Arava tablets 10 mg, 30 pcs. (Leflunomyd)
Special Price
$44.55
Regular Price
$45.00
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SKU
florida463130
Latin name
Arava Buy Arava tablets 10 mg, 30 pcs. (Leflunomyd) in florida free shipping. Fast international shipping USA, AU, EU, UK and others.
Arava Buy Arava tablets 10 mg, 30 pcs. (Leflunomyd) in florida free shipping. Fast international shipping USA, AU, EU, UK and others.
Latin name
Arava
release form coated tablets
Packing
30 pcs
Pharmacological action
Arava - basic antirheumatic drug. It has antiproliferative, immunomodulatory, immunosuppressive and anti-inflammatory properties.
The active metabolite of leflunomide A771726 inhibits the dehydroorotate dehydrogenase enzyme and has antiproliferative activity. A771726 in vitro inhibits mitogen-induced proliferation and DNA synthesis 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 metabolite A771726. Using radioisotope ligands, it was shown that A771726 selectively binds to the dehydroorotate dehydrogenase enzyme, which explains its ability to inhibit this enzyme and lymphocyte proliferation in stage G1. Lymphocyte proliferation is one of the key stages in the development of rheumatoid arthritis.
At the same time, A771726 inhibits the expression of interleukin-2 receptors (CB-25) and the Ki-67 and PCNA core antigens associated with the cell cycle.
The therapeutic effects of leflunomide have been shown in several experimental models of autoimmune diseases, including rheumatoid arthritis.
Leflunomide reduces symptoms and slows the progression of joint damage in the active form of rheumatoid arthritis.
The therapeutic effect usually manifests itself after 4-6 weeks and may increase in the future over 4-6 months.
Indications
As a basic treatment for adult patients with active rheumatoid arthritis in order to reduce the symptoms of the disease and delay the development of structural damage to the joints.
An active form of psoriatic arthritis.
Contraindications
liver dysfunction
severe immunodeficiency (including AIDS)
severe disturbances in bone marrow hematopoiesis or anemia, leukopenia, thrombocytopenia due to other causes (except for severe rheumatoid arthritis or severe leukemia) due to little clinical experience)
severe hypoproteinemia (including with nephrotic syndrome)
pregnancy
lactation (lactation)
children and sprout age 18 years
hypersensitivity to the drug.
Arava is contraindicated in women of childbearing age who do not use adequate contraceptives.
Men, receiving leflunomide treatment should be warned about the possible fetotoxic effect of the drug and the need to use adequate contraceptives.
Special instructions
Arava can be prescribed to patients only after a thorough medical examination.
Before starting treatment with Arava, it is necessary to remember the possible increase in the number of side effects in patients who previously received other basic drugs for the treatment of rheumatoid arthritis, which have hepatotoxic and hematotoxic effects.
The active metabolite of leflunomide, A771726, is characterized by a long elimination half-life, usually ranging from 1 to 4 weeks. Due to the long half-life of the active metabolite of leflunomide, A771726, serious undesirable effects (for example, hepatotoxicity, hematoxicity or allergic reactions, see below) may occur or persist even when treatment with leflunomide is discontinued. In this case, the “washing” procedure should be carried out. The procedure can be repeated according to clinical indications. If severe immunological / allergic reactions such as Stevens-Johnson syndrome or Lyell's syndrome are suspected, a full “laundering” procedure is mandatory.
Therefore, when such cases of toxicity occur or when you switch to taking another basic drug (for example, methotrexate) after treatment with leflunomide, it is necessary to carry out the “washing” procedure (see below).
Liver reactions
Since the active metabolite of leflunomide, A771726, is bound to proteins and excreted through hepatic metabolism and secretion of bile, it is suggested that plasma A771726 levels may increase in patients with hypoproteinemia. The drug Arava is contraindicated in patients with severe hypoproteinemia or impaired liver function. (see the section "Contraindications".).
Rare cases of the development of severe liver damage, in some cases fatal, have been reported in the treatment of leflunomide. Most of these cases were observed during the first six months of treatment. Although a causal relationship between these adverse events and leflunomide has not been established, and in most cases there were several additional suspicious factors, the exact implementation of recommendations for monitoring treatment is considered mandatory.
