Published: 23 December 2016

Committees

MINUTES OF THE 168th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING 1 DECEMBER 2016

MINUTES OF THE 168th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING 1 DECEMBER 2016

MARC MEMBERS PRESENT
Associate Professor D Reith (Chair)
Dr L Bryant
Dr N Cole
Professor C Frampton
Dr K Eggleton
Dr S Jayathissa
Dr P Jones
Associate Professor D Menkes
I Raiman
J Tatler
C Ryan
Dr M Tatley

MARC SECRETARIAT PRESENT
J Prankerd (Advisor, Pharmacovigilance)

MEDSAFE STAFF IN ATTENDANCE
S Kenyon (Principal Technical Specialist, Pharmacovigilance)
R Pollock (Acting Manager, Clinical Risk Management)
L Chan (Senior Advisor, Pharmacovigilance)
G Hill (Senior Medical Advisor, Pharmacovigilance)
M Zhan (Advisor, Pharmacovigilance)
C James (Group Manager, Medsafe) (part attendance)

1.0 MATTERS OF ADMINISTRATION

1.1 Welcome and Apologies

The Chair welcomed the attendees to the meeting. Apologies were received from Dr K Wallis.

1.2 Minutes of the 167th MARC Meeting

The Committee noted that an amendment is required to section 4.1 of the minutes for the 167th Medicines Adverse Reactions Committee meeting on 8 September 2016.

The report of increased INR resulting from an interaction between warfarin and topical miconazole cream should be under section 4.1.5 (Serious Non-Fatal Cases Causally Associated with Critical Terms in Patients Over 80 Years) rather than section 4.1.2 (Fatal Cases). The Committee noted that the minute and recommendation is correct it is only the section that is incorrect.

The remainder of the minutes of the 167th meeting were accepted as a true and accurate record of the meeting.

Recommendation 1

The Committee recommended the minutes to be amended to move the discussion to the correct section.

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.

2.0 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: http://www.medsafe.govt.nz/profs/MARC/Minutes.asp

2.1.1 Safety of metformin use in pregnancy

September 2016 minute item 3.2.1

Recommendation 5

The Committee recommended that Medsafe investigates the availability of consumer information on the use of metformin during pregnancy. If no suitable information is available, the Committee recommended that Medsafe develops a consumer information leaflet explaining the risks and benefits of treatment during pregnancy.

Outcome

Medsafe was unable to locate information for New Zealand consumers on using metformin in pregnancy.

Discussion

The Committee discussed the possibility of linking consumer medicine information with Health Navigator and recommended that Medsafe develops consumer medicine information for metformin.

Recommendation 2

The Committee recommended that Medsafe develops consumer medicine information for metformin.

There were no other standing agenda items for which the MARC made further recommendations.

2.2 Medsafe Pharmacovigilance Activities

The Committee noted the report detailing Medsafe's recent pharmacovigilance activities. A discussion was had around the assessment of Periodic Benefit Risk Evaluation Reports (PBRERs). The Committee is supportive of Medsafe to continue receiving and selectively reviewing PBRERs.

2.3 Prescriber Update Volume 37, Number 4, December 2016

The Committee noted the front page of the latest edition of Prescriber Update. The publication had not been published at the time of this meeting.

2.4 Quarterly Summary of Medsafe Early Warning System

The Committee noted the quarterly summary of Medsafe early warning system communications.

3.0 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 Ophthalmological monitoring and the use of hydroxychloroquine

Background

An article was published in the September 2015 edition of Prescriber Update titled 'Risks of Hydroxychloroquine'. This article covered ophthalmological reactions associated with the use of hydroxychloroquine including advice regarding ophthalmological examinations.

The article said "All patients should have an ophthalmological examination prior to treatment initiation and at least 6 monthly thereafter. Local guidance of monitoring requirements should also be considered."

The information in this article is based on information in the data sheet.

Feedback in response to this article was received by Medsafe relating to the recommendation for baseline screening. This matter was referred to the MARC to review the feedback received and ophthalmological examination recommendations for patients taking hydroxychloroquine.

Discussion

The Committee noted that in New Zealand patients taking hydroxychloroquine are usually referred to ophthalmologists for monitoring of ocular toxicity. Generally it is considered acceptable that patients will have screening in their first year of treatment rather than recommending monitoring prior to starting treatment. The Committee noted that some patients may experience immediate side effects and discontinue treatment so monitoring would not beneeded. Patients are likely to be referred to ophthalmologists more frequently than optometrists due to current provision for access to publically funded services.

The Committee discussed the use of hydroxychloroquine in New Zealand. Hydroxychloroquine is recommended for most people with systemic lupus erythematosus and some other connective tissue diseases. It is used as a primary treatment and for maintenance of remission, which may result in long term exposure and increased potential for harm. The Committee noted hydroxychloroquine takes a long time for beneficial treatment effects to be experienced and the effects of the medicine can be seen after discontinuation. The Committee considered that changes seen in the eye are specific to hydroxychloroquine and are not seen as part of the disease being treated. There is a need for early detection of eye effects since they may worsen even after stopping treatment, and visual impairment due to hydroxychloroquine is not reversible.

