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Published: 24 April 2019

Committees

MINUTES OF THE 177TH MEDICINES ADVERSE REACTIONS COMMITTEE MEETING

  • 1.0 MATTERS OF ADMINISTRATION
  • 2.0 MATTERS ARISING FROM THE NEW ZEALAND PHARMACOVIGILANCE CENTRE
  • 3.0 PHARMACOVIGILANCE ISSUES

    MINUTES OF THE 177th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING
    14 March 2019

    The one hundred and seventy seventh meeting of the Medicines Adverse Reactions Committee (MARC) was held on 14 March 2019 at Ministry of Health, 133 Molesworth Street, Wellington. The meeting commenced at 9am and closed at 3.30pm.

    MARC MEMBERS PRESENT

    Associate Professor D Reith (Chair)
    Dr S Jayathissa
    Ms L Te Karu
    Associate Professor D Menkes
    Dr C Cameron
    Professor L Stamp
    Dr K Eggleton
    Ms J Tatler
    Associate Professor L Parkin
    Dr M Tatley

    MARC SECRETARIAT PRESENT

    J Solloway

    MEDSAFE STAFF IN ATTENDANCE

    S Kenyon (Manager, Clinical Risk Management)
    G Hill (Senior Medical Advisor, Pharmacovigilance)
    M Oldridge (Advisor, Pharmacovigilance)
    A Kerridge (Senior Advisor, Pharmacovigilance)
    L Chan (Senior Advisor, Pharmacovigilance)
    M Storey (Senior Advisor, Pharmacovigilance)
    V Cheer (Senior Advisor, Pharmacovigilance)
    N Jones (Advisor, Science)

    1.0 MATTERS OF ADMINISTRATION

    1.1 Welcome and Apologies

    The Chair welcomed the attendees to the meeting. A special welcome was given to new members, Ms L Te Karu, Professor L Stamp and Associate Professor L Parkin. Apologies were received from I Raiman, S Hanna and C Ryan.

    1.2 Minutes of the 176th MARC Meeting

    The minutes of the 176th 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.

    2.0 MATTERS ARISING FROM THE NEW ZEALAND PHARMACOVIGILANCE CENTRE

    2.1 Centre for Adverse Reactions Monitoring (CARM) Quarterly Reports

    The new members of the Committee were introduced to the format of the Quarterly Report. It was noted that in the overview tables there was one fatal vaccine report. This report was received in 2016 and involved an episode of sudden unexpected death of an infant (SUDI) with a temporal relationship to a vaccine. The Coroner noted other risk factors that could have contributed to the risk. The Committee noted that there have been numerous studies investigating this association and none have shown that vaccines are causative. CARM encourages healthcare practitioners to always report these situations to ensure they are adequately monitored. The Committee noted that Medsafe published an article in the December 2016 edition of Prescriber Update highlighting that there is no causal link between vaccines and SUDI.

    2.1.1 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 130309 where a patient suffered a thromboembolic stroke following cessation of dabigatran treatment two weeks prior. The Committee considered a potential rebound effect may occur upon stopping dabigatran. This effect had been observed in clinical practice and noted in medical literature but there is no evidence or guideline on how to prevent or manage it. It is not known if this is dose-related. The Committee noted that CARM has previously received cases where clotting disorders occurred when an anticoagulant medicine was stopped. However, it is unknown whether these cases were due to a loss of effect or rebound. The Committee requested that Medsafe further investigates this potential safety concern.

    The Committee discussed case 130251 where a patient developed agranulocytosis while taking mirtazapine. Agranulocytosis is a known adverse effect of mirtazapine and is well described in the data sheet. The Committee noted that mirtazapine is used clinically in place of mianserin, a tetracyclic antidepressant, due to the lower risk of haematological toxicity. The Committee questioned whether current evidence still supports this and requested that Medsafe reviews the comparative safety of the two medicines.

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

    Recommendation 1

    The Committee recommended Medsafe writes to the sponsors of dabigatran, apixaban and rivaroxaban requesting a review of information in regards to rebound effects following cessation of treatment.

    Recommendation 2

    The Committee requested Medsafe reviews available information in regards to the safety of mirtazapine compared with mianserin.

    2.1.2 Special Populations: Serious Cases Causally Associated with Medicines in Children under 18 years

    Reports of serious cases associated with medicines in children under 18 years, of which CARM assessed the causality to be at least possible, were briefly outlined for the Committee.

