Updated 23 May 2013
Held in the Medsafe Boardroom, Level 6, Deloitte House, 10 Brandon Street, Wellington. Commencing at 9:30AM
Dr Stewart Jessamine (Chair)
Dr David Galler
Dr Jill Peckham
Dr Tim Healy
Ms Natalie Gauld
Dr Melissa Copland
Ms Carole Firth (Secretary)
Ms Alyssa Currie, Medsafe
Ms Andrea Kerridge, Medsafe
The Chairman welcomed everyone to the 41st meeting and introduced Dr Copland as the new committee member who had been nominated by the Pharmaceutical Society. Visitors and committee members introduced themselves briefly.
Dr Galler was only available for agenda items 5.1 to 6.1 and 6.5.
The minutes of the 40th meeting were accepted as an accurate record of that meeting and were signed by the Chairman.
One member declared a potential conflict of interest but the Committee concluded that it had no significance to any of the items on the current agenda. The member participated fully in all matters under discussion. All other members declared that they had no interests which would pose a conflict with any of the items on the agenda.
At the 40th meeting the Committee had recommended that there be no change to the current prescription medicine classification of lansoprazole 15 mg capsules unless additional supporting information was provided by the sponsor company.
As no new information was submitted to the Committee for the 41st meeting, this issue was not discussed further.
That there should be no change to the current prescription medicine classification of lansoprazole capsules.
At the 40th meeting the Committee recommended that chloramphenicol for ophthalmic use should remain classified as a prescription medicine except when sold in practice by a registered optometrist. The Committee had indicated their willingness to reconsider the request for reclassification from prescription medicine to restricted medicine if additional supporting information was provided.
The Pharmaceutical Society had now supplied this supporting material, including information on training for pharmacists and a treatment algorithm developed by the Royal Pharmaceutical Society of Great Britain that was proposed to be used in New Zealand.
There was considerable discussion regarding the need for correct diagnosis of eye conditions that could be treated with chloramphenicol. Some members expressed the opinion that best practice required direct examination of the eye by a doctor or optometrist. Other members felt that the training material and treatment algorithm provided by the Pharmaceutical Society would enable pharmacists to provide an accurate diagnosis.
A member observed that pharmacists already have some experience with diagnosing and treating conjunctivitis as they have access to sulfacetamide for ophthalmic use and propamidine isethionate (as a pharmacy only medicine).
The training material provided by the Pharmaceutical Society also listed conditions/symptoms needing referral to a doctor, including (but not limited to) pain within the eye, photophobia and blurred vision. These are alarm symptoms already used by pharmacists to refer patients to doctors. It was noted that pharmacists' awareness for referring all contact lens wearers could be improved but that this would be addressed in the treatment algorithm and training material.
Training material for pharmacists would obviously be essential if the classification change were to be recommended but the Committee stated that information for patients should also be mandatory. This could take the form of a self-care card or an information leaflet.
Issues of potential resistance were briefly discussed by the Committee. One member commented that chloramphenicol had been available over-the-counter (OTC) in the UK since 2005 and that a conference poster from last year showed no overall increase in resistance in the UK.
As agreed at the last meeting, there were no outstanding resistance or safety issues with regard to OTC use of chloramphenicol eye products per se.
Committee opinion ultimately remained divided, particularly regarding the issue of minimum requirements necessary for an accurate diagnosis. A vote was taken and the recommendation to classify chloramphenicol for ophthalmic use as a restricted medicine was passed by a majority, with dissenting votes from Dr Peckham and Dr Healy. The Committee stressed that this reclassification was dependent on the Pharmaceutical Society providing pharmacists with training and any other useful material as well as ensuring that appropriate information leaflets/self-care cards (that include when to see a doctor) are provided to patients when they purchase the medicine.
At the 39th meeting the Committee recommended that codeine be classified as a prescription medicine when in combination products containing more than 15 mg of codeine per dose unit. This recommendation was not put into effect due to a subsequent objection.
The Committee reviewed their recommendation again in light of both the objection and some additional comments received from interested bodies. It was agreed that a prescription medicine classification should be recommended but that a suitable cut-off quantity needed to be identified.
