Committees

Updated 20 March 2013

Minutes of the 145th Medicines Adverse Reactions Committee Meeting - 10 March 2011

MARC MEMBERS PRESENT

MARC SECRETARIAT PRESENT

MEDSAFE STAFF IN ATTENDANCE

INVITED GUESTS AND EXPERTS IN ATTENDANCE

1 MATTERS OF ADMINISTRATION

1.1 WELCOME AND APOLOGIES

1.2 MINUTES OF THE 144th MARC MEETING

1.3 DATES OF FUTURE MARC MEETINGS

1.4 POTENTIAL CONFLICTS OF INTEREST

2 STANDING AGENDA ITEMS

2.1 REPORT ON STANDING AGENDA ITEMS FROM PREVIOUS MEETINGS OF THE MARC

2.1.1 Consideration of Antitussive-expectorant and Antitussive-mucolytic Combination Cough and Cold Medicines under Section 36 of the Medicines Act 1981
2.1.2 Hepatic Failure with Paracetamol (92092)

3 PHARMACOVIGILANCE ISSUES

3.1 MATTERS REFERRED TO THE MARC UNDER SECTION 36 OF THE MEDICINES ACT 1981

3.1.1 Consideration of Bufexamac-containing Medicines Indicated for the Relief of Dermatitis, Rash and Hives under Section 36 of the Medicines Act 1981

3.2 MATTERS REFERRED TO THE MARC BY MEDSAFE

3.2.1 Adverse Reactions to Pioglitazone
3.2.2 Review and Proposals for the Adverse Reactions of Current Concern (ARCC) Scheme

4 MATTERS ARISING FROM THE NEW ZEALAND PHARMACOVIGILANCE CENTRE

4.1 CENTRE FOR ADVERSE REACTIONS MONITORING (CARM) QUARTERLY REPORTS

4.1.1 Potential Safety Signals from Single Case Reports
4.1.2 Fatal Cases (Causal Cases Only)
4.1.3 Special Populations: Serious Cases Associated with Medicines in Children under 18 years (Causal Cases Only)
4.1.4 Special Populations: Serious Cases Reporting Adverse Events Following Immunisation Terms with Vaccines in Children under 18 years
4.1.5 Special Populations: Serious Non-Fatal Cases Casually Associated with Critical Terms in Patients Over 80 Years
4.1.6 Special Reports: Annual Report of Accident Compensation Commission (ACC) Cases

5 OTHER BUSINESS

5.1 IMMP

5.2 CONTINUING MEDICAL EDUCATION

6 REFERENCES


Preface:

In order to protect the privacy of those involved, descriptions of unpublished case reports are not included in these minutes.

Names of individuals have also been deleted where that person's contribution is not in the public domain, or will not shortly be so. For example, the names of those to be approached to write an article are deleted, but the names of those who have contributed to a draft article are not usually deleted. In addition, names are not usually deleted when a contribution has been made in an official capacity.

The material listed as being considered on an issue is not intended to be exhaustive.

The recommendations of the Committee are in bold typeface.

Minutes:

The one hundred and forty-fifth meeting of the Medicines Adverse Reactions Committee (MARC) was held on 10 March 2011 in the Board Room, Medsafe, Wellington, New Zealand. The meeting commenced at 9.30 am and closed at 2 pm.

marc members present

Associate Professor M Rademaker (Acting Chair)
Dr L Bryant
Dr S Sime
Dr R Savage
Professor P Ellis
Associate Professor C Frampton
Dr S Jayathissa (until 12.30 pm)

marc secretariat present

M Prescott (Acting-MARC Secretary, Medsafe)

MEDSAFE STAFF IN ATTENDANCE

A Cutfield (Advisor, Pharmacovigilance)
J Hart (Manager, Clinical Risk Management)
C James (Senior Advisor, Pharmacy)
S Kenyon (Senior Advisor, Pharmacovigilance)
Dr E Yousuf (Principal Clinical Advisor)

Invited guests and experts IN ATTENDANCE

[..] (Senior Policy Analyst, Ministry of Health)

1. Matters of Administration

1.1 Welcome and Apologies

The Acting Chair welcomed the attendees to the meeting. Apologies were received from Associate Professor D Reith, Dr M Tatley and Dr K Wallis. The Acting Chair thanked Mrs Prescott for acting as Secretary for this meeting.

