Neotigazone - instructions for use, dose, side effects, contraindications

Active substanceAcitretinAcitretin

Similar drugsTo uncover

Neotigazon®

capsules inwards

Actavis PTS ehf Group Iceland

Dosage form: & nbspcapsules

Composition:

1 capsule 10 mg contains: active substance: Acitretin 10 mg (as a dry spray containing 25% active substance);

auxiliary substance: microcrystalline cellulose 50 mg.

1 capsule 25 mg contains: active substance: Acitretin 25 mg (as a dry spray containing 25 % active substance);

auxiliary substance: microcrystalline cellulose 125 mg.

The composition of the dry spray (per 1 g): acitretin 250 mg, gelatin 270 mg, maltodextrin 410 mg, sodium ascorbate 70 mg.

Description:

Capsules 10 mg: gelatin capsules number 4, body - white or slightly yellowish color, opaque; lid - brown, opaque; with an inscription of black color "10" on the case, with the inscription of black "actavis" on the lid. Content capsules - powder with compacted pieces from pale yellow to yellow.

Capsules 25 mg: gelatin capsules number 1, body - yellow, opaque; lid - brown, opaque; with the inscription black "25" on the case, with an inscription of black color "actavis"on the lid.

The contents of the capsules are powder with compacted pieces from pale yellow to yellow.

Pharmacotherapeutic group:Reparation of tissue stimulant

ATX: & nbsp

D.05.B.B Retinoids for the treatment of psoriasis

Pharmacodynamics:

Systemic retinoid.

Acitretin, the active substance of the drug Neotigazone®, aromatic analogue of retinoic acid. In preclinical studies on the tolerability of acitretin, there was no mutagenic or carcinogenic effect; there was also no indication of its direct hepatotoxicity. Acitretin had a pronounced teratogenic effect on animals.

Clinical studies have confirmed that with psoriasis and disorders of keratinization acitretin normalizes the processes of proliferation, differentiation and keratinization of epidermal cells, and its side effects, in general, are completely tolerable. The effect of the drug is purely symptomatic; its mechanism remains largely unknown.

Pharmacokinetics:

Suction

The maximum concentrations of acitretin in the plasma are observed 1-4 hours after administration. The best bioavailability of Acitretinum is reached at reception of a preparation during meal. Bioavailability of a single dose is about 60%, but it is subject to significant individual fluctuations (36-95%).

Distribution

Acitretin has a pronounced lipophilicity and easily penetrates into the tissues.Its binding to proteins exceeds 99%. In animal studies acitretin passed through the placental barrier in quantities capable of causing malformations in the fetus. The lipophilic properties of acitretin suggest that it enters significant quantities in breast milk.

Metabolism

Acitretin is metabolized by isomerization to the 13-cis-isomer (cis-acitretin), and also by the formation of glucuronides and the cleavage of the side chain.

Excretion

Studies with repeated administration of the drug to patients aged 21 to 70 years showed that the half-life (T_1/2) Acitretin is about 50 hours, and its main metabolite in plasma, cis-acitretin, which is teratogenic, is 60 hours. Given the longest half-life of acitretin (96 hours) and cis-acitretin (123 hours) in these patients, and also based on their linear kinetics, it can be predicted that more than 99% of the drug will be excreted within 36 days after discontinuation of long-term treatment. Moreover, within 36 days after cessation of treatment, the concentrations of acitretin and cis-acitretin in the plasma decreased below the sensitivity limit of the method (<6 ng / ml). Acitretin is excreted exclusively in the form of metabolites, approximately in equal amounts through the kidneys and bile ducts.

Indications:

Heavy forms of psoriasis, including, psoriatic erythroderma, localized or generalized pustular psoriasis.

Heavy dyskeratosis, such as congenital ichthyosis; red hair follicle; Darya's disease; other severe disorders of keratinization, resistant to traditional therapies.

Contraindications:

Hypersensitivity to the active or auxiliary substances of the drug, hypersensitivity to other retinoids;

severe hepatic impairment;

severe renal insufficiency;

severe chronic hyperlipidemia;

simultaneous administration with tetracyclines, methotrexate, vitamin A and other retinoids;

patients with glucose-galactose malabsorption;

the period of breastfeeding.

Neotigazone has a strong teratogenic effect and should not be given to pregnant women. The same applies to all women capable of giving birth, unless they use reliable contraceptives four weeks before the start of treatment, during treatment and for two years after it is completed (see below).