Cut-off values of 15 mg and 18 mg of codeine base were considered, with the latter quantity having been suggested in comments received from an interested body. The Committee was informed that New Zealand currently has no products on the market containing 18 mg of codeine base and, overall, they agreed that a 15 mg cut-off was reasonable on the grounds that medicines would not be suitable for self-selection above that strength of codeine. Therefore, it was recommended that combination products containing more than 15 mg of codeine base per dose unit should be classified as prescription medicines.
The Committee then discussed foreshadowing another codeine matter for the next meeting. They had been awaiting a report from the Australian National Drugs and Poisons Schedule Committee (NDPSC) before continuing discussions on codeine cut-off points and pack sizes for OTC sale.
The report was now available and had led the NDPSC to propose that codeine be classified in Schedule 3 of the SUSDP (Standard for the Uniform Scheduling of Drugs and Poisons) as a restricted medicine when:
This proposal means there would no longer be a pharmacy-only category for codeine in the Australian SUSDP.
The Committee discussed the NDPSC's proposal and noted that, if proposed for New Zealand, it would need to be modified slightly in order to align with the prescription medicine classification (recommended above). The New Zealand-specific proposal would be to classify codeine in combination products as a restricted medicine when:
Codeine would be classified as a prescription medicine, when in combination products, if these conditions were not met.
Some members queried whether the restricted medicine classification was too restrictive, particularly at lower doses of codeine. It was noted that many people purchase codeine-containing products for occasional use and that changing all products to restricted medicines would have a significant effect on pharmacist workload and on purchasers having to wait for the pharmacist and provide their name and address. This led the Committee to suggest an alternative proposal; that codeine in combination products be classified as a pharmacy-only medicine (rather than a restricted medicine) under the same three conditions.
The Committee commented that a pack size limit of not more than 5 days' supply seemed suitable as codeine access is appropriate for short-term use only, except on medical advice. It was also in line with the opinion expressed by the Committee at the 38th meeting regarding a 5 day pack size limit for another analgesic, diclofenac.
There was a brief discussion about codeine's addictiveness and the general public's lack of understanding about this.
The Committee agreed that no recommendation on the two options (restricted medicine versus pharmacy-only medicine) was required at this stage. The matter would be returned to the agenda of the 42nd meeting so interested bodies could comment on the proposals.
This is a company submission for the reclassification of 500 mg famciclovir tablets from prescription medicine to restricted medicine when sold in packs of three tablets for the treatment of recurrentHerpes labialis (cold sores).
Cold sores were discussed as being a self-limiting condition which were able to cause embarrassment to sufferers when visible. The Committee also commented that cold sores were suitable for self-diagnosis, with topical treatments already available OTC. The single dose oral treatment proposed in the submission may offer some advantages to the topical treatments, which often require multiple applications and are only likely to be applied to primary lesions.
The potential for off-label use was referred to but not thought to be a major risk.
Some concerns were raised regarding the risk of renal impairment, including in diabetics. Renal function is also more likely to be impaired in the elderly and, therefore, the Committee felt that an age limit would be warranted. A suggestion was made that pharmacists should not provide the treatment to those under 18 years of age or older than 60.
Further to the discussion on the renal effects of famciclovir, members queried whether it would be difficult for pharmacists to identify all patients at risk of renal impairment (e.g. those with a creatinine clearance of 40 mL/min/m² or less).
As the treatment is indicated only for immunocompetent adults, members also queried whether pharmacists would have difficulty in identifying patients who may be immunocompromised.
Overall the Committee felt that the submission had merit but that a few outstanding issues were still to be resolved, particularly with regards to information on suitable exclusion criteria if famciclovir was to be reclassified as a restricted medicine. The Committee agreed not to recommend a change at the current meeting but would be happy to review further information forwarded by the company for the following meeting. Such information should include warnings and precautions relating to age and to use in patients with diabetes as well as any other training material that would aid in identifying patients who may have impaired renal function or may be immunocompromised. Patient advice should also include information not to repeat treatment within the course of an illness.
That there should be no change to the current prescription medicine classification of famciclovir.
