Retinoids are used orally for the management of severe skin conditions that do not respond to other therapies.

Three retinoids are currently used orally:

• Isotretinoin (Roaccutane) used for the treatment of severe acne.
• Alitretinoin (Toctino) for the treatment of severe chronic hand eczema.
• Acitretin (Neotigason) for the treatment of severe extensive psoriasis resistant to other forms of therapy, palmo-plantar pustular psoriasis, severe congenital ichthyosis and severe Darier’s disease (keratosis follicularis).

Oral retinoids carry an extremely high risk of foetal malformation even when used at low dose or for a short period of time during pregnancy, consequently all oral retinoids are subject to a Pregnancy Prevention Programme (PPP) to minimise this risk. It is important that pharmacists are aware of the teratogenic nature of these drugs and ensure prescriptions issued to women of child bearing potential follow the PPP.

Treatment with an oral retinoid should be initiated by or under the supervision of a consultant dermatologist and under the conditions of the PPP. The prescriber should check that the patient understands the reasons for pregnancy prevention, and agrees to monthly follow up.

Pregnancy Prevention Programme (PPP)

The PPP is a combination of:

• education for healthcare professionals and patients.
• managing therapy including pregnancy testing before, during and after treatment.
• control of distribution of treatment.

Female patients who are not considered to be at risk of pregnancy should still be encouraged to comply with the PPP unless the prescriber considers there are strong reasons why a pregnancy would not occur, such as following a hysterectomy.

The PPP imposes specific restrictions on prescriptions for oral retinoids including limiting validity for 7 days from the date of writing and also limiting supply to a maximum of 30 days.

Prescriptions presented after seven days should be considered expired and the patient referred back to the prescriber for a new prescription as an additional pregnancy test may be required.

Prescriptions for more than 30 days treatment can be dispensed provided the patient is confirmed as not being under the PPP by the prescriber.

Pharmacists are also advised to not accept or supply oral retinoids against repeat, fax, or email prescriptions.

Telephone requests for an emergency supply of an oral retinoid should only be accepted where the request is made by a PPP specialist prescriber and they can confirm that the patient had a negative pregnancy test within the preceding seven days.

 Additional requirements of the PPP include:

• Pregnancy must be excluded before treatment with oral retinoids.
• Pregnancy tests must be documented 3 days or less before a prescription is issued.
• Female patients should be advised to use at least one, or preferably two, complementary forms of contraception (e.g. barrier and hormonal).
• Contraception should start 1 month before treatment and continue for the full treatment course and until the retinoids have left the patient’s system i.e.
  • At least one month after stopping isotretinoin.
  • At least one month after stopping alitretinoin.
  • At least 3 years after stopping acitretin.
• Specialist advice should be sought if pregnancy occurs during treatment.

The PPP does not apply to male patients prescribed oral retinoids as available data suggests maternal exposure from the semen of patients receiving an oral retinoid is not associated with teratogenic effects.

 Acitretin

The requirement of the PPP is the same for all three oral retinoids with the key exception that patient’s prescribed acitretin are required to use effective contraception for 3 years after stopping therapy. This is because acitretin (and its active metabolites) has a much longer half-life than either isotretinoin or alitretinoin.  It is important that the contraception chosen is suitable for use for the full duration of treatment and also for three years after treatment stops. During the three year period the patient should have 3 monthly checks with the dermatologist to ensure they continue to use contraception effectively.

The half-life of acitretin is only 2 days[1], but etretinate, a teratogenic metabolite, has a half-life of about 120 days.[2]  

Consumption of alcohol in patients treated with acitretin has been shown to result in the formation of etretinate. As a consequence the SPC for Neotigason specifies that “Women of childbearing age must not consume alcohol (in drinks, food or medicines) during treatment with acitretin and for 2 months after cessation of acitretin therapy”

Patient counselling

Pharmacists supplying oral retinoids to male and female patients should counsel the patient to:

• Never share their medication or give it to another person.
• Return all unused capsules to the pharmacy for disposal once treatment is completed.
• Not donate blood during treatment and for one month after stopping oral isotretinoin or 3 years after stopping acitretin (this is to avoid the risk of blood being transfused to a pregnant patient).
• Use sunscreen, lip balm and emollients during therapy and avoid exposure to UV light including sunlight. Isotretinoin can cause dryness and thinning of the skin.
• Avoid laser skin treatment, wax epilation (waxing) and dermabrasion during treatment and for 6 months after treatment cessation.
• Be aware that they may experience changes in their mood and/or behaviour and that they and their families should be alert to this, and speak to their doctor if this occurs.

 Additional counselling points for female patients:

• At least one method of contraception and ideally 2 forms of contraception should be used.
• Barrier methods of contraception alone are not sufficient but can be used in combination with other methods.
• Oral Progesterone-only contraceptives are not considered effective for the purposes of PPP.
• Contraception needs to be used one month before treatment, during treatment and at least one month after stopping isotretinoin and alitretinoin or 3 years after cessation of acitretin.

Patients should be referred to the prescriber where:

• Pregnancy occurs during treatment – the patient should be advised to discontinue retinoid treatment immediately and to seek prompt medical attention.
• Pregnancy occurs within 1 month of stopping isotretinoin or 3 years of stopping acitretin.
• The patient shows signs and symptoms of depression or worsening symptoms of depression.
• The patient reports visual difficulties.