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

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

    Reports of events associated with vaccines occurring in children under 18 years were briefly outlined for the Committee.

    The Committee briefly discussed recent reports of hypotonic-hyporesponsive episodes (HHE) following pertussis vaccination. The Committee noted that since the change in pertussis vaccine from whole-cell to acellular in 2000, reports of HHE to CARM have dramatically declined and are significantly less severe.

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

    2.1.4 Special Populations: Serious Non-Fatal Cases Causally Associated with Critical Terms in Patients over 80 Years

    Reports of serious events associated with critical terms occurring in patients over 80 years, of which CARM assessed the causality to be at least possible, were briefly outlined for the Committee.

    The Committee discussed case 130207 where a patient developed a pulmonary embolism three weeks after receiving dental treatment where gauze soaked in tranexamic acid was used following dental extraction. Embolic effects are an established part of tranexamic acid’s safety profile, however it is unknown how much is absorbed when given by this route. The Committee expressed uncertainty that an embolism could occur three weeks following administration of a single dose. The Committee noted the difficulty in assessing causality with this case but determined that it was worth communicating to the public in Prescriber Update.

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

    Recommendation 3
    The Committee recommended Medsafe publishes case 130207 in the Gathering Knowledge section of a future edition of Prescriber Update.

    2.1.5 Causal and Serious Cases in Patients Aged 18 to 80 Years

    Reports of causal and serious events occurring in patients between 18 and 80 years were briefly outlined for the Committee.

    The Committee discussed the brand-switch reports with venlafaxine. The Committee noted that report numbers were decreasing and concluded that there was no new safety signal.

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

    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 Fingolimod and tumefactive lesions

    Background

    Fingolimod is a first-line treatment for multiple sclerosis in adults. It is marketed under the brand Gilenya and was first approved in New Zealand on 13 November 2011. Tumefactive lesions are large tumour-like demyelinating lesions in the central nervous system that appear in approximately 1-3 per 1000 cases of multiple sclerosis.

    Tumefactive lesions were first identified as a possible adverse reaction to fingolimod by the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) following review of the Gilenya PSUR 8 (Periodic Safety Update Report; 1 March 2014 to 28 February 2015). Following a review by the EMA, the agency requested the market authorisation holder of Gilenya to update the product information to include a warning on this side effect in Section 4.4: Warnings and Precautions.

    Tumefactive lesions are not currently listed in the New Zealand Gilenya data sheet. This paper sought advice on whether there is sufficient evidence for an association between fingolimod and tumefactive lesions, and if so, if any regulatory action was required.

    Discussion

    The Committee noted the difficulty in assessing the causality of tumefactive lesions with fingolimod due to the known association between multiple sclerosis and tumefactive lesions. There may be a real association but the lesions can occur as a consequence of the disease, regardless of medicine use.

    The Committee discussed the presented case studies but considered them as weak evidence. The cases were confounded by the fact that tumefactive lesions can occur as a consequence of the disease. The Committee also considered there to be lack of biological plausibility for a drug-event association.

    Overall, the Committee concluded that there was no association between fingolimod and tumefactive lesions.

    However, the Committee noted the seriousness of tumefactive lesions, especially in the setting of disease relapse. Given the seriousness of the complication, a degree of vigilance is required. The Committee requested that Medsafe continues to monitor this potential safety concern through routine pharmacovigilance as there may be stronger evidence of an association in the future.

    The Committee determined that it was appropriate to have a warning in the data sheet of the potential association despite the lack of strong evidence. Due to the risk of serious harm, the data sheet should state that there have been cases reported. The Committee recommended the following wording for the data sheet warning “Rare cases of tumefactive lesions have been reported in the context of multiple sclerosis and its treatment.” and writes to the Multiple Sclerosis Treatment Assessment Committee to highlight the discussions.

    Recommendation 4
    The Committee recommended Medsafe requests the sponsor of Gilenya to update the data sheet for this product to include a warning for tumefactive lesions.
    Recommendation 5

    The Committee recommended the Chair writes to the Multiple Sclerosis Treatment Assessment Committee to make them aware of the discussions had at this meeting.

