Published: 20 October 2016
Revised: 6 March 2017

Committees

MINUTES OF THE 167th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING 8 SEPTEMBER 2016

MINUTES OF THE 167th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING 8 SEPTEMBER 2016

Friday 22 December 2016

Secretary’s note regarding the minute below from the 167th meeting of the Medicines Adverse Reactions Committee meeting held on 8 September 2016.

The Committee noted in the 168th meeting of Medicines Adverse Reactions Committee that the discussion of the report of increased INR resulting from an interaction between warfarin and topical miconazole cream was incorrectly placed under section 4.1.2 Fatal Cases (Causal Cases Only). This report should be discussed under section 4.1.5 Special Populations: Serious Non-Fatal Cases Causally Associated with Critical Terms in Patients Over 80 Years.

The Committee agreed that the discussion of this report should be moved to the correct section. The minutes have been updated below. 

The one hundred and sixty-seventh meeting of the Medicines Adverse Reactions Committee (MARC) was held on 8 September 2016 at The Rydges, 75 Featherston Street, Pipitea, Wellington, New Zealand. The meeting commenced at 9am and closed at 3pm.

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

MARC SECRETARIAT PRESENT
L Chan (Senior Advisor, Pharmacovigilance)

MEDSAFE STAFF IN ATTENDANCE
R Pollock (Acting Manager, Clinical Risk Management)
S Kenyon (Principal Technical Specialist, Pharmacovigilance)
J Prankerd (Advisor, Pharmacovigilance)
M Zhan (Advisor, Pharmacovigilance)
G Hill (Senior Medical Advisor, Pharmacovigilance)
S Sime (Senior Advisor, Pharmacovigilance)
H Hoang (Advisor Science (MAAC and MCC Secretary))

1.0 MATTERS OF ADMINISTRATION

1.1 Welcome and Apologies

The Chair welcomed the attendees to the meeting. Apologies were received from I Raiman.

1.2 Minutes of the 166th MARC Meeting

The minutes of the 166th 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.

Dr P Jones declared that he has a family member who is employed by a New Zealand owned company that markets glucose monitors. The Committee considered that this was not a conflict of interest and agreed that Dr P Jones is able to participate and vote in agenda item 3.2.1.

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

[Prof C Frampton and Assoc Prof D Menkes joined the meeting at this time.]

2.1.1 Misuse of quetiapine

At the 165th meeting held on 10 March 2016, the Committee recommended that Medsafe further investigates the misuse of quetiapine. Based on the results of this investigation, Medsafe should consider including an article on the use of quetiapine in New Zealand in a future edition of Prescriber Update.

Discussion

It was explained to the Committee that dispensing data for quetiapine between 2013 and 2015 do not include the indications for use. Therefore, it is not known if quetiapine was being prescribed appropriately in these instances. A study on the uses of quetiapine has been conducted by a Primary Health Organisation in a sample of approximately 2000 patients in the Wellington and Wairarapa regions. It is likely that results from this study will be published.

The Committee noted that the discussion of this topic has evolved into an area of medicines utilisation rather than medicines safety. There are other groups in the health sector such as the Best Practice Advocacy Centre, Health Quality & Safety Commission and PHARMAC that may have more interest and expertise in this area.

[Dr K Wallis joined the meeting at this time.]

Recommendation 1

The Committee recommended that Medsafe includes an article on the appropriate use of quetiapine in a future edition of Prescriber Update.

Recommendation 2

The Committee recommended that Medsafe communicates this discussion on the misuse of quetiapine with the Best Practice Advocacy Centre, Health Quality & Safety Commission and PHARMAC.

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.

The Committee noted that Medsafe has recently updated the data sheets for aciclovir-containing generic products to include confusion as an adverse effect. Aciclovir is used at high doses in the elderly for treatment of shingles. Use of high-dose aciclovir increases the risk of confusion and healthcare professionals should be reminded of this risk.