[..], a Senior Policy Analyst from the Immunisation Team, Ministry of Health, attended until 12.30 pm, as an observer.

1.2 Minutes of the 144th MARC Meeting

The minutes of the 144th meeting of the Committee had previously accepted as a true and accurate record of the meeting.

1.3 Dates of Future MARC Meetings

The dates for the 2011 MARC meetings are scheduled for 9 June 2011, 8 September 2011 and 8 December 2011.

1.4 Potential Conflicts of Interest

Committee members submitted their Conflict of Interest Declaration forms to the Secretary. The Acting Chair reminded the MARC members that, in addition to conflicts disclosed in the declaration forms, members should declare conflicts of interest at the commencement of discussion of any relevant agenda item.

There were no potential conflicts of interest which were considered likely to influence the discussions or decisions of the MARC at this meeting.

2. STANDING AGENDA ITEMS

2.1 Report on Standing Agenda Items from Previous Meetings of the MARC

The Committee reviewed the list of outstanding recommendations made by the MARC at previous meetings. Background information on these issues can be found in the minutes of previous MARC meetings from the Medsafe website at www.medsafe.govt.nz/profs/MARC/Minutes.asp.

Standing agenda items for which the MARC made further recommendations for action are summarised below.

2.1.1 Consideration of Antitussive-expectorant and Antitussive-mucolytic Combination Cough and Cold Medicines under Section 36 of the Medicines Act 1981
December 2010 minute item 2.1

MARC Recommendation

At the MARC meeting of 2 December 2010 it was suggested that the MARC recommendation be followed up with a letter to the Minister's delegate acknowledging the decision, expressing disappointment in the decision, and requesting the delegate to consider directing Medsafe to make a Medicines Classification Committee submission for the reclassification of these medicines to Pharmacist Only.

Discussion

The MARC noted that it was unclear whether the letter had been written. The Acting Chair of the meeting agreed to write to the Minister's Delegate if required.

Recommendation 1

The MARC recommended that Medsafe investigate whether a letter has been written to the Minister's delegate on the decision regarding antitussive-expectorant and antitussive-mucolytic combination cough and cold medicines.

2.1.2 Hepatic failure with paracetamol (92092)
December 2010 minute item 4.1.1.1

MARC Recommendation

The MARC recommended that Medsafe and the Centre for Adverse Reactions Monitoring (CARM) acquire more information on paracetamol-induced liver injury cases in children arising from unintentional overdose in New Zealand and present these data to the MARC at a further meeting.

Outcome

Further information was provided by Medsafe for consideration by the MARC.

Background

CARM presented a case of suspected chronic paracetamol overdosing to the MARC at its meeting on 2 December 2010. This case involved a three year old child who developed acute liver failure which required a liver transplant. At that time, the MARC acknowledged that limited information was available to CARM about the case as is usual for spontaneous reports, despite requests for further information from the Centre to the reporter. The MARC considered that information about the incidence of paracetamol overdosing in New Zealand was needed to determine the extent of any problem.

Medsafe presented the MARC with a review of the extent of paracetamol overdosing in children in New Zealand. This review found the following:

