Public Assessment Report UKPAR - mhra.gov.uk · Public Assessment Report UKPAR ... (intra-abdominal...

Public Assessment Report

UKPAR

Amoxicillin 125 mg/5 ml Oral Suspension Sugar Free

Amoxicillin 250 mg/5 ml Oral Suspension Sugar Free

(amoxicillin trihydrate)

UK Licence No: PL 30464/0088-0091

Athlone Pharmaceuticals Limited

UKPAR Amoxicillin 125 mg/5 ml and 250 mg/5 ml Oral Suspension Sugar Free PL 30464/0088-

0091

2

Lay Summary

Amoxicillin 125 mg/5 ml and 250 mg/5 ml Oral Suspension Sugar Free

(amoxicillin trihydrate)

This is a summary of the Public Assessment Report (PAR) for duplicate applications

for Amoxicillin 125 mg/5 ml and 250 mg/5 ml Oral Suspension Sugar Free (PL

30464/0088-0091). These medicinal products will be referred to as Amoxicillin Oral

Suspension in the remainder of this summary, for ease of reading.

This summary explains how the applications for Amoxicillin Oral Suspension were

assessed and their authorisation recommended, as well as their conditions of use. It is

not intended to provide practical advice on how to use these products.

For practical information about using Amoxicillin Oral Suspension, patients should

read the Patient Information Leaflet (PIL) or contact their doctor or pharmacist.

What is Amoxicillin Oral Suspension and what is it used for?

These medicines are the same as Amoxicillin 125 mg/5ml and 250 mg/5 ml Oral

Suspension Sugar Free BP/Respillin 125 mg/5ml and 250 mg/5 ml Oral Suspension

Sugar Free BP (PL 06453/0049-0050; Athlone Laboratories Limited), which are

already authorised and are held by the applicant (Athlone Pharmaceuticals Limited).

The company (Athlone Pharmaceuticals Limited) referred to data provided by

Athlone Laboratories Limited for the grant of licences for Amoxicillin 125 mg/5ml

and 250 mg/5 ml Oral Suspension Sugar Free BP/Respillin 125 mg/5ml and 250 mg/5

ml Oral Suspension Sugar Free BP (PL 06453/0049-0050) as the basis for the grant of

licences for Amoxicillin Oral Suspension (PL 30464/0088-0091).

Amoxicillin Oral Suspension can treat a wide range of infections including the

following:

- Chest (bronchitis or pneumonia)

- ears (otitis media)

- kidneys

- heart (endocarditis)

- tonsils (tonsillitis)

- sinuses (sinusitis)

- teeth

- blood (septicaemia)

- skin

- gums (abscesses)

- bone

- the bladder or the urethra (the tube which carries urine from the bladder)

- the female reproductive system including infections caused by difficulties

during childbirth (puerperal sepsis and septic abortion)

- abdomen (intra-abdominal sepsis and peritonitis)

- gonorrhoea (a sexually transmitted infection)

- infections associated with pregnancy

- typhoid and paratyphoid (fevers caused by a group of bacteria called

Salmonella)


0091

3

How does Amoxicillin Oral Suspension work?

Amoxicillin Oral Suspension contains the active ingredient amoxicillin trihydrate,

which belongs to a group of antibiotic medicines called penicillins.

This medicine works by interfering with the bacteria that causes the infection.

How is Amoxicillin Oral Suspension used?

Amoxicillin Oral Suspension is taken by mouth. The suspension may be taken before,

with or after food unless the label advises a specific time.

