Revised: 23 May 2013
Committees
Minutes of the 35th meeting of the Medicines Classification Committee - 9 June 2006
held in the Syndicate Room, Centra Auckland Airport Hotel, 9 June 2006 (immediately following the 34th Meeting at 1pm).
PRESENT
Dr S Jessamine (Chair)
Dr D Galler
Mrs A Shirtcliffe
Ms N Gauld
Dr J Peckham
Dr T Healy
Mrs C Smith (Secretary)
IN ATTENDANCE
Dr R Hammett (Chair, Australian National Drugs and Poisons Schedule Committee (NDPSC)
1. Welcome
Members had been welcomed to the 34th meeting.
2. Apologies
There were no apologies.
4. Declaration of conflicts of interest
Conflicts of interest had been declared at the 34th meeting.
5. matters arising
There were no matters arising.
6. Submissions for reclassification
6.1 Clotrimazole – product range for the treatment of vaginal thrush (Canesten, Bayer)
This was a company submission for the reclassification of its range of clotrimazole creams and pessaries for the treatment of vaginal thrush from restricted medicine to pharmacy-only medicine.
The safety profile of clotrimazole was considered to be acceptable for sale at pharmacy-only level. However, the Committee agreed that there were a number of issues relating to appropriate use which needed to be addressed. These issues were largely related to the degree of pharmacist intervention considered necessary to ensure appropriate use of the products and to the ease of correct self-diagnosis by the consumer.
It was noted that the Pharmacy Council supported the change to pharmacy-only medicine dependent on specific training of pharmacy assistants about when they should refer customers to a pharmacist. However, the Pharmacy Guild, the Pharmaceutical Society of New Zealand, a submitter employed by a large pharmacy, and opinion sought by a member from a Doctor involved in sexual health were against sale of thrush products without full pharmacist intervention. Reasons included the potential to mask more serious conditions and the risk of incorrect self-diagnosis.
The Committee discussed possible problems which could occur if a pharmacist were not involved in the sale of products for the treatment of vaginal thrush. It was noted that a reasonable number of consumers currently seeking treatment for thrush in pharmacies were being referred to their doctors and a significant number of sales were declined.
Pharmacists reported that many pharmacy assistants were keen for greater involvement in the sale of medicines and training could be provided. The Committee agreed that training of pharmacy assistants in the sale of thrush products would be necessary if the classification change were to occur. Some members said that they would be happy for thrush products to be sold as pharmacy-only medicines provided suitable training could be assured. Others felt that young pharmacy assistants, even though suitably trained, might not have the necessary experience to deal with insistent or reticent customers particularly with regard to a fairly sensitive subject.
The Committee discussed issues relating to self-diagnosis. There was concern that there were often other underlying infections associated with thrush. Chlamydia was particularly prevalent. While chlamydia testing was available in UK pharmacies, it was not yet available in New Zealand. Other sexually transmitted diseases (STDs) could also be present. It was generally acknowledged that there could be a high denial rate for STDs.
Masking of other conditions such as malignancies and bacterial vaginosis could also occur. If untreated during pregnancy, bacterial vaginosis could result in premature deliveries and low birth weight.
The Committee also discussed whether or not there would be problems associated with recurrent use by undiagnosed diabetic consumers. Members noted that information about diabetes was contained in the Consumer Medicine Information (CMI) leaflet but thought that this could be more specific. As diabetes presented with a number of other symptoms, masking of the condition was not considered to be a major risk.
Members concluded that as there were a number of problems associated with possible misdiagnosis or the presence of underlying infections or conditions, particularly bacterial vaginosis, it would be in the best interest of consumers to have a qualified pharmacist involved in the sale of these products as consumers with recurrent disease or atypical presentation would need advice and referral to a general practitioner. The Committee agreed that clotrimazole for the treatment of vaginal thrush should remain a restricted medicine.
Recommendation
That there be no change to the current restricted medicine classification for clotrimazole for the treatment of vaginal candidiasis.
6.2 Ibuprofen 400 mg tablets (Reckitt Benckiser)
This was a company submission for the reclassification of 400 milligram solid dose forms of ibuprofen from prescription medicine to pharmacy-only medicine when presented for the same indications, dose regime, maximum daily dose and maximum milligrams per pack as for 200 milligram over-the-counter tablets.
It was noted that 400 milligram tablets had recently been reclassified to S3 (restricted medicines) in Australia and that the company had changed its request for pharmacy-only classification to restricted medicine classification in order to harmonise with Australian requirements.
