Published: 4 April 2014
Committees
Minutes of the 157th Medicines Adverse Reactions Committee Meeting - 13 March 2014
2 MEDSAFE PHARMACOVIGILANCE ACTIVTIES
- 2.1 Report on Standing Agenda Items from Previous
Meetings of the MARC
2.2 Medsafe Pharmacovigilance Activities
2.3 Prescriber Update Volume 35, Number 1, March 2014
2.4 Quarterly Summary of Medsafe Early Warning System Communications
- 3.1 Matters Referred to the MARC under Section 36
of the Medicines Act 1981.
3.2 Matters Referred to the MARC by Medsafe.
4 MATTERS ARISING FROM THE NEW ZEALAND PHARMACOVIGILANCE CENTRE
-
4.1 Centre for Adverse Reactions Monitoring (CARM) Quarterly Reports.
- 4.1.1 Fatal cases (Causal Cases
Only)
4.1.2 Special Populations: Serious Cases Associated with Medicines in Children under 18 years (Causal Cases Only)
4.1.3 Special Populations: Serious Cases Reporting Adverse Events Following Immunisation Terms with Vaccines in Children under 18 years
4.1.4 Special Populations: Serious Non-Fatal Cases Causally Associated with Critical Terms in Patients Over 80 Years
4.1.5 Special Reports: Annual Report ACC Cases (January 2013 - December 2013)
- 3.2.1 Inclusion of rotavirus vaccine in the national
immunisation schedule
3.2.2 Varenicline and potential interaction with alcohol
3.2.3 Crisis management planning
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In order to protect the privacy of those involved, descriptions of unpublished case reports are not included in these minutes.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 OF THE 157th MEDICINES ADVERSE REACTIONS COMMITTEE
MEETING
13 MARCH 2014
The one hundred and fifty-seventh meeting of the Medicines Adverse Reactions Committee (MARC) was held on 13 March 2014 in the Board Room, Medsafe, Wellington, New Zealand. The meeting commenced at 9.02 am and closed at 2.40 pm.
MARC MEMBERS PRESENT
Associate Professor D Reith (Chair)
Dr L Bryant
Dr N Cole
Associate Professor C Frampton
Dr S Jessamine
Dr P Jones
Associate Professor D Menkes
C Ryan
Dr M Tatley
Dr K Wallis
MARC SECRETARIAT PRESENT
L Chan (MARC Secretary, Medsafe)
MEDSAFE STAFF IN ATTENDANCE
C James (Manager, Clinical Risk Management)
S Kenyon (Principal Technical Specialist, Pharmacovigilance)
R Pollock (Advisor, Pharmacovigilance)
A Taylor (Senior Advisor, Pharmacovigilance)
E Yousuf (Principal Clinical Advisor)
INVITED GUESTS AND EXPERTS IN ATTENDANCE
Dr R Savage
D Murfitt (Senior Advisor, Immunisation Programme) attended part of the
meeting.
1 MATTERS OF ADMINISTRATION
1.1 Welcome and Apologies
The Chair welcomed the attendees to the meeting. Apologies were received from Dr S Jayathissa.
1.2 Minutes of the 156th MARC Meeting
The minutes of the 156th meeting were accepted as a true and accurate record of the meeting.
1.3 Potential Conflicts of Interest
Committee members submitted their Conflicts of Interest Declaration forms to the Secretary. The 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 MEDSAFE PHARMACOVIGILANCE ACTIVITIES
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 on the Medsafe website.
2.2 Medsafe Pharmacovigilance activities
The Committee noted the report detailing Medsafe’s recent pharmacovigilance activities.
[Associate Professor C Frampton joined the meeting at this time.]
2.3 Prescriber Update Volume 35, Number 1, March 2014
The Committee noted the latest edition of Prescriber Update. The Committee noted they were in favour of the publication, in support of a user survey to be carried out by Medsafe, and in support of each Committee member individually promoting the publication within their own specialty and organisations.
2.4 Quarterly summary of Medsafe early warning system communications
The Committee noted the quarterly summary of Medsafe early warning system communications.
3 PHARMACOVIGILANCE ISSUES
3.1 Matters Referred to the MARC under Section 36 of the Medicines Act 1981
No items.
3.2 Matters Referred to the MARC by Medsafe
3.2.1 Inclusion of rotavirus vaccine in the national immunisation schedule
Background
The purpose of this paper was to determine whether any additional safety monitoring and/or risk mitigating activities are required for RotaTeq.
PHARMAC has recently announced changes to the National Immunisation Schedule. From 1 July 2014 the schedule will include RotaTeq (rotavirus vaccine).
The most important identified risk is intussusception.
Although rotavirus vaccines have been available in New Zealand, it has been used through private purchase of Rotarix. Therefore wide use of a different vaccine (RotaTeq) is likely to increase the number of reports of adverse effects following vaccination.
The Committee was asked to advise whether:
- Medsafe's proposed preparation actions are appropriate
- any other actions are required.