In adults (including the elderly) the total daily dose should not exceed 6 g in total,

given in divided doses. The usual dose for most infections is 5 ml of 250 mg/5 ml to

be taken 3 times a day. For more serious infections the dose may be doubled to 10 ml

of 250 mg/5 ml 3 times a day

• The following doses may be given in the following conditions:

- Severe or recurrent chest infections: 3 g twice daily

- Simple urinary tract infections: two 3 g doses 10 to 12 hours between doses

(short course)

- Dental abscesses: two 3 g doses given orally with 8 hours between doses

- Gonorrhoea: a single 3 g dose

• The following are the usual doses for preventing infection during dental

procedures or other surgery:

- If a general anaesthetic is not used, 3 g given orally one hour before surgery

and another dose six hours later if necessary

- If a general anaesthetic is used, 3 g given orally four hours before anaesthesia

and 3 g six hours after the initial dose

Children weighing more than 40 kg should be given the usual adult dosage. The total

daily dose in children less than 40 kg should not exceed 3 g in total, given in divided

doses. All doses are worked out depending on the child’s body weight in kilograms.

Advice is given by a doctor on how much medicine should be given to a baby or

child. The usual dose is 40 mg to 90 mg for each kilogram of body weight a day,

given in two or three divided doses.

Patients with kidney problems may be prescribed a lower dose than usual.

Amoxicillin Oral Suspension can only be obtained with a prescription from a doctor.

For further information on how Amoxicillin Oral Suspension is used, please see the

Summaries of Product Characteristics or the package leaflet available on the MHRA

website.

What benefits of Amoxicillin Oral Suspension have been shown in studies? As Amoxicillin Oral Suspension (PL 30464/0088-0091) is considered to be identical

to the reference products, Amoxicillin 125 mg/5ml and 250 mg/5 ml Oral Suspension

Sugar Free BP/Respillin 125 mg/5ml and 250 mg/5 ml Oral Suspension Sugar Free

BP (PL 06453/0049-0050), its benefits and risks are taken as being the same as those

for the reference products.

What are the possible side effects from Amoxicillin Oral Suspension?


0091

4

Like all medicines, this medicine can cause side effects, although not everybody gets

them.

For the full list of all side effects reported with Amoxicillin Oral Suspension, see

section 4 of the package leaflet.

For the full list of restrictions, see the package leaflet.

Why is Amoxicillin Oral Suspension approved?

No new or unexpected safety concerns arose from these duplicate applications. It was,

therefore, considered that the benefits of Amoxicillin Oral Suspension outweigh the

risks, and the grant of Marketing Authorisations was recommended.

What measures are being taken to ensure the safe and effective use of

Amoxicillin Oral Suspension?

A satisfactory pharmacovigilance system has been provided to monitor the safety of

these products. Safety information has also been included in the Summaries of

Product Characteristics and the package leaflet for Amoxicillin Oral Suspension,

including the appropriate precautions to be followed by healthcare professionals and

patients.

Other information about Amoxicillin Oral Suspension

Marketing Authorisations were granted in the UK on 9th

April 2015.

For more information about taking Amoxicillin Oral Suspension, read the patient

information leaflet (PIL), or contact your doctor or pharmacist.

The full PAR for Amoxicillin Oral Suspension follows this summary.

This summary was last updated in May 2015.


0091

5

Table of Contents

I Introduction Page 6

II Quality aspects Page 7

III Non-clinical aspects Page 9

IV Clinical aspects Page 10

V User consultation Page 10

VI Overall conclusion, benefit/risk assessment and

recommendation

Page 10

Table of content of the PAR update

Page 36


0091

6

I Introduction The Medicines and Healthcare products Regulatory Agency (MHRA) granted Athlone

Pharmaceuticals Limited Marketing Authorisations for the medicinal products

Amoxicillin 125 mg/5 ml and 250 mg/5 ml Oral Suspension Sugar Free (PL

30464/0088-0091) on 9th

April 2015. These products are prescription only medicines

(POM) indicated for the treatment of commonly-occurring bacterial infections

including, acute and chronic bronchitis, pneumonia, ear, nose and throat infections,

otitis media, urinary tract infection, gonorrhoea, invasive salmonellosis,

gynaecological infections, peritonitis, osteomyelitis, meningitis, endocarditis and

typhoid fever.

Prophylaxis of endocarditis in patients at risk from such procedures as dental

extractions.

In some of these infections initiation of treatment or indeed the whole course of

treatment may need to be by the parenteral route.

