Published: 17 January 2019

Committees

MINUTES OF THE 176TH MEDICINES ADVERSE REACTIONS COMMITTEE MEETING

MINUTES OF THE 176th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING

6 December 2018

The one hundred and seventy sixth meeting of the Medicines Adverse Reactions Committee (MARC) was held on 6 December 2018 at Te Papa, Cable Street, Wellington. The meeting commenced at 9am and closed at 2.30pm.

MARC MEMBERS PRESENT

Associate Professor D Reith (Chair)
Dr S Jayathissa
Dr L Bryant
Associate Professor D Menkes
Dr C Cameron
Mrs C Ryan
Dr K Eggleton
Ms J Tatler
Mrs I Raiman
Dr S Hanna
Dr M Tatley  

MARC SECRETARIAT PRESENT

M Oldridge (Advisor, Pharmacovigilance)

MEDSAFE STAFF IN ATTENDANCE

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

INVITED GUESTS AND EXPERTS IN ATTENDANCE

Mr B Simpson (Managing Editor, New Zealand Formulary), present for items 3.2.3, 3.2.4 & 5.1

1.0 MATTERS OF ADMINISTRATION

1.1 Welcome and Apologies

The Chair welcomed the attendees to the meeting. Apologies were received from Dr L Parkin.

1.2 Minutes of the 175th MARC Meeting

The minutes of the 175th 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

2.1.1 Fatal Cases (Causal Cases Only)

[J Tatler and C Ryan joined the meeting at this time]

Members were given a brief description of the fatal reports for which CARM had assessed the causality to be at least possible.

The Committee noted case 129379, where an elderly patient taking dabigatran was started on multiple analgesics including ibuprofen, paracetamol, morphine and tramadol. The patient subsequently developed melaena, rectal bleeding and acute kidney injury. The Committee expressed concern over the appropriateness of prescribing ibuprofen in this case.

The Committee agreed that this case report and the issues around frailty and prescribing of analgesics in elderly patients should be highlighted to the Chief Medical Officers (CMOs) of the District Health Boards (DHBs).

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

Recommendation 1

The Committee recommended that the Chair of the MARC writes to the Chief Medical Officers (CMOs) of the District Health Boards (DHBs) to highlight case 129379 and considerations when prescribing analgesia for elderly patients.

2.1.2 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 noted case 129616, where a patient received chloral hydrate and subsequently developed bradycardia and loss of consciousness. The Committee considered this to be a rare and unusual case given the nature and timing of the adverse events. The Committee commented that chloral hydrate has a toxic metabolite that can potentiate a pre-existing prolonged QT interval, which may provide an explanation for the adverse event. The Committee also noted that the metabolite is cleared by the kidneys and questioned whether the patient may have had pre-existing renal impairment. However, it is unknown whether the patient had either of these predispositions.

The Committee briefly reviewed the Starship Hospital guideline regarding sedation in children during non-invasive procedures and agreed that consideration of the quality and period of observation after chloral hydrate administration is necessary. The Committee commented that vital signs, in particular, blood pressure, heart rate and respiratory rate should be closely monitored prior to patient discharge. The Committee recommended that this case report along with considerations around chloral hydrate monitoring are communicated to Starship Hospital. The Committee also recommended asking Starship Hospital whether they are aware of any similar cases to this one.

The Committee noted case 130063, where a patient experienced acute hepatic failure after a suspected, supra-therapeutic paracetamol overdose. The Committee commented that the report did not provide an explanation as to how the suspected overdose occurred, but mentioned that in past cases some examples of contributing factors have included incorrect doses being given and patient/parent misunderstanding around paracetamol dosing intervals. The Committee also questioned whether inequity may be a contributing factor as this issue appears to be related to health literacy.

The Committee discussed other potential safety issues around the use of paracetamol in children including higher volumes of paracetamol liquid being prescribed, the fact that there are two different strengths of paracetamol liquid available (120mg/5mL and 250mg/5mL), and multiple children of different ages being dosed from the same bottle of paracetamol.