ALT levels 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 adjusting the dosing 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 normal, a dose reduction from 20 mg to 10 mg per day may allow continued administration of leflunomide, subject to careful monitoring of this indicator.
If 2-3 times the upper limit of the ALT norm is exceeded, or if there is a confirmed increase in the ALT level, exceeding the upper limit of the norm by more than 3 times, the administration of leflunomide should be discontinued and the “laundering” procedure should begin.
Due to possible additional hepatotoxic effects, it is recommended that you refrain from drinking alcohol when treated with leflunomide.
Hematologic reactions
A complete blood count, including determination of the leukocyte count and platelet count, should be performed before treatment with leflunomide, and every 2 weeks for the first 6 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 with a risk of developing such disorders, the risk of hematological disorders increases. If such phenomena occur, the “laundering” procedure should be used to reduce the level of A771726 in blood plasma.
In the event of serious hematologic reactions, including pancytopenia, it is necessary to stop taking Arava and any other concomitant medication that suppresses bone marrow hematopoiesis and begin the “washing” procedure.
Concurrent use with other treatments
There is currently no evidence regarding the combined use of leflunomide with antimalarial drugs used in rheumatology (for example, chloroquine and hydroxychloroquine), administered intramuscularly or orally with gold preparations, D-penicillamine, azathioprine and other immunosuppressive drugs ( excluding methotrexate). The risk associated with the appointment of complex therapy is not known, especially with prolonged treatment. Since this kind 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.
Switching to other types of treatment
Since leflunomide remains in the body for a long time, switching to another basic drug (for example, methotrexate) without the appropriate “washing” procedure may increase the risk of additional risk even after a long time after the transition (for example, kinetic interaction, organotoxicity).
Similarly, recent treatment with hepatotoxic or hematoxic drugs (e.g. methotrexate) may increase the incidence of side effects, therefore, starting treatment with leflunomide, it is necessary to carefully consider all the positive and negative aspects associated with taking this drug.
Skin reactions
In the event of ulcerative stomatitis, leflunomide should be discontinued.
Very rare cases of Stevens-Johnson syndrome or toxic epidermal necrolysis in leflunomide-treated patients have been reported. In case of skin reactions and / or reactions from the mucous membranes, it is necessary to stop taking the drug Arava and any other drug associated with it and immediately start the “washing” procedure. It is necessary to achieve complete elimination of the drug from the body. In such cases, repeated administration of the drug is contraindicated.
infections are known to be drugs that similar to leflunomide and possessing immunosuppressive properties, make patients more sensitive to various infections, including opportunistic infections (infections caused by fungi and microorganisms that can cause infections only in conditions of reduced immunity). Infectious diseases that occur are usually difficult and require early and intensive treatment. If a serious infectious disease occurs, it may be necessary to interrupt treatment with leflunomide and begin the “laundering” procedure.
Care should be taken to monitor patients with a positive reaction to tuberculin because of the risk of reactivation of tuberculosis.
Respiratory tract reactions
Rare cases of interstitial pulmonary process have been reported with leflunomide therapy. Symptoms such as coughing and dyspnea can cause leflunomide to stop taking.
Blood pressure
Before starting treatment with leflunomide and periodically after it began, the level of blood pressure should be monitored.
Interactions
Care should be taken when prescribing drugs that are metabolized by CYP2C9 (phenytoin, warfarin, tolbutamide), with the exception of NSAIDs (non-steroidal anti-inflammatory drugs).
Recommendations for men
There is no data on the risk of fetotoxicity (associated with the toxic effect of the drug on father sperm) when men use leflunomide. Experimental data in this direction have not been carried out. To minimize the possible risk for men, when planning the appearance of a child, it is necessary to stop taking leflunomide and use colestyramine 8 g 3 times a day for 11 days or 50 g of powdered activated carbon 4 times a day for 11 days.
Composition
Active ingredient: leflunomide 10 mg.
Dosage and Administration
Arava should be started under the supervision of a physician with experience in treating rheumatoid and psoriatic arthritis.
Treatment begins with a loading dose of 100 mg daily for 3 days. As a maintenance dose for rheumatoid arthritis, it is recommended to take a dose of 10 to 20 mg 1 time / day for psoriatic arthritis - 20 mg 1 time / day.