Pregnancy and lactation:

Pregnancy

Neotigazone is highly malignant. It is contraindicated in women who are able to become pregnant during treatment or within 2 years after discontinuation of treatment. The risk of having a child with congenital malformations is especially high if Neotigazone is taken before or during pregnancy, regardless of the dose and duration of therapy. Neotigazone is contraindicated in any woman capable of procreation, if at least one of the following conditions is not met:

1. The patient suffers from severe keratinization disorder, resistant to standard types of treatment.

2. You can be sure that the patient understands and complies with the doctor's instructions.

3. The patient is capable of using contraceptive means without any omission without a permit.

4. It is absolutely necessary that each woman fertility using effective contraceptive methods (preferably two contraceptive method simultaneously) without interruption within 4 weeks before treatment, during treatment and for two years after completion of treatment neotigazon. The main method of contraception is the use of a combined oral contraceptive orintrauterine contraceptives, the use of a condom or diaphragm (cap) is also recommended. It is not recommended to use low-dose progesterone monopreparations (minipilli) in view of a possible weakening of their contraceptive effect.

The patient should be instructed that if she is suspected of having a pregnancy, she should immediately consult a doctor.

5. Treatment should not begin before the 2nd or 3rd day of the next full-fledged menstrual cycle.

6. Three days before the start of treatment, a negative result of the pregnancy test should be obtained (the minimum sensitivity of the test is 25 mIU / ml). During treatment it is recommended to conduct a pregnancy test every 28 days. During these examinations, before the re-appointment of the drug should be given a negative result for pregnancy, which must be made no earlier than 3 days before the prescription at the next visit of the doctor. After discontinuation of treatment, the pregnancy test should be performed for 2 years at intervals of 1-3 months.

7. Before starting treatment with Neotigazone, the doctor should inform women in detail,the necessary precautions, the risk of developing very serious malformations of the fetus and the possible consequences of pregnancy during treatment with Neotigazone or within 2 years after its termination.

8. The same effective contraceptive measures should be continuously applied every time the course of treatment is repeated, regardless of its duration, and be followed for two years after the end of the course.

9. If, despite all the precautions, during pregnancy with Neotigazone or within two years after the end of pregnancy, there is a high risk of severe fetal malformations (for example, a hernia of the brain, malformations of the heart, vessels, central nervous system, skeleton and thymus), and the risk of spontaneous abortion increases. This risk is increased especially during treatment with acitretin and within 2 months after discontinuation of treatment. In 2 years after the end of treatment, this risk decreases (especially in those women who did not take alcohol during treatment), but it can not be ruled out completely (due to the possible formation of etretinate).

10. A woman should avoid drinking alcohol during treatment and within two months after the end of taking the drug.

Breastfeeding period

Neotigazone can not be prescribed to nursing women.

Dosing and Administration:

Because of individual differences in absorption and metabolic rate of acitretin, the dose should be selected individually. Capsules should be taken once a day during meals or with milk. The following are guidelines.

Adults

Initial daily dose 25 mg (ie 1 capsule of 25 mg) or 30 mg per day (ie 3 capsules of 10 mg) for 2-4 weeks can have a sufficient therapeutic effect.

Maintenance dose depends on the clinical efficacy and tolerability of the drug. Typically, the optimal therapeutic effect is achieved with a daily dose of 25-50 mg, taken for another 6-8 weeks. In some cases, it may be necessary to increase the dose to a maximum of 75 mg / day (ie 3 capsules of 25 mg).

After sufficient regression of psoriatic lesions, the treatment of patients psoriasis can be stopped. Relapses are treated as indicated above.

When dyskeratoses usually maintenance therapy is required, which is carried out as little as possible in doses. They can be below 20 mg per day and should not exceed 50 mg per day.

Children

Given the potential for serious side effects, long-term treatment should carefully compare the possible risk with the expected therapeutic effect. Acitretin It is necessary to appoint or nominate only at an inefficiency of all other methods of treatment. The daily dose depends on the body weight and is about 0.5 mg / kg. In some cases, higher doses may be required for a limited time, up to 1 mg / kg per day (not more than 35 mg / day). The maintenance dose should be as low as possible, taking into account possible adverse reactions during long-term treatment.

Combination Therapy

If Neotigazone is used in combination with other types of treatment, it is possible to reduce its dose depending on the individual reaction of the patient.

In the treatment with Neotigazone, conventional external treatment can be continued; it does not affect the effect of the Neotigazon.

Side effects:

Adverse reactions are noted in the majority of patients taking Neotigazone. However, they usually disappear after a dose reduction or drug withdrawal.Sometimes at the beginning of treatment there is an exacerbation of the symptoms of the disease.

The most frequent adverse reactions are symptoms of hypervitaminosis A, for example, dry lips, which can be removed with the use of a fatty cream.