This is a company submission for the reclassification from prescription medicine to general sales medicine of 600 mg and 1200 mg modified release guaiphenesin tablets for use as an expectorant to help relieve chest congestion. Guaiphenesin is currently a general sale medicine when for oral use in medicines containing 2% or less or 200 mg or less per dose form.
There appeared to be few safety issues associated with the use of guaiphenesin and the modified release dose form had been available OTC in the United States for 6-7 years. Nevertheless, the Committee was aware of a potential clinical risk of developing kidney stones at higher doses and considered that a warning about this should be included. It was also noted that guaiphenesin was not appropriate for patients with porphyria, though the incidence of this is low in New Zealand and a warning on the label was not essential.
The Committee discussed other warning statements and agreed that the sponsor's statement of "seek medical advice if your cough worsens or does not go away after a few days" was too vague. They recommended seeking medical advice if symptoms persist "after three days".
Additional label warning statements proposed by the sponsor, and supported by the Committee, included "Do not give to children under 12 years of age" and "Do not exceed the stated dose".
The submission had proposed pack sizes of up to 100 tablets. This quantity was deemed excessive for distribution as a general sale medicine. Anyone requiring that much medication to treat a cough should consult a doctor. Limiting the pack size to a 5 day supply was thought to be more appropriate. This would be in line with the pack sizes of immediate release medicines containing guaiphenesin that were already available for general sale. A limited pack size could also reduce the risk of self-medicating for off-label use, such as in those suffering from fibromyalgia.
The issue of a modified release dose form being available as a general sale medicine for treating coughs and colds was discussed but, ultimately, was not deemed to pose an obstacle to the medication being classified at this level.
Guaiphenesin's efficacy in a modified release dose form was also discussed. The Committee was assured by the Chairman that the sponsor would need to provide Medsafe with satisfactory efficacy data as part of the process of applying for consent to distribute the medicine in New Zealand.
In conclusion, the Committee felt that the submission was largely satisfactory. The Committee recommended reclassifying guaiphenesin in modified release dose form to general sale, with limits on pack size and daily intakes. Relevant warning statements, including those discussed above, should also be included on the packaging.
This was a company submission for the reclassification from prescription medicine to restricted medicine of pantoprazole 20 mg enteric coated tablets. Pack size was proposed to be limited to not more than 14 days' supply and the medicine was indicated for the symptomatic relief of heartburn, acid regurgitation and other symptoms associated with gastro-oesophageal reflux disease (GORD) in patients aged 18 and over.
It was noted that another protein pump inhibitor (PPI), 10mg omeprazole, had been recommended for reclassification from prescription medicine to restricted medicine at the previous meeting.
The current submission for pantoprazole was deemed to have similar merits to the omeprazole submission. In addition, pantoprazole may be faster acting and associated with fewer drug interactions than some PPIs on the market.
The only significant concerns expressed by the Committee related to a need for suitable warning and precaution statements on labels, particularly if pregnant, and the need to use terminology easily understood by the consumer. These issues could be resolved by permitting pantoprazole to be sold as a restricted medicine only when in packs approved for sale at that level.
Based on this, the Committee agreed to the reclassification of pantoprazole provided that the medicine met requirements similar to those detailed for the OTC sale of omeprazole in the New Zealand Regulatory Guidelines for Medicines. The requirements for the OTC sale of pantoprazole are:
This was a company submission for the reclassification from prescription medicine to restricted medicine of one prefilled nasal spray device containing 5 mg of zolmitriptan for the acute treatment of migraine with or without aura.
The Committee noted that, making a migraine medication in spray form available OTC had advantages for those unable to ingest medication orally, due to the gastrointestinal disturbances often associated with migraines.
There was some potential for users to "waste" their dose by attempting to prime the spray first. However, this risk was mitigated by the sponsor's inclusion of clear instructions in the Consumer Medicine Information (CMI) leaflet. Members commented that pharmacists could also remind patients purchasing the product that the medicine is a single dose only.
Although New Zealand experience with this medicine is lacking, there has been extensive use overseas. Furthermore, it is not the first triptan for migraine treatment recommended by the Committee for reclassification from prescription medicine to restricted medicine. The Committee had previously recommended reclassification of sumatriptan when sold in packs containing no more than two 50 mg tablets. The requirements associated with this recommendation are detailed in the minutes of the 35th meeting (June 2006).