The therapeutic effect is manifested after 4-6 weeks from the start of administration and may increase within 4-6 months. The tablets should be swallowed whole, washed down with a sufficient amount of liquid, regardless of food intake. Dose adjustment is not required for patients older than 65 years and in patients with mild renal failure.
Side effects
Classification of the estimated frequency of side effects: very frequent (more than 1/10), frequent (more than 1/100, but less than 1/10), infrequent (more than 1/1000, but less than 1/100), rare ( more than 1/10000, but less than 1/1000), very rare (less than 1/10000), is unknown (based on available data it is impossible to estimate).
- Cardiovascular System
Frequent: moderate increase in blood pressure.
Rare: marked increase in blood pressure
- Gastrointestinal tract
Frequent: diarrhea, nausea, vomiting, diseases of the oral mucosa (for example, aphthous stomatitis, ulceration of the lips), abdominal pain.
Infrequent: taste disturbances
Very rare: pancreatitis
- Respiratory system and mediastinal disorders
Rare: interstitial pulmonary process (including interstitial pneumonia), with a possible fatal outcome.
- metabolic disorders
Frequent: increased creatine phosphokinase (CPK)
Infrequent: hypokalemia, hyperlipidemia, hypophosphatemia.
Rare: elevated levels of lactate dehydrogenase (LDH)
Frequency unknown: hypuricemia
- Nervous system
Frequent: headache, dizziness, paresthesia.
Infrequent: Anxiety.
Very rare: peripheral neuropathy
- Musculoskeletal system
Frequent: tenosynovitis.
Infrequent: tendon rupture
- Skin and
derivatives Frequent: increased hair loss, eczema, rash (including maculopapular rash), itching, dry skin.
Infrequent: urticaria
Very rare: toxic epidermal necrolysis (Lyell syndrome), erythema multiforme, Stevens-Johnson syndrome.
- The immune system
Frequent: mild allergic reactions.
Very rare: serious anaphylactic / anaphylactoid reactions, vasculitis, including cutaneous necrotic vasculitis.
- Infections and infestations
Rare: the development of severe infections, including opportunistic infections, and sepsis, which can be fatal.
The number of possible infections (in particular, rhinitis, bronchitis, and pneumonia) may increase.
- Hematopoietic system and lymphatic system
Frequent: leukopenia (white blood cells> 2000 / μl).
Infrequent: anemia, mild thrombocytopenia (platelets <100,000 / μl).
Rare: pancytopenia (probably due to antiproliferative action), leukopenia (white blood cells <2000 / μl), eosinophilia.
Very rare: agranulocytosis.
recent, concomitant or subsequent use of potentially myelotoxic agents may be associated with a greater risk of hematologic effects.
- Hepato-biliary system
Frequent: increased activity of hepatic transaminases (especially alanine aminotransferase (ALT)), less commonly gamma-glutamyl transpeptidases (GGT) and alkaline phosphatase (ALP), hyperbilirubinemia.
Rare: hepatitis, jaundice / cholestasis.
Very rare: severe liver damage, such as liver failure, acute liver necrosis, which can be fatal
- General changes in
Frequent: anorexia, weight loss (usually minor), asthenia.
- From the reproductive system: Frequency unknown: slight decrease in sperm concentration, the total number of sperm and their motility
- From the side of the kidneys and urinary tract: Frequency unknown: renal failure
- Other
The risk of developing malignant, especially lymphoproliferative diseases, increases with the use of some immunosuppressive drugs.
Drug Interactions
An increase in adverse events may occur with the recent or concomitant use of hepatotoxic (including alcohol) or hematotoxic and immunosuppressive drugs or when these drugs are started after treatment with leflunomide without the “washing” procedure (see “Special Instructions”).
No pharmacokinetic interaction between leflunomide (10–20 mg per day) and methotrexate (10–25 mg per week) was found in patients with rheumatoid arthritis.
Patients taking leflunomide are advised not to give colestyramine or activated charcoal, as this leads to a rapid and significant decrease in plasma concentration of A771726 (active metabolite of leflunomide). Believed that this is due to a violation of A771726 recirculation in the liver and small intestine and / or a violation of its gastrointestinal dialysis.
