ROAKKUTAN

Active material: Isotretinoin
When ATH: D10BA01
CCF: Drug for the treatment of acne. Retinoid
When CSF: 29.12.02
Manufacturer: F.Hoffmann-La Roche Ltd. (Switzerland)

Pharmaceutical form, composition and packaging

Capsules reddish-purple (light purple) colors, opaque, Oval, inscribed on the surface of black ink “LENGTH 10”; contents of capsules – uniform suspension from yellow to dark yellow.

Excipients: soybean oil, beeswax yellow, Hydrogenated soybean oil, Soybean oil is partially hydrogenated.

The composition of the shell: gelatin, glycerol, Carrion 83 (potato starch digested, mannitol, sorbitol), canthaxanthin, Titanium dioxide.

Structure Ink: shellac, dye iron oxide black.

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Capsules one half reddish purple (lilac) colors, the other half is white, opaque, Oval, inscribed on the surface of black ink “LONG 20”; contents of capsules – uniform suspension from yellow to dark yellow.

Excipients: soybean oil, beeswax yellow, Hydrogenated soybean oil, Soybean oil is partially hydrogenated.

The composition of the shell: gelatin, glycerol, Carrion 83 (potato starch digested, mannitol, sorbitol), canthaxanthin, Titanium dioxide.

Structure Ink: shellac, dye iron oxide black.

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Pharmacological action

Isotretinoin, active substance Roaccutane, – stereoisomer of all-trans retinoic acid (tretinoin).

The exact mechanism of action has not been elucidated Roaccutane, however found, that the improvement of the clinical picture of severe acne is associated with a dose-dependent suppression of the activity of the sebaceous glands and histologically confirmed decrease in their size. Besides, proven anti-inflammatory effect of isotretinoin on the skin.

Pharmacokinetics

The dynamics of drug concentrations in blood can be predicted based on a linear model of pharmacokinetics.

Absorption

In healthy volunteers and in patients with cystic acne is the maximum plasma concentration (Cmax) after administration 80-100 mg isotretinoin were about 250 ng / ml and is reached through 1-4 o'clock.

Isotretinoin with food increases the bioavailability 2 times compared to the fasted, probably, resulting in improved absorption of the compound, having a high lipophilicity. Furthermore, Isotretinoin during the meal is accompanied by a, generally, decrease vibrations systemic bioavailability.

Distribution

Isotretinoin is highly bound to plasma proteins (99.9%), so that a wide range of therapeutic concentrations content of free (pharmacologically active) fraction of the drug is less than 0.1% its overall amount. The main binding protein is, apparently, albumin.

The volume of distribution of isotretinoin in man is unknown, as dosage forms for intravenous administration, there are no.

Isotretinoin passes through the placental barrier in quantities, that cause congenital malformations of the fetus. Lipophilicity isotretinoin causes high probability, it passes into breast milk.

Metabolism

The major metabolite of isotretinoin is 4-oxo-isotretinoin, which quickly formed after oral administration. Besides, Isotretinoin is metabolized in vivo and in an alternate path to form tretinoin (all-trans-retinoic acid). Convincing data glucuronidation metabolite in humans is not, However, its highly likely suggest animal studies. Research, conducted in humans and in dogs, suggest enterohepatic circulation of isotretinoin, which may play a role in individual differences in plasma concentrations of the drug.

Deduction

Apparently, Isotretinoin is derived almost exclusively by hepatic metabolism and biliary excretion. In healthy volunteers and patients with cystic acne half-life of the unmodified form of the drug after oral administration is, average, 20 hours (7 – 39 hours).

The average half-life of 4-oksoizotretinoina in patients with cystic acne longer more – average, 25 hours (from 17 to 50 hours).

Pharmacokinetics in special clinical situations

Since isotretinoin is contraindicated in violation of the liver or kidneys, data on the pharmacokinetics of the drug in this group of patients is not available.

Testimony

• severe nodular or cystic acne;
• acne, defy conducted prior therapy, in particular, kistoznыe and konglobatnыe acne, especially on body.

Dosage regimen

The initial dose – 0.5 mg / kg per day. Often at the beginning of the treatment observed transient exacerbation of acne. The efficacy and side effects of isotretinoin are different in different patients, so after about 4 weeks of therapy is necessary to individually correct maintenance dose in the range of 0.1 to 1.0 mg / kg per day. The highest daily dose (1 mg / kg) It should be used only for a limited time. Usually, treatment continues 16 weeks. Assessing the results, it should be remembered, which often continues to improve after the drug. Therefore, before the re-appointment of the course should take a break of at least 8 weeks. Repeated treatment is carried out in accordance with the above recommendations.

