Leflunomide Canon - instructions for use, dose, side effects, contraindications

Excipients: giprolose (hydroxypropyl cellulose) 4.6, mg, calcium hydrophosphate dihydrate 48.2 mg, corn starch 22.8 mg, croscarmellose sodium (impellose) 5 mg, magnesium stearate 1 mg, microcrystalline cellulose 28.4 mg.

Shell composition:

Selekoate AQ-02003 4 mg, including: hypromellose (hydroxypropylmethylcellulose) 2.4 mg, macrogol 6000 (polyethylene glycol 6000) 0.8 mg, titanium dioxide 0.8 mg.

Dosage of 20 mg:

One tablet, film-coated, contains:

Active substance: leflunomide 20 mg.

Excipients: giprolose (hydroxypropylcellulose) 6.7 mg, calcium hydrogen phosphate dihydrate 72 mg, corn starch 31.7 mg, croscarmellose sodium (impellose) 7.5 mg, magnesium stearate 1.5 mg, microcrystalline cellulose 40.6 mg.

Shell composition:

Selekoate AQ-02003 6 mg, including: hypromellose (hydroxypropylmethylcellulose) 3.6 mg, macrogol 6000 (polyethylene glycol 6000) 1.2 mg, titanium dioxide 1.2 mg.

Dosage of 100 mg:

One tablet, film-coated, contains:

Active substance: leflunomide 100 mg.

Excipients: giprolose (hydroxypropylcellulose) 7.5 mg, calcium hydrophosphate dihydrate 90 mg, corn starch 54.1 mg, croscarmellose; sodium (impellosis) 12.9 mg, magnesium stearate 2.5 mg, cellulose microcrystalline 43 mg.

Shell composition:

Selekoate AQ-02003 10 mg, including: hypromellose (hydroxypropylmethylcellulose) 6 mg, macrogol 6000 (polyethylene glycol 6000) 2 mg, titanium dioxide 2 mg.

Description:

The tablets covered with a film cover of white or almost white color, round, biconcave: On a cross section - almost white color.

Pharmacotherapeutic group:Immunosuppressive remedy

ATX: & nbsp

L.04.A.A.13 Leflunomide

L.04.A.A Selective immunosuppressants

Pharmacodynamics:

Leflunomide belongs to the class of basic antirheumatic drugs and has antiproliferative, immunomodulating, immunosuppressive and anti-inflammatory properties. The active leflunomide metabolite A771726 inhibits the enzyme dehydroorotate dehydrogenase and has antiproliferative activity. А771726 in conditions in vitro inhibits proliferation caused by mitogens and the synthesis of deoxyribonucleic acid (DNA) of T lymphocytes. The antiproliferative activity of A771726 appears, apparently, at the level of pyrimidine biosynthesis, since the addition of uridine to the cell culture eliminates the inhibitory effect of the metabolite A771726. Using radioisotope ligands it was shown that A771726 selectively binds to the enzyme dehydroorotate dehydrogenase, which explains its property to inhibit this enzyme and proliferation of lymphocytes in stage G1. Proliferation of lymphocytes is one of the key stages in the development of rheumatoid arthritis.

Simultaneously, A771726 inhibits the expression of receptors for interleukin-2 (CB-25) and antigens of the nucleus Ki-67 and PCNA, associated with the cell cycle.

The therapeutic effect of leflunomide was demonstrated in several experimental models of autoimmune diseases, including rheumatoid arthritis.

Leflunomide reduces symptoms and slows the progression of joint damage with an active form of rheumatoid arthritis.

Therapeutic: The effect usually manifests itself in 4-6 weeks and can grow further in 4-6 months.

Pharmacokinetics:

Leflunomide quickly turns into its active metabolite A771726 (primary metabolism in the intestinal wall and liver). In plasma, urine or feces only trace the amount of unchanged leflunomide. The only detectable metabolite is A771726, responsible for the basic properties of the drug in vivo.

When ingested absorbed from 82 to 95% of the drug. The maximum plasma concentrations of A771726 are determined from 1 to 24 hours after a single dose. Leflunomide can be taken with food. Because of the very long half-life (T1/2) A771726 (about 2 weeks) a loading dose of 100 mg per day was used for 3 days. This allowed us to quickly achieve the equilibrium state of the plasma concentration of A771726. Without a loading dose, it would take 2 months for the drug to reach an equilibrium concentration. In studies with repeated use of the drug, the pharmacokinetic parameters of A771726 were dose-dependent in the dose range of 5 to 25 mg.In these studies, the clinical effect was closely related to the plasma concentration of A771726 and the daily dose of leflunomide. At a dose ¹ 20 mg per day average plasma concentrations of A771726 at equilibrium state were 35 μg / ml.