Recommendation 3

The Committee recommended that Medsafe includes a brief reminder on the risk of confusion with the use of aciclovir, particularly at high doses, in a future edition of Prescriber Update.

2.3 Prescriber Update Volume 37, Number 3, September 2016

The Committee noted the latest edition of Prescriber Update. The Committee noted it was a good quality publication.

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 Safety of metformin use in pregnancy

Background

The incidence of both pregnancy in women with type 2 diabetes mellitus and gestational diabetes is increasing. There are increasing moves to use oral hypoglycaemic medicines in pregnancy in preference to insulin. This trend is reflected in Screening, Diagnosis and Management of Gestational Diabetes in New Zealand: A clinical practice guideline.

Medsafe received a consumer query regarding the safety of metformin in pregnancy due to conflicting advice being provided by different healthcare professionals. The conflicting advice was partly due to a lack of information in the data sheets to support a benefit risk decision.

The Committee was therefore asked to review the current evidence regarding use of metformin in pregnancy and consider if any updates to the data sheets are warranted.

Discussion

The Committee noted that there are risks to the health of the mother and child if diabetes is not treated in pregnancy.

The Committee noted that clinical trials generally exclude pregnant women so data on use of medicines during pregnancy are usually limited to observational studies.

Randomised controlled trials (RCTs) are available for the use of metformin during pregnancy both for use in the first trimester and for gestational diabetes diagnosed later in pregnancy.

The number of pregnant women in the first trimester exposed to metformin in RCTs and in subsequent meta-analyses of these data is low. Therefore the effect on the risk for birth defects is unknown.

The number of pregnant women with gestational diabetes exposed to metformin in RCTs and included in meta-analyses is moderate. It was noted that the data show the effects of metformin compared to insulin and the studies were only powered to assess the effect of weight gain. The meta-analyses showed some advantages of metformin treatment compared to insulin. The risk of hypertension in the mother was almost halved when comparing metformin with insulin and the 95% confidence intervals were narrow. The weight gain was lower in the mothers taking metformin. The incidence of large for gestational age in the neonates was lower in the metformin group and these neonates were less likely to experience hypoglycaemia.

Studies on long-term follow up of children and mothers are also available. However, these long-term follow up studies are limited by the small sample sizes, differences in the dose of metformin used in pregnancy and the relatively short follow up to date. It was noted that these follow up studies were conducted until the child was 2 years of age. However, neurodevelopmental disorders due to major birth defects are usually apparent by the age of 2 years.

Overall, the Committee considered that studies showed metformin to have a positive benefit risk profile for the outcomes that were studied and measured.

The Committee discussed the Australian categorisation system used for prescribing medicines in pregnancy. This categorisation system is currently used in New Zealand medicine data sheets. However, it was noted that other regulatory agencies, such as the European Medicines Agency, require the risks and benefits be described rather than using this categorisation system. Describing the risks and benefits allows more useful information to be provided so that healthcare professionals are able to make an educated decision when prescribing medicines during pregnancy.

The Committee discussed the available information for consumers. This information must be consumer-specific, open, honest and understandable. It was noted that the Canterbury District Health Board (www.healthinfo.org.nz) and Health Navigator (www.healthnavigator.org.nz) provide information to consumers on medicines and health. The Committee considered that information on the use of metformin during pregnancy should be available for consumers in appropriate language. This allows consumers to make an informed decision about the risks and benefits relating to the efficacy and safety of treatment during pregnancy.

Recommendation 4

The Committee recommended that Medsafe request the sponsors of metformin-containing products to update the data sheets with information on the risks and benefits of using metformin during pregnancy.

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.

3.2.2 Fluconazole and use in pregnancy

Background

This review was triggered by the publication of a paper by Mølgaard-Nielsen et al in The Journal of the American Medical Association which concluded there is an association between the use of oral fluconazole in pregnancy and the risk of spontaneous abortion and stillbirth. Oral fluconazole was compared with unexposed women and women with topical azole exposure in pregnancy.

