Special Investigation: Containing the impacts in NZ: Acne and isotretinoin III

Containing the impacts in NZ: Acne and isotretinoin III

[caption id="attachment_5712" align="alignleft" width="300"] Image of brochure from Docstoc website[/caption] New Zealand medical authorities have tended to follow the UK, Europe and the US in the use of isotretinoin.  This is because there are limits to the amount a small country can do in developing and researching a wide range of medicines. Regulation and guidelines in NZ Annette Fea is a clinical psychologist in Queenstown who has written about the negative effects of isotretinoin (Scroll down the document for Fea mention) In my phone conversation with her in April, she stressed the importance of restricting and monitoring the use of such powerful drugs. Fea acknowledges that there are some people for whom it is the only effective way to combat severe nodulo cystic acne: a debilitating condition, physically, and emotionally.  Nevertheless, the evidence of negative side effects, and the inadequate regulation can result in the lack of trust of health professionals, potentially limiting the benefits of the drug. Pharmac, Medsafe (New Zealand Medicines and Medical Devices Safety Authority) and NZ area health boards have taken notice of evidence pointing to the need to warn potential users of the possible side effects, of isotretinoin. The Orotane data sheet (2012) prepared by Douglas Pharmaceuticals, and the Isotane data sheet prepared by Mylan New Zealand Ltd (May 2015), are available on the Medsafe website. These data sheets state that isotretinoin is to be prescribed by physicians, preferably dermatologists They also stress the importance of prescribers having some knowledge of the use and potential impacts of the drug. See also, the Waitemata Area Health Board’s January 2015 guidelines for safe prescribing of isotretinoin. ‘Containment’ However, Fea considers this is not enough.  In my conversation with her, she talked about “containment”.  That is, restricting the number of people who can prescribe isotretinoin. That would make it easier to monitor the usage and effects, and provide easier oversight of how it is used. At the moment, nurses, dermatologists and GPs can prescribe it. Isotretinoin should only be used for the most severe cases of nodulo cystic acne, for which all other approaches have failed.  However, there is evidence here and overseas of the drug being prescribed for moderate acne. In New Plymouth NZ in 2011, a Dermatologist reported prescribing isotretinoin about 14 times a week. He said it was possible they were being pressured to ask for it by their peers, because teenage girls with “perfect skin” or just a few pimples, were requesting it.. Fea would prefer that prescribing is restricted to area health board dermatologists, who provide a free service, but whose limited availability would ensure only the severe cases are prescribed isotretinoin, as per the recommendations. Dermnet NZ reports:

Since March 2009, subsidy has been available [for isotretinoin] on Special Authority application by dermatologists and vocationally registered general practitioners.

Training and education Fea also argued for more training for prescribers of such a powerful drug, and more education of users. The online application forms (August 2015) through which health professionals submit requests to application for subsidy by special authority to prescribe isotretinoin, relies on the applicant ticking the boxes to say they have adequate knowledge/training. Pharmac has actually loosened guidance for prescribing the drug recently.  In 2014 the following recommendation was removed from the Pharmac Schedule, and is no longer to be included in an initial application for subsidy:

Patient has had an adequate trial on other available treatments and has received an inadequate response from these treatments or these are contraindiated

Pharmac Schedule Oct 2014 Pharmac Schedule December 2014 Furthermore, applications for renewals of the subsidy, the following has been removed from the Pharmac schedule::

2 Applicant is a vocationally registered dermatologist, vocationally registered general practitioner, or nurse practitioner working in a relevant scope of practice; and 3 Applicant has an up to date knowledge of the treatment options for acne and is aware of the safety issues around isotretinoin and is competent to prescribe isotretinoin; …

Fea is keen for there to be more education of both prescribers and user.  In her experience, strict regulation is not being followed.  Furthermore, she stated that many dermatologists don’t know enough about the psychiatric side effects, early indicators of these, or how to access mental health professionals with a good understanding of the potential brain-related consequences of isotretion use. In fact many mental health professional are not well enough educated on this either, which is what prompted Fea to publish her original article. Further research needed Fea is also concerned that there is not enough research into the way powerful medicines can interact with an individual’s genetic make-up. Genetic mix differs for individuals. With many strong drugs, most users don’t seem to experience negative side effects.  However, for a significant number, the impacts can be debilitating or deadly, as a result of the drug’s effect on an individual’s brain. The lack of comprehensive monitoring means that many who experience negative side effects may go under the radar. Most of the research is done by drug companies, and, as I stated in my earlier piece, the focus has been on demographic mapping of reactions. Fea is concerned that there is little funding for genetic/neurological related isotretinoin research. US professor Doug Bremner’s research, funded by a parent whose child suffered negative side effects, is a cautionary tale.  After he published his research findings, major drug companies tried to discredit him.  He wrote about his experiences in a book, Before You Take that Pill. Monitoring adverse reactions In NZ there is no mandatory monitoring or recording of the use and impacts of such powerful drugs. CARM (The Centre for Adverse Reactions Monitoring) invites medical practitioners to submit data about adverse drug reactions they have seen.  But the process is very subjective, and, according to CARM’s supporting caveat, can be affected by such things as relevant news coverage. Fea says that it is up to practitioner’s discretion about reporting to CARM.  This involves various subjective choices. Many practitioners don’t report adverse reactions.  Sometimes, this is because the user and/or health professional don’t make a connection between the taking of the drug and the adverse reaction. Fea has taken isotreinoin. She subsequently experienced joint pain but at the time she was advised by her GP that it was probably early onset arthritis.  It was only later when she learned more about possible isotertinoin effects, that she went back and checked dates and reconsidered. The joint pain has subsided over time, so was most likely associated with the isotretioin us at that time. Medsafe produces reports generated from the CARM statistics. I accessed some statistics for Suspected Medicine Adverse reactions (SMARS) for isotretinoin on the Medsafe website, by clicking on “I want to … search for adverse reactions to medicines”. It showed a range of adverse reactions were reported.  However, these include a small number for most reactions.  One criteria with the highest number of reported reactions was for “depression”. However, these statistics alone are inadequate for drawing any conclusions, the number averaging to about one report per year of a depression reaction.  There is no indication of how this relates to the rate of isotretinoin use. This would seem to reinforce Fea’s desire for more “containment” by restricting the numbers of people who can prescribe the drug. I submitted this article to CARM and Medsafe as requested in the disclaimer below. The Medsafe correspondent asked that this also be included with reference to the adverse reactions reports:

An assessment of the safety of a medicine cannot be made using only the information contained in SMARS. Medsafe advises patients not to make any changes to their medicine treatment based on information contained in SMARS. Changes to treatment should only be made following consultation with a healthcare professional. As you are aware the data from SMARS does not summarise the complete known safety profile of a medicine. The data available comes from spontaneous adverse reaction reports and only represent suspected adverse reactions. This does not necessarily mean that the medicine did cause the reaction. Not all reports submitted to CARM are included in SMARS due to the reasons stated in the disclaimer.

See below for the disclaimer indicating the limitations and nature of these statistics. ]]>