If the patient is already taking non-steroidal anti-inflammatory drugs (NSAIDs) and / or corticosteroids, they can continue to be taken after the start of treatment with leflunomide.
Enzymes involved in the metabolism of leflunomide and its metabolites are not exactly known. An in vivo study of its interaction with cimetidine (a non-specific inhibitor of cytochrome P450) showed the absence of a significant interaction. After the concomitant administration of a single dose of leflunomide to subjects receiving multiple doses of rifampicin (a non-specific cytochrome P450 inducer), 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.
In vitro studies have shown that A771726 inhibits the activity of cytochrome P4502C9 (CYP2C9). In clinical trials, there were no problems with the combined administration of leflunomide and NSAIDs metabolized by CYP2C9. With extreme caution,
leflunomide should be given along with other non-NSAID drugs metabolized by CYP2C9, such as phenytoin, warfarin and tolbutamide. An increase in prothrombin time has been reported with the simultaneous administration of leflunomide and warfarin.
In a study in which leflunomide was given to healthy female volunteers together with three-phase oral contraceptives containing 30 μg of ethinyl estradiol, no decrease in the contraceptive effect of the tablets was found, and the pharmacokinetics of A771726 completely fell within the prescribed range.
Currently, there is no information on the combined use of leflunomide with antimalarial drugs used in rheumatology (for example, chloroquine and hydroxychlorin), Au preparations (IM or oral), D-penicillamine, azathioprine and other immunosuppressive drugs (with the exception of methotrexate ) There is no known risk associated with complex therapy, especially with prolonged 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 (for example, methotrexate) are undesirable. Recent concomitant or subsequent use of potentially myelotoxic agents may be associated with a greater risk of hematologic effects. Immunosuppressants increase the risk of developing infections, as well as malignant, especially lymphoproliferative diseases.
Vaccination
There is no clinical evidence regarding the efficacy and safety of vaccination in patients treated with leflunomide. However, vaccination with live vaccines is not recommended. The long half-life of Arava should be considered when planning vaccination with a live vaccine after discontinuing Arava.
overdose Symptoms of
Chronic overdose has been reported in patients receiving leflunomide at doses up to 5 times the recommended daily dose, as well as reports of acute overdose in adults and children. In most cases, the development of undesirable effects was not reported. Emerging adverse events were comparable to the safety profile of leflunomide. The most commonly observed undesirable effects were diarrhea, abdominal pain, leukopenia, anemia, and elevation of liver function tests.
Treatment
In case of overdose or toxicity, it is recommended to take cholestyramine or activated charcoal to accelerate the body's cleansing.
Cholestyramine, taken by three healthy volunteers orally at
8 g three times a day for 24 hours, reduced blood plasma levels of A771726 by about 40% after 24 hours and by 49-65% after 48 hours.
It is shown that the introduction of activated carbon (powder, orally or via a gastric tube (50 g every 6 hours during the day) reduced the concentration of the active metabolite A771726 in plasma by 37% after 24 hours and by 48% after 48 hours.
These "laundering" procedures can be repeated on a clinical basis.
Studies with hemodialysis and HAPD (chronic outpatient peritoneal dialysis) indicate that A771726, the major metabolite of leflunomide, is unable to be excreted by dialysis.
Storage Conditions
Do not store above 25 ° C.
Shelf life
3 years.
Deystvuyushtee substance
Leflunomide
Sanofi-Aventis, France
Arava tablets 10 mg, 30 pcs. (Leflunomyd) florida in pharmacy online. Cheap price, instruction, side effects, dosage. Arava tablets 10 mg, 30 pcs. - Sale. PayPal accept. Free shipping florida. Fast international shipping.
Arava
release form coated tablets
Packing
30 pcs
Pharmacological action
Arava - basic antirheumatic drug. It has antiproliferative, immunomodulatory, immunosuppressive and anti-inflammatory properties.
The active metabolite of leflunomide A771726 inhibits the dehydroorotate dehydrogenase enzyme and has antiproliferative activity. A771726 in vitro inhibits mitogen-induced proliferation and DNA synthesis 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 metabolite A771726. Using radioisotope ligands, it was shown that A771726 selectively binds to the dehydroorotate dehydrogenase enzyme, which explains its ability to inhibit this enzyme and lymphocyte proliferation in stage G1. Lymphocyte proliferation is one of the key stages in the development of rheumatoid arthritis.