The Committee noted that paracetamol liquid is a pharmacy-only medicine, meaning that there is an opportunity for a pharmacist to provide education on the appropriate use of paracetamol to the patient/parents at the point of sale.

The Committee considered the possibility of a public awareness campaign about paracetamol use in children. The Committee recommended that the Chair of the MARC communicate with the Pharmaceutical Society of New Zealand (PSNZ), Accident Compensation Corporation (ACC), The Pharmaceutical Management Agency (PHARMAC) and the Choosing Wisely group about the possibility of generating consumer information and increasing public awareness on this issue.

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

Recommendation 2

The Committee recommended that the Chair of the MARC write to the chief pharmacist at Starship Hospital, highlighting case 129616 and considerations around the quality and period of observation after administration of chloral hydrate.

Recommendation 3

The Committee recommended that the Chair of the MARC write to PSNZ, ACC, PHARMAC and the Choosing Wisely group about the possibility of generating consumer information and increasing public awareness about the safety issues around paracetamol use in children.

2.1.3 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.

2.1.4 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.

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

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

The Committee reconsidered the safety of venlafaxine.

The Committee began by revisiting the bioequivalence data for Enlafax XR, which has been published on Medsafe’s website. The Committee commented that the data are impressive and that they meet international standards. The Committee noted that Enlafax XR has been approved in a number of countries including Australia and no quality issues have been identified with the product.

The Committee then reviewed the reports received by CARM and considered that although the number of ADR reports was concerning, it was not unexpected given the response to previous brand switches. In addition, the Committee considered that there did not appear to be a difference in the type of adverse effects being reported with Enlafax XR from the known ADR profile of venlafaxine, ADRs that were reported with the previous brand Efexor XR, and those that could be attributed to the patient’s underlying condition.

The Committee were informed of an exploratory analysis of hospitalisation data that Medsafe had conducted in response to the increase in reports of suicidality. No increase was identified in the number of people requiring hospitalisation for mental health conditions while taking venlafaxine in the six months following the brand switch to Enlafax XR. The Committee were reassured that Medsafe had had taken these reports seriously and that there had been no change in hospitalisation.

The Committee questioned whether it was possible that consumers had lost confidence in Enlafax XR as a result of the publicity that encouraged ADR reporting. The Committee also mentioned that in countries that haven’t experienced a high number of venlafaxine brand switch reports there is no restriction on choice in contrast to New Zealand, where only one product is funded and available.

The Committee considered the nocebo effect as an explanation for the high number of ADR reports. The Committee emphasized that using the nocebo effect as an explanatory model is not to say that the adverse reactions that have been reported are not real or serious events. The Committee referenced a meta-analysis by Mitsikostas et al that quantified the nocebo effect in patients participating in clinical trials for depression. In patients taking placebo the nocebo effect, was so significant and severe that 4.5% of patients had to stop taking the placebo.

The Committee emphasized the importance of being transparent with the public on this topic. The Committee considered that a media statement may help reassure the public that Enlafax XR is being actively and carefully monitored. The Committee recommended that Medsafe publish a press release on their website regarding Enlafax XR on behalf of the Committee. In addition, the Committee also recommended that information of public interest related to Enlafax XR should be published on Medsafe’s website as it becomes available.

The Committee stated that although a quality issue with Enlafax XR has not been identified at this time that the situation should continue to be monitored closely.

The Committee empathised with the distressing experiences described by patients in the CARM reports and urged anyone experiencing adverse effects from venlafaxine to return to their doctor as soon as possible.

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

Recommendation 4

The Committee recommended that Medsafe publish a press release on Enlafax XR on behalf of the Committee, highlighting the discussion had at this meeting.

Recommendation 5

The Committee recommended that Medsafe publish information of public interest relating to Enlafax XR on their website as it becomes available.

Recommendation 6

The Committee recommended that Medsafe continue to closely monitor Enlafax XR.