  • There are a large number of products containing paracetamol liquid approved for distribution in New Zealand. Although pack sizes of up to 2L are approved, the usual maximum pack size sold in pharmacies is 200mL.
  • All over-the-counter (OTC) paracetamol suspensions have child resistant closures. However, there is no legislative requirement for measuring devices to be provided with these products, or for datasheets or consumer information to be included (other than dosing and frequency on the labels). Medsafe understands that pharmacists routinely charge patients or their carers for measuring devices if they are requested.
  • Paracetamol dosing guidelines on the labels of paracetamol liquids sold over the counter in New Zealand are consistent with the latest edition of the British National Formulary for Children (BNFc) for pain and pyrexia. These are age range dosing recommendations.
  • Auckland Starship Hospital's paracetamol dosing guidelines for children are consistent with the Royal Melbourne Paediatric Pharmacopoeia. Starship recommends higher doses of paracetamol for inpatients when advised by the specialist pain service, for short periods only. There is no indication that Starship routinely recommends paracetamol doses of up to 20 mg/kg/dose (or 90 mg/kg/day) in the community setting or on discharge.
  • Data obtained from the National Poisons Centre suggest there has been a gradual increase in reports of paracetamol overdose, both unintentional and exploratory, over the last five years. Of note is the increasing trend in child exploratory overdoses associated with paracetamol tablets and capsules.
  • Data obtained from the Poisons Centre is difficult to interpret because chronic unintentional paracetamol overdoses are less likely to be reported by parents. In addition hospitals are unlikely to routinely contact the Poisons Centre for paracetamol overdoses. i.e. local treatment protocols would be followed instead.
  • A breakdown of the Poisons Centre data by age indicates that the greatest level of unintentional overdoses occurs in very young children year on year (0 - 2 years). This indicates very young children may be the most at risk group, possibly due to factors such as changing weight, wide dosing ranges, or parents not used to giving medicines.
  • Several organisations have raised concerns about paracetamol dosing and overdosing in New Zealand. The Paediatric Society of New Zealand has raised concerns with PHARMAC, including the large volumes of paracetamol being dispensed and the lack of child resistant closures for one litre bottles. However PHARMAC data suggest the number of prescriptions issued for large volumes is actually very small and has confirmed that use of child resistant closures for paracetamol are included in pharmacy dispensing contracts. PHARMAC has indicated that education leaflets for the public could be used to improve the safe use of paracetamol liquid in children.
  • Further details relating to the report of a child needing a liver transplant following chronic paracetamol overdosing has not been obtained. It is unclear whether three cases of liver transplant, as reported in the media, were actual cases relating to paracetamol overdosing. The two additional cases have not been reported to CARM and have not been confirmed after contacting Auckland Starship Hospital.
  • Products sold in New Zealand containing paracetamol liquid do not routinely contain a measuring device, with the exception of infant drops. The medicines legislation does not allow Medsafe to require companies to include measuring devices, or for Medsafe to require pharmacists to provide measuring devices when dispensing.

Medsafe concluded that:

  • There is currently insufficient evidence that would support enforcing changes to paracetamol liquid labels or product packaging. In addition, there is limited ability under legislation to require companies to include measuring devices or provide consumer information.
  • A collaborative approach including the Paediatric Society of New Zealand, PHARMAC, and the professional colleges may be an effective way to minimise the volume of paracetamol issued on prescription, to ensure correct dosing via a dosing chart, and to ensure child resistant containers are fitted to all dispensed paracetamol liquids.
  • Medsafe can provide a general reminder to healthcare professionals via a Prescriber Update article on safe paracetamol prescribing practice in children. In addition, raising public awareness through an education leaflet, as suggested by PHARMAC, may reduce unintentional overdosing of paracetamol in children.
Discussion

The MARC reviewed the report provided by Medsafe.

The MARC was advised that although larger pack sizes appear to have been approved for OTC sale in New Zealand, 200mL was the maximum pack size sold in pharmacies.

Members asked whether information had been obtained from hospital discharge data that indicates paracetamol overdosing in children. The Committee was advised that this data is difficult to obtain and would be unlikely to provide insight into the extent of unintentional overdosing in children.

Members asked whether additional warnings about overdosing and potential liver damage could be added to OTC package labels. Medsafe advised that companies would be unlikely to agree to New Zealand specific labels given the majority of products are harmonised with Australia. Medsafe advised that New Zealand was currently working to harmonise the paracetamol dosing guidelines with those of Australia.

The Committee agreed that a collaborative approach would be the best method to improve patient education and to provide advice to healthcare professionals about paracetamol prescribing in children. Medsafe advised that a Prescriber Update article could be a way to raise awareness among healthcare professionals about safe paracetamol prescribing in children.

Recommendation 2

The MARC recommended that the Committee write to the Paediatric Society, the Royal New Zealand College of General Practitioners, the Pharmaceutical Society and PHARMAC to highlight the problem of paracetamol overdosing in children and to encourage the prescription and dispensing of smaller volumes of liquid preparations as a preventive measure.