The Committee commented that the adverse event profile of 5 mg zolmitriptan was similar to that of 100 mg sumatriptan. The two medications also share similar pharmacological mechanisms of actions.
As for sumatriptan, the Committee agreed that zolmitriptan should only be indicated for the acute relief of migraine attacks, with or without aura, in patients who have a stable, well-established pattern of symptoms. This, in combination with a Migraine Treatment Questionnaire to be used by the pharmacist, should help reduce the risks of misdiagnosis and inappropriate use of the medication.
A Migraine Treatment Questionnaire to be used by pharmacists when assessing a patient's suitability for receiving the medication had been submitted by the sponsor. This questionnaire seemed reasonable, though the Committee suggested that the sponsor company seek comment from the Pharmaceutical Society before finalising the document.
The Committee also discussed the importance of including specific warnings on the package and not just the CMI leaflet. It was recommended that Medsafe review the packaging of any zolmitriptan medication seeking approval for sale as a restricted medicine, with particular emphasis on the inclusion of warnings about use during pregnancy and use if allergic to sulfonamides.
The Committee agreed that zolmitriptan, as a single 5 mg nasal spray dose, is suitable for sale as a restricted medicine providing controls around its sale are the same as those already in place for sumatriptan. These controls include:
This was a Medsafe submission requesting that analogues of sildenafil, vardenafil and tadalafil be classified as prescription medicines. The parent compounds are already classified as prescription medicines.
As sildenafil, vardenafil and tadalafil and their analogues act as inhibitors of phosphodiesterase type 5 (PDE-5), the submission also requested that PDE-5 inhibitors be classified as prescription medicines.
A Medsafe representative attended the meeting for this agenda item and provided a brief summary of the submission. A number of analogues of the prescription medicines sildenafil, tadalafil and vardenafil have been found in adulterated herbal products, both in New Zealand and overseas. Many of these analogues possess significant PDE-5 inhibitory activity and are therefore likely to share the same adverse event profile as the known PDE-5 inhibitors.
The Chairman explained to Committee members that, although scheduling a substance does result in the scheduling of any of that substance's salts and esters, it does not extend to the scheduling of its structural analogues.
All Committee members agreed that the analogues of sildenafil, tadalafil and vardenafil should be scheduled as prescription medicines.
Discussion then focussed on the proposal to schedule PDE-5 inhibitors as a class. A submission had been received from a company concerned that classification based on PDE-5 inhibitory activity would inadvertently capture some natural substances. Examples given by the submitter included icariin (a constituent of some Epimedium species) and caffeine.
The Medsafe representative was questioned on this issue and explained that a number of naturally-occurring substances possess very weak and clinically insignificant PDE-5 inhibitory effects. For instance, when compared in vitro, caffeine possessed one millionth the activity of sildenafil. It was not Medsafe's intention for substances with clinically insignificant activity to be captured by the proposed classification.
The Committee acknowledged this and, on the grounds of the potential public health risk posed by clinically significant PDE-5 inhibitors, agreed in principal with the proposal to schedule PDE-5 inhibitors as a class. However, they requested that Medsafe identify appropriate wording for the schedule entry to ensure that caffeine and other substances with very weak, clinically insignificant activity at the PDE-5 receptor are not inadvertently covered. Medsafe's proposed wording will be discussed by the Committee at the next meeting.
The following new chemical entities were submitted to the Medicines Classification Committee for classification.
Ambrisentan is a propanoic acid-class, endothelin receptor antagonist that is selective for the endothelin type A (ETA) receptor. Selective inhibition of the ETA receptor inhibits phospholipase C-mediated vasoconstriction and proteinkinase C-mediated cell proliferation while preserving nitric oxide and prostacyclin production, cyclic GMP- and cyclic AMP-mediated vasodilation, and endothelin-1 clearance that is associated with the endothelin type B (ETB) receptor.
The proposed indication is for the treatment of:
in patients with WHO functional class II, III or IV symptoms.
That ambrisentan should be classified as a prescription medicine.
