Lefno 30s ™ 20 mg coated tablets

The instruction for medical use

of medicine



LefnoTM





A trade name

LefnoTM



Mezhdunarodnoye the unlicensed





name Leflunomid Lekarstvennaya

the Tablet form, coated 10 mg or 20 mg



Structure

One tablet contains

active agent - leflunomid 10 mg or 20 mg,

excipients: starlak, K-30 povidone, sodium of a kroskarmelloz, sodium lauryl sulfate, silicon dioxide colloidal anhydrous, talc, structure of a cover: kollikoat IR white.



Description

Round (10 mg) or oval (20 mg) biconvex tablets of white color, coated.



Pharmacotherapeutic group

of Immunodepressanta selection.

The code of automatic telephone exchange L04A A13



the Pharmacological

Pharmacokinetics properties

LefnoTM by primary metabolism in a wall of intestines and in a liver quickly turns into an active metabolite A771 726 with which practically all activity LefnoTM is connected and which is the only defined metabolite revealed in trace quantities in blood plasma, urine, Calais.

Absorption of drug does not depend on meal and is 82 - 95%.

Cmax of a metabolite A771726 is defined within 1-24 hours after once accepted dose. In A771726 plasma quickly contacts albumine. Untied fraction A771726 makes 0.62%. Binding of an active metabolite of A771726 varies and decreases at patients with a pseudorheumatism or in chronic kidney disease a little.

Pharmacokinetic A771726 parameters have direct dependence at doses on 5 mg to 25 mg. In these researches the clinical effect is closely connected with plasma concentration of A771726 and a daily dose of a leflunomid. At a dose of 20 mg/days average Css A771726 made 35 mkg/ml.

Leflunomid is metabolized to one main (A771726) metabolite and several minor metabolites, including 4-trifluorometilalanin. Biotransformation of a leflunomid in A771726 and the subsequent metabolism of the A771726 are controlled by several enzymes and happen in microsomal and other cellular fractions.

In plasma, urine and Calais trace quantities of a leflunomid are defined. Removal of A771726 from an organism slow, clearance makes 31 ml/h of T1/2 - about 2 weeks. It is removed equally with urine (in the form of glucuronides - derivatives of a leflunomid, and oxanic acid derivative A771 726 and with a stake in not changed look.

Pharmacodynamics

LefnoTM immunomodulatory drug of an izoksazolovy row. Renders anti-proliferative, immunomodulatory (immunosuppressive) and anti-inflammatory action. The active metabolite of a leflunomid of A771726 inhibits enzyme degidroorotat-dehydrogenase and has anti-proliferative effect on activated lymphocytes which play an important role in pathogenesis of rheumatic diseases, such as pseudorheumatism, psoriasis arthritis and also at skin manifestations of psoriasis which is to autoimmune T - cellular - the mediated disease.

Lefno reduces symptoms and slows down progressing of damage of joints at an active form of a pseudorheumatism.


Indications

- a pseudorheumatism at adults, an active phase

- psoriasis arthritis, the active



phase Route of administration and doses

Treatment begins with the saturating dose which makes 100 mg of 1 times a day within 3 days. Further the recommended maintenance dose in a pseudorheumatism makes 20 mg of 1 times a day. At bad shipping the maintenance dose is reduced to 10 mg of 1 times a day.

The recommended maintenance dose for treatment of patients with psoriasis arthritis in an active phase makes 20 mg of 1 times a day.

The therapeutic effect begins to be shown in 4 weeks from an initiation of treatment and can amplify within 4 - 6 months. As a rule, it is necessary to take the drug a long time under control of the attending physician.

Dose adjustment for patients of advanced age is not required.

Tablets follows, to swallow without chewing, washing down with enough water.



Side effects

- a headache, dizziness, an asthenia, paresthesia

- arterial hypertension insignificant

- diarrhea, nausea, vomiting, anorexia, damage of a mucous membrane

of an oral cavity (aphthous stomatitis, lip ulcers), an abdominal pain

- increase in indicators of hepatic tests of transaminases, alkaline

phosphatase, bilirubin

- a tendovaginitis

- the strengthened hair loss, eczema, xeroderma

- a leukopenia, insignificant thrombocytopenia, an eosinophilia,

a pancytopenia (perhaps, owing to anti-proliferative effect

of drug), anemia

Seldom

- an agranulocytosis, a vasculitis

- abnormal liver functions in the form of hepatitis, a cholestasia, jaundice

Is very rare

- peripheral neuropathy

- interstitial pneumonia with a possible lethal outcome

- severe damages of a liver (a liver failure, sharp

gepatonekroz with a possible lethal outcome)

- pancreatitis

In some cases

- makulopapulezny rashes, a skin itching, a small tortoiseshell,

Stephens-Johnson's syndrome, a toxic epidermal necrolysis,

a polymorphic erythema

- disturbance of flavoring feelings, concern

- insignificant degrowth of a body



of the Contraindication

- hypersensitivity to a leflunomid or other components

of drug

- heavy immunodeficiency, including AIDS

- heavy abnormal liver functions

- the significant disturbances of a marrowy hemopoiesis or anemia,

a leukopenia, thrombocytopenia as a result of other reasons (except

a pseudorheumatism)

- infections of a heavy course

- a moderate or heavy renal failure, a heavy

hypoproteinemia, including at a nephrotic syndrome

- pregnancy and the period of a lactation

- women of reproductive age who do not apply reliable

contraception during treatment or after treatment provided that

the level of an active metabolite A771 726 in blood plasma is

more than 0.02 mg/l

- children's and teenage age up to 18 years

during reception LefnoTM is not recommended vaccination by live vaccines.