Recommendation 3

The MARC recommended that Medsafe consider publishing an article in Prescriber Update to raise awareness about the safe prescribing of paracetamol in children.

3. pharmacovigilance issues

3.1 Matters Referred to the MARC under Section 36 of the Medicines Act 1981

3.1.1 Consideration of bufexamac-containing medicines indicated for the relief of dermatitis, rash and hives under section 36 of the Medicines Act 1981.

One member declared a possible conflict of interest. The conflict of interest was discussed but was not considered to influence the discussion or decision.

Background

In April 2010, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended that the marketing authorisations for medicines containing bufexamac be withdrawn in the European Union based on concerns of allergic contact reactions. This action prompted Medsafe to initiate a review of the risk-benefit profile for medicines containing bufexamac under section 36 of the Medicines Act 1981. The sponsors of such medicines in New Zealand were required to provide safety and efficacy data to support the continued consent for distribution of their medicines in New Zealand.

On behalf of the Director-General of Health, Medsafe reviewed the data provided by the sponsors. Medsafe considered that in the case of Paraderm which is indicated for the relief of dermatitis, rash and hives, the data provided by the sponsor was inadequate in addressing the concerns raised. Therefore, under section 36(2) of the Medicines Act 1981, the matter was referred to the MARC.

An overview of the data considered at this meeting is attached. (Adobe PDF document 61KB)

Discussion

The MARC reviewed the report provided by Medsafe.

There is only one bufexamac-containing medicine available in New Zealand which is indicated for the relief of dermatitis, rash and hives - Paraderm. This is a different product to Paraderm Plus which is indicated for the treatment of cuts, abrasions, insect bites, stings, itches, sunburn and minor burn. Therefore Paraderm Plus was not included in this review by the MARC.

The MARC noted that the primary safety concern with bufexamac-containing medicines identified in Europe was a high rate of allergic contact dermatitis following topical administration. The European Committee was particularly concerned that as allergic contact dermatitis may be very similar to the condition being treated, there could be a delay in correct diagnosis and treatment of the adverse event. This could also result in prolongation of the underlying condition due to ineffective treatment and increase the likelihood of secondary complications such as infection occurring.

The MARC noted that there were differences in the approved indications for bufexamac-containing medicines between New Zealand and Europe which could have an effect on the safety profile. In particular, bufexamac-containing medicines were approved in Europe for proctological indications, for which bufexamac is not approved in New Zealand. One member informed the MARC that anal mucosa is particularly prone to contact dermatitis.

The MARC noted the sponsor had provided Medsafe with limited data in support of the efficacy of bufexamac in the relief of dermatitis. The few controlled trials found no significant difference between the efficacy of bufexamac and that of topical corticosteroids. However, the Committee considered that these trials, carried out in the 1970s and 1980s, were of a lower standard than expected with today's good clinical research practice. Furthermore, the studies were underpowered and subject to significant bias and confounding, including observer bias. Furthermore, improvement by chance could not be ruled out in these studies. The Committee noted that one of the larger studies carried out in 193 patients found no significant difference between the efficacy of bufexamac and that of placebo, and inferiority of bufexamac compared to topical corticosteroids. The Committee was also concerned that there were no studies provided to support the efficacy of bufexamac in the relief of rash and/or hives.

The MARC noted that the data provided by the sponsor demonstrated a concerning number of hospitalisations due to either adverse contact allergic events to bufexamac or deterioration of the underlying condition due to ineffective treatment with bufexamac. The MARC considered this to be out of keeping with that expected from the safety of an over-the-counter product.

Safety studies suggest a frequency of bufexamac sensitisation of 1-2%, in populations of patients who were already referred for patch-testing and were therefore likely to be atopic and prone to sensitisation. The MARC considered it was therefore unclear what the frequency of bufexamac sensitisation would be in the general population. However, it was probably generalisable to the population of patients being treated with bufexamac for dermatitis who might also be expected to be at increased risk of sensitisation. Furthermore, for conditions such as dermatitis, rash and hives which are likely to cover large areas of body surface, the MARC noted that greater quantities of creams such as bufexamac are likely to be applied to greater proportions of the skin, particularly skin with already reduced barrier function. This could result in increased absorption and therefore an increased potential for sensitisation.

