Introduction

This OTC Medicine Monograph outlines the requirements for Australian market authorisation of oral medicines containing ibuprofen as a single active ingredient when applied for as an OTC New Medicine N2 application. Proposed medicines must comply with all aspects of the monograph relevant to their strength and dosage form to qualify for evaluation as an N2 application.

This monograph should be read in conjunction with the document Requirements for OTC new medicine N2 applications.

Active substance

This monograph only applies to medicines containing ibuprofen (CAS no. 15687-27-1) and excludes preparations containing any salts and derivatives of ibuprofen.

Dosage forms and strengths

Acceptable dosage forms and strengths are shown in the table below.

Active substance	Dosage strengths	Dosage forms (excludes modified release dosage forms)
Ibuprofen	200 mg	Coated tablets
	200 mg	Orally disintegrating tablets
	20 mg/mL (100 mg/5 mL)	Suspension, liquids
	40 mg/mL (200 mg/5 mL)	Suspension, liquids

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Indications

Therapeutic indications for inclusion in the Australian Register of Therapeutic Goods (ARTG)

Temporary relief of pain and/or inflammation associated with headache, migraine headache, tension headache, sinus pain, toothache, dental procedures, backache, muscular aches and pains, arthritis, osteoarthritis, rheumatic pain, period pain, fibrositis, neuralgia, sore throat, tennis elbow, and colds and flu. Reduces fever.

For paediatric formulations, in addition to any of the indications above that are appropriate to the age group, the following indications would be acceptable: relief of pain associated with teething, earache and/or immunisation.

Label indications

All or most of the indications listed above should be included as label indications, as appropriate, depending on the intended age group. Label indications must not be restricted to, or emphasise, a single indication or subset of indications (eg. cold and flu symptoms only, period pain only or headache only). Terms should be exactly as specified above and qualified by the words "temporary relief of pain [and/or inflammation] associated with...".

Directions for use

Adults and children 7 years and over (solid dose oral preparations)

Dosages must be as shown in the table below.

Dosage form & strength	Age	Single dose	Dose interval	Maximum daily dose
200 mg tablet	7-12 years	1 tablet	Every 6-8 hours when necessary	4 tablets in 24 hours
200 mg tablet	Adults and children 12 years and over	1 - 2 tablets	Every 4-6 hours when necessary	6 tablets in 24 hours

Include the statement Do not give to children under x years (where 'x' years is the youngest age for which dosage instructions are included on the labels).

Children 3 months to 12 years (oral liquid suspension)

Dosages for ibuprofen oral liquid suspension in children 3 months to 12 years must be consistent with those shown in the 'Recommended dosages' table below or, alternatively, with those shown in the 'Alternative acceptable dosages' table below.

Recommended dosages:

Age	Average body weight (kg)	Dose (mg)	Dose (mL) from 20 mg/mL suspension	Dose (mL) from 40 mg/mL suspension
3-6 months	6-8 kg	40-60 mg	2-3 mL	1-1.5 mL
6-12 months	8-10 kg	60-80 mg	3-4 mL	1.5-2 mL
1-2 years	10-12 kg	80-100 mg	4-5 mL	2-2.5 mL
2-3 years	12-14 kg	100-120 mg	5-6 mL	2.5-3 mL
3-4 years	14-16 kg	120-140 mg	6-7 mL	3-3.5 mL
4-5 years	16-18 kg	140 mg	7 mL	3.5 mL
5-6 years	18-20 kg	140-160 mg	7-8 mL	3.5-4 mL
6-7 years	20-22 kg	160-180 mg	8-9 mL	4-4.5 mL
7-8 years	22-25 kg	180-200 mg	9-10 mL	4.5-5 mL
8-9 years	25-28 kg	200-220 mg	10-11 mL	5-5.5 mL
9-10 years	28-32 kg	220-240 mg	11-12 mL	5.5-6 mL
10-11 years	32-36 kg	240-280 mg	12-14 mL	6-7 mL
11-12 years	36-41 kg	280-300 mg	14-15 mL	7-7.5 mL

Doses should be given every 6-8 hours as necessary, with no more than four doses in 24 hours.

Wider age ranges than those listed above could be specified for children aged 1 year and over. Age ranges of "1-3 years" or "2-4 years" would be acceptable, but "1-4 years" or "2-5 years" would not be acceptable. Beyond 3 years of age, age groupings of 2 or 3 years would be acceptable (e.g. 2-4 years, 4-6 years... or 3-6 years, 6-9 years...). Doses must still be consistent with the above table. For children under 12 months, age ranges must be specified as shown in the table.

Alternative acceptable dosages:

Age	Average body weight (kg)	Dose (mg)	Dose (mL) from 20 mg/mL suspension	Dose (mL) from 40 mg/mL suspension
3-6 months	6-8 kg	60-80 mg	3-4 mL	1.5-2.0 mL
6-12 months	8-10 kg	80-100 mg	4-5 mL	2.0-2.5 mL
1-3 years	10-14 kg	100-140 mg	5-7 mL	2.5-3.5 mL
3-5 years	14-18 kg	140-180 mg	7-9 mL	3.5-4.5 mL
5-7 years	18-22 kg	180-220 mg	9-11 mL	4.5-5.5 mL
7-9 years	22-28 kg	220-280 mg	11-14 mL	5.5-7.0 mL
9-12 years	28-40 kg	280-400 mg	14-20 mL	7.0-10 mL