Capsules are taken with food, small doses- once a day, higher doses – in one or more steps day.

At the same time conducted external treatment

Co-administration of other drugs for the treatment of acne, having keratolytic or exfoliative action, as well as UV-therapy, not shown. Patients should avoid sun exposure. If necessary, you can assign external anti-acne preparations mild.

Side effect

Most side effects of Roaccutane are dose dependent. Usually, the appointment of the recommended doses of the risks and benefits, taking into account the severity of the disease, acceptable to the patient.

Symptoms, associated with hypervitaminosis A: often – xerosis, mucosal lip, nasal (bleeding), hypopharynx (hoarseness), eye (conjunctivitis, reversible corneal opacities and intolerance to contact lenses).

The skin and its appendages: rash, itch, facial dermatitis, Sweating, pyogenic granuloma, paronixii, onihodistrofii, increased proliferation of granulation tissue, persistent hair thinning, reversible hair loss, fulminant forms of acne, girsutizm, giperpigmentatsiya, photosensitivity.

Musculo-skeletal system: muscle aches, joint pain, hyperostosis and other bone changes, tendinitы. One patient described the development of the spine hyperostosis and calcification of ligaments, followed by vertebral compression of the spinal cord at long (for several years) treatment of other drugs of retinoids – Tigasonom (эtretinatom). Roaccutane is not designed for prolonged use; but keep in mind about the likelihood of this side effect if improperly (too long) use of the drug.

Central nervous system and mental health: behavioral disturbances, depression, headache, intracranial hypertension, seizures.

Senses: individual cases of violations of visual acuity, hearing loss in a certain range of sound waves, photophobia, violation of dark adaptation (alleviation of twilight), Cataract, keratit.

Gastrointestinal tract: nausea, inflammatory bowel disease (colitis, ileitis), bleeding; transient and reversible elevation of transaminases, individual cases of hepatitis. In many cases, these changes do not go beyond the limits of normal and returned to baseline parameters during treatment, However, in some situations, there was a need to reduce the dose or cancel Roaccutane.

Respiratory: bronchospasm.

Blood System: reduction in the number of leukocytes and erythrocytes, increase or decrease the number of platelets, ESR acceleration.

Laboratory changes: hypertriglyceridemia, hypercholesterolemia, hyperuricemia; individual cases lowering HDL, especially in the appointment of the drug in the high dose patients predisposed (with a family history, burdened by disorders of fat metabolism, saxarnomu diaʙetu, obesity or alcoholism). These changes are also in a dose-dependent and normalized after dose reduction or discontinuation of therapy.

The immune system: local or systemic infection, caused by Gram-positive pathogens (Staphylococcus aureus).

Other: lymphadenopathy, hematuria, proteinuria, pancreatitis (particularly high risk patients with hypertriglyceridemia > 800 mg), vasculitis (granulematoz Wegener).

Contraindications

• pregnancy (cm. further),
• liver and kidney failure,
• hypervitaminosis A,
• marked hyperlipidemia and increased sensitivity to the drug.

Pregnancy and lactation

The drug is contraindicated.

Cautions

Roaccutane should appoint a doctor, predpočtitelʹno dermatologists, with experience in the use of systemic retinoids and knowledgeable about the risk of teratogenicity using Roaccutane during pregnancy.

It is recommended to monitor liver function before treatment, through 1 a month after it began, and then every 3 of the month. It should also determine the level of fasting serum lipid (before treatment, through 1 month after the start and at the end of 3-4 months of treatment).

In rare cases, patients, treated with Roaccutane, describes depression, psychotic symptoms and suicide attempts. Although their causal relationship to the use of the drug has not been established, Special care is needed in patients with a history of depression and watch all the patients on the subject of depression in the course of treatment, if necessary, direct them to the appropriate specialist.

Because of the possibility of bone changes prescribe Roaccutane should be only in severe forms of the disease, carefully evaluating the ratio of potential benefits and risks and restricting use of the drug only severe cases.

Overdose

In case of overdose may be signs of hypervitaminosis A. In the first few hours of the overdose may require gastric lavage.

Drug Interactions

Because of the possible increase in symptoms of hypervitaminosis A Avoid co-administration of Roaccutane and vitamin A. As tetracyclines may also cause increased intracranial pressure, their use in combination with Roaccutane is contraindicated.

Isotretinoin can weaken the effectiveness of progesterone micropyles, so you should not use contraceptives, containing small doses of progesterone

Conditions and terms

Keep out of reach of children at a temperature of 25 ° C. Storage life – 5 years.