(This is our first blog post)
The current UK ‘Summary of Product Characteristics‘ for doctors states :
‘4.4 Special warnings and precautions for use
|Teratogenic effects Roaccutane is a powerful human teratogen inducing a high frequency of severe and life threatening birth defects. Roaccutane is strictly contraindicated in: – Pregnant women – Women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met|
Pregnancy Prevention Programme
This medicinal product is TERATOGENIC
Isotretinoin is contraindicated in women of childbearing potential unless all of the following conditions of the Pregnancy Prevention Programme are met:
• She has severe acne (such as nodular or conglobate acne or acne at risk of permanent scarring) resistant to adequate courses of standard therapy with systemic anti-bacterials and topical therapy (see section 4.1 ”Therapeutic indications“).
• The potential for pregnancy must be assessed for all female patients.
• She understands the teratogenic risk.
• She understands the need for rigorous follow-up on a monthly basis.
• She understands and accepts the need for effective contraception, without interruption, 1 month before starting treatment, throughout the entire duration of treatment and for 1 month after the end of treatment. At least one highly effective method of contraception (i.e. a user-independent form) or two complementary user-dependent forms of contraception should be used.
• Individual circumstances should be evaluated in each case, when choosing the contraception method, involving the patient in the discussion, to guarantee her engagement and compliance with the chosen measures.
• Even if she has amenorrhea [no periods] she must follow all of the advice on effective contraception.
• She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy or if she might be pregnant.
• She understands the need and accepts to undergo regular pregnancy testing before, ideally monthly during treatment and 1 month after stopping treatment.
• She has acknowledged that she has understood the hazards and necessary precautions associated with the use of isotretinoin.
These conditions also concern women who are not currently sexually active unless the prescriber considers that there are compelling reasons to indicate that there is no risk of pregnancy.
The prescriber must ensure that:
• The patient complies with the conditions for pregnancy prevention as listed above, including confirmation that she has an adequate level of understanding.
• The patient has acknowledged the aforementioned conditions. […]
• Negative pregnancy test results have been obtained before, during and 1 month after the end of treatment. The dates and results of pregnancy tests should be documented.
If pregnancy occurs in a woman treated with isotretinoin, treatment must be stopped and the patient should be referred to a physician specialised or experienced in teratology for evaluation and advice. […]’
The patient information leaflet (‘PIL’) begins:
CAN SERIOUSLY HARM AN UNBORN BABY’
We believe that ‘can seriously harm’ may be read very variably by patients. Despite the capital letters, many might read it as informing them of a risk of one in a million, rather than the ‘high risk’ stated in the SPC.
So a female teenager who obtains a supply of isotretinoin from someone else who has decided to stop it, or from the internet, and who just looks at the first part of the 10-page PIL, may not appreciate the true risk of harm.
And patients (both male and female) usually receive little or no information about the toxicity of the drug to their own teenage or adult body. The PIL states that isotretinoin/Roaccutane is ‘a substance related to vitamin A, and one of a group of medicines called retinoids’. But not that vitamin A is itself so toxic that official NHS advice for everyone is not to eat liver (or liver paté) more than once a week, and for women who might become pregnant, not at all.
Future blog pieces will look in more detail at the toxicity of isotretinoin/vitamin A in various parts of the body. One recent scientific paper outlined how in humans, ‘Retinoid-induced hepatotoxicity leads to a form of cholestatic liver dysfunction in which bile regurgitates into the circulation, raising the level of all biliary substances in the blood.’
Among the ‘very common side effects (more than 1 in 10 people)’ listed in the PIL are ‘Raised liver enzymes seen in blood tests’ and ‘Changed levels of fats in the blood (including HDL or triglycerides)’. There is no guarantee that these signs of hepatotoxicity, and any symptoms they cause, will later disappear: ‘…side effects are generally reversible after changing the dose or stopping treatment, however some may continue after treatment has stopped.’