A member of the MARC also advised that once sensitised to a substance (such as bufexamac) the individual's immune system will always react to subsequent exposure, regardless of the indication for use. In addition, a previously sensitised individual could potentially experience a very severe reaction with subsequent exposures.

New Zealand data from CARM does not suggest a signal, with just three reports of skin reactions associated with bufexamac. However, the MARC noted that bufexamac-containing medicines are sold over-the-counter and therefore adverse events to these medicines are likely to be underreported.

The risks and benefits of alternative medicines such as corticosteroids or other topical NSAIDs and non-pharmacological options such as moisturisers were not formally reviewed at this meeting. However, the MARC's expert opinion was that topical NSAIDs are not generally favoured as treatment options for dermatitis, rash or hives in dermatological practice. Furthermore, specialists in dermatology do not consider that there is a place for bufexamac in current clinical practice. The MARC noted that this opinion was supported by the fact that there appears to be no clinical need for bufexamac in the relief of dermatitis, rash and hives, given no such medicines have been marketed in New Zealand for almost ten years.

The Committee agreed that as bufexamac-containing medicines in Europe had similar indications to Paraderm in New Zealand, the European assessment of the risk-benefit profile of these medicines is directly applicable to Paraderm in New Zealand.

The Committee unanimously concluded that the risk-benefit profile of bufexamac-containing medicines was unfavourable in the indications for the relief of dermatitis, rash and hives. However, the MARC considered that the risk-benefit profile for use in other indications could not be determined at this time.

The MARC considered that as there was no clinical need for Paraderm in New Zealand the most appropriate risk management strategy in New Zealand was to revoke the consent to distribute bufexamac-containing medicines indicated for the relief of dermatitis, rash and hives.

Recommendation 4

The MARC recommended that the consents to distribute bufexamac-containing medicines indicated for the relief of dermatitis, rash and hives be revoked.

3.2 Matters Referred to the MARC by Medsafe

3.2.1 Adverse Reactions to Pioglitazone

Background

The glitazones were placed on the active monitoring list for annual review in March 2006. In 2007 the Actos (pioglitazone) data sheet was revised as a result of these discussions to include more information on the risks of heart failure and bone fracture. A Prescriber Update article on fluid retention, heart failure and macular oedema with glitazones was published in November 2007.

The Committee were provided with a report updating them on any regulatory actions taken, published literature, information provided by the company and reports submitted to CARM in the last 12 months.

The MARC reviewed the report provided by Medsafe.

The MARC noted the information provided regarding an ongoing epidemiological study investigating the possible association between pioglitazone treatment and bladder cancer. The Committee noted that there appeared to be a possible trend of increase in risk with increasing time on treatment or higher cumulative dose. However, it was not clear that the investigators had fully managed to account for the increase in risk of malignancy as the patient's diabetes progressed. The Committee considered that there was no immediate cause for concern.

Overall review of the data provided by the company and of the published scientific literature did not raise any new safety concerns.

The Committee was asked to advise whether any safety issues warranting further action had been identified as a result of this review and whether pioglitazone should remain on scheduled review.

The Committee considered that pioglitazone should not remain on scheduled review. However, Medsafe should update the Committee on the progress of the epidemiological study.

Recommendation 5

The MARC recommended that Medsafe provide updates on the progress of the epidemiological study investigating the possible association between pioglitazone and bladder cancer; this should be provided as an oral report.

Recommendation 6

The MARC recommended that Medsafe should continue to monitor the safety of pioglitazone and inform the Committee if any further safety issues are identified.

3.2.2 Review and Proposals for the Adverse Reactions of Current Concern (ARCC) Scheme

At previous meetings the MARC had recommended that Medsafe and the New Zealand Pharmacovigilance Centre (NZPhVC) proceed with the implementation of a scheme to highlight adverse reactions of current concern. A presentation was made by Medsafe on the scheme.

The MARC was informed that the new scheme is to be known as M² ('M squared'), which stands for Medicines Monitoring. A section of the Medsafe website has been dedicated to the scheme. The MARC was advised that promotional material will be placed in the next edition of MIMS and article will be published in the March 2011 Prescriber Update to introduce the scheme to prescribers.

