ISOTRETINOIN-WGR

What it is

ISOTRETINOIN-WGR contains 10 mg or 20 mg of isotretinoin as the active ingredient in soft gelatin capsules. Isotretinoin is a retinoid that inhibits sebaceous gland function and keratinisation.

Approved indications

— Severe cystic acne.

Dosing overview

The therapeutic response to isotretinoin is dose related and varies between patients, necessitating individual adjustment of dosage according to the response of the condition and the patient's tolerance of the drug. In most cases complete or near complete suppression of acne is achieved with a 16 week course of treatment. All patients should initially receive doses up to 0.5 mg/kg bodyweight daily for a period of two to four weeks. Satisfactory initial responses have been reported from 0.05 mg/kg/day, although relapse rates on the lower doses are higher, with a second course required in about two-thirds of patients on 0.1 mg/kg/day for 16 weeks. 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.

Key safety warnings

Isotretinoin must not be used by females who are pregnant or who may possibly become pregnant. Major human foetal abnormalities including hydrocephalus, microcephalus, abnormalities of the external ear, eye abnormalities, cardiovascular abnormalities, facial dysmorphia, cleft palate, and cerebellar malformation have been reported, and there is an increased incidence of spontaneous abortion. A pregnancy test should be performed within two weeks prior to isotretinoin therapy, therapy should start on the second or third day of the next normal menstrual period, and an effective form of contraception should be used for at least one month before and throughout isotretinoin therapy. Because of significant adverse effects associated with its use, isotretinoin should be reserved for patients with severe cystic acne who are unresponsive to conventional therapy, including systemic antibiotics. Post-marketing reports of severe skin reactions including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been associated with isotretinoin therapy. These reactions may be serious and result in death, life-threatening events, hospitalisation or disability, and patients should be monitored closely with discontinuation considered if warranted. Isotretinoin use has been associated with benign intracranial hypertension, with early signs including papilloedema, headache, nausea and vomiting, and visual disturbances. Patients who develop benign intracranial hypertension should discontinue isotretinoin immediately. Rises in alanine and aspartate aminotransferase enzymes have been reported, and liver function tests, especially AST and blood lipids should be measured before therapy and at monthly intervals during therapy. Isotretinoin causes elevation of serum triglycerides and cholesterol and a decrease in high-density lipoprotein, and at doses greater than 1 mg/kg/day, approximately one in four patients have been found to develop elevated triglycerides. Acute pancreatitis, which is potentially fatal and sometimes associated with serum triglyceride levels greater than 8 g/L, has been reported, and isotretinoin should be discontinued if uncontrolled hypertriglyceridaemia or symptoms of pancreatitis occur. Depression, depression aggravated, psychotic symptoms, anxiety, aggressive tendencies, mood alterations, psychosis and, rarely, suicide, suicidal ideation and suicide attempts have been reported. All patients should have an assessment of their mental health and family history of mental health conditions before starting treatment, particular care needs to be taken in patients with a history of depression, and if symptoms of depression develop or worsen, the drug should be discontinued promptly. Impaired hearing has been reported in patients taking isotretinoin, with symptoms including tinnitus, impaired hearing at certain frequencies and deafness. In some cases, hearing impairment has persisted after therapy has been discontinued, and anyone who experiences these symptoms should immediately seek medical advice and undergo urgent formal audiology assessment. Isotretinoin has been associated with inflammatory bowel disease in patients without a prior history of intestinal disorders, and patients experiencing abdominal pain, rectal bleeding or severe diarrhoea should discontinue isotretinoin immediately.

Contraindications

Isotretinoin is contraindicated in females who are pregnant or who may possibly become pregnant, and women of childbearing potential should not be given isotretinoin until pregnancy is excluded. Isotretinoin is contraindicated in patients who are breast-feeding, and in patients with severely impaired liver function and chronic abnormally elevated blood lipid values. Isotretinoin is contraindicated in patients with 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 is contraindicated in patients allergic to soya. Concomitant treatment with tetracyclines is contraindicated.

Regulatory history

ISOTRETINOIN-WGR 10 mg capsules (ARTG 432371) and 20 mg capsules (ARTG 432370) were first listed on the ARTG on 30 May 2024.