Plasma rapidly binds A771726 to albumins. The unbound fraction of A771726 is approximately. 0.62%. Binding of A771726 is more variable, and somewhat decreases in patients with rheumatoid arthritis or chronic renal failure.

Leflunomide is metabolized to one major (A771726) and several secondary metabolites, including 4-trifluoromethylalanine. Biotransformation of leflunomide in A771726 and subsequent metabolism of A771726 itself are controlled several enzymes and occur in microsomal and other cell fractions. Investigations of interaction with cimetidine (nonspecific inhibitor of cytochrome P450) and rifampicin (nonspecific inducer of cytochrome P450) showed that in vivo CYP-enzymes are involved in the metabolism of leflunomide only in an insignificant degree. Excretion of A771726 from the body is slow and characterized by a clearance of 31 ml / h. Leflunomide is excreted with feces (probably due to biliary excretion) and urine. (T1 / 2) is about 2 weeks.

The pharmacokinetics of A771726 in patients on chronic outpatient peritoneal dialysis (HAFA) are similar to those in healthyvolunteers. A faster excretion of A771726 is observed in patients on hemodialysis, which is not due to the extraction of the drug into the dialysate, but to its removal from the bond with the protein. Although the clearance of A771726 increases approximately 2-fold, the final (T1 / 2) is similar to that of healthy individuals, since the volume of distribution simultaneously increases.

Data on the pharmacokinetics of the drug in patients with hepatic insufficiency are absent.

Pharmacokinetic characteristics in patients under the age of 18 years have not been studied. In elderly patients (65 years and older), the pharmacokinetic data roughly correspond to the average age group.

Indications:

- As a basic agent for the treatment of adult patients with active form of rheumatoid arthritis in order to reduce the symptoms of the disease and delay the development of structural damage to the joints;

- Active form of psoriatic arthritis.

Contraindications:

- Hypersensitivity to leflunomide or any other component of the drug; ,

- Dysfunction of the liver;

- Severe immunodeficiency (including acquired immunodeficiency syndrome);

- Significant disturbances of bone marrow hematopoiesis or severe anemia, leukopenia or thrombocytopenia due to other causes (except rheumatoid arthritis);

- Severe, uncontrolled infections;

- Moderate or severe renal failure (creatinine clearance less than 60 ml / min, due to small experience in clinical observation);

- Severe hypoproteinemia (eg, with nephrotic syndrome);

- In pregnant women or women of childbearing age who do not use methods of reliable contraception during the treatment with leflunomide and as long as the plasma level of the active metabolite remains above 0.02 mg / l (see section "Use during pregnancy and during breastfeeding "). Pregnancy should be excluded before treatment with leflunomide;

- During breastfeeding (see section "Use during pregnancy and during breastfeeding");

- Children's age (under 18 years of age), due to lack of data on effectiveness and safety.

Men receiving treatment with leflunomide,should be warned about the possible fetotoxic action of the drug (associated with its possible effect on the sperm of the father) and the need for reliable contraceptives.

Pregnancy and lactation:

Leflunomide can not be used by pregnant women or women of childbearing age who do not use reliable contraception in leflunomide treatment and for a certain time after this treatment (waiting period or shortened period of "laundering", see below). Before the beginning of treatment with Leflunomide Canon, you need to make sure that there is no pregnancy.

Patients should be informed that as soon as there is a delay in menstruation or if there is another reason to presume pregnancy, they should immediately notify the doctor about it to make a pregnancy test. In the case of a positive pregnancy test, the doctor should discuss with the patient the possible risk to which this pregnancy is exposed. It is possible that a rapid decrease in the level of active metabolite in the blood using the procedure described below for the removal of the drug will help at the first delay of the month to reduce the risk to which the fetus is exposed by leflunomide.

Women who take leflunomide and want to become pregnant, it is recommended that you follow one of the following procedures to ensure that the fetus is not exposed to toxic concentrations of A771726 (control concentration below 0.02 mg / L).

Waiting period

It can be expected that the concentration of A771726 in the blood plasma can be above 0.02 mg / L for a long period. It is believed that its concentration, may become less <0.02 mg / L 2 years after the cessation of treatment with leflunomide. The first time the concentration of A771726 in blood plasma is measured after a two-year waiting period.