The frequency of adverse reactions with acitretin is distributed as follows: very often (> 10%); often (> 1% and <10%); infrequently (> 0.1% and <1%); rarely (> 0.01% and <0.1%); very rarely (<0.01%), the frequency is unknown (can not be established based on available data).

Infectious and parasitic diseases: frequency unknown - vulvovaginitis caused by Candida albicans.

From the immune system: the frequency is unknown - hypersensitivity.

From the nervous system: often - headache; infrequently - dizziness; rarely - peripheral neuropathy; very rarely - increased intracranial pressure.

On the part of the organ of vision: very often - dryness and mucosal inflammation (e.g., conjunctivitis, xerophthalmia), which may lead to intolerance of contact lenses; infrequent - reduced vision; very rarely - hemorrhagia (night blindness), corneal ulcers.

From the side of the hearing organ and labyrinthine disorders: the frequency is unknown - hearing impairment, tinnitus.

From the side of the vessels: the frequency is unknown - the "tides" of blood to the face.

On the part of the respiratory system, chest and mediastinal organs: very often - dryness and inflammation of the mucous membrane (eg, epistaxis, rhinitis).

From the gastrointestinal tract: very often - dryness of the oral mucosa, thirst; often - stomatitis, abdominal pain, diarrhea, nausea, vomiting; infrequently - gingivitis; frequency is unknown - a violation of taste sensations, rectal bleeding.

From the liver and biliary tract: infrequently - hepatitis; very rarely - jaundice.

From the skin and subcutaneous tissues: very often - cheilitis, itching, alopecia, scaling of the skin throughout the body, especially on the palms and soles; often - fragility of the skin, sticky skin, dermatitis, changes in hair structure, fragility of nails, paronychia, erythema; infrequent - cracks in the skin, bullous dermatitis, photosensitivity reactions; frequency unknown - pyogenic granuloma, madarose, angioedema, urticaria.

From the osteomuscular and connective tissue: often - arthralgia, myalgia; very rarely - bone pain, hyperostosis (supportive therapy can lead to an increase in the existing hyperostosis of the spine, the emergence of new hyperostosis and calcification of soft tissues, as observed with prolonged systemic use and other retinoids).

General disorders and disorders at the injection site: often - peripheral edema.

Laboratory and instrumental data: very often a reversible increase in the activity of aminotransferases and alkaline phosphatase, a reversible increase in serum triglycerides and cholesterol, especially in high-risk patients (see section Special instructions) and long-term treatment. If these disorders persist, an increased risk of atherogenesis can not be ruled out.

Childhood

After long-term treatment with etretinate, there were reports of changes in bone tissue in children, including premature closure of the epiphyses, hyperostosis of the skeleton, and extra-ocular calcification. The appearance of these phenomena can be expected in the treatment of acitretin.

Diabetes

Retinoids can alter (improve or worsen) glucose tolerance.

Overdose:

In case of acute overdose, Neopthygasone should be immediately discontinued. No other special measures are required, since the acute toxicity of the drug is low. Symptoms of overdose are identical to those in acute hypervitaminosis A (headache, dizziness, nausea, vomiting, drowsiness, irritability, skin itching).

Interaction:

Because of the risk of hypervitaminosis A, simultaneous use of vitamin A and other retinoids should be avoided.

Since both Neotigazone and tetracyclines can cause an increase in intracranial pressure, their simultaneous use is contraindicated.

There are reports of an increased risk of hepatitis in the combined use of methotrexate and tigason (etretinate), so the appointment of methotrexate concomitantly with Neotigazone is also contraindicated.

Neotigazone does not affect the binding of anticoagulants coumarin series (warfarin) with proteins.

If Neotigazone is prescribed concomitantly with phenytoin, it should be noted that Neotigazone partially reduces the degree of binding of phenytoin to proteins.

Low-dose monotherapy progesterone (minipilli) may not be a reliable contraceptive during therapy with acitretin.

Other interactions between Neotigazone and other drugs (eg, digoxin, cimetidine, combined estrogen / progestogen oral contraceptives) have not been found to date.

In a study in healthy volunteers, a single dose of acitretin together with ethyl alcohol led to the formation of etretinate (previously it was found in vitro). In recent studies, some patients who took Neotigazone, the formation of etretinate was also found. Until this phenomenon is fully explained, it is necessary to take into account the pharmacokinetic features of etretinate: since the half-life period is approximately 120 days, contraceptive means should be used within two years after the end of treatment.

Special instructions:

Neotigazone can be prescribed only by physicians with experience in using systemic retinoids and understanding the risk of teratogenic effects of acitretin.