Due to the increased risk of vaginal candidiasis in pregnant women and the use of fluconazole in New Zealand, Medsafe considered that these safety concerns should be reviewed by the Committee.

[Dr K Eggleton left the meeting at this time.]

Discussion

The Committee discussed the use of propensity scores to adjust for confounders in the Mølgaard-Nielsen et al study. It was noted that information on propensity scores was contained in a supplement to the paper; it was not otherwise reported in detail in the main paper. The adjusted analysis for the hazard ratios changed significantly after adjustment. This indicates that the variables included in the propensity score influenced the results significantly. The Committee did not consider that the methodology of the study was robust. In addition, the results from this study indicate a significantly increased risk of spontaneous abortion irrespective of dose. However, the risk of stillbirth was only significantly increased at high doses (350 to 5600 mg) with a wide confidence interval.

Overall, the Committee considered that the Mølgaard-Nielsen et al study did not provide sufficient evidence to suggest that single low-dose fluconazole in pregnancy increases the risk of spontaneous abortion or stillbirth.

The Committee noted that the US FDA is currently evaluating the results of the Mølgaard-Nielsen et al study. It was considered that the US FDA’s review and conclusion should be reported back to the Committee at a future meeting. The Committee was also interested on any data on the bioavailability of azole antifungals when used vaginally, topically and orally.

Recommendation 6

The Committee recommended that this issue be reported back to the Committee at a future meeting once the US FDA’s review and conclusion following their evaluation of the Mølgaard-Nielsen et al study is known. The Committee will recommend any further actions at this time. Data should also be presented on the bioavailability of azole antifungals when used vaginally, topically and orally.

3.2.3 National immunisation schedule change to Gardasil 9 as a 2 dose schedule and expanded access to include people up to the age of 26 years

Background

PHARMAC recently announced changes to the National Immunisation Schedule. For human papillomavirus (HPV) vaccine the following changes will take place from 1 January 2017:

  • Funded access will be widened to include people up to the age of 26 years.
  • A two-dose regimen will be funded for those children aged 14 years and under. The two-dose regimen was recently approved by Medsafe.
  • A three-dose schedule will be funded for people aged 15–26 years inclusive.
  • The 4 valent (Gardasil) HPV vaccine will be replaced with the 9 valent (Gardasil 9) vaccine.
  • Females who have started a three-dose regimen of 4 valent Gardasil will be able to complete their remaining doses in 2017.

This is a significant change to the current programme which provides three doses of Gardasil and is given only to girls.

This paper summarised the efficacy and safety of Gardasil 9 identified from the marketing authorisation studies.

Discussion

The Committee were reminded of the benefit risk profile for Gardasil. In particular the Committee noted that protection with Gardasil had now been shown to last for nine years and that behavioural studies had not shown any change in sexual behaviour between those not vaccinated and those vaccinated with Gardasil. The Committee noted that the majority of studies had been published in the scientific literature. The Committee considered that the safety profile for Gardasil 9 was very similar to that of Gardasil. The major difference being an increased rate of injection site reactions. It was noted that saline was used as the placebo comparator in one study; injection site reactions were lower with the saline placebo, but the rate of systemic reactions was very similar.

The Committee noted that sample sizes for the two dose studies were small with narrow age bands. However, this is not a concern as immunogenicity studies such as these tend to have smaller sample sizes.

It was proposed that the Centre for Adverse Reactions Monitoring prepares monthly reports summarising suspected adverse drug reaction (also known as adverse events following immunisation) reports to Gardasil 9. These reports will be closely monitored by Medsafe and provided to the Committee. Information on the safety profile of Gardasil 9 will be included in a future edition of Prescriber Update and additional information will be published in the publications section of the Medsafe website (www.medsafe.govt.nz/publications/OIAContents.asp).

In addition, the company has planned activities to monitor the long-term safety and effectiveness of Gardasil 9. Periodic Benefit Risk Evaluation Reports will be provided and assessed by Medsafe.