After this, it is necessary to measure the concentration of A771726 in blood plasma, at least after 14 days. If the value of both measurements is less than 0.02 mg / l, no teratogenic risk is expected.

The procedure for "laundering"

- Colestyramine 8 g is administered 3 times a day for 11 days;

- as an alternative, 50 g of activated carbon pulverized into a powder, is administered 4 times a day for 11 days.

Regardless of the chosen "laundering" procedure, two separate tests should be tested at intervals of at least 14 days and wait one and a half months from the moment when the concentration of the drug in the plasma for the first time is fixed below 0.02 mg / l, until fertilization.

It is necessary to inform women of childbearing age about what should take 2 years after stopping treatment with leflunomide before they can attempt to become pregnant. If the 2-year waiting period with reliable contraception seems unreasonable, advise to carry out the procedure of "laundering" for preventive purposes.

AND colestramine and Activated carbon can affect the absorption of estrogens and progestogens, so reliable oral contraceptives do not give a one hundred percent guarantee during the "laundering" period with the help of colestyramine or activated carbon. It is recommended to use alternative methods of contraception.

Studies in animals have shown that leflunomide or its metabolites pass into breast milk, so women who are breast-feeding should not take the drug.

Dosing and Administration:

Treatment with leflunomide should begin under the supervision of a physician with experience in the treatment of rheumatoid arthritis and psoriatic arthritis.

Recommendations for treatment control, see section "Special instructions".

Tablets should be taken regardless of food intake, swallow whole,with enough liquid.

The treatment with leflunomide begins with ingestion of a shock dose of 100 mg once a day, for 3 days. As a maintenance dose for rheumatoid arthritis, it is recommended to take 10 mg to 20 mg leflunomide once a day, with psoriatic arthritis - 20 mg 1 time per day.

The therapeutic effect usually manifests itself in 4-6 weeks and can increase in further up to 4-6 months.

No dose adjustment is required for patients over 65 years of age.

Side effects:

The frequency of side effects is given in the following gradation: very often (more than 1/10); often (more than 1/100, less than 1/10); infrequently (more than 1/1000, less than 1/100); rarely (more than 1/10000, less than 1/1000); very rarely (less than 1/10000), including individual messages.

From the side of the cardiovascular system

Often: moderate increase in blood pressure;

Rarely: marked increase in blood pressure;

Frequency unknown: Angina pectoris, migraine, heart palpitations; tachycardia, varicose veins, vasculitis, vasodilation.

From the gastrointestinal tract

Often: diarrhea, nausea, vomiting, diseases of the oral mucosa (eg, aphthous stomatitis, ulceration of the lips), abdominal pain;

Infrequently: a violation of taste sensations;

Rarely: pancreatitis;

Frequency unknown: Gingivitis, candidiasis of the oral cavity, esophagitis, gastritis; gastroenteritis, indigestion, colitis, constipation,flatulence, melena.

From the hepato-biliary system

Often: increased activity of "hepatic" transaminases (alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (GGT), alkaline phosphatase (ALF), hyperbilirubinemia;

Rarely: hepatitis, cholestasis, jaundice, cholelithiasis;

Rarely: severe liver damage (including liver failure, acute liver necrosis), which can be fatal.

On the part of the respiratory system

Often: respiratory infections of the upper respiratory tract, cough;

Rarely: interstitial pulmonary process (including interstitial pneumonia and pulmonary fibrosis) with possible fatal outcome;

Frequency unknown: asthma, shortness of breath, nosebleeds.

Disorders of metabolism and nutrition

Often: increase of creatine phosphokinase (CK);

Infrequently: hypokalemia, hyperlipidemia, hypophosphatemia;

Rarely: increased lactate dehydrogenase;

Frequency unknown: hypouricemia, diabetes mellitus, hyperthyroidism, peripheral edema.

From the nervous system

Often: headache, dizziness, paresthesia;

Infrequently: anxiety;

Rarely: peripheral neuropathy;

Frequency unknown: anxiety, depression, dryness of the oral mucosa, sleep disorders, neuralgia, neuritis, increased sweating.

From the side of the musculoskeletal system

Often: tenosynovitis;

Infrequently: rupture of tendons;

Frequency unknown: arthralgia, synovitis, muscle spasms, arthrosis, bone necrosis, bursitis, myalgia.