Although there were still some concerns about confusion of doses and potential to misuse or abuse the product, the Committee felt generally happier that the product would be sold at the restricted medicine level of access rather than as a pharmacy-only medicine. This approach would allow a pharmacist to assess the need for use of a higher dose and provide advice at the point of purchase.
Members agreed that the 400 milligram restricted medicine pack should be clearly differentiated from 200 milligram pharmacy-only and general sales packs. In addition the restricted medicine pack should reflect the same warnings as required on the general sale packs. Medsafe should be asked to put in place the mechanisms necessary to ensure that the Committee's recommendation was put into effect.
Secretary's note
In order to carry out the Committee's recommendation the restricted medicine
schedule entry for 400 milligram ibuprofen tablets should follow the format
used for pharmacy-only and general sale ibuprofen in that the product should
be sold only when in packs approved for sale at this level. Medsafe could
then be asked to add the requirements for restricted medicine ibuprofen
to the current ibuprofen guidelines in the New Zealand Regulatory Guidelines
for Medicines.
Recommendation
- That 400 milligram ibuprofen tablets should be reclassified from prescription medicine to restricted medicine when in packs approved by the Minister or the Director-General to their sale as restricted medicines
- That Medsafe should be asked to update the relevant section of the New Zealand Regulatory Guidelines for Medicines to reflect the Committee's requirements for the sale of 400 milligram ibuprofen tablets as restricted medicines.
6.3 Ibuprofen 200 mg tablets
This was a submission from the Pharmaceutical Society of New Zealand for the reclassification from general sale medicine to pharmacy-only medicine of 200 milligram tablets or capsules in packs containing not more than 25 dose units and when in packs which had received the consent of the Minister or the Director-General to their sale as general sale medicines.
The Committee agreed that, in order to reverse the previous reclassification to general sale medicine there would need to be convincing safety data to justify the change. Members felt that such data were not contained in the submission. Studies to support the submission needed to be pertinent to short-term, intermittent, OTC use rather than to long-term use on prescription. The Committee concluded that there was insufficient evidence in the material supplied to overturn the current classification status.
Recommendation
That there should be no change to the general sale of ibuprofen when sold in packs approved for general sale
6.4 Omeprazole (Losec MUPS 20mg, AstraZeneca)
This was a company submission for the reclassification from prescription medicine to pharmacy-only medicine of 20 milligram tablets for the short-term treatment and prevention of symptoms of frequent acid heartburn in adults 18 years and older. This submission followed two earlier similar submissions in December 2001 and November 2002. On both occasions reclassification had been declined because of issues relating to indications and dose instructions for OTC use.
The Committee noted that omeprazole had recently become available over the counter in the United Kingdom and in the United States. It had been available over the counter in Sweden for a number of years. Pantoprazole had been recommended for rescheduling to restricted medicine (S3) in Australia later in the year when in limited pack sizes and for limited indications. However, until issues relating to the training of pharmacists had been resolved it would not be marketed in Australia.
Members agreed that omeprazole would provide immediate relief for only a small number of consumers as the product normally took up to 4 days to become fully effective. They thought that the target population might have different expectations and that there were already other OTC products available which would provide immediate relief for the proposed indication. However, it was acknowledged that there were consumers who were not satisfied with antacids or H2 receptor antagonists who would benefit from this product. While the need for continuous use over two weeks was considered to be unsuitable for OTC availability, one member pointed out that the criteria for OTC use had been changing and there were now a number of OTC medicines available for longer term use. However, if the symptoms were chronic, then the Committee agreed that proper diagnosis was necessary.
Issues relating to masking of more serious conditions were considered. Although masking of stomach cancers might occur to a certain extent members upheld the earlier committee opinion that this risk was insufficient to prevent OTC sale.
Interstitial nephritis was raised as a potential concern. Although interstitial nephritis was recognised to be a rare or very rare side effect of all proton-pump inhibitors, omeprazole was recognised as the commonest cause of this adverse effect. This was more likely to be because of the large number of people using it as long-term therapy rather than to it being less safe than other members of this therapeutic group of medicines. While the risk was extremely low for short-term use, the Committee agreed that it would like to see a warning in the consumer information to reflect this safety risk.