The Committee noted different tests are available to use for ophthalmological monitoring and that newer tests can detect changes in the retina earlier. There are a mixture of structural and functional tests, and that these can be provided by optometrists as well as by ophthalmologists.

The Committee discussed the use of dosing by ideal body weight compared to real body weight. The Committee considered there is insufficient evidence at this time to recommend data sheet changes regarding dosing by weight. It was noted that hydroxychloroquine is only available as an unscored 200 mg tablet and this may sometimes lead to complicated dosing regimens.

A number of risk factors relating to hydroxychloroquine induced eye toxicity were discussed in the literature. The Committee considered there was reasonably good support for eye monitoring in the first year of therapy and at five years of treatment. After five years of use, the Committee considered the frequency of ophthalmological monitoring is dependent on the patient's risk factors however should be done at least yearly. The Committee considered that there is currently insufficient evidence of higher risk in Asian and other populations or with the concomitant use of tamoxifen. The Committee noted there may be some confounding by indication with regards to hypertension as a risk factor.

The Committee also discussed alternatives to hydroxychloroquine. The Committee noted that these are likely to be more immunosuppressive with more side effects.

The Committee also discussed the need for consumers to be informed with regards to what to expect when starting treatment with hydroxychloroquine. In addition there is a need for consistency in the accessibility of information around New Zealand.

Recommendation 3

The Committee recommended that Medsafe requests the sponsors of hydroxychloroquine products update the data sheet information regarding the monitoring of patients taking hydroxychloroquine.

Recommendation 4

The Committee recommended Medsafe communicates this discussion with the New Zealand Formulary and suggests including further information regarding monitoring and possibly linking to the recent American Academy of Ophthalmology Guidelines.

Recommendation 5

The Committee recommended Medsafe communicates this discussion with the Health Quality and Safety Commission.

Recommendation 6

The Committee recommended Medsafe develops a consumer information leaflet explaining what patients can expect to experience on early treatment.

Recommendation 7

The Committee recommended Medsafe includes an article in a future edition of Prescriber Update to communicate the outcome of this discussion.

[C Frampton joined the meeting at this time.]

3.2.2 Risk communication

Background

Statistical illiteracy is widespread among the general public and medical experts. This can present a severe obstacle to informed treatment choice. The understanding of numerical information and evaluating benefits and harms can differ largely between individuals making it extremely difficult to provide useful information to healthcare professionals and consumers to help make informed choices.

In order to achieve better decision making by all parties it is necessary to understand the psychology involved in decision making and subsequently the best way of providing numerical data and information about risk.

The purpose of this paper is to summarise some of the principles of decision making and risk communication. Consumer information was used as an example to apply some of these principles.

Discussion

The Committee discussed the information presented, including factors involved in decision making, and particular difficulties in understanding and communicating risk.

The Committee also discussed different strategies for communication, for example the use of diagrams versus words in different target populations.

The Committee discussed 'debiasing' strategies and how these might apply to the communication of risk information to patients. The Committee considered it is important to provide the data that people need in a simple format.

The Committee noted the need for experts to be able to communicate information in different ways depending on the target population; the Committee recognised that peoples' information needs vary, as do their cognitive and communication styles.

The Committee considered that there are a number of ways to communicate and it is important to consider who the audience is. Communication methods should be tailored to the individual, based in part on a person's interest, knowledge and fluency, in order to help them make an informed decision. It is likely that different materials may be needed for different people.

The Committee considered the paper should now be used to inform Medsafe's internal processes on communication.

4.0 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 a report concerning a patient with chronic kidney disease taking enoxaparin.

The Committee discussed a medication error report concerning a patient who experienced lithium toxicity.

Recommendation 8

The Committee recommended that caution around the use of low molecular weight heparin in patients with impaired renal function should be highlighted in the MARC's Remarks section of Prescriber Update for this meeting.

Recommendation 9

The Committee recommended that an article be published in a future edition of Prescriber Update to remind healthcare professionals of possible interactions involving lithium.

The Committee did not consider any 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 did not consider any of the 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 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: New Zealand Paediatric Surveillance Unit Annual Report

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

[S Jayathissa left the meeting at this time]

5.0 OTHER BUSINESS

5.1 Continuing Medical Education

Dr N. Cole gave a presentation on Targeted Cancer Therapies.

[N Cole left the meeting at this time]

5.2 HiView demonstration and discussion

The Committee was given a demonstration on the use of the HiView decision making software.

5.3 Therapeutic products regulation project - Update

[C James joined the meeting at this time]

The Committee was given an update on the therapeutic products regulation product.

[C James left the meeting at this time]

6.0 ANNEXES

3.2.1 Ophthalmological monitoring and the use of hydroxychloroquine

  1. Marmor, M.F., et al., Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology, 2016. 123(6): p. 1386-94.
  2. Melles, R.B. and M.F. Marmor, The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol, 2014. 132(12): p. 1453-60.

The Chair thanked members, the Secretariat and Medsafe staff for their attendance and closed the meeting at 2.20 pm.

Associate Professor D Reith
Chair, Medicines Adverse Reactions Committee

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