Containing the impacts in NZ: Acne and isotretinoin III
Investigation by Carolyn Skelton.
In my previous pieces I addressed problems with acne and a last resort anti-acne drug (isotretinoin); a drug which has tended towards being overused and under-regulated. Many of the problems arose from the impatient pursuit of profit by Big Pharma. Pharmaceutical corporations have researched and developed some very valuable medicines. However, there need to be checks to ensure the seeking of profits doesn’t result in some powerful drugs doing harm. For instance, in the US, there was a rush to market isotretinoin to combat “severe [nodulo]cystic acne and conglobate acne resistant to other treatments”.
Subsequent brand names have included Accutane, Oratane and Isotane.
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.
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
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.
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.
Any publication, in whole or in part, of the obtained information must have published with it a statement: (i) of the source of the information (ii) that the information is not homogenous at least with respect to origin or likelihood that the pharmaceutical product/vaccine caused the adverse reaction (iii) that the information does not represent the opinion of the NZPhvC or CARM.
Suspected Medicine Adverse Reaction Search
Essential information about the Suspected Medicine Adverse Reaction Search (SMARS)
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.
When using SMARS you should remember that:
- The likelihood of experiencing an adverse reaction to a medicine cannot be estimated from this database as there is no information on how many people have taken the medicine and the extent of underreporting is not known.
- For these reasons, it is also not possible to directly compare the risks of different medicines using SMARS.
- Reports are sent to the Centre for Adverse Reactions Monitoring (CARM) if the reporter suspects that a medicine caused a reaction. This does not necessarily mean that the medicine did cause the reaction.
- CARM and Medsafe staff consider many factors when assessing whether a medicine has caused an adverse reaction.
- The number of reports for a medicine can be influenced by how many patients are taking the medicine, media attention, the nature of the reactions and other factors which vary over time.
- The quality of the information in SMARS is limited by the quality of the original report.
- The information contained in SMARS may change over time due to quality control procedures and/or receipt of further information.
- Reactions may also be caused by other ingredients in the medicine (excipients).
SMARS contains anonymised information from reports of suspected adverse reactions to medicines but does not include the following:
- Reports not causally related to the medicine (assessed by CARM).
- Any report where it is considered that the patient may be identifiable (e.g. due to the rareness of the reaction).
- Reports from the last three months.
Please note that some non-causally related suspected adverse reactions may be included in SMARS if the report also contained a causally related suspected adverse reaction.
About the release of this information
This information is released in keeping with the purpose of the Official Information Act 1982 to progressively increase the availability of official information to the people of New Zealand. The data contained in SMARS does not include any personal information within the meaning of the Privacy Act 1993.
Use of SMARS data
If you wish to copy or circulate information from SMARS please ensure that a copy of these guidelines is provided. Prior to any publication of this data you must contact CARM and Medsafe and include in the publication:
- the source of the information
- the limitations of the information
- that the information does not represent the opinion of CARM or Medsafe.
If you require further information please contact Medsafe by emailing firstname.lastname@example.org or by telephoning 04 819 6800.