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Modifications to Drug Scheduling - a Case Study for Rational Change

Deon Schoombie
From a Self Medication Industry Perspective

Issue 72: June 2008
Page: 1 of 1 Author's Profile | Send to a Friend | Printer Version

Editor's Note: The recent upscheduling of popular cough mixtures for use in children under the age of 2, caught most of the Pharmaceutical Industry (as well as pharmacists) by surprise.
Deon Schoombie, scientific director for the Australian Self Medication Industry has provided comment and has noted that regulatory change needs to occur with solid evidence and for all stakeholders to be involved.
I think most pharmacists would agree with his commentary that follows.

The intersection of two separate regulatory processes recently resulted in considerable confusion for industry and healthcare professionals alike.

The publication of the outcomes of the February 2008 meeting of the National Drugs and Poisons Schedule Committee (NDPSC) on 9 April coincided with an announcement by TGA regarding the broader issue of the use of cough and cold medicines in children.

From 1 September 2008 products containing sedating antihistamines can only be supplied on prescription by a doctor if indicated for children under two. This follows a decision of the NDPSC at its February 2008 meeting to reschedule eight non-phenothiazine antihistamines (brompheniramine, chlorpheniramine, dexchlorpheniramine, diphenhydramine, diphenylpyraline, doxylamine, pheniramine and triprolidine) to Schedule 4 when indicated for children under 2 years of age.


The decision was a further step in the process of harmonising medicines schedules between Australia and New Zealand. The NZ Medicines Classification Committee (MCC) had already classified sedating antihistamines, when indicated either singly or in combination for use in children under 2, as Prescription Medicines. This was based on reports of misuse and abuse and safety concerns. It was recommended in 2006 that NDPSC harmonise with the MCC decision. The matter was considered at the February 2007, June 2007 and February 2008 NDSPC meetings.

ASMI’s Submission to NDPSC

In its submissions to NDPSC, ASMI raised concerns about the quality and paucity of the evidence relied upon and argued that a scheduling action could not be justified on the basis of the evidence before the Committee. However, at the June 2007 meeting promethazine and trimeprazine were rescheduled to Schedule 4 (when indicated for children under 2) and consideration of the scheduling of the remaining antihistamines was foreshadowed for the February 2008 meeting.

An unexpected and very unusual twist was added to the NDPSC debate when “an applicant” requested in a submission that all non-phenothiazine antihistamines for use in children under 2 be rescheduled to Schedule 4. Parties and individuals are not identified in the Record of Reasons of NDPSC meetings, but in this particular instance it provides for interesting investigative reading.

The Committee justified its decision to ‘up-schedule’ the remaining sedating antihistamines on the premise that the apparent lack of efficacy and side effect profiles “may warrant further evaluation before these products could be safely used in children <2 years of age and that the risks might outweigh any potential benefit from their use”.

Initial Developments in the US

Against this background, the FDA’s Non-prescription Drugs Advisory Committee and the Paediatric Advisory Committee at a joint meeting in October 2007 considered the safety and efficacy of OTC cough and cold products marketed for paediatric use. The meeting was in response to a citizen’s petition. The FDA Advisory Panel recommended that certain OTC antitussives, expectorants, nasal decongestants, antihistamines and combination cough/cold products should not be used in children under 2 and between 2 and 6 years, but that the products should continue to be available for children aged 6 – 12 years.

ASMI Consultations and Response

ASMI anticipated that this issue would appear on the TGA’s radar and in December 2007 called a meeting of all sponsors of paediatric cough/cold products to consider strategies to protect the product category. In a position paper to the TGA, ASMI highlighted two key points:

first, the lack of local evidence of comparable patterns of misuse or abuse reported in the US, and
second, the critical differences between the regulatory schemes in Australia and the US in terms of pre-market evaluation, access restrictions through scheduling and stringent labelling requirements.

ASMI argued that OTC cough/cold medicines have a very long history of safe use by Australian consumers. Furthermore, the Australian regulatory environment provides significant additional safeguards to ensure the quality use of these medicines. The lack of evidence of patterns of misuse or abuse suggested there was no need for any changes in current regulatory requirements. However, ASMI did support a review by NDPSC of the scheduling of sedating antihistamines for use in children less than 2 years of age on a substance by substance basis, provided it was based on sound evidence. ASMI did not receive any response to its submission.