Discussion
The Committee discussed the causes, presentation, complications, and treatment of intussusception. The Committee was advised that intussusception is a potentially fatal condition if not treated. The most common treatment for intussusception is an air enema which can have resource implications as hospitals require the facilities and expertise to perform this procedure.
The Committee also noted that rotavirus infection could be severe requiring hospital treatment. In resource poor countries rotavirus infection can be fatal.
The Committee concluded that the risk benefit profile is favourable.
The Committee discussed how the risks of harm should be communicated, including the risk of intussusception. A rotavirus vaccine resource for parents is being developed by the immunisation team and this resource will include information on intussusception. Minimising the risk of the vaccine being administered as an injectable rather than through the oral route was also discussed.
The Committee reviewed the proposed monitoring actions and considered them appropriate. The Committee suggested that additional monitoring of intussusception may be possible through the New Zealand Paediatric Surveillance Unit and the New Zealand Child and Youth Epidemiology Service. The Committee also noted that given the rarity of intussusception and the very small increase attributed to vaccination it would take many years of monitoring in New Zealand before a difference could be seen.
Recommendation 1
The Committee considered Medsafe’s proposed monitoring actions to be appropriate.
Recommendation 2
The Committee recommended that Medsafe consider contacting the New Zealand Paediatric Surveillance Unit to identify cases of intussusception.
3.2.2 Varenicline and potential interaction with alcohol
Background
The purpose of this paper was to review information on a possible interaction between varenicline and alcohol consumption, based on New Zealand reports and information provided by the sponsor of Champix.
Following Medsafe’s review of the Champix (varenicline) PSUR 09 (10 May
2011 to 9 May 2012) and a review of cases reported to the Centre of Adverse
Reactions Monitoring (CARM) involving patients taking varenicline who also
consumed alcohol, Medsafe placed varenicline and interaction with alcohol
on the medicines monitoring scheme
.
A Medsafe monitoring communication to alert healthcare professionals that Medsafe was seeking additional information on this issue was published on the Medsafe website on 17 June 2013.
Following the monitoring period, this information along with the company information was reviewed.
Animal models indicate a potential interaction between alcohol and varenicline but no mechanism has been determined. However, this interaction may depend on the history of alcohol consumption and the amount of varenicline exposure.
Clinical trials in humans provide limited information about adverse events in patients taking varenicline and consuming alcohol as the majority of studies were designed to look at smokers who were alcohol dependent or who had a history of heavy alcohol consumption.
Both in New Zealand and worldwide there have been post-marketing reports of adverse neuropsychiatric events or reduced alcohol tolerance events in patients taking varenicline. However, in both the New Zealand cases and the company post-marketing cases it is difficult to determine if there was an interaction between varenicline and alcohol or whether varenicline alone, alcohol use and/or smoking cessation independently contributed to the events.
The Committee was asked to advise whether:
- the data sheet for varenicline (Champix) should be updated to include information about alcohol and neuropsychiatric/reduced alcohol tolerance events from the post-marketing reports
- the company should be requested to include information about alcohol and neuropsychiatric/reduced alcohol tolerance events in the consumer medicine information (CMI).
Discussion
The Committee noted that the data available on this potential interaction are limited both in quality and quantity.
The Committee discussed what the available information may indicate and the significance of this potential interaction.
The Committee reviewed the information provided on this potential interaction in other countries, and in other smoking cessation products available in New Zealand to see if a similar approach could be adopted for varenicline.
The Committee discussed the level of information required for prescribers to make a decision regarding individual patients, and whether information on this potential interaction should be communicated to patients when varenicline is being prescribed.
The Committee’s majority decision was that the information regarding the potential interaction between varenicline and alcohol should be strengthened in the Champix data sheet.
Recommendation 3
The Committee recommended that Medsafe request the sponsor of Champix to update the data sheet to include the following wording in the interactions section:
"Although clinical data do not identify a pharmacokinetic interaction between varenicline and alcohol, there have been occasional reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients drinking alcohol during varenicline treatment."
Recommendation 4
The Committee recommended that there should be no change to the Champix consumer medicine information (CMI) at this time as the CMI already contains advice that reducing consumption of alcohol could help while giving up smoking.
3.2.3 Crisis management planning
Background
The purpose of this paper was to seek input and advice from the committee about the proposed crisis management plan for the Clinical Risk Management (CRM) branch of Medsafe.
Risk is measured by the degree of hazard and level of outrage/concern. Proposed responses based on these two factors have been developed. These responses also determine whether the Critical Incident Management (CRIM) is activated. CRIM is a Medsafe policy which shapes the operational practices that are adopted when dealing with a reported incident or situation that has the potential to have a significant negative impact on public safety or consumer confidence.
The Committee was asked to advise whether the overall crisis management plan for the CRM branch was considered appropriate and was asked for their input into how the Committee fits into this overall plan.
Discussion
The Committee discussed and agreed with the overall process of the crisis management plan. The Committee discussed whether the identified stakeholders were relevant, and whether the examples provided based on the degree of hazard and level of outrage/concern were appropriate.
The Committee discussed examples of incidents in the past where this process could have been applied based on the level of perceived risk.
