Acne drug Accutane's harm to fetus a worry despite prevention efforts

Doctors stress that a powerful drug prescribed to fight acne needs to be taken under strict guidelines to prevent serious harm to a fetus, as a new study commissioned by Health Canada points to many failures in preventing pregnancy.  

Isotretinoin was commonly sold as Accutane when it entered the market in Canada in 1983 to treat severe acne, which can cause scarring such as pockmarks. The medication is now available as Accutane Roche and in several generic forms. It's also prescribed for more moderate cases.

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Since the drug can cause damage to the head, face, heart, central nervous system and limbs of a fetus, the prescribing information in Canada requires written consent from the patient, two negative pregnancy tests before treatment and the use of two reliable methods of birth control. These conditions apply to prescriptions dispensed to women of child-bearing age.

The study, published in Monday's issue of the Canadian Medical Association Journal, suggests the pregnancy prevention program is not effective, with between 30 per cent to 50 per cent of women taking the drug not complying.

"The program is probably half as effective as it should be," said the study's lead author, Dr. David Henry, a senior scientist at the Institute for Clinical Evaluative Sciences and a professor at the University of Toronto.

Henry and his team used hospital and vital statistical data to study 59,271 female patients aged 12 to 48 in British Columbia, Saskatchewan, Manitoba and Ontario for about 15 years. Over that time, nearly 1,473 pregnancies, about 100 a year, occurred during the vulnerable period during and after treatment with isotretinoin. The risky period includes any time during the 42 weeks of a pregnancy. 

Pregnancy losses

Of these pregnancies, 1,331 or 90 per cent weren't completed. The majority, 70 per cent, were medically terminated because the patient and health-care provider were worried about the risk to the fetus or had ultrasounds showing abnormalities. Another 20 per cent of the pregnancies were lost spontaneously. 

Of the remaining 10 per cent of live births, a total of 11 babies or nine per cent were born with abnormalities, which amounts to one or two children each year. Researchers don't know the severity of the abnormalities or if use of the acne drug directly caused the congenital abnormalities. 

Henry said he believes greater familiarity with the effective drug, which is generally well tolerated, has led to its use in less severe cases of acne.

"It should be reserved for more severe cases [of acne] because that just cuts down the number of women of childbearing age who are going to be exposed to the drug," Henry recommended. 

It's estimated the average age of isotretinoin users in Canada is 24.

"Conjecture is that physicians who are coming through these days didn't get the same scary messages that we did," Henry said.

Dr. Shannon Humphrey is a dermatologist in Vancouver and a professor in the dermatology department at the University of British Columbia. She is a spokeswoman for the Acne and Rosacea Society of Canada and wasn't involved in the study.

Humphrey said for many of her patients, the benefits of isotretinoin outweigh the risks.

"As physicians, we should not become complacent," Humphrey said. "There are absolutely patients who have moderate acne, who've tried other alternatives and who are suffering, who have anxiety or depression or are not engaging in their daily life because of the stigma of acne. And for that patient, as long as they can understand the side-effect profile, as long as they can engage with the pregnancy prevention recommendations very stringently, that may very well be an ideal candidate for this medication."

Outside of birth defects, the majority of side-effects from the drug include dry skin and sensitivity, she said. Doctors also monitor blood work to check cholesterol levels and liver function after prescribing the drug, which is generally taken for three to four months.

Now that isotretinoin is generic, there's less emphasis on education about it for specialists, said Humphrey, who welcomes greater awareness.

Henry stressed that physicians need to be reminded of their obligations to comply with the prescribing guidance for the drug.

Robyn Sheremeta is a university student in Toronto who describes her acne as moderate and persistent. More than a year ago when she was 22, Sheremeta booked an appointment with a dermatologist at her family's hometown in Edmonton. She thought she'd be prescribed antibiotics or another oral drug to "dull the acne."

Sheremeta was already taking birth control pills. The dermatologist prescribed her a year's supply of a different kind of birth control pill and mentioned using a second method when having sex, she said.

"There was zero monitoring,"  Sheremeta recalled. "I didn't do a single pregnancy test, no blood work. I was given a four-month set of [isotretinoin] pills." 

Sheremeta completed the treatment, the acne disappeared and she now feels it is back to mild to moderate. 

Both Henry and Humphrey also said pharmacists can act as a second line of defence when dispensing the drug. 

One of the limitations of the study was it only captured prescriptions, including for birth control, from provincial drug benefit insurance programs.

About one-quarter to one-third of women in the study filled birth control prescriptions, which was about the same as before they started the acne treatment.

Studies in Europe also suggest that changing contraceptive behaviour among isotretinoin users is difficult, the researchers said.

A spokesman for Health Canada said pregnancy rates for women taking the drug in other international jurisdictions are similar to those reported in Canada. The department is reviewing the results of the study. 
 
Physicians are expected to follow a manufacturer's risk management program if one is in place, as recommended by Health Canada, said a spokeswoman for the College of Physicians and Surgeons of Ontario.

Doctors are expected to practise competently and to maintain the applicable standard of practice when prescribing drugs, including when prescribing isotretinoin products, the college said. 

The study was conducted by the Canadian Network for Observational Drug Effect Studies, or CNODES, which is funded by the Canadian Institutes of Health Research (CIHR).