FDA Issues Recommendation

In January 2008, the FDA released a recommendation that cough and cold products should not be used in children under 2 because “the products have not been shown to be safe or effective in this age group”. In the same statement the FDA advised that it was still reviewing the data for 2 – 12 year olds and that it intended to issue recommendations once the review has been completed.

UK Follows the US Lead

On 27 March 2008, the UK medicines regulator, MHRA, announced that their Commission on Human Medicines had reviewed OTC cough/cold products used in children and advised that certain antitussives, expectorants, decongestants and antihistamines should no longer be used in children and would no longer be licensed for use in children under 2 years.

The MHRA also announced that industry had voluntarily agreed to remove dosage instructions for children under 2 from labels and to add additional instructions in relation to children aged 2-6 years. It noted that products with the updated advice on their packaging would be in pharmacies and stores by October 2008.

TGA Reaction

This action by MHRA appears to have prompted the TGA to follow suit swiftly. Sponsors were taken by surprise by a letter dated 28 March 2008 in which the TGA advised them of an additional condition of registration under provisions of the Therapeutic Goods Act. The additional condition, which would take effect 28 days after the date of the notice, entails removal of dosage instructions relating to use in children under 2 and a mandatory statement not to use in children under 2. The 28 day notice period was particularly surprising given the long history of use in Australia and lack of local reports of serious adverse events.

Following this letter to sponsors, the TGA approached ASMI for the first time, seeking feedback on the wording of a draft letter to pharmacists, as well as a proposed TGA website announcement outlining the regulatory changes. On 9 April the TGA communicated the new restrictions on the use of cough and cold medicines in children in a letter to pharmacists and also announced it on the TGA website.

The website announcement referred to the NDPSC decision in relation to the rescheduling of sedating antihistamines and advised that these medicines would not be available for supply to children under 2 years of age from 1 September 2008 without a prescription from a medical practitioner. It also stated that the TGA would be writing to pharmacists and medical practitioners about this scheduling change.

The letter to pharmacists advised that products containing the antihistamines brompheniramine, chlorpheniramine and diphenhydramine; the antitussives, dextromethorphan and pholcodine; the expectorants, guaifenesin and ipecacuanha; and the decongestants, phenylephrine and pseudoephedrine should not be administered to children less than 2 years of age.

A letter was also sent to medical practitioners on 11 April advising them that products containing the ingredients mentioned above should not be administered to children less than 2 years of age.

The reasons for the new restrictions were cited as “a number of overseas reports of serious adverse effects among infants and children linked to misuse, medication error, accidental overdose, accidental exposure and concurrent use of multiple products”; “recent announcements made by the FDA and the MHRA“ and “several reviews of the evidence indicating a lack of efficacy”.

Several questions have been raised:

  • Brompheniramine, chorpheniramine and diphenhydramine become prescription only from 1 September 2008. Should products containing those ingredients not be prescribed regardless?
  • Will products currently in the supply chain be allowed to ‘run out’?
  • What are the legal implications and who is responsible when a parent uses a product (with current labelling) in a child under 2, in spite of advice to the contrary, and a serious adverse event occurs?
  • Generations of parents have relied on these products to treat their children—what options will be available in future when a toddler needs relief from cough and cold symptoms?
  • It is a real possibility that parents will “titrate down” dosage instructions for older children to administer to children under 2. How will this be addressed?
  • Is this signalling a change in regulation from a substance-based approach to a therapeutic category/demographic– based approach?

ASMI has been advised that the use of cough and cold products in children 2 – 12 will be reviewed in the near future. We hope that the above case study will serve as a learning experience and that all stakeholders will be involved from the outset to contribute to a coordinated and comprehensive implementation strategy if further regulatory changes are considered. Further interventions need to be based on solid evidence and due consideration needs to be given to the risk/benefit equation.

Industry remains committed to the quality use of medicines and protection of public health and safety but it is simply not realistic to regulate either for zero risk or to a lowest common denominator.


Deon Schoombie

Scientific Director, ASMI


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