The MARC agreed with Medsafe's recommendation that each medicine-reaction combination should remain on the scheme for a six month period but this time can be extended if required.

The MARC was reassured that M² is designed to complement and not to replace New Zealand's existing spontaneous reporting scheme. In addition, it is not a replacement for the Intensive Medicines Monitoring Programme (IMMP).

Recommendation 7

The MARC recommended that Medsafe investigate the feasibility of including the M² logo next to the monitored medicines on the data sheet and CMI search results pages on the Medsafe website.

4. Matters arising from the New Zealand Pharmacovigilance Centre

4.1 Centre for Adverse Reactions Monitoring (CARM) Quarterly Reports

Spontaneous reporting programme

All spontaneous reports presented at the MARC meeting have been assessed by the Centre for Adverse Reactions Monitoring (CARM) and responses have been sent to the reporters. The purpose of these responses is to assist the practitioner to discharge his/her responsibility to patients. These individual replies include as appropriate:

  • comment about causality;
  • information about similar suspected adverse reactions reported with the same or related medicines;
  • prescribing advice;
  • advice related to the care of the patient, including information that may assist the practitioner to make a risk:benefit assessment for future treatment; and
  • any specific action being taken by the Centre, including entering the reaction into the National Health Index against the patient's name, presenting the case report to the MARC, etc.

Note: In the discussion notes for each report, the case has been given a causality designation using terms and definitions developed by the World Health Organization (WHO). The precise definitions are available on the website of the The Uppsala Monitoring Centre, which is the WHO Collaborating Centre for International Drug Monitoring - http://www.who-umc.org/ These designations (certain, probable, possible, unlikely, unclassified and unclassifiable) refer to the degree of certainty about the relationship between the medicine and the adverse event. The terms should not be understood literally. For example, "certain" means that the appropriate elements are present to match the international definition. It does not mean there is absolute certainty that the medicine caused the adverse event. Explanations of these terms can be found on the Medsafe website via the hyperlink at each causality designation.

4.1.1 Potential Safety Signals from Single Case Reports

4.1.1.1 Venlafaxine and glaucoma (92236 and 92813)

Discussion

MARC members stated that they had not previously been aware of the risk of angle closure glaucoma in association with the use of venlafaxine. The MARC considered that the two reports highlighted by CARM and the literature presented provided evidence for this association. It was noted that the data sheets for venlafaxine and paroxetine (an SSRI) do include a warning about the risk of acute glaucoma. The MARC questioned whether the association also extended to other SSRIs and SNRIs. The Committee considered it would be appropriate to seek further information on the potential risk and that the data sheets for all SSRIs and SNRIs be reviewed to ensure they are appropriate with regard to this potential risk.

Recommendation 8

The MARC recommended that Medsafe consider writing to the relevant SSRI sponsors to request that they provide Medsafe with a review of the risk of angle closure glaucoma in association with the use of their products.

Recommendation 9

The MARC recommended that Medsafe consider publishing an article in Prescriber Update on the risk of angle closure glaucoma in association with the use of SNRIs such as venlafaxine, and SSRIs if the evidence supports an association. An electronic version of this article should be sent to ophthalmologists and optometrists.

4.1.2 Fatal Cases (Causal Cases Only)

Members were given a brief description of the fatal reports for which CARM had assessed the causality to be at least possible. The Committee were given the option of requesting that any particular reports be discussed at the current or a subsequent meeting if they considered that there may be a safety issue that prescribers should be informed about or for which regulatory action was required.

Discussion

The MARC noted the Report of Fatal Cases assessed as causal.

The Committee noted a fatal case report for which clozapine was listed as one suspect medicine which was reported as multi-organ failure as a result of lactic acidosis aggravated by clozapine-induced toxic megacolon (Case Report 093086). The MARC noted that a large number of adverse events have been reported over recent years due to gastrointestinal-related problems in patients using clozapine. This is not a new trend but the MARC considered that prescribers should be reminded of these adverse events as they could become serious.

