Upfront: The isotretinoin debate

From March 1, 2009, general practitioners (GPs) and nurse practitioners have become eligible to prescribe funded isotretinoin, under special authority. The decision to widen access to this drug has resulted in considerable debate, especially among dermatologists who until now, were the sole prescribers of funded isotretinoin. Countries such as the UK and Australia debated the same issues, but the outcome was that specialist restriction of isotretinoin remained. Has PHARMAC made a questionable decision, or should it be commended for opening up access to a drug, that until now has been predominantly prescribed to those who have access to a dermatologist, and can afford the consultation fees?

There are two major safety concerns with isotretinoin :

• It is teratogenic at all therapeutic doses and durations of exposure
• It may be linked to depressive illness or suicidal ideation

It is, however, a highly effective treatment for severe acne that has not responded to any other therapy. Isotretinoin should be available, but prescribing must be closely aligned with extreme vigilance in providing concurrent contraception and counselling about its teratogenic effects, and monitoring for behavioural changes.

The debate in Australia*

In 2008 concern was raised by Australian pharmacists that some prescribers of isotretinoin (predominantly dermatologists) were not warning patients about teratogenicity, did not prescribe concurrent contraception and had not documented any pregnancy tests. In Australia over the last five years there were 66 case reports of exposure to isotretinoin during pregnancy and an estimated four or five live births. There was also concern that despite isotretinoin being indicated for severe acne and only after other treatments fail, it is being increasingly prescribed as first-line therapy for mild cases.

Community Pharmacy in Australia suggested that GPs may be better placed to prescribe isotretinoin, as they are more familiar with a patient’s overall clinical history. It was also proposed that a negative pregnancy test should be mandatory for a prescription, and patients should sign consent forms to indicate they understand the risks and precautions that need to be taken. An electronic data system could be used to regulate prescribing. The idea was that access could be broader but regulation more stringent.

The following points were put forward to support GP prescribing:

• GPs have better awareness of overall clinical circumstances, gynaecological, sexual, social and psychological history
• Dermatologists may not have the experience or close rapport with the patient, to effectively address the potentially complex counselling issues and decide on appropriate contraception
• GPs are experienced prescribers of many complex medicines and the duty of care would not alter if the drug was isotretinoin
• Patients should not have to travel long distances or wait for a specialist appointment to access isotretinoin
• If access was to be widened training for GPs would be essential

In responding to the concerns raised by Community Pharmacy, Australian dermatologists said it was a valuable opportunity to reinforce the message of vigilance in providing contraception and pregnancy information to women who are prescribed isotretinoin. However they felt that dermatologists were still the most appropriate prescribers of isotretinoin. They made the following points:

• Dermatologists may only prescribe isotretinoin after completing a four year fellowship under a qualified dermatologist. GPs who lack this training may find it difficult to ascertain an individual dose requirement (which depends on the severity of the acne and weight of the patient) and to manage side effects.
• If prescribing was opened up to GPs, a larger number of pregnancies exposed to isotretinoin would occur and therefore a larger number of terminations and increased numbers of children born with significant disabilities
• Widening access would expose more people to potentially serious mental health related side effects
• GPs would be disadvantaged because they see acne patients only every month or two, whereas dermatologists see acne patients every day
• GPs would be under pressure to prescribe isotretinoin

After considering the evidence, the National Drugs and Poisons Schedule Committee ruled that the status quo should remain and that isotretinoin should only be prescribed by dermatologists and specialist physicians. The committee agreed that dose titration could be successfully carried out by medical practitioners other than dermatologists. However they did not believe that widening prescribing rights would alleviate the concerns about the reported failure of some prescribers to give contraceptive advice. They expected a commitment from relevant Colleges to remind prescribers about the need for vigilance. The committee also commented that a computer based system for tracking prescriptions was not warranted in Australia and that the 66 pregnancies in five years did not indicate that the current system was failing.

The debate in New Zealand

In New Zealand, isotretinoin has been restricted by funding rather than by regulation. GPs could always prescribe isotretinoin, but until recently dermatologists were the only speciality that could prescribe the drug fully subsidised. However following a decision by PHARMAC, from March 1, 2009, vocationally registered GPs may also prescribe subsidised isotretinoin under special authority.

Dermatologists in New Zealand strongly opposed this decision. They had similar concerns to their Australian counterparts, including the lack of expertise by non-dermatologist prescribers in managing isotretinoin, the potential increase in pregnancy exposures and increase in the incidence of suicidal ideation, inappropriate pressure on GPs to prescribe isotretinoin, increased rate of reported adverse events and the bureaucracy involved with special authority.

In response to these concerns PHARMAC states that:

• GPs will receive training in prescribing and managing isotretinoin. It is anticipated that the RNZCGP will accredit and promote relevant training programmes
• If more people are taking isotretinoin, then there may be an absolute increase in the number of affected pregnancies, but the proportion of affected pregnancies will not necessarily be expected to increase. GPs will also be encouraged to be vigilant about giving contraception and pregnancy advice
• GPs are well placed to know a patient’s medical history and be better positioned to detect symptoms of mental ill-health including depression and suicidal thoughts
• The pressure to prescribe is equally present for any type of doctor

PHARMAC says its decision was motivated by a desire to combat equity of access issues. Analysis of subsidised isotretinoin use showed that a person was 2.5 times more likely to be using this drug if they were living in the least deprived area (quintile 1) of New Zealand.**

PHARMAC is confident that GPs who prescribe the drug will be aware of the precautions with this medication and monitor patients closely. The special authority requirement for isotretinoin will ensure that all prescribers are reminded of the issues involved with prescribing this drug, it also allows for closer control and audit of prescribing activity.

Final word

Concerns about increased exposure and adverse effects are valid regardless of who prescribes isotretinoin. Now that access has been widened, it is essential that all prescribers ensure that process is followed 100% of the time when isotretinoin is prescribed, and that it is reserved for severe cases of acne when all other treatment options have been tried and failed.

Rather than anticipating an increase in adverse effects and potential pregnancy exposures, prescribers should be aiming, through vigilance, to reduce these occurrences. If a GP does not feel confident in prescribing this drug, patients can still be referred to another GP or dermatologist.

It remains to be seen what the effect of widening access to isotretinoin will be. People who found difficulty in accessing a dermatologist, may finally receive a successful treatment for their acne, but this comes with the responsibility of protecting these people and their future children from potentially serious health risks. Only time will tell.

See here for more information on treating acne.