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 Hydrochlorothiazide (HCTZ) and Non-Melanoma Skin Cancer (NMSC)

Background

Medsafe reviewed a Danish case control study by Pedersen et al, published in the Journal of the American Academy of Dermatology. The study examined cumulative hydrochlorothiazide use and Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC) of the skin. Medsafe was of the opinion that the results from this study warranted further investigation of this signal.

Internationally, the Pharmacovigilance Risk Assessment Committee (PRAC) has completed a signal assessment of this topic. Their assessment was based on the results of two Danish studies, including Pedersen et al, as well a prior study by Pottegard et al that examined hydrochlorothiazide use and SCC of the lip.

Currently, non-melanoma skin cancer is not described in the New Zealand data sheets for hydrochlorothiazide-containing products.

The advice sought from the Committee was whether the New Zealand data sheets for hydrochlorothiazide-containing products should be updated to include safety information related to non-melanoma skin cancer, given the literature, international regulatory action and company responses.

Discussion

The Committee reviewed the results of the Danish case-control studies and noted that the odds ratios and the dose-response relationship were higher for cumulative hydrochlorothiazide and squamous cell carcinoma than for basal cell carcinoma. The Committee also noted that the odds ratios were greater with long term use of hydrochlorothiazide.

The Committee then considered the PRAC’s recommendation to update the European product information. The Committee agreed with most of the content in their proposed update but stated that the risk of non-melanoma skin cancer should be not listed as ‘unknown’ as recommended in Medsafe’s guidelines. The Committee recommended that safety information relating to non-melanoma skin cancer should be included in the New Zealand data sheets for all hydrochlorothiazide containing products.

The Committee then discussed the need to communicate with the public and prescribers about this issue. The Committee recommended that Medsafe publish an alert communication on their website highlighting this issue and the results of the Danish studies. The Committee commented that the alert should mention that the risks of discontinuing antihypertensive treatment would outweigh the risk of developing a non-melanoma skin cancer. The Committee also suggested the alert provide advice around general sun safety measures while taking hydrochlorothiazide. The Committee commented on the difficulty of communicating the baseline risk of basal cell carcinoma and squamous cell carcinoma in the alert as cases of these cancers are not collected by the New Zealand Cancer Registry.

The Committee noted that Medsafe had previously communicated on photosensitizing medicines in previous editions of Prescriber Update. The Committee recommended that this topic is highlighted again in a future edition of Prescriber Update.

Recommendation 7

The Committee recommended that Medsafe request the sponsors of all New Zealand hydrochlorothiazide containing products to update the data sheets to include information about the risks of non-melanoma skin cancer.

Recommendation 8

The Committee recommended that Medsafe publish an alert on their website about hydrochlorothiazide and non-melanoma skin cancer, highlighting the results of the Danish studies.

Recommendation 9

The Committee recommended that Medsafe include an article about photosensitizing medicines in a future edition of Prescriber Update.

3.2.2 Viekira Pak/Viekira Pak-RBV and psychiatric changes

Background

As part of routine pharmacovigilance, Medsafe identified possible safety signals of hallucination associated with ribavirin (CARM ID 127069) and psychotic symptoms associated with Viekira Pak-RBV (CARM ID 127641). Further investigation of these case reports revealed that both patients were taking Viekira Pak-RBV, of which, ribavirin is an active component.

Hallucination or psychotic disorder are not listed as adverse events in the Viekira Pak-RBV data sheet. Medsafe asked the sponsor, AbbVie, to provide a company review of psychiatric changes (in particular, hallucinations and psychosis/psychotic disorders) associated with the use of Viekira Pak/Viekira Pak-RBV.

The data sheet for ribavirin (Copegus, Roche) includes information relating to psychotic disorder and hallucination which is prefaced as “uncommon to rare” in patients receiving peginterferon alfa-2a/Copegus combination or peginterferon alfa-2a monotherapy during clinical trials.

Section 4.8 of the Viekira Pak-RBV datasheet was recently updated to include the following statement: Please also refer to the currently approved datasheet for Ribavirin Tablets (eg, Copegus) for further information and a list of ribavirin-associated adverse reactions.

Medsafe also asked Roche to provide the data behind these listed adverse events for Copegus, and any other information that may be useful.