From the skin and subcutaneous tissue

Often: increased hair loss, alopecia, eczema, skin rash (including maculopapular), itching, dry skin;

Infrequently: hives;

Rarely: toxic epidermal necrolysis (Lyell's syndrome), erythema multiforme, Stevens-Johnson syndrome;

Frequency unknown: acne, contact dermatitis, fungal dermatitis, hair color change, herpes simplex, shingles, nail damage, skin pigmentation, skin ulceration.

From the immune system

Often: allergic reactions;

Rarely: serious anaphylactic / anaphylactoid reactions, angioedema.

Infections and invasions

Rarely: severe infections (including opportunistic and sepsis), which can be fatal;

Increased risk of infectious diseases, in particular, rhinitis, bronchitis and pneumonia.

System of hematopoiesis and lymphatic system

Often: leukopenia (leukocytes> 2000 / μl);

Infrequently: anemia, thrombocytopenia of mild degree (platelets> 100 000 / μl);

Rarely: pancytopenia (apparently due to antiproliferative action), eosinophilia, leukopenia (leukocytes <2000 / μl);

Rarely: agranulocytosis.

The recent, concurrent or subsequent use of potentially myelotoxic agents may be associated with a greater risk of hematological effects.

From the side of the reproductive system

Frequency unknown: a slight decrease in the concentration of sperm, the total number of spermatozoa and their mobility.

From the side of the kidneys and urinary system

Frequency unknown: urinary tract infection, renal failure, albuminuria, cystitis, dysuria, hematuria, prostate cancer, frequent urination, vaginal candidiasis.

From the sense organs

Frequency unknown: indistinctness, visual perception, cataract, conjunctivitis, taste disorders.

Are common

Often: anorexia, weight loss (usually minor), asthenia;

Frequency unknown: fever, weakness.

Other

The risk of malignant, especially lymphoproliferative, diseases increases with the use of certain immunosuppressive drugs.

Overdose:

Symptoms

There were reports of chronic overdose in patients who received leflunomide in a dose up to five times the recommended daily dose, as well as reports of acute overdose in adults and children. In most cases, an overdose has not been reported on the development of adverse reactions. The resulting adverse reactions were comparable to the safety profile of leflunomide. The most frequently observed adverse reactions were diarrhea, abdominal pain, leukopenia, anemia, and an increase in the tests of the functional state of the liver.

Treatment

In case of overdose or toxicity, it is recommended to take colestramine or Activated carbon, to accelerate the cleansing of the body.

Kolestiramin, taken orally 8 g 3 times a day during the day, reduces the A771726 plasma content by about 40% after 24 hours, at 49-65 % in 48 hours. The administration of activated carbon (as a suspension) orally or through a gastric tube (50 g every 6 hours for 24 hours) reduces the concentration of the active metabolite A771726 in plasma by 37% after 24 hours, and 48% after 48 hours.

These procedures can be repeated according to clinical indications.

Studies with hemodialysis and HAFA indicate that A771726, the main metabolite of leflunomide, is not able to be eliminated by dialysis.

Interaction:

Increased side effects may occur in the case of a recent or concomitant use of hepatotoxicity (including alcohol) or hematotoxic and immunosuppressive drugs or when taking these drugs after treatment with leflunomide without the procedure of "laundering" (see "Special instructions").

In patients with rheumatoid arthritis, there was no pharmacokinetic interaction between leflunomide (10-20 mg per day) and methotrexate (10-25 mg per week).

Patients receiving leflunomide, simultaneous reception is not recommended colostiramine or activated carbon, as this leads to a rapid and a significant decrease in the concentration of A771726 in blood plasma. It is believed that this is caused by a violation of recirculation of A771726 in the liver and small intestine and / or a violation of his gastrointestinal dialysis.

If the patient is already taking non-steroidal anti-inflammatory drugs (NSAIDs) and / or corticosteroids, they can continue to be taken after treatment with leflunomide.

The enzymes involved in the metabolism of leflunomide and its metabolites are not exactly known. Study in vivo its interaction with cimetidine (nonspecific inhibitor of cytochrome P450) showed no significant interaction. After the concomitant administration of a single dose of leflunomide to subjects receiving multiple doses of rifampicin (nonspecific, inducer of cytochrome P450), peak levels of A771726 increased by about 40%, while the area under the concentration-time curve did not change significantly. The mechanism of this effect is not clear. Research in vitro showed that A771726 inhibits the activity of cytochrome P4502C9 (CYP2C9). In clinical studies there was no, no problem at combined use of leflunomide and NSAIDs metabolized by CYP2C9. With a special caution should be applied leflunomide together with other drugs, not NSAIDs metabolized by CYP2C9, such as phenytoin, warfarin and tolbutamide. An increase in prothrombin time with the simultaneous use of leflunomide and warfarin.