The physician must provide all patients, both men and women, with complete information about the teratogenic effect of Neotigazone and measures to prevent pregnancy.

Women of childbearing age during treatment with Neotigazone and within 2 months after cessation of treatment should not consume alcohol, as well as alcohol-containing beverages, foods and medicines, as there are clinical data that while concomitant administration of acitretin and alcohol in the body can form etretinate.Etretat is highly teratogenic and has a longer T1 / 2 (approximately 120 hours) compared with acitretin. Pregnancy and pregnancy testing should be performed within 2 years after the end of treatment with Neotigazone (see Application during pregnancy and during breastfeeding).

Women of childbearing age can not receive blood from patients who receive Neotigazone. Therefore, during treatment with Neotigazone and for two years after its completion, blood donation is prohibited.

Because of the risk of developing congenital fetal pathologies, the drug should not be given to other patients. Unused or overdue medication should be disposed of in accordance with current legislation.

It is necessary to monitor liver function before starting treatment with Neotigazone, every 1 to 2 weeks during the first two months after the start of treatment, and then every 3 months. If the results of the tests indicate a pathology, the control should be carried out weekly. If the liver function does not normalize or worsen further, the Neotigazone should be canceled.In this case it is recommended to continue to monitor liver function for at least 3 more months.

It is necessary to monitor the level of cholesterol and triglycerides of fasting serum, especially in patients at risk (lipid metabolism disorders, diabetes mellitus, obesity, alcoholism) before the start of treatment, within a month after the start of treatment, and then every 3 months.

Care must be taken to monitor for visual impairment.

In rare cases, benign intracranial hypertension was reported. When severe headaches, nausea, vomiting and visual disturbances appear, Nyotigazon should be immediately discontinued, and the patient should be referred to a neurologist.

Adults, especially elderly patients receiving prolonged therapy with Neotigazone, should be regularly inspected, taking into account the possibility of anomalies of ossification (see section Side effects). In the event of these complications, the course of subsequent treatment should be discussed with the patient on the basis of a thorough assessment of the relationship between benefit and risk.

Children need to carefully monitor the parameters of growth and development of bones. Currently, not all the effects of Neotigazone, which can occur throughout life with prolonged use of the drug Neotigazone, are known.

The influence of ultraviolet (UV) radiation on the body is enhanced when taking retinoids. Patients should avoid excessive exposure to sunlight and limit the use of UV lamps (eg, procedures in the solarium).

If necessary, use sunscreens with a high protection factor (not less than SPF 15). Treatment with high doses of retinoids can cause a change in mood, including irritability, aggression and depression.

Patient risk groups:

In patients with diabetes mellitus, alcoholism, obesity, with the presence of risk factors from the cardiovascular system or lipid metabolism disorders taking Neotigazone, it is necessary to more often monitor the level of cholesterol and / or glucose concentration or observe the symptoms indicating the possible development of complications from the cardiovascular system (for example, to measure blood pressure).

In patients with diabetes mellitus retinoids can improve or worsen glucose tolerance, so in the early stages of treatment, the concentration of glucose in the blood should be checked more often than usual.

For all patients at risk, in whom the observed complications of the cardiovascular system do not normalize or worsen further, the dose of Neotigazone should be reduced or a decision should be made to abolish it.

The preparation contains maltodextrin, which includes glucose, so Neotigazone should not be used in patients with a rare hereditary disease - glucose-galactose malabsorption.

Based on available data on the extent to which birth defects are affected by the fertilization of semen and semen by male patients taking acitretin, we can conclude that there is a minimal risk of teratogenic effects.

Effect on the ability to drive transp. cf. and fur:

Due to the possibility of visual impairment in low light conditions, at dusk and at night, patients should be warned about this fact and about the need to be cautious when driving a car or working with cars and mechanisms in the dark.

Form release / dosage:

Capsules 10 mg or 25 mg.

Packaging:

For 5 or 10 capsules per blister PVC / Al / PVDC.For 6, 10 or 20 blisters for 5 capsules or 3, 5 or 10 blisters for 10 capsules with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C, in a place protected from light and moisture.

Keep out of the reach of children!

Shelf life:

3 years. The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N016163 / 01

Date of registration:23.08.2010

The owner of the registration certificate:Actavis PTS ehf GroupActavis PTS ehf Group Iceland

Manufacturer: & nbsp

PATHEON, Inc. Canada

Representation: & nbspAktavis, Open Company Aktavis, Open Company

Information update date: & nbsp04.10.2013

Illustrated instructions

Instructions

Neotigazon® (Neotigason®)