    3.2.2 NSAIDs and cardiovascular risk: an update

    Background

    At the 173rd MARC meeting on 8 March 2018, Medsafe sought advice about a Changed Medicine Notification (CMN) from the sponsor of Celecoxib Pfizer (celecoxib) 100 mg and 200 mg capsules. The CMN proposed to relocate the contraindication for patients with significant established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease to the precaution section of the data sheet. The sponsor had submitted the results of the Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen (PRECISION) Study in support of the proposed change. Medsafe asked the Committee to consider whether the proposed change is appropriate and, if approved, should similar changes be made to the data sheets for all non-aspirin NSAIDs.

    The Committee was not satisfied that the PRECISION study data supported the proposed downgrading of the contraindication to a precaution in patients with significant cardiovascular disease. The Committee also expressed concern that there is a high risk of worsening heart failure with NSAIDs.

    Medsafe has previously presented papers to the MARC on the cardiovascular risk associated with specific NSAIDs in June 2013 (diclofenac) and March 2015 (ibuprofen).

    The Committee requested a review of the risk of adverse cardiovascular events with NSAIDs following the recent publication of a number of studies on this topic. This paper examined the medical literature that has been published since the previous MARC reviews.

    Discussion

    The Committee discussed the PRECISION study, and noted that the lack of dose equivalence in the treatment arms limited the interpretation of the study findings. The mean daily dose of ibuprofen (2045 ± 246 mg) and naproxen (852 ± 103 mg) used in the PRECISION study were near the high end of the approved dose range at the time, while the mean daily dose of celecoxib (209 ± 37 mg) remained close to the low end of the then approved dose range. High dose ibuprofen, in the range used in the PRECISION study, has since been associated with an increased cardiovascular risk. Consequently, the Committee determined that demonstration of non-inferiority of celecoxib compared to high dose of ibuprofen does not infer that celecoxib has an acceptable cardiovascular safety profile.

    The Committee considered the recent published literature on the cardiovascular risks of NSAIDs, and noted that it is very hard to differentiate between individual NSAIDs.

    The Committee noted information on cardiovascular risk was harmonised in some NSAID data sheets after reviews in June 2013 and March 2015. The Committee reviewed the cardiovascular event warnings in the current form of the data sheets. The Committee determined that the statement “small increase in risk of arterial-thrombotic events” minimises the risk. Based on current evidence, all NSAIDs carry an established risk of adverse cardiovascular events, which should not be minimised in data sheet warnings. The Committee recommended that the word “small” should be removed from the statement to reflect current evidence.

    The Committee discussed whether NSAIDs should be contraindicated in New York Heart Association class II (NYHA II) heart failure and above. The current NSAID data sheets state they are contraindicated in severe heart failure (NYHA IV). The exception to this is celecoxib, where it is contraindicated in patients with NYHA II-IV heart failure. The Committee also noted the data sheets contain a warning for use in patients with a history of heart failure. Due to the lack of evidence on the safety of NSAIDs in each stage of heart failure, the Committee could not recommend any changes to the current contraindications.

    The Committee expressed concern that the data sheets currently only reflect cardiovascular risk associated with the long-term use of NSAIDs. The evidence shows that there is also a risk associated with short-term use, and therefore all warnings concerning cardiovascular risk should be stated without reference to only long durations of use.

    The Committee recommended these discussions and the recommended changes should be widely communicated to all healthcare practitioners. The Committee considered an article in Prescriber Update would be an appropriate means of communicating this information.

    Recommendation 6

    The Committee recommended that Medsafe writes to the sponsors of all NSAID products requesting the warnings for cardiovascular events in their data sheets are updated to remove the word “small” in relation to the magnitude of the risk, and state that adverse cardiovascular events can occur with short term use.

    Recommendation 7

    The Committee recommended that an article in a future edition of Prescriber Update should be written on this topic.

    3.2.3 Use of methadone during breastfeeding

    Background

    There have been worldwide cases of deaths in infants exposed to methadone through breast milk. Small amounts of methadone can be passed to infants through breast milk and this may lead to respiratory depression, heart problems and death.

    Methadone is predominantly used for opioid substitution treatment (OST) in New Zealand. It is also used in treating moderate to severe pain. The pharmacokinetics of methadone varies greatly between individuals. Plasma concentrations can vary widely between patients and fluctuate greatly within the same patient. It is possible that genetic differences result in some infants being more sensitive to effects of methadone than others but these genetic factors are not well understood.

