with statutory requirements. In line with current legislation, the applicant has also included the name of the product in Braille on the outer packaging and has included sufficient space for a standard UK pharmacy dispensing label. 7. CONCLUSIONS The data submitted with the application are acceptable. A Marketing Authorisation should be granted.


PRECLINICAL ASSESSMENT No new preclinical data have been supplied with this application and none are required for an application of this type. The Marketing Authorisation Holder has provided adequate justification for not submitting an Environment Risk Assessment (ERA). As the application is for an identical version of an already authorised reference product, it is not expected that the environmental exposure to chloramphenicol will increase following the marketing approval of the proposed product.


CLINICAL ASSESSMENT As this is a duplicate application, no new clinical data have been supplied and none are required.

The Marketing Authorisation Holder has provided adequate justification for not submitting a Risk Management Plan (RMP). As the application is for an identical version of an already authorised reference product, for which safety concerns requiring additional risk minimisation have not been identified, a risk minimisation system is not considered necessary. The reference product has been in use for many years and the safety profile of the active ingredient is well-established. The Marketing Authorisation Holder has provided details of a suitable pharmacovigilance system that fulfils the requirements and provides adequate evidence that the Marketing Authorisation Holder has the services of a qualified person responsible for pharmacovigilance and has the necessary means for the notification of any adverse reaction suspected of occurring either in the Community or in a third country.


OVERALL CONCLUSION AND BENEFIT/RISK ASSESSMENT QUALITY The data for this application is consistent with that previously assessed for the cross-reference product and as such have been judged to be satisfactory. PRECLINICAL No new preclinical data were submitted and none are required for an application of this type. EFFICACY This application is identical to a previously granted application for Chloramphenicol 1.0% w/w Eye Ointment (PL 17918/0004). No new or unexpected safety concerns arise from this application. The SPC, PIL and labelling are satisfactory and consistent with that for the cross-reference product. BENEFIT/RISK ASSESSMENT The quality of the product is acceptable and no new preclinical or clinical safety concerns have been identified. The applicant’s product is identical to the cross-reference product. Extensive clinical experience with chloramphenicol is considered to have demonstrated the therapeutic value of the compound. The benefit/risk is, therefore, considered to be positive.



STEPS TAKEN FOR ASSESMENT

1 The MHRA received the marketing authorisation application on 20 December 2007.

2 Following standard checks and communication with the applicant the MHRA considered the application valid on 14 January 2008.

3 Following assessment of the application the MHRA requested further information on 28 July 2008.

4 The applicant responded to the MHRA’s request, providing further information on 1 August 2008.

5 Following assessment of the response the MHRA requested further information on 29 March 2010.

6 The applicant responded to the MHRA’s request, providing further information on 19 May 2010.

7 The application was determined on 29 July 2010.



STEPS TAKEN AFTER ASSESSMENT

Date submitted

Application type

Scope Outcome



SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT

Tubilux Infected Eyes Eye Ointment 2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each gram of ointment contains Chloramphenicol 1.0% w/w. For full list of excipients, see Section 6.1

3 PHARMACEUTICAL FORM

Eye ointment. A yellowish-white ointment 4 CLINICAL PARTICULARS 4.1 Therapeutic indications

Chloramphenicol is a broad spectrum antibiotic for the treatment of bacterial conjunctivitis caused by chloramphenicol susceptible organisms. Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration Topical administration to the eye only. Adults, children and infants: The recommended dosage for adults, children and infants of all age groups is a small amount of the ointment to be applied to the affected eye every 3 hours or more frequently if required. Treatment should be continued for 48 hours after the eye appears normal. Elderly: As for adults. Chloramphenicol has been used successfully at normal dosages in elderly patients. The pattern and incidence of adverse effects does not appear to differ from younger adults.

4.3 Contraindications

The ointment must not be administered to: Patients who have a history of hypersensitivity to chloramphenicol or to any other ingredient of the ointment Patients who have experienced bone marrow suppression during previous exposure to chloramphenicol.