In children with urinary tract infection, the need for further clinical investigation

should be considered.

These applications were submitted as abridged simple applications, according to

Article 10c of Directive 2001/83/EC, as amended. The applicant has cross-referred to

Amoxicillin 125 mg/5 ml and 250 mg/5 ml Oral Suspension Sugar Free BP/Respillin

125 mg/5 ml and 250 mg/5 ml Oral Suspension Sugar Free BP, which were

authorised to Athlone Laboratories Limited (PL 06453/0049-0050) on 22nd

July 1997.

Amoxicillin is a broad spectrum antibiotic which is bactericidal for both gram positive

and gram negative bacteria. Amoxicillin is well absorbed by the oral route. Oral

administration, usually at convenient three-times-a-day dosage, produces high serum

levels independent of the time at which the food is taken. Amoxicillin gives good

penetration into bronchial secretions and high urinary concentrations of unchanged

antibiotic. It is rapidly bactericidal and possesses the safety profile of a penicillin.

No new data were submitted nor were they necessary for these simple applications, as

the data are identical to those of the previously granted cross-reference products.

The MHRA has been assured that acceptable standards of Good Manufacturing

Practice (GMP) are in place for these product types at all sites responsible for the

manufacture and assembly of these products.


0091

7

II Quality aspects II.1 Introduction

These are abridged applications for Amoxicillin 125 mg/5 ml and 250 mg/5 ml Oral

Suspension Sugar Free, submitted under Article 10c of Directive 2001/83/EC, as

amended. The applicant has cross-referred to Amoxicillin 125 mg/5 ml and 250 mg/5

ml Oral Suspension Sugar Free BP/Respillin 125 mg/5 ml and 250 mg/5 ml Oral

Suspension Sugar Free BP, which were authorised to Athlone Laboratories Limited

(PL 06453/0049-0050) on 22nd

July 1997. The current applications are considered

valid.

II.2 Drug Substance Amoxicillin trihydrate

The drug substance specification is identical to that of the reference products and is

acceptable.

II.3 Medicinal Product Name

The proposed product names for these applications are Amoxicillin 125 mg/5 ml Oral

Suspension Sugar Free and Amoxicillin 250 mg/5 ml Oral Suspension Sugar Free.

The products have been named in line with current requirements.

Strength, pharmaceutical form, route of administration, container and pack size

Amoxicillin Sugar Free Suspension 125 mg/5ml and 250 mg/5 ml contains

amoxicillin trihydrate equivalent to amoxicillin 125 mg and 250 mg respectively. The

route of administration is oral.

The finished product is packaged in to high-density polyethylene bottles with tamper-

evident and child-resistant cap containing 100 ml of the suspension. The carton may

also contain a polypropylene spoon, medispoon or a dosing syringe with a bottle neck

adaptor.

The proposed shelf-life is 30 months for 125 mg/5 ml and 3 years for 250 mg/5 ml for

the unopened bottle with a storage condition for the dry powder of “Store in a dry

place below 25°C”. Reconstituted suspension may be stored for up to 14 days at 2°-

8°C in a refrigerator. These are acceptable.

The proposed packaging, shelf-life and storage condition are consistent with the

details registered for the cross-reference products.

Legal status

These products are prescription only medicines (POM).

Marketing Authorisation Holder/Contact Persons/Company

Athlone Pharmaceuticals Limited, Ballymurray, Co. Roscommon, Ireland.

The Qualified Person (QP) responsible for pharmacovigilance is stated and a

satisfactory CV has been provided.


0091

8

Manufacturers

The proposed manufacturing sites are consistent with those registered for the

cross-reference products and evidence of Good Manufacturing Practice (GMP)

compliance has been provided.

Qualitative and quantitative composition

The proposed compositions are consistent with the details registered for the

cross-reference products.

Manufacturing processes

The proposed manufacturing processes are consistent with the details registered for

the cross-reference products and the maximum batch size is stated.

Finished product/shelf-life specifications The proposed finished product specifications, at release and shelf life, are in line with

the details registered for the cross-reference products.