    Changes in the timing of feeds and methadone doses may affect the concentrations of methadone transferred into breast milk and to the infant. Furthermore, mothers taking methadone who suddenly stop breastfeeding may induce withdrawal symptoms in their infants.

    The New Zealand Practice Guidelines for Opioid Substitution Treatment 2014 and methadone data sheets for products indicated for opioid substitution generally encourage mothers on methadone to breastfeed.

    This paper reviewed information on the use of methadone during breastfeeding to ascertain if any regulatory action should be taken to reduce the risk of adverse effects in the infant.

    Discussion

    The Committee did not discuss the risk-benefit of breast feeding while taking methadone for non OST-related therapy.

    The Committee noted the unpredictable pharmacokinetics of methadone. Methadone would not ordinarily be used for neonatal abstinence syndrome (NAS) because of this; morphine is considered the preferred agent. The Committee noted that these babies would likely be under the care of a neonatologist who would monitor for poor feeding or sedation to pick up babies at risk of harm. However, monitoring may not be frequent enough to pick up all cases.

    The Committee reviewed the cases presented. The Committee noted the cases were multifactorial and did not provide evidence of a significant issue in New Zealand. However, the Committee noted the potential risk associated with methadone use in breast feeding and considered that additional risk minimisation measures could be in place to reduce the risk of harm.

    The Committee noted that the highest risk of harm was during the first three weeks following birth. Risk minimisation measures should target increased monitoring during this period. The main concerns that need monitoring are sedation in the baby and poor feeding.

    The Committee considered the recommendations on breast feeding for people on opioid substitution therapy (as per The New Zealand Practice Guidelines for Opioid Substitution Treatment 2014). The Committee agreed that breast feeding is beneficial and should be encouraged. Despite the potential risk of adverse effects in the child, the Committee concluded the risk-benefit of breast feeding a baby while taking methadone for opioid substitution therapy remained positive.

    The Committee discussed the maternity/neonatology service availability in different areas of New Zealand. OST patients in main centres would likely be under the care of an obstetrician/neonatologist who can carry out regular monitoring to ensure healthy outcomes for the child. However, in more rural areas, patients are less likely to have access to a specialist and resources for monitoring may be more limited. The services a rural patient has access to may not have the knowledge of methadone required to adequately manage the risk.

    The Committee reviewed the methadone data sheets and noted they did not make a statement in regards to more frequent monitoring for children being breast fed by a mother taking methadone. The Committee recommended that section 4.6, Use in Lactation, is updated to include more frequent monitoring in the first 3 weeks of life for sedation and poor feeding.

    The Committee considered the comparative safety of methadone to buprenorphine. The Committee noted that there is no buprenorphine-only product approved in the New Zealand. As no evidence was presented on this topic the Committee could not make further recommendations on this.

    The Committee recommended the relevant clinical groups and colleges should be notified of these updates to ensure maternity carers can adequately manage the risks discussed.

    Recommendation 8

    The Committee recommended that Medsafe writes to the sponsors of methadone products requesting an update to the breastfeeding section of the data sheet to include more frequent monitoring in the first 3 weeks following birth.

    Recommendation 9

    The Committee recommended communication with the relevant colleges highlighting this discussion and the recommendation for increased monitoring for sedation and poor feeding during the first 3 weeks of life.

    3.2.4 Update on nitrofurantoin use in renal impairment

    Background

    The United Kingdom has the lessened the contraindication to use of nitrofurantoin in patients with renal impairment to patients with an eGFR of less than 45 mL/min. However, a short course of three to seven days may be used with caution in certain patients with an eGFR of 30 to 44 mL/min that have a urinary tract infection (UTI) due to suspected or proven multidrug resistant pathogens, when the benefits of nitrofurantoin are considered to outweigh the risk of adverse effects.

    In New Zealand, the use of nitrofurantoin in renal impairment was discussed by the MARC at the 163rd meeting on 10 September 2015. The Committee reviewed the available literature presented by Medsafe and considered that the contraindication for nitrofurantoin use should remain at a creatinine clearance (CrCl) of less than 60mL/min.

    Since then, new literature has been published that may suggest a lower CrCl cut off may be acceptable. The advice sought from the Committee was whether the new evidence was sufficient to warrant a change to the current contraindication point of CrCl <60mL/min. The advice sought applied to treatment only and not prophylaxis.