Medicinal interactions

Strengthening of severity of side effects is possible in cases of recent use of hepatotoxic or gematotoksichesky drugs, previous and also simultaneous with LefnoTM, and also at use of these drugs after treatment LefnoTM without the period necessary for full elimination of drug from an organism.

Use of a holestiramin or activated carbon is led to fast and considerable reduction of concentration of an active metabolite by LefnoTM. When carrying out a research of interaction between LefnoTM and a methotrexate increase in level of liver enzymes was revealed.

There are messages about increase in a prothrombin time when using LefnoTM in combination with warfarin.

Simultaneous use LefnoTM with antimalarial drugs which are used for treatment of rheumatic diseases, gold drugs, Penicillaminum, Azathioprinum and other immunosuppressive drugs is studied insufficiently.

LefnoTM with other drugs is not present data on incompatibility.

Patients who received treatment by non-steroidal anti-inflammatory drugs and/or glucocorticoids in low doses prior to treatment LefnoTM can apply them and further.



Special instructions

as a result of long elimination half-life of active component of drug side effects can arise or proceed after the reception termination LefnoTM.

Before an initiation of treatment it is necessary to make the developed general complete blood count test, including calculation of quantity of thrombocytes, especially at patients to whom therapy by immunodepressants or drugs with gematotoksichesky properties was carried out or carried out recently, patients with cases of disturbances have blood pictures in the past.

At emergence of heavy hematologic reactions (including a pancytopenia) it is necessary to stop use LefnoTM and any drugs oppressing function of marrow and to take measures for acceleration of elimination of a leflunomid from an organism.

Risk of development of side effects from bodies of a hemopoiesis considerably increases if along with reception LefnoTM potentially myelotoxic drugs are used (and also at their use up to treatment).

Before an initiation of treatment LefnoTM and also every month within the first 6 months of treatment and each 8 weeks further it is necessary to take hepatic samples (to check the AlAT level). In case of permanent increase in activity of AlAT of norm 2 - 3 times higher than the upper bound the dose decline from 20 mg to 10 mg a day on condition of regular control of concentration of drug in blood is shown. If after a dose decline the permanent increase in level of activity of AlAT remains (by 2 - 3 times more), LefnoTM it is necessary to cancel.

Patients can become more susceptible to infections, including opportunistic, at use of the medicines possessing immunosuppressive action. Infections can demand intensive care as their course can be heavy. When developing a serious infection the need for treatment interruption LefnoTM and purpose of the procedure of its elimination from an organism can appear.

Measurement of arterial blood pressure should be taken before an initiation of treatment.

The men receiving treatment LefnoTM have to be warned about possible fetotoksichesky effect of drug and about need to use adequate contraceptives. For minimization of potential negative impact, men before the planned conception of the child should stop administration of drug and to apply the special procedure of elimination LefnoTM from an organism.

Use during pregnancy or feeding by a breast

It is necessary to exclude a possibility of pregnancy before an initiation of treatment LefnoTM.

In case of approach of pregnancy it is possible to reduce risk for a fruit in connection with reception LefnoTM due to fast decrease in level of an active metabolite in blood by purpose of the procedure of elimination LefnoTM from an organism which is described below.

After the reception termination LefnoTM 3 times a day for 14 days or on 50 g of activated carbon 4 times a day for 14 days apply holestiramin in a dose 8 g. Irrespective of the chosen way of elimination of drug by the time of fertilization at least 14 days follow twice, with an interval, to check concentration A771 726 in blood plasma then to wait for at least 45 more days until fertilization since that moment when in blood the concentration of a metabolite of A771 726 lower than 0.02 mg/l is for the first time recorded.

Oral introduction to the patient of suspension of activated carbon or a holestiramin considerably accelerates and increases removal A771 726. Consider that the similar effect arises thanks to the mechanism of gastrointestinal dialysis and/or interruption of enterohepatic recirculation.

It is necessary to consider that without procedure of elimination decrease in concentration of a metabolite A 771,726 lower than 20 mkg/l occur in 2 years.

Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms

At the Lefno drug treatment of TM speed of psychomotor reactions and ability of the patient to concentration of attention owing to such side effect as dizziness can be broken. In similar cases the patient should refrain from control of motor transport and work with potentially dangerous mechanisms.



Overdose

Symptoms: diarrhea, abdominal pain, nausea, vomiting, changes of function of a liver, anemia, leukocytemia

Treatment: use of a holestiramin or activated carbon for acceleration of removal of drug from an organism

the Procedure of elimination can be repeated in the presence of clinical indications. Primary metabolite LefnoTM A771 726 is not dialyzed.



Forms of release and packing

of the Tablet, coated 10 mg or 20 mg on 10 tablets in planimetric cell or in planimetric bezjyacheykovy packing. On 3 planimetric cell or planimetric bezjyacheykovy packing together with the instruction for medical use in cardboard packing.





To Store storage conditions at a temperature not higher than 25 wasps in the dry, protected from light place.

To store out of children's reach!





2 years

not to use a period of storage after the termination of the expiration date specified on packing!



Prescription status

According to the prescription





the Producer Kusum Heltker Pvt.

Ltd., JV 289 (A), Riiko Indl. Chopanki's Area, Bkhivadi (Raj.), India



the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods)

Representative office of Kusum Heltker Pvt Association. Ltd., India in RK

Almaty, Tulebayev St., 38

ph. / fax: 273-93-74, 273-68-10

the e-mail address:











To develop Office-kusumhealthcare@intelsoft.kz