Recommendation 7

The Committee considered Medsafe’s proposed monitoring and communication for the National Immunisation Schedule change to Gardasil 9 as a two dose schedule to be adequate.

3.2.4 Hepatitis B reactivation with direct-acting antivirals for hepatitis C


[Dr K Eggleton re-joined the meeting at this time.]

Background

Direct-acting antivirals (DAAs) have recently received regulatory approval in a number of countries including New Zealand. The World Health Organization now recommends that DAA regimens are used for the treatment of persons with hepatitis C infection rather than regimens with pegylated interferon and ribavirin. Interferons are known to act against both hepatitis B and C viruses which may be present at the same time in some patients. In contrast, DAAs have no activity against hepatitis B.

In March 2016, the European Medicines Agency (EMA) announced a review of possible hepatitis B reactivation with DAAs for hepatitis C. This review was triggered by reports of hepatitis B reactivation in patients who have been infected with hepatitis B and C viruses, and who were treated with DAAs for hepatitis C. Since DAAs have no activity against hepatitis B it has been unclear why hepatitis B reactivation would occur. The EMA review has been extended to include the risk of liver cancer, but this safety concern was not reviewed in this paper.

The purpose of this paper was to review the available information on the possible risk of hepatitis B reactivation with DAAs for hepatitis C.

Discussion

The Committee noted that there are a number of planned activities by the Ministry of Health and the Hepatitis Foundation of New Zealand to raise awareness and increase diagnosis rates and treatment for hepatitis C. The planned activities will also help to support healthcare professionals and patients.

Funding for DAAs is currently either subject to approval by a Hepatitis C Treatment Panel or restricted to specialists. However, the restriction to specialists will be removed and prescribing extended to general practitioners from 1 October 2016. There are some general practices that have audited their client base to identify patients with hepatitis C so that genotyping and FibroScans can occur.

However, this is a new treatment area for general practitioners and it was considered that advice from Medsafe on the safely profile of DAAs would be useful. The Committee also noted that there are many drug interactions that can occur with these medicines.

The Committee noted that hepatitis B reactivation has been reported in temporal association with DAA treatment. However, it was noted that patients may get flares of hepatitis B at any time so the cases may be coincidental. It was also noted that hepatitis C may have a suppressant effect on hepatitis B and the flare could be an indirect effect of treatment of the hepatitis C infection. The Committee noted that clinical trials of DAAs for hepatitis C had excluded HBV/HCV coinfected patients. Most of the data sheets state that the safety and efficacy of DAAs have not been established in patients coinfected with hepatitis B.

Although the Committee considered that there is insufficient evidence to confirm a causative association, this is a potentially life threatening effect which healthcare professionals should be informed about. The Committee considered the data sheets should therefore include a warning regarding hepatitis B reactivation, and patients who are being prescribed DAAs should be assessed, tested and closely monitored for hepatitis B. The Committee noted that the side effect profile of DAAs is better than previous treatment regimens containing inferferons and DAAs have a shorter duration of treatment.

The Committee considered additional communication to healthcare professionals would be important for new prescribers of DAAs. The communication should include general information on DAAs with some information on the risk of hepatitis B reactivation. Healthcare professionals should also be encouraged to report any adverse reactions to the Centre for Adverse Reactions Monitoring.

Recommendation 8

The Committee recommended that Medsafe request the sponsors of DAA-containing products to update the data sheets with information on the risk of hepatitis B reactivation.

Recommendation 9

The Committee recommended that Medsafe includes a general article on DAAs with information on the risk of hepatitis B reactivation in a future edition of Prescriber Update.

4.0 MATTERS ARISING FROM THE NEW ZEALAND PHARMACOVIGILANCE CENTRE

4.1 Centre for Adverse Reactions Monitoring (CARM) Quarterly Reports

4.1.1 Safety Signals from Reporting Trends

At the 166th meeting, the Committee discussed a potential safety signal relating to an interaction between roxithromycin and warfarin. The Committee recommended that this issue be reported back at a future meeting.