Clevidipine butyrate is a dihydropyridine L-type calcium channel blocker. L-type calcium channels mediate the influx of calcium during depolarization in arterial smooth muscle. Preclinical studies have shown that clevidipine butyrate reduces mean arterial blood pressure by decreasing systemic vascular resistance. Clevidipine butyrate does not reduce cardiac filling pressure (pre-load), confirming lack of effects on the venous capacitance vessels.
The proposed indication is the reduction of blood pressure when rapid and predictable control is desired.
That clevidipine should be classified as a prescription medicine.
Doripenem is a synthetic carbapenem antibacterial agent. Doripenem inactivates multiple essential penicillin-binding proteins (PBPs), resulting in inhibition of cell wall synthesis and subsequent cell death.
The proposed indication is for the treatment of the following infections in adults:
That doripenem should be classified as a prescription medicine.
Rivaroxaban is a highly selective direct Factor Xa inhibitor and is therefore described as an antithrombotic agent. Factor Xa directly converts prothrombin to thrombin through a prothrombinase complex, which ultimately leads to fibrin clot formation and activation of platelets by thrombin.
The proposed indication is the prevention of venous thromboembolism (VTE) in adult patients who have undergone major orthopaedic surgery of the lower limbs.
That rivaroxaban should be classified as a prescription medicine.
Gemtuzumab ozogamicin is a drug-antibody conjugate for the treatment of acute myeloid leukemia. It is an alternative to chemotherapy for patients who are 60 years of age or older who have suffered a relapse.
That gemtuzumab ozogamicin should be added to the New Zealand schedule as a prescription medicine.
Cilostazol is a quinolone derivative which inhibits cellular phosphodiesterase (more specifically for phosphodiesterase III). It is used in the management of peripheral vascular disease.
That cilostazol should be added to the New Zealand schedule as a prescription medicine.
Bazedoxifene is a selective oestrogen receptor modulator (SORM) developed for the prevention and treatment of postmenopausal osteoporosis.
That bazedoxifene should be added to the New Zealand schedule as a prescription medicine.
Methylnaltrexone bromide is a peripherally-acting antagonist of the mu-opioid receptor which targets binding sites in tissues, such as the gastrointestinal tract, decreasing opioid-associated constipation without compromising the analgesic effects in the central nervous system.
That methylnaltrexone should be added to the New Zealand schedule as a prescription medicine.
No discussion required by the Committee as there were no unresolved recommendations.
The Chairman explained that Medsafe is in the process of updating the First Schedule to the Medicines Regulations 1984. Parliamentary Counsel had raised some queries during this process and, as a result, Medsafe was now requesting confirmation from the Committee on the following entries:
Sabadilla and S.officinale are synonyms. The Committee had agreed to harmonise with Australia on the entry for these herbs at the 36th meeting (February 2007). However, a typographical error meant that when the entries were gazetted, the classification cut-off limit was based on the whole plant rather than its alkaloids. The Committee was therefore asked to agree that the schedule be amended to align with their original intent. The proposed wording is:
In order to achieve consistency between New Zealand and Australia in the way schedule entries are worded, the two countries had adopted a principle of listing the plant name followed by 'spp' when three or more species of a plant are used. Individual species are listed if only one or two species of a plant are used.
The Committee was asked to:
These entries were intended to cover all species of Strophanthus and Veratrum, respectively. To clarify this intent, and to align with the species naming principle described above, the Committee was asked to agree to the addition of the word "spp" to these entries.
Ipecacuanha is a general term used to refer to Cephaelis acuminata and Cephaelis ipecacuanha. To clarify this, the Committee was asked to agree that the current schedule entry for Ipecacuanha be retained and that entries for Cephaelis acuminata and Cephaelis ipecacuanha be added. The entries would contain the same restriction as currently used for Ipecacuanha:
Ibritumomab tiuexetan is the recommended International Non-Proprietary Name (rINN) while the equivalent name in the Australian schedule is Ibritumomab. The Committee was asked to agree to retain the rINN name of Ibritumomab tiuexetan rather than harmonise with the Australian name.
The Committee was asked to agree that the entry for Strophanthin-k be removed as it is covered by the general entry for Strophanthins.