The purpose of this paper was to seek advice on whether there is sufficient evidence for an association between Viekira Pak/Viekira Pak-RBV and psychotic disorder and/or hallucinations and whether any regulatory activity is required.

Discussion

After consideration of the available evidence, the Committee agreed that there was insufficient evidence of an association between ribavirin and hallucinations and psychotic disorders.

However, the Committee noted that the Viekira-Pak RBV data sheet refers to another sponsor’s data sheet (Copegus, Roche) as a source of safety information for ribavirin. The Committee commented that data sheets should be stand-alone documents and recommended that the Viekira-Pak RBV data sheet be updated to include safety information for ribavirin.

Recommendation 10

The Committee recommended that Medsafe request the sponsor of Viekira-Pak RBV to update their data sheet to include the safety information for ribavirin.

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

Background

Earlier this year, The New Zealand Formulary (NZF) asked Medsafe why the New Zealand dosing recommendations for elderly patients (75-79 years and 80+ years) taking dabigatran for the treatment or prevention of DVT/PE differ from those in Europe. After further investigation of the EU and NZ product information Medsafe found additional dosage reduction considerations/recommendations for certain sub-populations in the EU that are not currently considered/recommended in New Zealand for this indication. These sub-populations included patients with moderate renal impairment (CrCl 30-50mL/min), those taking concomitant verapamil, and those at an increased risk of bleeding.

Dabigatran is approved in New Zealand for the following two indications where the dosage is generally 150 mg twice daily:

  • prevention of stroke, systemic embolism and reduction of vascular mortality in patients with atrial fibrillation (SPAF) – approved 1/7/2011
  • treatment of acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and prevention of related death, as well as prevention of recurrent DVT and/or PE and related death– approved 17/7/2014.

For the SPAF indication, 110 mg twice daily is recommended in the NZ datasheet for patients aged 80 years or above, and may be considered for patients with:

  • moderate renal impairment (CrCl: 30 to 50 mL/min), if the bleeding risk is high and the thromboembolic risk is low.
  • patients aged 75-80 years if their thromboembolic risk is low and bleeding risk is high
  • patients at risk of bleeding with one or more than one of the following risk factors: age ≥75 years, moderate renal impairment (CrCl: 30-50 mL/min), concomitant treatment with strong P-gp inhibitors, anti-platelets or previous gastro-intestinal bleed (see Annex 1: NZ datasheet).

These dose reductions are not currently recommended for the DVT/PE indication.

The purpose of this paper was to seek advice about the appropriateness of harmonising dose reductions for some special populations for the oral direct thrombin inhibitor Pradaxa (dabigatran) across these two indications.

Discussion

[S Jayathissa left the meeting at this time]

The Committee were informed that the study programme for the SPAF indication assessed both the 110mg twice daily and 150mg twice daily dose regimens of dabigatran, whereas the study programme for the treatment/prevention of DVT/PE only assessed the 150mg twice daily dose regimen. As a result of this the Sponsor recommended that 150mg twice daily be used in all patients for the treatment/prevention of DVT/PE.

The Committee noted that the European Medicines Agency (EMA) considered dosage reductions for the DVT/PE indication in certain subpopulations including: elderly patients, those at increased risk of bleeding, and those with moderate renal impairment. The dose reduction recommendations were based on extrapolation of data from the SPAF study programme. Review of the pharmacokinetic data from the study investigating treatment/prevention of DVT/PE showed that dabigatran exposure is essentially similar to that seen in the SPAF study. The Sponsor agreed to EMA’s dosage reduction recommendations for the DVT/PE indication.

The Committee considered the available information and discussed whether different concentrations of anticoagulation are required for the treatment/prevention of DVT/PE compared with SPAF. The Committee mentioned that it would be important to know if a higher concentration is needed for the treatment/prevention of DVT/PE because the results from the SPAF study programme showed that the lower dose of 110mg twice daily is less effective than 150mg twice daily in preventing stroke, although less bleeding occurs at the lower dose. The Committee were informed that a measure of anticoagulation, the activated Partial Thromboplastin Time (aPPT), was compared between the SPAF and DVT/PE populations and was found to be similar between the two populations. The Committee also pointed out that the SPAF study programme looked at the mean effect of dabigatran, which showed that the 150mg twice daily dose is more effective than 110mg twice daily in the average patient, but that the dose reductions being considered were not for the average patient.

