Isotretinoin Other names: Isotretinoin

Concurrent administration of isotretinoin with topical keratolytic or exfoliative anti-acne agents should be avoided as local irritation may increase.

Isotretinoin is contraindicated in patients with hepatic insufficiency.

Renal insufficiency and renal failure do not affect the pharmacokinetics of isotretinoin. Therefore, isotretinoin can be given to patients with renal insufficiency. However, in patients with severe renal insufficiency treatment should be started at a lower dose (e.g. 10 mg/day). The dose should then be increased up to 1 mg/kg/day or until the patient is receiving the maximum tolerated dose.

Isotretinoine reduces the energy/activity of carbamazepine.

Exposure to intense sunlight or to UV rays should be avoided. Where necessary a sun-protection product with a high protection factor of at least SPF 15 should be used.

Depression, depression aggravated, anxiety, aggressive tendencies, mood alterations, psychotic symptoms and, very rarely, suicidal ideation, suicide attempts and suicide have been reported in patients treated with isotretinoin. Particular care needs to be taken in patients with a history of depression and all patients should be monitored for signs of depression and referred for appropriate treatment if necessary. However, discontinuation of isotretinoin may be insufficient to alleviate symptoms and therefore further psychiatric or psychological evaluation may be necessary. Awareness by family or friends may be useful to detect mental health deterioration.

Aggressive chemical dermabrasion and cutaneous laser treatment should be avoided in patients on isotretinoin for a period of 5-6 months after the end of the treatment because of the risk of hypertrophic scarring in atypical areas and more rarely post inflammatory hyper or hypopigmentation in treated areas. Wax depilation should be avoided in patients on isotretinoin for at least a period of 6 months after treatment because of the risk of epidermal stripping.

Cases of benign intracranial hypertension have been reported, some of which involved concomitant use of tetracyclines. Signs and symptoms of benign intracranial hypertension include headache, nausea and vomiting, visual disturbances and papilloedema. Patients who develop benign intracranial hypertension should discontinue isotretinoin immediately.

Isotretinoin has been associated with inflammatory bowel disease (including regional ileitis) in patients without a prior history of intestinal disorders. Patients experiencing severe (haemorrhagic) diarrhoea should discontinue isotretinoin immediately.

Oral administration

Pregnancy is an absolute contraindication to treatment with isotretinoin. Women of childbearing potential have to use effective contraception one month before, during and up to one month after treatment. If pregnancy does occur in spite of these precautions during treatment with isotretinoin or in the month following, there is a great risk of very severe and serious malformation of the foetus.

The foetal malformations associated with exposure to isotretinoin include central nervous system abnormalities (hydrocephalus, cerebellar malformation/abnormalities, microcephaly), facial dysmorphia, cleft palate, external ear abnormalities (absence of external ear, small or absent external auditory canals), eye abnormalities (microphthalmia), cardiovascular abnormalities (conotruncal malformations such as tetralogy of Fallot, transposition of great vessels, septal defects), thymus gland abnormality and parathyroid gland abnormalities. There is also an increased incidence of spontaneous abortion.

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.

Cutaneous use

Topical isotretinoin is contraindicated in pregnancy, or in women planning a pregnancy. If the product is being used during pregnancy, or if the patient becomes pregnant while taking this drug, treatment should be discontinued.

There are limited data available from the use of topical isotretinoin in pregnant women. However, studies totalling 1535 women exposed to topical tretinoin (an isomer of isotretinoin) in early pregnancy did not provide evidence of an increased risk of congenital abnormalities, including retinoic acid embryopathy or major structural defects.

In the clinical setting however, use of topical tretinoin in early pregnancy has been temporally associated with retinoic acid specific embryopathy. There are also a few reports of the rare birth defect category, holoprosencephaly (defects associated with incomplete midline development of the forebrain). The significance of these reports in terms of risk to the foetus is uncertain, since no causal association has been established from these cases and these effects have not been reproduced.

Isotretinoin is highly lipophilic, therefore the passage of isotretinoin into human milk is very likely. Due to the potential for adverse effects in the child exposed via mothers' milk, the use of isotretinoin is contraindicated in nursing mothers.

There is insufficient information on the excretion of topically applied isotretinoin in human milk.

A risk to the newborns/infants cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from isotretinoin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

Isotretinoin, in therapeutic dosages, does not affect the number, motility and morphology of sperm and does not jeopardise the formation and development of the embryo on the part of the men taking isotretinoin.

There are no data on the effect of topical isotretinoin on fertility in humans.

Oral administration

Isotretinoin could potentially have an influence on the ability to drive and use machines. A number of cases of decreased night vision have occurred during isotretinoin therapy and in rare instances have persisted after therapy. Because the onset in some patients was sudden, patients should be advised of this potential problem and warned to be cautious when driving or operating machines.

Drowsiness, dizziness and visual disturbances have been reported very rarely. Patients should be warned that if they experience these effects, they should not drive, operate machinery or take part in any other activities where the symptoms could put either themselves or others at risk.

Cutaneous use

Not applicable; the product is a topical preparation which acts locally at the site of application.