In a study in which leflunomide gave healthy female volunteers together with three-phase oral contraceptives containing 30 mcg ethinyl estradiol, no reduction in contraceptive effect contraception was not found, and the pharmacokinetics of A771726 completely was within the specified range.

Currently, there is no information on the combined use of leflunomide with antimalarial drugs used in rheumatology (for example, chloroquine and hydroxychloroquine), gold preparations (intramuscularly or orally), Dpenicillamine, azathioprine, and other immunosuppressive drugs (with the exception of methotrexate). The risk associated with the combination therapy is unknown, especially with long-term treatment.Since this kind of therapy can lead to the development of additional or even synergistic toxicity (for example, hepato- or hematoxicity), combinations of this drug with other basic drugs (eg, methotrexate) are undesirable. The recent concomitant or subsequent use of potentially myelotoxic agents may be associated with a greater risk of hematological effects.

Immunosuppressants increase the risk of infections, as well as malignant, especially lymphoproliferative diseases.

Vaccination

There are no clinical data on the efficacy and safety of vaccination in the treatment of leflunomide. However, it is not recommended to carry out vaccination with live vaccines. When planning vaccination with a live vaccine, long-term T1 / 2 leflunomide should be considered after drug withdrawal.

Special instructions:

Leflunomide can be used in patients only after a thorough medical examination.

The procedure for "laundering"

The "laundering" procedure is carried out according to the following scheme:

- Colestyramine 8 g is administered 3 times a day for 11 days;

- as an alternative, 50 g of activated carbon powdered into powder, is administered 4 times a day for 11 days.

Adverse Reactions

Before starting treatment with Leflunomide Canon, it is necessary to remember the possible increase in the number of adverse reactions in patients who previously received other basic drugs for the treatment of rheumatoid arthritis, which have hepato- and hematotoxic effects. The active metabolite leflunomide A771726, characterized by a long T1 / 2, usually ranging from 1 to 4 weeks. Due to the long half-life of the active metabolite leflunomide, even with the cessation of leflunomide treatment, serious undesirable effects may or may persist. In this case, the "laundering" procedure should be carried out according to the above scheme. The procedure can be repeated according to clinical indications. If suspected of severe immunological / allergic reactions such as Stevens-Johnson syndrome or Lyell's syndrome, a full procedure for "laundering" is mandatory.

If such cases of toxicity occur or when you switch to receiving another ₍(for example, methotrexate) after treatment with leflunomide, it is necessary to carry out the "laundering" procedure (see above).

Reactions of the liver

Since the active metabolite leflunomide A771726 is bound to proteins and excreted through hepatic metabolism and bile secretion, it is suggested that the level of A771726 in the blood plasma may increase in patients with hypoproteinemia. Leflunomide contraindicated in patients with severe hypoproteinemia or impaired liver function (see section "Contraindications"). Leflunomide is not recommended for patients with previous acute or chronic liver disease, and patients whose ALT level before the start of treatment is 2 times higher than the upper limit of the norm.

There have been reports of rare cases of severe liver damage, in some cases fatal, with leflunomide treatment. Most, these cases were observed during the first six months of treatment. Although there is no causal relationship between these undesirable events and leflunomide, and in most cases there were several additional suspicious factors, the precise implementation of the treatment control recommendations is considered mandatory.

The ALT level should be checked before starting leflunomide therapy, and then every 2 weeks for the first 6 months of treatment, followed by a check once every 6-8 weeks. There are the following recommendations for correcting the dosage regimen or stopping the drug depending on the severity and persistence of increasing ALT levels. With a confirmed 2-3-fold excess of the upper limit of ALT norm, a dose reduction from 20 mg to 10 mg per day may allow further leflunomide administration provided that the indicator is closely monitored. If 2-3 times the upper limit of the ALT norm is maintained, or if there is a confirmed elevation in ALT levels that exceeds the upper limit of the norm by more than 3 times, the leflunomide should be discontinued and the "laundering" procedure should begin.

Because of the possible additional hepatotoxic effects, it is recommended to refrain from taking alcohol while taking Leflunomide Kanon.

Hematologic reactions

A complete clinical blood test, including the definition of the leukocyte count and the number of platelets, should be performed prior to the initiation of leflunomide treatment, and every 2 weeks during the first6 months of treatment and then every 6-8 weeks.