Additional information on this potential safety signal was presented to the Committee. The pharmacokinetic studies conducted to study the effect of roxithromycin and warfarin, and CYP3A4-mediated drug interactions were explained to the Committee.

The Committee noted that since there were case reports where INR levels measured at day 3 was very high, it was possible that a high INR level may have started at day 2 in these patients. Because of this, the Committee discussed whether monitoring should occur earlier than day 3. However, it remains unclear as to whether other antibiotics are more or less likely to interact with warfarin or if the underlying infection being treated is causing the high INR levels.

The Committee considered that close monitoring should occur when macrolides are used concomitantly with coumarin anticoagulants and it should be noted that increased INR levels have been reported.

Recommendation 10

The Committee recommended that there should be close monitoring of patients using macrolides and coumarin anticoagulants concomitantly and high INR levels have been reported to the Centre for Adverse Reactions Monitoring from day 3.

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 did not consider any of the reports required further action.

4.1.3 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.

4.1.4 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 did not consider any of the reports required further action.

4.1.5 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 noted that there was a report of increased INR resulting from an interaction between warfarin and topical miconazole cream which was applied to the patient’s toes. This interaction is known to occur with the oral gel formulation of miconazole but is much less known with topical treatment.

Recommendation 11

The Committee recommended that Medsafe updates the Label Statements Database to include a compulsory warning regarding an interaction with warfarin for all miconazole-containing products.

The Committee did not consider other reports required further action.

5.0 OTHER BUSINESS

5.1 Comments on sections 3 and 4 of the agenda

The Committee discussed sections 3 and 4 of the agenda. The Committee considered that no changes were required to these sections.

5.2 Therapeutic products regulation project — Update

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

6.0 ANNEXES

3.2.1 Safety of metformin use in pregnancy

  1. Butalia S, Gutierrez L, Lodha A, et al. 2016. Short- and long-term outcomes of metformin compared with insulin alone in pregnancy: a systematic review and meta-analysis. Diabet Med doi: 10.1111/dme.13150. [Epub ahead of print].
  2. Rowan JA, Hague WM, Gao W, et al. 2008. Metformin versus insulin for the treatment of gestational diabetes. The New England Journal of Medicine 358: 2003–2015.

3.2.2 Fluconazole and use in pregnancy

  1. U.S. Food and Drug Administration. 2016. FDA Drug Safety Communication: FDA to review study examining use of oral fluconazole (Diflucan) in pregnancy. Avaialble at: www.fda.gov/Drugs/DrugSafety/ucm497482.htm (accessed 17 June 2016).
  2. Mølgaard-Nielsen D, Svanström H, Melbye M, et al. 2016. Association between use of oral fluconazole during pregnancy and risk of spontaneous abortion and still birth. JAMA 315(1): 58–67.

3.2.3 National immunisation schedule change to Gardasil 9 as a 2 dose schedule and expanded access to include people up to the age of 26 years

  1. Joura EA, Giuliano, AR, Iversen O, et al. 2015. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. The New England Journal of Medicine 372: 711–723.
  2. Van Damme P, Olsson SE, Block S, et al. 2015. Immunogenicity and safety of a 9-valent HPV vaccine. Pediatrics 136(1): e28–39.
  3. Schilling A, Parra MM, Gutierrez M, et al. 2015. Coadministration of a 9-valent human papillomavirus vaccine with meningococcal and Tdap vaccines. Pediatrics 136(3): e563–72.
  4. Garland SM, Cheung TH, McNeill S, et al. 2015. Safety and immunogenicity of a 9-valent HPV vaccine in females 12–26 years of age who previously received the quadrivalent HPV vaccine. Vaccine 33(48): 6855–64.
  5. Kosalaraksa P, Mehlsen J, Vesikari T, et al. 2015. An open-label, randomized study of a 9-valent human papillomavirus vaccine given concomitantly with diphtheria, tetanus, pertussis and poliomyelitis vaccines to healthy adolescents 11­–15 years of age. Pediatr Infect Dis J 34(6): 627–37.
  6. Vesikari T, Brodszki N, van Damme P, et al. 2015. A randomized, double-blind, phase III study of the immunogenicity and safety of a 9-valent human papillomavirus L1 virus-like particle vaccine (V503) versus Gardasil in 9–15-year-old girls. Pediatr Infect Dis J 34(9): 992–8.
  7. Moreira ED Jr, Block SL, Ferris D, et al. 2016. Safety profile of the 9-valent HPV vaccine: a combined analysis of 7 phase III clinical trials. Pediatrics 138(2): pii: e20154387.