At the same time, A771726 inhibits the expression of interleukin-2 receptors (CB-25) and the Ki-67 and PCNA core antigens associated with the cell cycle.
The therapeutic effects of leflunomide have been shown in several experimental models of autoimmune diseases, including rheumatoid arthritis.
Leflunomide reduces symptoms and slows the progression of joint damage in the active form of rheumatoid arthritis.
The therapeutic effect usually manifests itself after 4-6 weeks and may increase in the future over 4-6 months.
Indications
As a basic treatment for adult patients with active rheumatoid arthritis in order to reduce the symptoms of the disease and delay the development of structural damage to the joints.
An active form of psoriatic arthritis.
Contraindications
liver dysfunction
severe immunodeficiency (including AIDS)
severe disturbances in bone marrow hematopoiesis or anemia, leukopenia, thrombocytopenia due to other causes (except for severe rheumatoid arthritis or severe leukemia) due to little clinical experience)
severe hypoproteinemia (including with nephrotic syndrome)
pregnancy
lactation (lactation)
children and sprout age 18 years
hypersensitivity to the drug.
Arava is contraindicated in women of childbearing age who do not use adequate contraceptives.
Men, receiving leflunomide treatment should be warned about the possible fetotoxic effect of the drug and the need to use adequate contraceptives.
Special instructions
Arava can be prescribed to patients only after a thorough medical examination.
Before starting treatment with Arava, it is necessary to remember the possible increase in the number of side effects in patients who previously received other basic drugs for the treatment of rheumatoid arthritis, which have hepatotoxic and hematotoxic effects.
The active metabolite of leflunomide, A771726, is characterized by a long elimination half-life, usually ranging from 1 to 4 weeks. Due to the long half-life of the active metabolite of leflunomide, A771726, serious undesirable effects (for example, hepatotoxicity, hematoxicity or allergic reactions, see below) may occur or persist even when treatment with leflunomide is discontinued. In this case, the “washing” procedure should be carried out. The procedure can be repeated according to clinical indications. If severe immunological / allergic reactions such as Stevens-Johnson syndrome or Lyell's syndrome are suspected, a full “laundering” procedure is mandatory.
Therefore, when such cases of toxicity occur or when you switch to taking another basic drug (for example, methotrexate) after treatment with leflunomide, it is necessary to carry out the “washing” procedure (see below).
Liver reactions
Since the active metabolite of leflunomide, A771726, is bound to proteins and excreted through hepatic metabolism and secretion of bile, it is suggested that plasma A771726 levels may increase in patients with hypoproteinemia. The drug Arava is contraindicated in patients with severe hypoproteinemia or impaired liver function. (see the section "Contraindications".).
Rare cases of the development of severe liver damage, in some cases fatal, have been reported in the treatment of leflunomide. Most of these cases were observed during the first six months of treatment. Although a causal relationship between these adverse events and leflunomide has not been established, and in most cases there were several additional suspicious factors, the exact implementation of recommendations for monitoring treatment is considered mandatory.
ALT levels 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 adjusting the dosing 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 normal, a dose reduction from 20 mg to 10 mg per day may allow continued administration of leflunomide, subject to careful monitoring of this indicator.
If 2-3 times the upper limit of the ALT norm is exceeded, or if there is a confirmed increase in the ALT level, exceeding the upper limit of the norm by more than 3 times, the administration of leflunomide should be discontinued and the “laundering” procedure should begin.
Due to possible additional hepatotoxic effects, it is recommended that you refrain from drinking alcohol when treated with leflunomide.
Hematologic reactions
A complete blood count, including determination of the leukocyte count and platelet count, should be performed before treatment with leflunomide, and every 2 weeks for the first 6 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 with a risk of developing such disorders, the risk of hematological disorders increases. If such phenomena occur, the “laundering” procedure should be used to reduce the level of A771726 in blood plasma.
In the event of serious hematologic reactions, including pancytopenia, it is necessary to stop taking Arava and any other concomitant medication that suppresses bone marrow hematopoiesis and begin the “washing” procedure.