The Committee recommended that an article be published in Prescriber Update to highlight constipation and related adverse events for patients taking clozapine.

Recommendation 10

The MARC recommended that Medsafe consider publishing an article in Prescriber Update on the potential adverse event of constipation and related adverse events in patients taking clozapine.

4.1.3 Special Populations: Serious Cases Associated with Medicines in Children under 18 years (Causal Cases Only)

Reports of serous cases associated with medicines in children under 18 years were briefly outlined for the Committee. The Committee were given the opportunity to request further information on particular reports which may be discussed at a future meeting.

The Committee did not consider any of the reports required further action.

4.1.4 Special Populations: Serious Cases Reporting Adverse Events Following Immunisation Terms with Vaccines in Children under 18 years

Reports of events occurring in children under 18 years were briefly outlined for the Committee. The Committee were given the opportunity to request further information on particular reports which may be discussed at a future meeting.

The Committee did not consider any of the reports required further action.

Medsafe advised the MARC that a significant increase in narcolepsy had been reported in Scandinavia in patients who had received Pandemrix vaccine. There has been no increase in other parts of the European Union. The vaccine is not yet approved for use in New Zealand.

Medsafe advised the MARC that Japan had suspended use of Prevenar-7 vaccine together with Act-HIB vaccine due to four deaths in children. A Japanese expert committee has initially found no causal links but the use of both vaccines have been suspended until the investigation has been completed.

**Secretary's Note**

Since the MARC meeting, Medsafe has been informed that the Japanese Health Ministry resumed use of Prevenar-7 and Act-HIB in Japan on 1 April 2011.

4.1.5 Special Populations: Serious Non-Fatal Cases Casually Associated with Critical Terms in Patients Over 80 Years

Reports of events occurring in patients over 80 years were briefly outlined for the Committee. The Committee had the opportunity to request further information on particular reports which may be discussed at a future meeting.

The Committee did not consider any of the reports required further action.

4.1.6 Special Reports: Annual Report of Accident Compensation Commission (ACC) Cases

An annual report of ACC case reports received in the period October 2009 to September 2010 was outlined for the Committee. These ACC reports were received by CARM via Medsafe for entry into the CARM database.

Discussion

The Committee noted the report of ACC case reports.

The Committee did not consider any of the reports required further action.

The Medsafe representative on the MARC presented an overview of the action previously undertaken by Medsafe and/or CARM to address the medicine safety issues identified from ACC reports.

5. OTHER BUSINESS

5.1 IMMP

Dr Savage gave a verbal report on recent Intensive Medicines Monitoring Programme (IMMP) publications from Dr M Harrison-Woolrych, Head, IMMP, New Zealand Pharmacovigilance Centre.

The MARC asked Dr Savage to convey the Committee's thanks to Dr Harrison-Woolrych.

5.2 Continuing Medical Education

[..] gave a presentation on the pre-market assessment of medicines.

6. References

3.1.1. Consideration of bufexamac-containing medicines indicated for the relief of dermatitis, rash and hives under section 36 of the Medicines Act 1981

  1. Review of risk-benefit profile of bufexamac-containing medicines indicated for the relief of dermatitis, rash and hives under section 36 of the Medicines Act 1981
  2. New Zealand data from CARM
  3. Summary of the European review
  4. Summary of the PSUR for Parfenac
  5. List of references provided by sponsor
  6. French SPC for Parfenac

3.2.1 Adverse Reactions to Pioglitazone

  1. ARCC-Pioglitazone. 1 April 2010 to 31 December 2010
  2. Alisa Femia, Peter Klein. Iatrogenic lipomatosis: A rare manifestation of treatment with a peroxisome proliferators-activated receptor gamma agonist. Dermatology Online Journal. 2010. 16(4):15
  3. Karakurt et al. July 2009. Pioglitazone Induced Reversible Pancytopenia. Exp Clin Endocrinal Diabetes. 2010. 118:96-97
  4. Actos New Zealand datasheet dated 27 August 2010

The Acting Chair thanked members, the Secretariat and invited guests and experts for their attendance and closed the meeting at 2 pm.

Associate Professor M Rademaker
Acting Chair
Medicines Adverse Reactions Committee