The size of the packs proposed in the submission was discussed. Members agreed that they would prefer a smaller pack if the product were to become available over the counter. They noted that the directions on the proposed label for the 28 tablet pack warned against use for more than 14 days, even though the pack contained sufficient for 28 days' treatment. Although a course of treatment for up to 28 days had been approved for OTC sale in the United Kingdom, members considered this to be too long for OTC use and would support only a maximum of 14 tablets for this level of classification.
Member compared the proposals in the submission to the other conditions governing the OTC sale of omeprazole in the United Kingdom. They felt that the United Kingdom indication, 'for the relief of reflux-like symptoms', was preferable to the indication in the New Zealand submission and queried the reasons for the company's decision to use different wording in New Zealand.
The Committee noted that the strength for OTC sale in the United Kingdom was for 10 milligram tablets only, whereas 20 milligram tablets were proposed in the company submission. While the initial OTC dose in the United Kingdom was 20 milligrams, tablets of this strength did not allow for later reduction to the lowest effective dose as recommended in the United Kingdom. The Committee agreed that 10 milligrams was the maximum strength tablet which they would recommend for OTC sale in New Zealand.
The Committee concluded that the submission to reclassify omeprazole should be declined as there were concerns about the indications, duration of treatment and dose that the company has requested. However, it was prepared to consider a submission for reclassification as a restricted medicine on the basis that:
- the pack size allowed for treatment for a maximum of 14 days
- the tablet size should not exceed 10 milligrams
- that the indication for OTC sale in New Zealand should be the same as for OTC sale in the United Kingdom - that is, for the relief of reflex-like symptoms in sufferers aged 18 and over
- that the package information should reflect safety risks, including that of interstitial nephritis.
Recommendation
That there be no change to the current prescription medicine classification of omeprazole.
6.5 Sumatriptan 50 mg tablets (Imigran, GlaxoSmithKline)
This was a company submission for the reclassification from prescription medicine to restricted medicine of 50 milligram tablets in packs of two tablets for the treatment of migraine.
Although cost might be a barrier to use by some sectors of the community, members agreed that there would be considerable customer convenience for the right group of people. They felt that this medicine would be suitable for OTC sale in that migraine was a self-limiting condition. Once the condition had been correctly diagnosed it was easily recognised by the consumer.
The safety profile had been thoroughly investigated by the Medicines and Healthcare products Regulatory Agency (MHRA) in Britain and the Committee was satisfied that the safety profile for sumatriptan was acceptable for OTC sale provided that adequate safely information was provided with the product. This included warnings on the package against:
- use of the product with irregular heartbeat
- use with allergy to sulfonamides
- use with other migraine medicines
The Committee liked the wording of the indication approved in the United Kingdom for OTC sumatriptan – "for the acute relief of migraine attacks, with or without aura, in patients who have a stable, well-established pattern of symptoms". Members agreed that a history of migraine should first have been diagnosed either by a doctor or by a pharmacist using the questionnaire proposed by the company. They agreed that OTC sale should not be for a first attack or for a consumer over the age of 65.
It was noted that misuse of the medicine would be limited by the pack size of two tablets as well as by the cost of the product. A further safeguard would be effected by the need for either the use by the pharmacist of the Migraine Treatment Questionnaire before making an initial sale or by the subsequent presentation of a migraine card by the consumer. The Committee felt that the proposed protocol for sale of the product and the requirement for an annually updated Migraine Treatment Card to be carried by the consumer, would provide an effective tool to ensure proper diagnosis and to ensure that the product was not misused for cluster headaches or analgesic abuse headaches caused by excessive use. It would also ensure that the consumer could be referred to a doctor if the results of the questionnaire or the questions asked by the pharmacist in the protocol for sale indicated that referral was appropriate. There was discussion about whether or not the consumer migraine card should be valid in other pharmacies once it had been issued. The Committee concluded that the card should be valid only at the pharmacy of issue and that the consumer would need to complete another Treatment Questionnaire if he or she wished to make a purchase at a different pharmacy.
The Committee concluded that, provided the above requirements were met, packs containing two sumatriptan tablets should be available as restricted medicines.
Recommendation
That 50 milligram sumatriptan tablets should be reclassified from prescription medicine to restricted medicine when sold in packs containing no more than two 50 milligram tablets and:
- are indicated for the acute relief of migraine attacks with or without aura, in patients who have a stable, well-established pattern of symptoms.
- when contraindications to use, including a warning about possible cross allergy to sulfonamides, are included on the pack
- the Migraine Treatment Questionnaire protocol is used by the pharmacist at each consultation unless it has previously been completed in the same pharmacy within the previous 12 months.
