ISOTRETINOIN

What it is

APO-Isotretinoin contains isotretinoin 10 mg or 20 mg as the active ingredient in soft gelatin capsules. Isotretinoin is a retinoid that inhibits sebaceous gland function and keratinisation. Clinical improvement in cystic acne patients occurs in association with a reduction in sebum secretion, which is reversible and reflects a reduction in sebaceous gland size and an inhibition of sebaceous gland differentiation.

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. 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. Doses up to 1 mg/kg/day may be used in patients refractory to initial treatment at lower doses. The daily dosages of isotretinoin should be continued for 16 weeks to complete the course of treatment. 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 whilst undergoing treatment, as major human foetal abnormalities including hydrocephalus, microcephalus, abnormalities of the external ear, eye abnormalities, cardiovascular abnormalities, facial dysmorphia, cleft palate, thymus gland abnormality, parathyroid gland abnormalities and cerebellar malformations have been reported, along with an increased incidence of spontaneous abortion. An effective form of contraception should be used for at least one month before and throughout isotretinoin therapy, and it is recommended that contraception be continued for one month following discontinuation of isotretinoin therapy. Post-marketing reports have described severe skin reactions including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis associated with isotretinoin therapy, which may be serious and result in death, life-threatening events, hospitalisation or disability, and patients should be monitored closely for severe skin reactions. Isotretinoin use has been associated with benign intracranial hypertension, with early signs and symptoms including 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; 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. Isotretinoin causes elevation of serum triglycerides and cholesterol and a decrease in high-density lipoprotein; at doses greater than 1 mg/kg/day, approximately one in four patients develop elevated triglycerides; acute pancreatitis, which is potentially fatal, sometimes associated with serum triglycerides levels greater than 8 g/L, has been reported, and isotretinoin should be discontinued if uncontrolled hypertriglyceridaemia or symptoms of pancreatitis occur.

Contraindications

Isotretinoin must not be used by females who are pregnant or who may possibly become pregnant whilst 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 contraindicated due to reports of benign intracranial hypertension.

Regulatory history

APO-Isotretinoin received initial approval on 28 November 2002. ISOTRETINOIN Gx variants (10 mg and 20 mg capsules) were first listed on the ARTG on 27 July 2016, and ISOTRETINOIN LUPIN variants (10 mg and 20 mg capsules) were first listed on 2 December 2019.