In patients with previous anemia, leukopenia and / or thrombocytopenia, as well as in patients with impaired bone marrow function or the risk of developing such disorders, increases the risk of hematological disorders. If such a phenomenon occurs, you should use the "laundering" procedure to reduce the level of A771726 in blood plasma.

In case of serious hematologic reactions, including pancytopenia, it is necessary to stop taking Leflunomide Canon and any other concomitant medication that suppresses bone marrow hematopoiesis and begin the procedure of "laundering".

Joint application with other types of treatment

Currently, there is no information on the combined use of leflunomide with antimalarial drugs used in rheumatology (for example, chloroquine and hydroxychloroquine) administered intramuscularly or orally, with preparations of gold, Dpenicillamine, azathioprine and other immunosuppressive agents, with the exception of methotrexate. There is no known risk associated with the use of combination therapy, especially with long-term treatment.Since this type of therapy can lead to the development of additional or even synergistic toxicity (for example, hepatotoxicity or hematotoxicity), combinations of this drug with other basic drugs (for example, methotrexate) are not desirable.

Transition to other types of treatment

Because the leflunomide long remains in the body, the transition to the reception of another (for example, methotrexate) without an appropriate "laundering" procedure may increase the possibility of additional risk even after a long time after the transition (eg, kinetic interaction, organotoxicity).

Similarly, recent treatment hepatotoxic or hematotoxic drugs (for example, methotrexate) can lead to an increase in the number of side effects, therefore, starting treatment with leflunomide, should be carefully considered all the positive and negative aspects associated with taking this drug.

Skin Reactions

If ulcerative stomatitis develops, Leflunomide should be discontinued.

Very rare cases of Stevens-Johnson syndrome or toxic epidermal necrosis have been reported in patients who received leflunomide. In case of skin reactions and / or reactions from the mucous membranes, Leflunomide canon should be withdrawn and any other and immediately begin the procedure of "laundering". It is necessary to achieve complete removal of the drug from the body. In such cases, the repeated administration of the drug is contraindicated.

Infections

It is known that drugs like leflunomide and possessing immunosuppressive properties make patients more susceptible to various kinds of infections, including opportunistic infections (infections caused by fungi and microorganisms that can cause infections only in conditions of decreased immunity). Emerging infectious diseases occur, as a rule, hard and require early and intensive treatment. When a severe infectious the disease may need interruption of treatment with leflunomide and the beginning of the procedure for "laundering".

It is necessary to carefully monitor patients with a positive reaction to tuberculin because of the risk of reactivation of tuberculosis.

Respiratory system reactions

In the treatment with leflunomide, rare cases of interstitial pulmonary process were noted.Symptoms such as cough and dyspnea can cause reception of leflunomide.

Arterial pressure

Before beginning treatment with leflunomide and periodically after its onset, to control the level of arterial pressure.

Interactions

You should be careful when using drugs that are metabolized by action CYP2C9 (phenytoin, warfarin, tolbutamide), with the exception of NSAIDs.

Recommendations for men

There is no data on the risk of fetotoxicity associated with the toxic effect of the drug on the father's spermatozoa, when leflunomide is used by men. To minimize the possible risk to men in planning the appearance of a child, it is necessary to stop taking leflunomide and carry out the procedure "laundering".

Application for violations of kidney function

Contraindicated in patients with moderate or severe renal failure (due to limited experience in clinical observations). There are no special recommendations for dosage in patients with mild renal insufficiency.

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

Reception of the drug may be accompanied by a headache, dizziness.In this regard, patients receiving leflunomide, caution should be exercised when managing dangerous mechanical means, including by car.

Form release / dosage:

Tablets coated with a film coat of 10 mg, 20 mg or 100 mg.

Packaging:

For tablets with a dosage of 10 mg and 20 mg: 10, 20 or 30 tablets in a contour cell packaging made of a polyvinylchloride film and aluminum foil printed lacquered. By 3, 6, 10 contiguous cell packs of 10 tablets or 3, 5 contiguous cell packs of 20 tablets or by 1,2, 3, 4 contour cell packs of 30 tablets together with instructions for use are placed in a pack of cardboard.

For tablets with a dosage of 100 mg: on 3 or 10 tablets in a contour cellular packing from a film of polyvinylchloride and a foil of the aluminum printed varnished.

For 1 contour pack of 3 tablets or 1 contour pack of 10 tablets together with the instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001528

Date of registration:22.02.2012

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Information update date: & nbsp13.11.2015

Illustrated instructions

Instructions

Leflunomide Canon (Leflunomide Canon)