Doses should be given every 6-8 hours as necessary, up to 3 times a day

The following points also apply (regardless of which dosage table above is used):

• A medicine label could include only a subset of the age groups - for example, doses only for children aged from 7-12 years.
• Doses must be presented on the labels with ages (in months or years), weights (kg) and volumes (mL). Dosage instructions must also include advice consistent with the following:
• If you know that your child's weight is less than the weight corresponding to their age in the table, choose the dose for their weight.
• Labels must state the maximum daily dose. For liquid preparations that include doses for more than one age group, this should be stated as: Do not give more than 4 doses in 24 hours (or 3 doses in 24 hours, depending on the doses specified).
• Where dosage instructions for infants aged 3-12 months of age are included on the labels, the dosage instructions must include a statement advising that the medicine should only be given to infants aged 3-12 months following medical advice.
• The dosage instructions must include the following statement:
• Do not give to children [or infants] under x years [or months] (where 'x' years / months is the youngest age for which dosage instructions are included on the labels).
• A statement to 'Shake the bottle before use' must be included.
• Instructions on how to use a supplied measuring device may be included if necessary. Requirements for measuring devices are included under Container/measuring device.

Labelling

Labelling must comply with all relevant Australian regulatory requirements, as detailed in the document Requirements for OTC new medicine N2 applications,  including all required warning statements.

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Quality requirements

In addition to the quality requirements outlined in the document Requirements for OTC new medicine N2 applications, the following specific requirements apply to ibuprofen monograph medicines:

Active premixes

Where ibuprofen is sourced by the finished product manufacturer as part of an active premix, the finished product manufacturer must, as a minimum, control the premix for appearance/description, identification (one chromatographic and one non-chromatographic test), assay, related substances, residue on ignition or sulfated ash, and heavy metals. The limits applied should be taken from either the BP or USP monograph for ibuprofen (with all limits to be taken from the same monograph), adjusted where necessary to account for the presence of excipients in the mixture (for example, assay). Additional requirements in relation to active premixes are specified in the document Requirements for OTC new medicine N2 applications.

Finished product specifications

In addition to other requirements specified in the document Requirements for OTC new medicine N2 applications, the finished product specifications must comply, at a minimum, with the relevant set of requirements below.

The requirements below include all relevant BP general monograph/USP General Chapter requirements and TGO 78 requirements. Further reference to these is not required. References to pharmacopoeial monographs below refer to the current monograph at time of application.

Coated tablets

The tests and limits in the BP monograph Ibuprofen Tablets with the addition of:

• tablet appearance
• dissolution (900 mL phosphate buffer pH 7.2, paddle at 50 rpm, 80% (Q) after 60 minutes)¹
• uniformity of dosage units (BP)
• content of 4'-isobutylacetophenone² (NMT 0.3% wrt ibuprofen)
• microbiological quality, in compliance with TGO 77.

Orally disintegrating tablets (uncoated)

The tests and limits in the USP monograph Ibuprofen Tablets with the addition of:

• tablet appearance
• tighter limits for ibuprofen content of 92.5-107.5% (in accordance with TGO 78)
• BP/Ph. Eur test and limit (within 3 min) for disintegration, using water R at 15-25°C
• test and limits for individual unspecified impurities (0.3%) and total impurities (0.7%)³
• microbiological quality, in compliance with TGO 77.

Oral suspensions

The tests and limits in the BP monograph Ibuprofen Oral Suspension with the addition of:

• suspension appearance
• dissolution (900 mL phosphate buffer pH 7.2, paddle at 50 rpm, 80% (Q) after 60 minutes)⁴
• content of any preservatives included in the formulation
• suitable test and limits for pH
• suitable test and limits for viscosity
• individual unspecified impurities (0.3%) and total impurities (0.7%)³
• microbiological quality, in compliance with TGO 77.

or

The tests and limits in the USP monograph Ibuprofen Oral Suspension with the addition of:

• suspension appearance
• content of any preservatives included in the formulation
• suitable test and limits for viscosity
• individual unspecified impurities (0.3%) and total impurities (0.7%)³
• microbiological quality, in compliance with TGO 77.

Container/measuring device

• Ibuprofen products must be sold in containers that comply with Therapeutic Goods Order No 80, Child Resistant Packaging Requirements for Medicines.
• If a measuring device is to be supplied with the medicine, calibrations must be exclusively in metric units and must allow all the doses shown on the labels to be measured accurately. Details of the calibrations on the measuring device must be provided with the submission (a sample may also be requested). Further considerations and requirements regarding measuring devices are detailed in ARGOM Appendix 2: Guidelines on quality aspects of OTC applications, 8. Finished product container.

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Footnotes

1. From Ibuprofen Tablets USP
2. Use assay method specified for Ibuprofen Oral Suspension BP or Ibuprofen Tablets USP, or an alternative equivalent or superior method. The method must be appropriately validated as described in Requirements for OTC new medicine N2 applications.
3. Use assay method specified for Ibuprofen Tablets BP or alternative equivalent or superior methods. Methods must be appropriately validated as described in Requirements for OTC new medicine N2 applications.
4. From Ibuprofen Oral Suspension, USP

Copyright

© Commonwealth of Australia 2013
This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted under the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the TGA Copyright Officer, Therapeutic Goods Administration, PO Box 100, Woden ACT 2606 or emailed to <tga.copyright@tga.gov.au>.

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Version	Description of change	Author	Effective date
V1.0	Original publication	OTC Medicines Evaluation/Office of Medicines Authorisation	06/09/2013