4.4 Special warnings and precautions for use

Chloramphenicol is absorbed systemically from the eye and systemic toxicity has been reported (see section 4.8). Bone marrow hypoplasia, including aplastic anaemia and death, has been reported following topical use of chloramphenicol. Whilst the hazard is a rare one, it should be borne in mind when assessing the benefits expected from the use of the compound. If the eye ointment is to be used on a long-term or intermittent basis, it may be advisable to perform a routine blood profile before therapy and at appropriate intervals thereafter to detect any haemopoietic abnormalities. In severe bacterial conjunctivitis and in cases where infection is not confined to the conjunctivae, the topical use of chloramphenicol should be supplemented by appropriate systemic treatment. Chloramphenicol does not provide coverage against Pseudomonas spp. or serratia marcescens. The use of topical chloramphenicol may occasionally result in overgrowth of non-susceptible organisms including fungi. If any new infection appears during treatment, the antibiotic should be discontinued and appropriate treatment given. It is recommended that all types of contact lenses be avoided during ocular infections.


4.5 Interaction with other medicinal products and other forms of interaction

None Known If a concomitant topical treatment to the eye is required, the administration of the different products should be separated by an adequate period of time.

4.6 Pregnancy and lactation

The safety of topical chloramphenicol in pregnancy and lactation has not been established. It should therefore only be used when considered essential by the physician and only if it is considered that the anticipated benefit outweighs the potential risk.

4.7 Effects on ability to drive and use machines Blurring of vision can occur with the ointment and patients should be warned not to drive or operate machinery unless their vision is clear.

4.8 Undesirable effects

Transient burning or stinging sensations may occur with the use of ophthalmic chloramphenicol. Serious side effects include hypersensitivity reactions that may manifest as angioneurotic oedema, anaphylaxis, urticaria, fever, and vesicular and maculopapular dermatitis. Treatment must be discontinued immediately in such cases. Bone marrow suppression, including the idiosyncratic type of irreversible and fatal aplastic anaemia that is recognized to occur with systemic therapy, has been reported in association with topical administration of chloramphenicol.

4.9 Overdose

Accidental overdose or accidental ingestion of the ointment is unlikely to cause systemic toxicity due to low content of chloramphenicol in the product.

5 PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties

ATC Code: S01AA01 Mechanism of Action: Chloramphenicol exerts its antibacterial effect by binding to bacterial ribosomes and inhibiting bacterial protein synthesis at an early stage. Susceptibility: The following bacterial species are recognised conjunctival pathogens and may be susceptible to chloramphenicol. However due to the prevalence of acquired resistance to chloramphenicol in these species, the results of susceptibility testing should be taken into account as soon as these are available. If no susceptibility test result is available, the choice of antibacterial agent should be influenced by local information on the likely prevalence of resistance to chloramphenicol in species that are commonly pathogenic in the eye. Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae Other beta-haemolytic streptococci Haemophilius influenzaeMoraxella catarrhalis Neisseria gonorrhoeae Resistance: Acquired resistance to chloramphenicol has been described in all the above species. Most commonly this is mediated by bacterial production of a chloramphenicol acetyl transferase that inactivates the drug. Chloramphenicol is not generally active against the enterobacteriaceae and is not active against non-fermenters such as Pseudomonas aeruginosa.

5.2 Pharmacokinetic properties

Chloramphenicol is found in measurable amounts in the aqueous humour following local application to the eye. Systemic exposure to chloramphenicol occurs at a very low level after topical ophthalmic use.

5.3 Preclinical safety data

Pre-clinical safety data does not add anything of further significance to the prescriber.


6 PHARMACEUTICAL PARTICULARS 6.1 List of excipients

Liquid paraffin, White soft paraffin

6.2 Incompatibilities Not Applicable

6.3 Shelf life

2 years unopened, 28 days opened 6.4 Special precautions for storage

Do not store above 25°C. 6.5 Nature and contents of container

Aluminium tube with epoxy-phenolic-ureic resin internal coating. Polyethylene screw cap and nozzle. Pack size, 4g tube

6.6 Special precautions for disposal Dispose of any unused ointment 28 days after opening the pack. Do not use if the pack is open when supplied.

7 MARKETING AUTHORISATION HOLDER Tubilux Pharma SpA Via Costarica, 20/22 – 00040 Pomezia Rome, Italy

8 MARKETING AUTHORISATION NUMBER(S)

PL 17918/0011

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 29/07/2010 10 DATE OF REVISION OF THE TEXT

29/07/2010


PRODUCT INFORMATION LEAFLET


LABELLING

G


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