The Committee commented that renal function declines with age. Therefore, the same dose of dabigatran given to elderly patients versus younger patients would result in a higher concentration in elderly patients. A dose reduction for elderly patients seems appropriate due to their reduced renal function compared to younger patients.

While the Committee expressed some discomfort about the lack of efficacy studies for the 110mg twice daily dosing in the treatment/prevention of DVT/PE, the Committee considered that with the current lack of ability to monitor dabigatran it seemed that it would be the best option for those subpopulations at increased risk of bleeding, including the elderly and those with moderate renal impairment, to consider a lower dose of dabigatran.

The Committee were informed that investigations are underway to determine whether particular populations, such as the elderly, should have regular monitoring.

The Committee concluded that that the dabigatran dosage recommendations for the treatment/prevention of DVT/PE should be harmonised with the dosage recommendations for the SPAF indication.

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.

3.2.4 Fetal exposure to lithium during pregnancy

Background

Lithium is a common treatment for bipolar disorder. This illness is diagnosed in many women of childbearing age. There have been concerns about teratogenicity and both maternal and offspring complications if lithium is used in pregnancy, especially during the first trimester. Results of animal and human studies have not been consistent in this respect. However, many of the clinical studies included small numbers of patients, which adds uncertainty to the results.

In August 2018, an international collaborative meta-analysis of six cohorts of pregnant women and their children was published aiming to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity and congenital malformations.

The purpose of this paper was to review the article, other published data and reported cases to assess if any updates to the data sheets of products containing lithium are required, and if further communication of this issue is needed.

Discussion

[S Jayathissa rejoined the meeting at this time]

The Committee considered the literature presented and stated that although the risk of fetal abnormalities associated with lithium use in pregnancy appeared to be lower than previously thought, the risk of use in pregnancy is still greater than for antipsychotic medicines.

The Committee commented that lithium could be changed to a medicine of demonstrated lower risk if ongoing treatment in pregnancy was necessary. However, the Committee accepted that there may be reluctance to withdraw lithium if good control of symptoms has been achieved, particularly in brittle bipolar disorder, or if the patient has failed to respond to other treatment options. The Committee emphasised the importance of a joint discussion between prescriber and patient when considering continuation of lithium treatment in pregnancy.

The Committee reviewed the lithium data sheets and commented that while there is information on major malformations there is no information on learning disorders or autism, which have been identified as issues with a similar medicine, valproate. The Committee questioned whether it should be stated in the data sheets that we do not currently have this information for lithium.

The Committee also noticed that the lithium data sheets strongly recommend discontinuation of lithium before a planned pregnancy but do not state how long before a planned pregnancy to stop treatment. The Committee commented that the data sheet should include information to help prescribers provide good information to women wanting to have a baby so that the person is fully informed.

The Committee asked how information on medicines use in pregnancy is described in the New Zealand Formulary (NZF). The Committee were informed that the NZF have recently updated the pregnancy and lactation advice presented on their website. The information is more descriptive about use of medicines in each trimester and also contains contraception advice for women of childbearing age. However, there is still a lack of information for women planning on becoming pregnant or becoming pregnant around which medicine to use. It was mentioned that the NZF currently has a switching table for antidepressants and the Committee were asked whether a similar table would be useful for medicines used in bipolar disorder as it could provide good information on which medicine(s) to use in certain situations. The Committee supported the possibility of the production of a switching table in the formulary.

The Committee recommended that the lithium data sheets should be updated to include up to date information on the risk of fetal abnormalities with lithium use in pregnancy, including the absolute risk for infant cardiac malformations after exposure to lithium during the first trimester. Further information on the need for effective contraception throughout treatment and the need for a joint decision between prescriber and patient when considering continuation of lithium treatment in pregnancy should also be included in the data sheets.