    Discussion

    The Committee noted that the recommended dose in the UK was 50 mg four times daily and that this is lower than the recommended dose in NZ of 50-100 mg four times daily. The Committee questioned whether this lower dose recommendation allowed for people with poorer renal function to use the medicine. However, it is not known whether the 50 mg dose is as efficacious as 100 mg in the context of renal impairment. Additionally, the microbiology trends in the UK may be different to that of New Zealand.

    The Committee discussed the newly published literature presented by Medsafe. The Committee commented that overall the evidence appeared to be weak and that some of the studies did not use appropriate end points. The Committee considered the strength of the evidence insufficient to warrant a) a reduction in the contraindication point for renal impairment and b) what the lowered rate would be. The Committee concluded that the cut-off should remain unchanged at a creatinine clearance of 60mL/min.

    3.2.5 Ergotamine containing medicines and pancreatitis

    Background

    The Centre for Adverse Reactions (CARM) recently received a report of a patient who developed acute pancreatitis. The patient had been taking a number of medicines including Cafergot (caffeine + ergotamine).

    Cafergot is indicated for the management of migraines. However, it is not first-line treatment and it is not available in many countries. Considering the circumstances of the case report, Medsafe considered that the case and safety of Cafergot (and other ergotamine containing products) should be reviewed by the MARC.

    Discussion

    The Committee considered the efficacy of Cafergot for migraines. The Committee noted that there had been no efficacy trials done for these medicines. Ergotamine containing medicines were grandfathered and therefore no review of their initial efficacy was required for marketing approval.

    The Committee considered the risk of harm from Cafergot. The Committee noted there was significant evidence of harm without any evidence of efficacy. The issue of pancreatitis was not considered significant as the only case reported in New Zealand was confounded by multiple concomitant medicines.

    The Committee considered the use of Cafergot outside of New Zealand. It was noted that most countries have withdrawn Cafergot and other ergotamine-containing products due to the unfavourable benefit-risk profile. The Committee questioned whether Cafergot should remain on the New Zealand market.

    The Committee recommended that Medsafe undertakes a risk-benefit review of Cafergot under section 36 of the Medicines Act 1981. The Committee also requested that consideration should be given to the clinical opinion of specialist groups that may use this medicine.

    The Committee considered circumstances where Cafergot may be used. It is expected that they are almost solely used by specialists such as neurologists. The Committee recommended that Medsafe should approach relevant specialist groups for comment on the use, safety and efficacy of ergotamine containing medicines.

    Recommendation 10

    The Committee recommended Medsafe requests a review of the safety and efficacy of Cafergot under Section 36 of the Medicines Act 1981.

    Recommendation 11

    The Committee recommended that Medsafe writes to the Australian and New Zealand Association of Neurologists, Royal Australasian College of Physicians and the Neurological Foundation of New Zealand notifying them of this safety review and requesting any information and/or opinions they have on the use, safety and efficacy of ergotamine (as Cafergot).

    4.0 MEDSAFE PHARMACOVIGILANCE ACTIVITIES

    4.1 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

    4.1.1 172nd MARC Meeting 7 December 2017

    2.1.1 Fatal Cases (Causal Cases Only)

    Recommendation 3

    The Committee recommended Medsafe includes information on using Cockroft-Gault rather than eGFR for calculating doses for patients with renal impairment in a future edition of Prescriber Update.

    Outcome

    Medsafe will include information on using Cockroft-Gault rather than eGFR for calculating doses for patients with renal impairment in a future edition of Prescriber Update. Medsafe has had an initial discussion with the New Zealand Formulary regarding inclusion of this information on the formulary

    Discussion

    The Committee noted that this item has been on the standing agenda for an extended period of time. Medsafe cannot publish the Prescriber Update article until the New Zealand Formulary takes action. Therefore the Committee considered other measures that Medsafe could do instead.

    The Committee considered that either eGFR or Cockroft-Gault can be used in determining medicine dosing at various stages of renal impairment. The data sheet recommendations made by the sponsor on renal clearance cut offs (eg, 40 mg of medicine X at 30mL/min and 20mg at 15mL/min) should reflect the calculation method used in the clinical trial. Healthcare practitioners could then use the same calculation to determine renal function when calculating what dose to use.

    The Committee noted that Medsafe’s guidelines on writing data sheets was coming up for review. This would provide an opportune time to incorporate these requirements.

