Brand name: Isotret Hexal
Active ingredient (generic name): Isotretinoin
Manufacturer: Hexal
Importer: Behestan Darou
Pharmacotherapeutic group: anti-acne
Pharmaceutical form: 20mg Capsules
The exact mechanism of action of isotretinoin has not yet been elucidated in detail, but it has been established that the improvement observed in the clinical picture of severe acne is associated with suppression of sebaceous gland activity and a histologically demonstrated reduction in the size of the sebaceous glands. Furthermore, a dermal anti-inflammatory effect of isotretinoin has been established.
Hypercornification of the epithelial lining of the pilosebaceous unit leads to shedding of corneocytes into the duct and blockage by keratin and excess sebum. This is followed by formation of a comedone and, eventually, inflammatory lesions. Isotretinoin inhibits proliferation of sebocytes and appears to act in acne by re-setting the orderly program of differentiation. Sebum is a major substrate for the growth of Propionibacterium acnes so that reduced sebum production inhibits bacterial colonisation of the duct.
Pharmacokinetic:
The absorption of isotretinoin from the gastro-intestinal tract is variable and dose-linear over the therapeutic range.
In humans little information is available on the distribution of isotretinoin into tissue.
The major metabolite is 4-oxo-isotretinoin with plasma concentrations at steady state that are 2.5 times higher than those of the parent compound.
After oral administration of radiolabelled isotretinoin approximately equal fractions of the dose were recovered in urine and faeces. Following oral administration of isotretinoin, the terminal elimination half-life of unchanged drug in patients with acne has a mean value of 19 hours. The terminal elimination half-life of 4-oxo-isotretinoin is longer, with a mean value of 29 hours.
Therapeutic indication:
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Isotretinoin capsules are indicated for the treatment of severe forms of acne (such as nodular or conglobate acne or acne at risk of permanent scarring), resistant to adequate courses of standard therapy with systemic antibacterials and topical therapy. |
Dosage and administration:
The capsules should be taken with food once or twice daily.
Isotretinoin therapy should be started at a dose of 0.5 mg/kg daily. The therapeutic response to isotretinoin and some of the adverse effects are dose-related and vary between patients. This necessitates individual dosage adjustment during therapy. For most patients, the dose ranges from 0.5-1.0 mg/kg per day.
Long-term remission and relapse rates are more closely related to the total dose administered than to either duration of treatment or daily dose. It has been shown that no substantial additional benefit is to be expected beyond a cumulative treatment dose of 120-150 mg/kg. The duration of treatment will depend on the individual daily dose. A treatment course of 8-12 weeks is normally sufficient to achieve remission.
In the majority of patients, complete clearing of the acne is obtained with a single treatment course. In the event of a definite relapse a further course of isotretinoin therapy may be considered using the same daily dose and cumulative treatment dose. As further improvement of the acne can be observed up to 8 weeks after discontinuation of treatment, a further course of treatment should not be considered until at least this period has elapsed.
Adverse reaction:
The following symptoms are the most commonly reported undesirable effects with isotretinoin:
Gram positive (mucocutaneous) bacterial infection, anemia, red blood cell sedimentation rate increased, Thrombocytopenia, neutropenia, allergic skin reaction, anaphylactic reactions, hypersensitivity, suicidal ideation, Lymphadenopathy, diabetes mellitus, depression, headache, blurred vision, cataract, Color blindness, colitis, Ileitis, dry throat, gastrointestinal hemorrhage, hemorrhagic diarrhea and inflammatory bowel disease, Nausea, Pancreatitis
Contraindication:
Isotretinoin is contraindicated in women who are pregnant or breastfeeding.
Isotretinoin is contraindicated in women of childbearing potential unless all of the conditions of the Pregnancy Prevention Program are met.
Isotretinoin is also contraindicated in patients with hepatic insufficiency and excessively elevated blood lipid values.
Pharmacokinetic interactions:
Cases of benign intracranial hypertension (pseudotumor cerebri) have been reported with concomitant use of isotretinoin and tetracyclines. Therefore, concomitant treatment with tetracyclines must be avoided
Special warnings:
Isotretinoin is contraindicated in women of childbearing potential.
Female patients must be provided with comprehensive information on pregnancy prevention and should be referred for contraceptive advice if they are not using effective contraception.
Male patients
The available data suggests that the level of maternal exposure from the semen of the patients receiving isotretinoin is not of sufficient magnitude to be associated with the teratogenic effects of isotretinoin.
Male patients should be reminded that they must not share their medication with anyone, particularly not females.
Additional precautions
Patients should be instructed never to give this medicinal product to another person and to return any unused capsules to their pharmacist at the end of treatment.
Patients should not donate blood during therapy and for 1 month following discontinuation of isotretinoin because of the potential risk to the foetus of a pregnant transfusion recipient.
Educational material
In order to assist prescribers, pharmacists and patients in avoiding foetal exposure to isotretinoin the Marketing Authorisation Holder will provide educational material to reinforce the warnings about the teratogenicity of isotretinoin, to provide advice on contraception before therapy is started and to provide guidance on the need for pregnancy testing.
Full patient information about the teratogenic risk and the strict pregnancy prevention measures as specified in the Pregnancy Prevention Programme should be given by the physician to all patients, both male and female.
Psychiatric disorders
Depression, depression aggravated, aggressive tendencies, mood alterations, psychotic symptoms and, very rarely, suicidal ideation, suicide attempts and suicide have been reported in patients treated with isotretinoin.
Skin and subcutaneous tissues disorders
Acute exacerbation of acne is occasionally seen during the initial period but this subsides with continued treatment, usually within 7-10 days, and usually does not require dose adjustment.
Eye disorders
Dry eyes, corneal opacities, decreased night vision and keratitis usually resolve after discontinuation of therapy. Dry eyes can be helped by the application of a lubricating eye ointment or by the application of tear replacement therapy. Intolerance to contact lenses may occur which may necessitate the patient to wear glasses during treatment.
Hepatobiliary disorders
Liver enzymes should be checked before treatment, 1 month after the start of treatment, and
Lipid Metabolism
Serum lipids (fasting values) should be checked before treatment, 1 month after the start of treatment, and subsequently at 3 monthly intervals unless more frequent monitoring is clinically indicated.
Gastrointestinal disorders
Isotretinoin has been associated with inflammatory bowel disease (inlcuding regional ileitis) in patients without a prior history of intestinal disorders.
High Risk Patients
In patients with diabetes, obesity, alcoholism or a lipid metabolism disorder undergoing treatment with isotretinoin, more frequent checks of serum values for lipids and/or blood glucose may be necessary. Elevated fasting blood sugars have been reported, and new cases of diabetes have been diagnosed during isotretinoin therapy.
Pregnancy and lactation:
Pregnancy is an absolute contraindication to treatment with isotretinoin .If pregnancy does during treatment with isotretinoin or in the month following, there is a great risk of very severe and serious malformation of the foetus.
Isotretinoin is highly lipophilic, therefore the passage of isotretinoin into human milk is very likely. Due to the potential for adverse effects in the mother and exposed child, the use of isotretinoin is contraindicated in nursing mothers.
Storage temperature:
Room temperature (15-25 C)
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