7. New Medicines for classification
7.1 New Chemical Entities referred by MAAC
The following new chemical entities were referred by the Medicines Assessment Advisory Committee for classification by the Medicines Classification Committee:
Exenatide (Byetta) solution for injection
Exenatide is an incretin mimetic agent that enhances glucose – dependent insulin excretion and mimics several other antihyperglycemic actions of the incretin glucagon-like-peptide1 (GLP-1). The compound is chemically known as a synthetis 37 amino acid peptide.
Exenatide can improve glycaemic control in patients with type 2 diabetes by lowering fasting and postprandial glucose concentrations.
The proposed indication is as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus who are taking metformin, a sulfonylurea, or a combination of metformin and a sulfonylurea.
Varenicline tartrate (Champix) tablets.
Varenicline is a highly selective partial agonist of the α4β2 acetylcholine nicotinic receptor that was specifically designed for use in smoking cessation. Mainly found in the brain, this receptor mediates the reinforcing properties of nicotine in animal models. Because of its agonist properties, varenicline is expected to reduce the severity of nicotine craving and nicotine withdrawal symptoms experienced upon cessation of smoking. Additionally, because of its antagonist properties, varenicline is expected to reduce the satisfaction associated with smoking, thereby decreasing the likelihood that a lapse during a quit attempt will lead to a return to regular smoking. These two properties are expected to provide increased rates of abstinence, both at the end of the treatment and in the long term.
The proposed indication is for smoking cessation.
Sitagliptin phosphate (Januvia) tablets.
Sitagliptin phosphate is an orally-active, potent, and highly selective inhibitor of the dipeptidyl peptidase 4 (DPP-4) enzyme for the treatment of type 2 diabetes. The DPP-4 inhibitors are a class of agents that act as incretin enhancers. By inhibiting the DPP-4 enzyme, sitagliptin phosphate increases the levels of two known active incretin hormones, glucagons-like peptide-1 (GLP-1) and glucose dependent insulinotropic peptide (GIP). Incretin hormones physiologically regulate blood glucose levels by increasing insulin response from pancreatic beta cells and suppressing glucagon secretion from pancreatic alpha cells when blood glucose levels are normal or elevated. These effects are not observed when blood glucose levels are low. Sitagliptin phosphate differs in chemical structure and pharmacological action from GLP-1 analogues, insulin, sulfonylureas or meglitinides, biguanides, peroxisome proliferators-activated receptor gamma (PPARg) agonists, alpha-glucosidase inhibitors, and amylin analogues.
Januvia is indicated:
- as an adjunct to diet and exercise to improve glycaemic control in patients with type 2 diabetes mellitus.
- in patients with type 2 diabetes mellitus to improve glycaemic control in combination with metformin or a PPARg agonist (e.g. thiazolidinedione) when diet and exercise, plus the single agent do not provide adequate glycaemic control.
Telbivudine (Sebivo) tablets.
Telbivudine is a specific and selective nucleoside with preferential inhibition of the synthesis of the 2nd strand HBV DNA synthesis.
Telbivudine is a synthetic thymidine nucleoside analogue with activity against HBV DNA polymerase. It is efficiently phophorylated vy cellular kinases to the active triphosphate form, which has an intracellular half-life of 14 hours. Telbivudine-5'-phosphate inhibits HBV DNA polymerase by competing with the natural substrate, thymidine 5'-triphosphate. Incorporation of telbivudine-5'-triphosphate into viral DNA causes DNA chain termination, resulting in inhibition of HBV replication.
The proposed indication is the treatment of chronic hepatitis B in patients with evidence of viral replication and active liver inflammation.
Sorafenib tosylate (Nexavar) tablets.
Sorafenib is a multikinase inhibitor targeting both tumour cells and the tumour vasculature. Sorafenib inhibits tumour growth of the murine renal cell carcinoma, RENCA, and a broad spectrum of human tumour xenografts in athymic mice accompanied by a reduction of tumour angiogenesis.
The proposed indication is the treatment of patients with advanced renal cell carcinoma.
The Committee agreed that these medicines should be classified as prescription medicines.
Recommendation
That the following new chemical entities should be added to the schedule as prescription medicines.
- Exenatide
- Varenicline tartrate
- Sitagliptin phosphate
- Telbivudine
- Sorafenib tosylate
7.2 Diphenhydramine
Medsafe had received a new medicine application for a day/night pack containing diphenhydramine in the night-time dose. The proposed new product was the first in which the sedating antihistamine, which was in the night-time dose, was presented in liquid form and in a separate primary container from the day-time dose.