The Committee was asked to agree that the entry for Quebracho be removed from the Schedule in order to harmonise with Australia. Quebracho is a South American plant which contains yohimbine. Yohimbine would remain scheduled as a prescription medicine.
The Committee was asked to agree that the words "except for use as an excipient" be added to the prescription medicine entry for phenacetin. This would result in harmonisation with Australia.
Sodium nitrite was discussed at the 37th meeting (May 2007) as a harmonisation issue. At that time, the Committee was advised that the pharmacy-only entry for sodium nitrite in New Zealand included the condition "except for use as an excipient". This was incorrect and the Committee was now asked to agree that the exception be added to the entry in order to align with their original intent.
The Committee was asked to agree that the words "for internal use" be added to the prescription medicine entry for sodium cellulose phosphate. This would result in harmonisation with Australia.
The Committee was asked to agree that the wording of the ketoconazole entry be changed to refer to "medicine for treatment of the scalp" instead of "shampoo" to:
The Committee had recommended at the 27th and 33rd (May 2002 and June 2005) meetings that classification of benzocaine should be harmonised with Australia (except for the oral use of medicines containing 200 mg or less). However, the wording relating to the total content of local anaesthetic was never included in the Schedule. Therefore, the Committee was asked to agree that the schedule be amended to align with their original intent. The proposed wording for benzocaine is:
Individual hormones are already scheduled and all of these are prescription medicines. The Committee was now asked to agree to the addition of a generic prescription medicine entry for "pituitary hormones" in the Schedule. This would be of use for cross-referencing purposes and would also result in harmonisation with Australian wording.
The Committee was asked to agree that a prescription medicine entry for etonogestrel be added to the Schedule. Etognogestrel is already covered by the generic prescription medicine entry for "progestogens" but this new entry would result in harmonisation with Australian wording.
The NDPSC has recommended that a prescription medicine entry for human chorionic gonadotrophin be added to the Schedule. A separate entry already exists for gonadotrophic hormones.
The Committee was asked to agree to this recommendation. The proposed wording is:
Stramonium is a term that refers to the species Datura stramonium. The Committee had agreed to harmonise with Australia on the wording for the Datura spp entry at the 27th and 33rd meetings (May 2002 and June 2005). An oversight meant that the Stramonium entry was not updated (or deleted) at the same time.
The Committee is therefore asked to agree to retain the entry for Datura spp as is and to amend the Stramonium entry to match that of the Datura spp entry. The proposed wording for the Stramonium entry is:
No products were expected to be affected by any of these minor changes and the Committee agreed to all the proposals.
That all queries received from the Parliamentary Counsel as part of the process of updating the First Schedule of the Medicines Regulations 1984 have been resolved to the satisfaction of the Committee.
The Chairman reminded the Committee that, at the last meeting, blood and blood products had been recommended for reclassification as general sale medicines. An unintended consequence of this had recently been identified; some products containing blood clotting factors also contained small amounts of heparin as an excipient. Heparin remains classified as a prescription medicine, thereby preventing these products from being reclassified to general sale as had been the intention. Medsafe proposes that the Committee discuss exempting heparin, when for use as an excipient, from prescription medicine status at the next meeting.
Another potential item for discussion at the next meeting is mebeverine. Whether or not this would be considered would depend largely on whether a submission for reclassification was received from sponsor companies or other interested bodies.
One member also raised the issue of access to Epipen at schools. The Chairman indicated that Medsafe had sent a letter to schools regarding this issue some years ago. He would locate a copy of the letter for the Committee.
An article had been published in the New England Medical Journal on March 5 2009 entitled "Global Transmission of Oseltamivir-Resistant Influenza". The Committee discussed this article briefly with regards to their previous decision to classify oseltamivir as a prescription medicine except when sold by a registered pharmacist, between the months of May to September inclusive, for the treatment of seasonal influenza to a consumer 12 years of age or more presenting in a pharmacy with early symptoms of influenza.
The Committee noted the data but concluded that there was insufficient evidence of resistance associated with exposure to Tamiflu (compared to resistance associated with spontaneous mutations) that would cause them to reconsider the current classification status of oseltamivir.
The meeting closed at 3pm.