TSE Compliance

None of the excipients contain materials of animal or human origin. This is consistent

with the cross-reference products.

Bioequivalence

No bioequivalence data are required to support these simple abridged applications as

the proposed products are manufactured to the same formula utilising the same

processes as the cross-reference products, Amoxicillin 125 mg/5 ml and 250 mg/5 ml

Oral Suspension Sugar Free BP/Respillin 125 mg/5 ml and 250 mg/5 ml Oral

Suspension Sugar Free BP (PL 06453/0049-0050).

Expert Report

The applicant cross-refers to the data for Amoxicillin 125 mg/5 ml and 250 mg/5 ml

Oral Suspension Sugar Free BP/Respillin 125 mg/5 ml and 250 mg/5 ml Oral

Suspension Sugar Free BP (PL 06453/0049-0050) to which this application is claimed

to be identical. This is acceptable. The applicant has included detailed expert reports

of the applications. Signed declarations and copies of the experts’ CVs are enclosed

for the quality, non-clinical and clinical experts. All are considered to have sufficient

experience for their responsibilities.

II.4 Discussion on chemical, pharmaceutical and biological aspects The data submitted with the applications are acceptable. The grant of Marketing

Authorisations is recommended.


0091

9

III Non-clinical aspects Introduction

As these are abridged applications submitted under Article 10c of Directive

2001/83/EC, as amended, no new non-clinical data has been supplied and none are

required.

Ecotoxicity/environmental risk assessment (ERA)

A suitable justification has been provided for not submitting an environmental risk

assessment.

Discussion on the non-clinical aspects

The grant of Marketing Authorisations is recommended.


0091

10

IV Clinical aspects As these are abridged applications submitted under Article 10c of Directive

2001/83/EC, as amended, no new clinical data have been supplied and none are

required.

The grant of Marketing Authorisations is recommended.

Risk Management Plan (RMP)

A satisfactory pharmacovigilance system has been provided, which fulfils the

requirements and provides adequate evidence that the applicant 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. A satisfactory justification has been provided for not

submitting a risk management plan.

V User consultation User-testing of the patient information leaflet (PIL) for Amoxicillin 125 mg/5 ml and

250 mg/5 ml Oral Suspension Sugar Free has been accepted based on the bridging

report provided by the applicant making reference to the successful user-testing of the

PIL for Amoxicillin 125 mg/5 ml and 250 mg/5 ml Oral Suspension Sugar Free

BP/Respillin 125 mg/5 ml and 250 mg/5 ml Oral Suspension Sugar Free BP (PL

06453/0049-0050) as the ‘parent PIL’.

VI Overall conclusion, benefit/risk assessment and

recommendation The quality of the products is acceptable, and no new non-clinical or clinical concerns

have been identified. The applicant’s products are identical to the reference products.

Extensive clinical experience with amoxicillin trihydrate is considered to have

demonstrated the therapeutic value of the compounds. The benefit-risk assessment is,

therefore, considered to be positive.


0091

11

Summary of Product Characteristics, Patient Information Leaflet &

Labels In accordance with Directive 2012/84/EU, the current approved UK versions of the

SmPCs and PIL for these products are available on the MHRA website.

Labelling


0091

12


0091

13


0091

14


0091

15


0091

16


0091

17


0091

18


0091

19


0091

20


0091

21


0091

22


0091

23


0091

24


0091

25


0091

26


0091

27


0091

28


0091

29


0091

30


0091

31


0091

32


0091

33


0091

34


0091

35


0091

36

Table of content of the PAR update

Steps taken after the initial procedure with an influence on the Public Assessment

Report (Type II variations, PSURs, commitments)

Date

submitted

Application

type

Scope Outcome

Date post:	17-Jun-2019
Category:	Documents
Upload:	dinhnhu
View:	305 times
Download:	0 times

Public Assessment Report UKPAR - mhra.gov.uk · Public Assessment Report UKPAR ... (intra-abdominal...

Documents