The Committee discussed how they fit into this overall plan. It was agreed that whether the Committee is involved should be determined by both the urgency of the incident and whether expert advice is required. There could also be occasions where expert advice is sought from individual Committee members without a full Committee meeting being called.
The Committee agreed that communicating with the media would require input from the Ministry of Health’s communication team. In the event of approach for comment without (or before) involvement of the Committee, members should make it clear that any comments made did not represent the views or position of the Committee.
Recommendation 5
The Committee recommended that Medsafe informs all Committee members when the Critical Incident Management has been activated relating to a pharmacovigilance concern regardless of whether advice was sought from the members.
Recommendation 6
The Committee recommended that Medsafe can obtain expert advice from the Committee where this is required.
4 MATTERS ARISING FROM THE NEW ZEALAND PHARMACOVIGILANCE CENTRE
4.1 Centre for Adverse Reactions Monitoring (CARM) Quarterly Reports
4.1.1 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 discussed case report 109175 involving pneumonitis with amiodarone. The patient was also taking methotrexate and a member asked whether methotrexate could have been a possible suspect agent along with amiodarone.
The Committee did not consider any of the other reports required further action.
4.1.2 Special Populations: Serious Cases Associated with Medicines in Children under 18 years (Causal Cases Only)
Reports of serious cases associated with medicines in children under 18 years were briefly outlined for the Committee.
The Committee discussed case report 108871 involving two complementary and alternative medicines, both thought to contain echinacea, causing reactions including jaundice and abnormal hepatic function. The Committee concluded that further information was required before these reactions could be attributed to echinacea.
Recommendation 7
The Committee recommended that CARM obtain further information on this case which will be discussed at a future MARC meeting.
The Committee discussed case report 109077 involving atomoxetine contributing to depression, suicidal tendency and thoughts of self-harm. All three reactions are described in the atomoxetine data sheet. However, PHARMAC has widened the funding criteria for atomoxetine from 1 February 2014 which could see an increase in prescribing of this medicine.
Recommendation 8
The Committee recommended that an article on this safety concern should be published in Prescriber Update to remind prescribers of this reaction.
The Committee did not consider any of the other reports required further action.
4.1.3 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 noted that CARM had been advised of a report of death the day following Gardasil vaccination. No further details were available as at the time of this meeting. It was understood that the case was still subject to further investigation.
The Committee did not consider any of the reports required further action.
4.1.4 Special Populations: Serious Non-Fatal Cases Causally 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 did not consider any of the reports required further action.
4.1.5 Special Reports: Annual Report ACC Cases (January 2013 – December 2013)
The Committee did not consider any of the reports required further action.
5 OTHER BUSINESS
5.1 ANZTPA Update
The Committee was advised of the progress of the ANZTPA Project to date.
5.2 Other Publications of Interest
No Items
6 ANNEXES
3.2.1 Inclusion of rotavirus vaccine in the national immunisation schedule
- RotaTeq data sheet (3 July 2013)
- RotaTeq consumer medicine information (July 2013)
- CARM proposed reporting template
- Proposed website information
- Carlin JB, Macartney KK, Lee KJ et al 2013 'Intussusception risk and disease prevention associated with rotavirus vaccines in Australia’s national immunisation program' Clin Inf Dis 57: 1427-34
- Shui IM, Baggs J, Patel M et al 2012 'Risk of intussusception following administration of a pentavalent rotavirus vaccine in US infants' JAMA 307: 598-604
- Weintraub ES, Baggs J, Duffy J et al 2014 ‘Risk of intussusception after monovalent rotavirus vaccination’ NEJM DOI: 10.1056/NEJMoa1311738
- Yih WK, Lieu TA, Kulldorff M et al 2014 'Intussusception risk after rotavirus vaccination in US infants' NEJM DOI: 10.1056/NEJMoa. 1303164
- CDC rotavirus - Fact sheet for parents
- CDC - Questions & answers about intussusception
- TGA rotavirus immunisation - information for parents and guardians
3.2.2 Varenicline and potential interaction with alcohol
- Medsafe. 2013.
Champix (varenicline) and a possible interaction with alcohol based
on post-marketing reports. 'Monitoring Communication' 17 June 2013
- Pfizer Inc. 2013. Chantix (varenicline tartrate) and alcohol ingestion [confidential]. ‘Response to FDA information request regarding varenicline and alcohol ingestion’ 12 August 2013
- Centre for Adverse Reactions Monitoring. 2014.
Varenicline and interaction with alcohol.
'Outcome'
4 February 2014
- Champix data sheet (12 November 2013)
- Champix consumer medicine information (January 2014)
3.2.3 Crisis management planning
- Medsafe policy statement 'Critical incident management' (9 January 2012)
- Pharmaceutical services division, Ministry of health, Malaysia 'Crisis management guidelines' (May 2010)
The Chair thanked members, the Secretariat and Medsafe staff for their attendance and closed the meeting at 2.40pm.
Associate Professor D Reith
Chair, Medicines Adverse Reactions Committee
