GDS No: 29, Update 1: TSC 3:
• Addition of the agreed wording from a PRAC recommendation on Drug Reaction with eosinophilia and systemic symptoms (DRESS) syndrome to:
-SmPC Sections 4.4 Special warnings and precautions for use
-SmPC 4.8 Undesirable effects

-PIL Section 4. Possible side effects
• Addition of ‘contains penicillin’ to Labelling Section 7. Other special warning(s) - for IE only, as this warning was already present on UK cartons
• Addition of ‘EXP’ abbreviation to PIL Section 5. (How to store Amoxil)
• Update of MHRA adverse event reporting details in Section 4.8 of SmPC and Section 4 of PIL (UK only - all except for the combined PIL for Amoxil Vials for Injection 500 mg and 1 g)

Workshare variation Procedure Number: FR/H/XXXX/WS/101

Section 4.2 SmPC:
• The current dosing recommendations for adults undergoing haemodialysis in the EU SmPC are incorrect. What is currently recommended in the EU SmPC is actually dosing recommendations for children ≤ 40 kg. Therefore, Section 4.2 of the SmPC has been amended to reflect the correct dosing recommendations for oral amoxicillin in adults and children ≥ 40 kg undergoing haemodialysis.  There are no updates to the PIL or Labelling components as a result of this change. This update is also in line with GDS 28 which was updated in parallel.

·         Section 2 – addition of excipients

·         Section 3 – editorial changes

·         Section 4.1 – harmonisation of indications across the EU

·         Section 4.2 – harmonisation of the recommendations on how to use Amoxil.

·         Section 4.3 – editorial changes

·         Section 4.4 – harmonisation of warnings across the EU including excipient warnings

·         Section 4.5, 4.6, 4.7, 4.8, 4.9, 5.1, 5.2, 5.3 – harmonisation of information across the EU

·         Section 4.8 - addition of reporting of suspected adverse reactions
Sections 6.1, 6.2 – harmonisation of pharmaceutical information across the EU

·         Section 6.3, 6.4 – addition of reconstituted storage and shelf life

·         Section 6.5 - harmonisation of pharmaceutical information

·         Section 6.6 – editorial changes

·         Section 9 – editorial changes

·         Section 11 – legal status removed

Section 4.4- Administrative changes

Section 4.5- Administrative changes

Section 4.6- Additional information about use in pregnancy.

Section 4.8- Removal of ‘for suspension and chewable tablets only’. Administrative changes, and the addition of reporting side effects.

Summary of track changes for the SPC:

Amoxil Paediatric 125mg/1.25ml Powder for Oral Suspension

Section 2. QUALITATIVE AND QUANTITATIVE COMPOSITION

125mg amoxicillin per 1.25ml as amoxicillin trihydrate

For excipients see section 6.1.

List of excipients with known effects:

Aaspartame (E951)                              4 mg/1.25 ml

Sodium benzoate (E211)         2.125 mg/1.25 ml

Sulphur dioxide (E220)                      0.11 µg/1.25 ml

Maltodextrin (contains glucose)          7 mg/1.25 ml

Section 3. PHARMACEUTICAL FORM

Powder for oral suspension

White free flowing powderWhite powder with yellowish grains

Section 4.4 Special warnings and precautions for use

Addition of the following warnings:

‘Amoxil’ Paediatric Suspension contains sodium benzoate which is a mild irritant to the skin, eyes and mucous membrane. It may increase the risk of jaundice in newborn babies.

Amoxil contains Aspartame (E951) which is a source of Phenylalanine. This may be harmful for people with phenylketonuria.

The lemon-peach-strawberry flavour contains sulphur dioxide (E220) which may rarely cause severe allergic reaction (called hypersensitivity reaction) and tightness in your chest (called “bronchospasm”). 

This medicinal product contains maltodextrin (contains glucose). Patients with rare glucose-galactose malabsorption should not take this medicine.

Deletion of the following warning:

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Section 6.1.List of excipients

            Sodium benzoate (E211)

Sodium carboxymethyl cellulosecarmellose sodium (E466)

Crospovidone

Xanthan gum

Silica hydrophobic colloidal

Magnesium stearate

Lemon-peach-strawberry flavour (containing sulphur dioxide (E220) & maltodextrin (contains glucose).

)

Aspartame (E951)

peach dry flavour

strawberry dry flavour

lemon dry flavour

sucrose.

Section 6.5. Nature and contents of container

A clear 45ml glass bottle moulded from type III Ph. Eur. glass. The bottles are fitted with an aluminium roll-on pilfer-proof (ROPP), internally lacquered, externally enamelled closure containing a flowed-in PVC liner or polyolefin liner. These primary packs are placed in a carton with a 6mL syringe.

Section 6.6. Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product

At time of dispensing, the dry powder should be reconstituted to form a citrus flavoured, colourless an oral suspension, as detailed below:

•         Check cap seal is intact before use.

•         Invert and shake bottle to loosen powder.

•         Fill the bottle with water to just below the mark on bottle label.

•         Invert and shake well, then top up with water to the mark. Invert and shake again.

•         Shake well before taking each dose.

Volume of water to be added to reconstitute                           13ml                           

Nominal bottle size                                                                  4530ml                                   

Final volume of reconstituted oral suspension                         20ml

4.2        Posology and Method of Administration

Children up to 10 years of age Children weighing < 40 kg:

The usual total daily dosage is 375mg in divided doses (i.e. 125mg three times daily by the oral route).

The daily dosage for children is 40 - 90 mg/kg/day in two to three divided doses* (not exceeding 3 g/day) depending on the indication, severity of the disease and the susceptibility of the pathogen (see special dosage recommendations below and sections 4.4, 5.1 and 5.2).

*PK/PD data indicate that dosing three times daily is associated with enhanced efficacy, thus twice daily dosing is only recommended when the dose is in the upper range.

In severe or recurrent acute otitis media, especially where compliance may be a problem, 750mg twice a day for two days may be used as an alternative course of treatment in children aged 3 to 10 years.

Dry Powder:
Do not Store above 25C. Keep bottle tightly closed in order to protect from moisture

Reconstituted Suspension:

Do not store above 25C