APO-ISOTRETINOIN

What it is

APO-ISOTRETINOIN is a capsule formulation containing 10 mg or 20 mg of isotretinoin as the active ingredient. Isotretinoin is a retinoid that inhibits sebaceous gland function and keratinisation.

Approved indications

— Severe cystic acne.

Dosing overview

All patients should initially receive doses up to 0.5 mg/kg bodyweight daily for a period of two to four weeks, when their responsiveness to the drug will usually be apparent. In most cases complete or near complete suppression of acne is achieved with a 16 week course of treatment. Doses up to 1 mg/kg/day may be used in patients refractory to initial treatment at lower doses. The daily dosage should be taken with food in the nearest number of whole capsules, either as a single dose or in two divided doses during the day, whichever is more convenient.

Key safety warnings

Isotretinoin must not be used by females who are pregnant or who may possibly become pregnant while undergoing treatment. Major human foetal abnormalities related to isotretinoin administration have been reported, including hydrocephalus, microcephalus, abnormalities of the external ear, eye abnormalities, cardiovascular abnormalities, facial dysmorphia, cleft palate, thymus gland abnormality, parathyroid gland abnormalities and cerebellar malformation/abnormalities. There is also an increased incidence of spontaneous abortion. An effective form of contraception should be used for at least one month before and also throughout isotretinoin therapy. It is recommended that contraception be continued for one month following discontinuation of isotretinoin therapy. There have been post-marketing reports of severe skin reactions (e.g. erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis) associated with isotretinoin therapy. These reactions may be serious and result in death, life-threatening events, hospitalisation or disability. Isotretinoin use has been associated with a number of cases of benign intracranial hypertension (pseudotumour cerebri), some of which involved the concomitant use with tetracyclines. Early signs and symptoms of benign intracranial hypertension include papilloedema, headache, nausea and vomiting, and visual disturbances. Patients who develop benign intracranial hypertension should discontinue isotretinoin immediately. Depression, depression aggravated, psychotic symptoms, anxiety, aggressive tendencies, mood alterations, psychosis and, rarely, suicide, suicidal ideation and suicide attempts have been reported with isotretinoin. All patients should have an assessment of their mental health, and of family history of mental health conditions, before starting treatment 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. Isotretinoin causes elevation of serum triglycerides and cholesterol as well as a decrease in high-density lipoprotein (HDL). Acute pancreatitis, which is potentially fatal, sometimes associated with serum triglycerides levels > 8 g/L, has been reported. Hence isotretinoin should be discontinued if uncontrolled hypertriglyceridaemia or symptoms of pancreatitis occur. Isotretinoin has been associated with inflammatory bowel disease (including regional ileitis) in patients without a prior history of intestinal disorders. Patients experiencing abdominal pain, rectal bleeding or severe (haemorrhagic) diarrhoea should discontinue isotretinoin immediately.

Contraindications

Isotretinoin must not be used by females who are pregnant or who may possibly become pregnant while undergoing treatment. Isotretinoin is contraindicated in patients who are breast-feeding, in patients with severely impaired liver function and in patients with chronic abnormally elevated blood lipid values. Isotretinoin is contraindicated in patients who have pre-existing hypervitaminosis A and in patients with hypersensitivity to the drug or any of the other ingredients or to other retinoids. Isotretinoin contains soya oil and partially hydrogenated soya oil, therefore isotretinoin is contraindicated in patients allergic to soya. Concomitant treatment with tetracyclines is therefore contraindicated.

Regulatory history

APO-ISOTRETINOIN was first approved on 28 November 2002. Both the 10 mg and 20 mg capsule formulations were first listed on the ARTG on 15 December 2011 under licence category RE.