The Committee then considered whether further communication about lithium use in pregnancy is required. The Committee questioned how many women taking lithium are likely to be in secondary care services. The Committee commented that when lithium is effective patients will often be discharged to primary care for ongoing monitoring, so there are likely to be patients treated in the community and also patients in secondary care. The Committee recommended that a letter is written to the College of Psychiatrists, highlighting the discussion had at this meeting and referencing the briefing document on this topic provided to the Committee members once it has been published on Medsafe’s website.

The Committee noted that the NICE guideline on antenatal and postnatal mental health provides good guidance on the use of lithium in pregnancy. The Committee recommended that the guideline is referred to in Prescriber Update.

Recommendation 11

The Committee recommended that Medsafe requests the sponsors of all New Zealand lithium products to update the pregnancy section of their data sheets to include additional and up to date information on lithium use in pregnancy.

Recommendation 12

The Committee recommended that Medsafe write to the College of Psychiatrists, highlighting the discussion had at this meeting about lithium use in pregnancy and referencing this paper once it is published on Medsafe’s website.

Recommendation 13

The Committee recommended that Medsafe make reference to the NICE guideline on antenatal and postnatal mental health in Prescriber Update.

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 Brand switches in New Zealand

September 2018 minute item 3.2.1

Recommendation 7

The Committee recommended that Medsafe discusses strategies for managing brand switches and communicating to the public with other experts.

Outcome

Medsafe is evaluating pathways for further discussion and action. In the interim, Medsafe is publishing more information on venlafaxine on the website.

Discussion

The Committee were informed that the Enlafax XR bioequivalence study, correspondence between Medsafe and PHARMAC, and OIA responses regarding venlafaxine have been published on Medsafe’s website.

The Committee commented that education on the nocebo effect should be provided to healthcare professionals as it is not widely understood and considered that information about this phenomenon should be communicated in a future Prescriber Update article.

Recommendation 14

The Committee recommended that Medsafe include an article about the nocebo effect in a future edition of Prescriber Update.

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.

The Committee were given a brief update on the progress of the Therapeutic Products Bill (TPB).

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.

The Committee were informed that after this edition, Prescriber Update will only be available electronically which will give Medsafe the opportunity to include photographs in each edition. The Committee highlighted the need for Medsafe to obtain informed consent before including images in the publication.

4.4 Quarterly Summary of Medsafe Early Warning System

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

5.0 OTHER BUSINESS

5.1 Signal management of ADRs when medicines are used during pregnancy

The Committee was briefed on Medsafe’s signal management of adverse drug reactions (ADRs) when medicines are used during pregnancy. The Committee made suggestions of how this could be enhanced.

6.0 ANNEXES

3.2.1 Hydrochlorothiazide (HCTZ) and Non-Melanoma Skin Cancer (NMSC)

  1. Pedersen et al
  2. Pottegard et al
  3. Jensen et al
  4. Schmidt et al
  5. Kaae et al
  6. FDA epidemiological review
  7. PRAC signal assessment

3.2.2 Viekira Pak/ Viekira Pak-RBV and psychiatric changes

  1. AbbVie Company Report
  2. Roche – Drug Safety Abbreviated Report
  3. NZ Society of Gastroenterology HCV Treatment Guidelines

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

  1. Pradaxa NZ data sheet
  2. CDER Summary Review
  3. FDA Label
  4. EMA Assessment Report
  5. EMA Product Information
  6. TGA assessment report
  7. TGA Product Information

3.2.4 Fetal exposure to lithium during pregnancy

  1. Munk-Olsen et al
  2. CARM summary

5.1 Signal management of ADRs when medicines are used during pregnancy

  1. Current and revised ADR reporting form
  2. CARM line-listing of congenital anomaly reports

The Chair thanked members, the Secretariat and Medsafe staff for their attendance and closed the meeting at 2:30pm.

Associate Professor David Reith
Chair, Medicines Adverse Reactions Committee
Date: 6 December 2018

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