Cosmin Gel## (null smpc)

Severe Recalcitrant Nodular Acne Isotretinoin capsules are indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. "Severe," by definition, 2 means "many" as opposed to "few or several" nodules. Because of significant adverse effects associated with its use, isotretinoin capsules should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. …

• Isotretinoin capsules should be administered with a meal (see PRECAUTIONS: Information for Patients )
• The recommended dosage range for isotretinoin capsules are 0.5 to 1 mg/kg/day given in two divided doses with food for 15 to 20 weeks
• In studies comparing 0.1, 0.5, and 1 mg/kg/day 8 , it was found that all dosages provided initial clearing of disease, but there was a greater need for retreatment with the lower dosages
• During treatment, the dose may be adjusted according to response of the disease and/or the appearance of clinical side effects – some of which may be dose related
• Adult patients whose disease is very severe with scarring or is primarily manifested on the trunk may require dose adjustments up to 2 mg/kg/day, as tolerated
• Failure to take isotretinoin capsules with food will significantly decrease absorption
• Before upward dose adjustments are made, the patients should be questioned about their compliance with food instructions
• The safety of once daily dosing with isotretinoin capsules have not been established
• Once daily dosing is not recommended
• If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, the drug may be discontinued
• After a period of 2 months or more off therapy, and if warranted by persistent or recurring severe nodular acne, a second course of therapy may be initiated
• The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth
• Long-term use of isotretinoin capsules, even in low doses, has not been studied, and is not recommended. …

• The use of isotretinoin capsules
• Pediatric patients less than 12 years of age has not been studied
• The use of isotretinoin capsules
• For the treatment of severe recalcitrant nodular acne
• Pediatric patients ages 12 to 17 years should be given careful consideration, especially for those patients where a known metabolic or structural bone disease exists (see PRECAUTIONS: General ). …

Clinical studies of isotretinoin did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Although reported clinical experience has not identified differences in responses between elderly and younger patients, effects of aging might be expected to increase some risks associated with isotretinoin therapy (see WARNINGS and PRECAUTIONS ).

• See PRECAUTIONS and Boxed CONTRAINDICATIONS AND WARNINGS
• Patients must be instructed to read the Medication Guide supplied as required by law when isotretinoin capsules are dispensed
• The complete text of the Medication Guide is reprinted at the end of this document
• For additional information, patients must also be instructed to read the iPLEDGE REMS patient educational materials
• All patients must sign the Patient Enrollment Form for Patients who cannot get Pregnant. …

• Pregnancy Category X See Boxed CONTRAINDICATIONS AND WARNINGS
• Allergic Reactions Isotretinoin capsules are contraindicated in patients who are hypersensitive to this medication or to any of its components (see PRECAUTIONS: Hypersensitivity )

Vitamin A: Because of the relationship of isotretinoin capsules to vitamin A, patients should be advised against taking vitamin supplements containing vitamin A to avoid additive toxic effects. Tetracyclines: Concomitant treatment with isotretinoin capsules and tetracyclines should be avoided because isotretinoin capsules use has been associated with a number of cases of pseudotumor cerebri (benign intracranial hypertension), some of which involved concomitant use of tetracyclines. Micro-dosed Progesterone Preparations: Micro-dosed progesterone preparations ("minipills" that do not contain an estrogen) may be an inadequate method of contraception during isotretinoin capsules therapy. …

Psychiatric Disorders Isotretinoin capsules may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors. No mechanism of action has been established for these events (see ADVERSE REACTIONS: Psychiatric ). Prescribers should read the brochure, Recognizing Psychiatric Disorders in Adolescents and Young Adults: A Guide for Prescribers of Isotretinoin. Prescribers should be alert to the warning signs of psychiatric disorders to guide patients to receive the help they need. …

Clinical Trials and Postmarketing Surveillance The adverse reactions listed below reflect the experience from investigational studies of isotretinoin , and the postmarketing experience. The relationship of some of these events to isotretinoin therapy is unknown. Many of the side effects and adverse reactions seen in patients receiving isotretinoin are similar to those described in patients taking very high doses of vitamin A (dryness of the skin and mucous membranes, e.g. of the lips, nasal passage, and eyes). Dose Relationship Cheilitis and hypertriglyceridemia are usually dose related. …

Pregnancy Category X See Boxed CONTRAINDICATIONS AND WARNINGS . Pregnancy Category X See Boxed CONTRAINDICATIONS AND WARNINGS .

The oral LD 50 of isotretinoin is greater than 4000 mg/kg in rats and mice (>600 times the recommended clinical dose of 1 mg/kg/day after normalization of the rat dose for total body surface area and >300 times the recommended clinical dose of 1 mg/kg/day after normalization of the mouse dose for total body surface area) and is approximately 1960 mg/kg in rabbits (653 times the recommended clinical dose of 1 mg/kg/day after normalization for total body surface area). …

Storage Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]. Protect from light.

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.