    Recommendation 12

    The Committee recommended that Medsafe includes, in their next update of the New Zealand Data Sheet Template Explanatory Guide, a requirement for sponsors to state the method of calculating renal function in their clinical trials to support dosing regimens in patients with renal impairment.

    4.1.2 176th MARC Meeting 6 December 2018

    3.2.3 Dose reductions for Pradaxa (dabigatran etexilate): DVT/PE indications

    Recommendation 10

    The Committee recommended that the dosage recommendations for Pradaxa (dabigatran etexilate) for the treatment and prevention of DVT/PE indications are harmonised with the dosage recommendations for the SPAF indication.

    Outcome

    Medsafe has sent a letter to the sponsor of Pradaxa, requesting that they harmonise the DVT/PE dose recommendations with the SPAF dose recommendations.

    Discussion

    Medsafe informed the Committee of the company’s response to the letter. The company recommended awaiting the results of an ongoing observational study, investigating the efficacy and safety of the lower dose (110mg twice daily) in the DVT/PE indication, before changing the data sheet. The results of this study would be available by the end of the year.

    The Committee considered this response and the time frames around it. The Committee noted that they would not have the opportunity to review the results of the study until at least March 2020. In that time, patients will be exposed to significant risk which the Committee considered unacceptable.

    The Committee recommended that the data sheets should be updated now to reflect current evidence and the topic can be revisited if the study results produce significant findings.

    Recommendation 13

    The Committee recommended that Medsafe requests updates to the dabigatran data sheet as soon as possible and does not accept the companies proposal to await the results of an up-coming trial before making changes.

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

    4.2 Medsafe Pharmacovigilance Activities

    The Committee noted the report detailing Medsafe’s recent pharmacovigilance activities.

    4.3 Prescriber Update Volume 39, Number 4, December 2018

    The Committee noted the latest edition of Prescriber Update. The Committee noted they were very impressed with the quality of the publication.

    4.4 Quarterly Summary of Medsafe Early Warning System

    The Committee noted the quarterly summary of Medsafe safety communications.

    5.0 OTHER BUSINESS

    5.1 Consumer reporting

    The Committee reviewed a sample of adverse drug reaction reports made through the Centre for Adverse Reactions Monitoring online consumer reporting form.

    The Committee noted the form was being used as intended and reports from this group continued to provide valuable reports.

    5.2 QlikSense

    The Committee were shown the current QlikSense applications developed by Medsafe for use in pharmacovigilance.

    5.3 Therapeutics Products Bill update

    The Committee were given an overview of areas of interest of the Therapeutics Products Bill consultation draft. The Committee determined they should write a collective response to the consultation.

    Recommendation 14

    The Committee recommended a collective response is written to the consultation draft proposal of the Therapeutics Products Bill.

    6.0 ANNEXES

    3.2.1 Fingolimod and tumefactive lesions

    1. Novartis response to EMA request LEG 036 [confidential]
    2. Novartis response to EMA request LEG 036.1 [confidential]
    3. LEG 036.1 Supportive listings [confidential]

    3.2.2 NSAIDs - an update on CVD risk

    1. Diclofenac and cardiovascular risk – 154th MARC meeting, 13 June 2013
    2. Ibuprofen and cardiovascular risk – 161st MARC meeting, 12 March 2015
    3. Gunter 2017
    4. Nisseen 2016
    5. MacDonald 2017
    6. Schmidt 2018
    7. Sondergaard 2017
    8. Bally 2017
    9. Arfe 2016
    10. CARM data

    3.2.3 Use of methadone during breastfeeding

    1. New Zealand practice guideline for OST 2014

    3.2.4 Update on nitrofurantoin use in renal impairment

    1. Nitrofurantoin use in renal impairment – 163rd MARC meeting, 10 Sep 2015
    2. Nifuran NZ data sheet
    3. Ahmed et al
    4. Muller et al
    5. Cunha et al
    6. Santos et al
    7. Hoang et al
    8. Loh et al
    9. Ingalsbe et al

    3.2.5 Ergotamine containing products and pancreatitis

    1. Report from AFT Pharmaceuticals [confidential]

    5.1 Consumer reporting

    1. Description of consumer reports of venlafaxine problems
    2. Consumer reports anonymised [confidential]

    The Chair thanked members, the Secretariat and Medsafe staff for their attendance and closed the meeting at 3:30pm.

    Associate Professor David Reith
    Date: 14 March 2019
    Chair, Medicines Adverse Reactions Committee

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