The concern of both Medsafe and the Committee was that once the night-time dose containing diphenhydramine was removed from the secondary container, it would be inappropriately classified on the primary container as a pharmacy-only medicine.
The Committee felt that the product did not fulfil the intent of the classification as a pharmacy-only medicine and agreed that Medsafe should be asked to reword the schedule entry to differentiate between solid dose forms containing day and night doses in the same platform and liquid day and night packs containing two primary containers, one of which contained a sedating antihistamine.
Recommendation
- That diphenhydramine and other sedating antihistamines contained in the night time dose of day/night preparations should be pharmacy-only medicines only when in the same primary container
- That the NDPSC should be recommended to harmonise with this requirement for sedating antihistamines.
8. Harmonisation of NZ and Australian schedules
8.1 Recommendations to the MCC made by the NDPSC in October 2005 8.1.1 Anagrelide
The NDPSC had recommended that anagrelide should be added to the New Zealand schedule as a prescription medicine.
Anagrelide was used to reduce platelet production and inhibit platelet aggregation. There were no products registered in New Zealand which contained this medicine and anagrelide was not scheduled. In accordance with the principles of harmonisation, the Committee agreed that anagrelide should be added to the schedule as a prescription medicine.
Recommendation
That anagrelide should be added to the schedule as a prescription medicine.
8.1.2 Brugmansia spp
The NDPSC recommendation was to add brugmansia to the New Zealand schedule as a prescription medicine. While it was thought that brugmansia was probably covered by the schedule entries for datura, the Committee agreed that the addition of brugmansia would avoid possible confusion.
Recommendation
That brugmansia species should be added to the schedule as prescription medicines.
8.1.3 Sedating antihistamines
The NDPSC had recently removed the indications from the schedule entries for pharmacy-only sedating antihistamines so that they were not limited only to the treatment of coughs, colds or 'flu at this level of access. The MCC agreed that, provided the same conditions currently required for pharmacy-only sale continued to apply to any other indications, members were happy to allow the combination products to be used for other conditions such as allergy or hay fever at that level of classification.
Recommendation
That the indications for the use of sedating antihistamines
as pharmacy-only medicines should be removed from the schedule entries for
all medicines in this category.
8.1.4 Thenyldiamine
As there were no products containing thenyldiamine in either New Zealand or Australia, the NDPSC had removed all entries other than the prescription/S4 entry and had recommended that New Zealand harmonise by removing the pharmacy-only and restricted medicine entries from the New Zealand schedule.
The Secretary added that two further antihistamines, phenyltoloxamine and diphenylpyraline had been treated in a similar way in Australia although there had been no recommendation to date for New Zealand to harmonise. Both were now S4 medicines only in Australia and there were no products containing these antihistamines in either country. The Committee agreed that, in the interest of harmonisation, phenyltoloxamine and diphenylpyraline should be classified as prescription medicines in New Zealand and any less restrictive entries should be deleted from the schedule.
Recommendation
That thenyldiamine, phenyltoloxamine and diphenylpyraline
should be classified as prescription medicines.
8.1.5 Aciclovir
The NDPSC recommendation was to remove the pharmacy-only entry from the New Zealand schedule. The Secretary explained that this entry had been included when 5% aciclovir for herpes labialis in limited pack sizes had moved to general sale so that there would still be a pharmacy-only category to cover medicines for the same indication but with higher concentrations and/or larger pack sizes. As New Zealand had since increased the permissible pack sizes for general sale from 3 grams to 10 grams there were no longer any products in this category in either New Zealand or Australia. The Committee agreed that the pharmacy-only entry should be removed from the schedule
Recommendation
That the pharmacy-only entry for aciclovir should be removed from the schedule.
9. For the next meeting
There were no suggestions for medicines for consideration at the next meeting
10. General business
There were no general matters relating to Committee business.
The Chairman gave a brief account of the Roadshows held in Australia and New Zealand in which he had been a participant and which were being held in preparation for the formation of the Australia New Zealand Therapeutic Products Authority. In addition, he outlined the likely nature of the scheduling committee proposed under the new agency which would replace the MCC and the NDPSC and which would comprise members elected for their expertise in a particular field rather than as representatives of professional bodies.
The meeting closed at 6:05pm