3.2.4 Hepatitis B reactivation with direct-acting antivirals for hepatitis C

  1. Gane E, Stedman C. 2016. NZ Society of Gastroenterology HCV treatment guidelines. Available at: www.nzsg.org.nz/cms2/uploads/Hepatitis%20C%20Guidance_FINAL%20July%2011.pdf (accessed 4 August 2016).

4.1.1 Safety signals from reporting trends

  1. Ghose K, Ashton J, Rohan A. 1995. Possible interaction of roxithromycin with warfarin. Clinical Drug Investigation 10(5): 302–309.
  2. Paulsen O, Nilsson LG, Saint-Salvi B, et al. 1988. No effect of roxithromycin on pharmacokinetic or pharmacodynamic properties of warfarin and its enantiomers. Pharmacol Toxicol 63(4): 215–20.
  3. Ohno Y, Hisaka A, Suzuki H. 2007. General framework for the quantitative prediction of CYP3A4-mediated oral drug interactions based on the AUC increase by coadministration of standard drugs. Clin Pharmacokinet 46(8): 681–96.
  4. Backman JT, Aranko K, Himberg JJ, et al. 1994. A pharmacokinetic interaction between roxithromycin and midazolam. Eur J Clin Pharmacol 46(6): 551–5.
  5. Yamazaki H, Shimada T. 1998. Comparative studies of in vitro inhibition of cytochrome P450 3A4-dependent testosterone 6beta-hydroxylation by roxithromycin and its metabolites, troleandomycin, and erythromycin. Drug Metab Dispos 26(11): 1053–7.
  6. Adverse Drug Reactions Advisory Committee (ADRAC). 2006. Interactions with macrolides. Australian Adverse Drug Reactions Bulletin 25(2). Available at: www.tga.gov.au/publication-issue/australian-adverse-drug-reactions-bulletin-vol-25-no-2 (accessed 5 September 2016).
  7. Rotella J-A, Taylor DM. 2015. Concomitant roxithromycin use among elderly patients taking warfarin resulting in significant over-anticoagulation. Journal of Pharmacy Practice and Research 45(2): 182–185.
  8. Thompson A. 2015. Concomitant roxithromycin use among elderly patients taking warfarin resulting in significant over-anticoagulation. (Letter to the editor). Journal of Pharmacy Practice and Research 45(4): 486.
  9. Medsafe. 2008. Roxithromycin-warfarin interaction of increased INR. Prescriber Update 29(1): 2–4.
  10. Medsafe. 2015. Check INR after starting roxithromycin for patients on warfarin. Prescriber Update 36(1): 3.
  11. Actavis New Zealand Limited. Arrow - Roxithromycin Data Sheet 11 May 2015. Available at: www.medsafe.govt.nz/profs/datasheet/a/ArrowRoxithromycintab.pdf (accessed 5 September 2016).
  12. sanofi-aventis Australia pty ltd. Rulide Product Information 21 January 2015. Available at: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-06117-3&d=2016050416114622483&d=2016090416114622483 (accessed 5 September 2016).

The Chair thanked members, the Secretariat and Medsafe staff for their attendance and closed the meeting at 3pm.

Associate Professor D Reith

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