Introduction
Uses
Contraindications
How to use
How it works
Dosage
Course duration
Drug interactions
General side effects and risks
Cutaneous side effects
Managing side effects
Dose-related side effects
Rare side effects
Monitoring
Contraption considerations for women
Isotretinoin and pregnancy
Contraption considerations for men
Efficacy
Recurrent treatment
Precautions for pilots
Isotretinoin (13-cis retinoic acid) is a vitamin-A derivative (retinoid). The liver naturally makes small quantities of isotretinoin from vitamin-A, but the prescribed drug is made synthetically.
Isotretinoin was developed in the 1950s, but only started being used in the mid 1970s. The original brand names were Accutane® and Roaccutane®, but there are now many generic versions on the market, of varying potency. In New Zealand, oral isotretinoin is available as 5 mg, 10 mg and 20 mg capsules (Oratane® brand). It is funded by PHARMAC on Special Authority application.
Isotretinoin is a very effective medication for the treatment of acne. Originally licensed for use in severe disease, it is increasingly prescribed for all grades of acne.
Isotretinoin is also useful for other follicular conditions, such as:
It is also prescribed off-label for many other skin diseases. Examples include:
It has also been used as an adjuvant in neuroblastoma.
Isotretinoin must not be taken in pregnancy, or if there is a significant risk of pregnancy.
Blood donation by males and females on isotretinoin is not allowed in case the blood is used for a pregnant woman.
There has been controversy regarding the use of isotretinoin in peanut allergic individuals - isotretinoin contains purified soya oil (where there is a possible risk of cross sensitivity) and in a study of 60 peanut sensitive individuals, none had a reaction to oral isotretinoin exposure.
In acne, isotretinoin:
The range of doses used each day for acne is less than 0.1 to over 1 mg/kg body weight. Some patients may only need a small dose once or twice a week. A course of treatment may be completed in a few months or continue for several years. For acne, some prescribers have targeted a total cumulative dose of 120–140 mg/kg, in the hope of reducing relapse, but the evidence for this remains controversial. The general trend has been to use lower dosages, unrelated to body weight (eg, 10 mg/day).
The individual dose prescribed by the dermatologist depends on:
Isotretinoin is better taken with water or milk after food to help with its absorption. It may be taken on an empty stomach, but absorption may be halved. There is no particular advantage in splitting the dose over the day. A newer formulation (isotretinoin-lidose) can be taken without food.
Most patients should be treated until their skin condition clears and then for a further few months. However, courses have often been restricted to 16–30 weeks (4–7 months) to minimise the risk of teratogenicity (risk of congenital abnormalities), and to comply with local regulatory authorities. Isotretinoin may be prescribed for years, usually in low dose or intermittently.
Care should be taken with the following medications:
The side effects of isotretinoin are dose dependent; at 1 mg/kg/day, nearly all patients will have some side effects, whereas, at 0.1 mg/kg/day, most patients will not. The range and severity of the side effects also depend on personal factors and the disease being treated.
Patients with significant liver or kidney disease, high blood fats, diabetes and depression may be advised not to take isotretinoin or to be on a lower dose than usual and to have regular follow-up visits.
Most of the side effects due to isotretinoin are cutaneous or mucocutaneous and relate to the mode of action of the drug. When side effects are troublesome, isotretinoin may need to be withheld or the dose reduced. The most common side effects are listed here:
The causality of the listed side effects may not have been confirmed.
The effect of isotretinoin on mood is a very controversial area; the majority of acne sufferers have improved mood commensurate with the improvement in their acne. Rarely, isotretinoin induces depression and low mood, when on stopping the drug, depression lifts but returns with reintroduction of the medication. Acne itself can be the source of distress, anxiety and depression. In rare instances, suicidal ideation and completed suicide occurs during isotretinoin treatment, but this can also rarely be the case in people taking antibiotics for acne, so it is difficult to be certain whether the changes are due to the disease, scarring, the drug, or something else.
The largest meta-analysis reviewing the data of 1.6 million people identified the 1 year absolute risk of suicide, suicidal ideation, completed suicide, and self harm to be less than 0.5% each, and depression 3.8%, all being lower than the risk in the general adolescent population, suggesting that there was no increased relative risk of psychiatric condition in isotretinoin users. In the 2-4 years after isotretinoin the psychiatric illness rate was lower than those who had not had isotretinoin. There was a slightly increased risk of depression in those who had isotretinoin and had a past history of depression. Patients and their families should however remain aware of rare psychiatric events and monitored by their doctors for them.
Pregnancy must be excluded before and during treatment with isotretinoin
In an otherwise healthy individual, blood tests are generally not needed, but monitoring may be a variable prescribing requirement in some countries. If using high dose isotretinoin (1 mg/kg/day), a prolonged course (> 12 months), or if a patient has specific risk factors (eg, family history of dyslipidaemia, viral hepatitis, or high alcohol intake), these tests are indicated prior to treatment and at intervals:
Isotretinoin must not be taken in pregnancy because of a very high risk of serious congenital abnormalities in the baby. Caution needs to be used during breastfeeding as it enters the breast milk and might affect the baby.
All females who could biologically have a child should take the following precautions during treatment with isotretinoin and for four weeks after the medication has been discontinued:
A prescription for emergency contraception may be available from a medical practitioner (GP or family planning clinic) or accredited pharmacy. It prevents 85% of pregnancies if taken within 72 hours of unprotected sexual intercourse.
If contraception fails, termination of pregnancy (an abortion) may be advised if pregnancy arises during treatment with isotretinoin or within a month of discontinuing it.
Isotretinoin has a very high chance of resulting in a spontaneous miscarriage or a severe birth deformity if a fetus is exposed to it during the first half of pregnancy. The deformities affect the growth of tissues developing at the time of exposure to the drug:
Isotretinoin has no effect on sperm or male fertility and has not been shown to cause birth defects in children fathered by men taking it.
Although isotretinoin is usually very effective for acne, occasionally it responds unexpectedly slowly and incompletely. Poor response is associated with:
Options available to slow responders include:
At least fifty percent of patients with acne have a long-lasting response after a single adequate course of isotretinoin. In others, acne may recur a few months to a few years after the medication has been discontinued. Relapse is more common in females than in males, and in patients > 25 years of age. These patients may receive further courses of isotretinoin.
Long-term treatment (> 1 year) is often used for patients with:
Good night vision is important for airline pilots and those flying after dark. Night vision may be affected by isotretinoin. Pilots taking isotretinoin or considering a course of isotretinoin must report to their national aviation authority to discuss how this treatment affects their flying privileges.
In New Zealand, this is the Civil Aviation Authority of New Zealand. Civil aviation licence holders, including Air Traffic Controllers, have an obligation under section 27 C of the Civil Aviation Act to ground self and report to CAA in case of any change in medical condition that may affect flight safety. CAA considers the use of isotretinoin to be a change in medical condition.
Approved datasheets are the official source of information for medicines, including approved uses, doses, and safety information. Check the individual datasheet in your country for information about medicines.
We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).