Concurrent use with other treatments
There is currently no evidence regarding the combined use of leflunomide with antimalarial drugs used in rheumatology (for example, chloroquine and hydroxychloroquine), administered intramuscularly or orally with gold preparations, D-penicillamine, azathioprine and other immunosuppressive drugs ( excluding methotrexate). The risk associated with the appointment of complex therapy is not known, especially with prolonged treatment. Since this kind 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.
Switching to other types of treatment
Since leflunomide remains in the body for a long time, switching to another basic drug (for example, methotrexate) without the appropriate “washing” procedure may increase the risk of additional risk even after a long time after the transition (for example, kinetic interaction, organotoxicity).
Similarly, recent treatment with hepatotoxic or hematoxic drugs (e.g. methotrexate) may increase the incidence of side effects, therefore, starting treatment with leflunomide, it is necessary to carefully consider all the positive and negative aspects associated with taking this drug.
Skin reactions
In the event of ulcerative stomatitis, leflunomide should be discontinued.
Very rare cases of Stevens-Johnson syndrome or toxic epidermal necrolysis in leflunomide-treated patients have been reported. In case of skin reactions and / or reactions from the mucous membranes, it is necessary to stop taking the drug Arava and any other drug associated with it and immediately start the “washing” procedure. It is necessary to achieve complete elimination of the drug from the body. In such cases, repeated administration of the drug is contraindicated.
infections are known to be drugs that similar to leflunomide and possessing immunosuppressive properties, make patients more sensitive to various infections, including opportunistic infections (infections caused by fungi and microorganisms that can cause infections only in conditions of reduced immunity). Infectious diseases that occur are usually difficult and require early and intensive treatment. If a serious infectious disease occurs, it may be necessary to interrupt treatment with leflunomide and begin the “laundering” procedure.
Care should be taken to monitor patients with a positive reaction to tuberculin because of the risk of reactivation of tuberculosis.
Respiratory tract reactions
Rare cases of interstitial pulmonary process have been reported with leflunomide therapy. Symptoms such as coughing and dyspnea can cause leflunomide to stop taking.
Blood pressure
Before starting treatment with leflunomide and periodically after it began, the level of blood pressure should be monitored.
Interactions
Care should be taken when prescribing drugs that are metabolized by CYP2C9 (phenytoin, warfarin, tolbutamide), with the exception of NSAIDs (non-steroidal anti-inflammatory drugs).
Recommendations for men
There is no data on the risk of fetotoxicity (associated with the toxic effect of the drug on father sperm) when men use leflunomide. Experimental data in this direction have not been carried out. To minimize the possible risk for men, when planning the appearance of a child, it is necessary to stop taking leflunomide and use colestyramine 8 g 3 times a day for 11 days or 50 g of powdered activated carbon 4 times a day for 11 days.
Composition
Active ingredient: leflunomide 10 mg.
Dosage and Administration
Arava should be started under the supervision of a physician with experience in treating rheumatoid and psoriatic arthritis.
Treatment begins with a loading dose of 100 mg daily for 3 days. As a maintenance dose for rheumatoid arthritis, it is recommended to take a dose of 10 to 20 mg 1 time / day for psoriatic arthritis - 20 mg 1 time / day.
The therapeutic effect is manifested after 4-6 weeks from the start of administration and may increase within 4-6 months. The tablets should be swallowed whole, washed down with a sufficient amount of liquid, regardless of food intake. Dose adjustment is not required for patients older than 65 years and in patients with mild renal failure.
Side effects
Classification of the estimated frequency of side effects: very frequent (more than 1/10), frequent (more than 1/100, but less than 1/10), infrequent (more than 1/1000, but less than 1/100), rare ( more than 1/10000, but less than 1/1000), very rare (less than 1/10000), is unknown (based on available data it is impossible to estimate).
- Cardiovascular System
Frequent: moderate increase in blood pressure.
Rare: marked increase in blood pressure
- Gastrointestinal tract
Frequent: diarrhea, nausea, vomiting, diseases of the oral mucosa (for example, aphthous stomatitis, ulceration of the lips), abdominal pain.
Infrequent: taste disturbances
Very rare: pancreatitis
- Respiratory system and mediastinal disorders
Rare: interstitial pulmonary process (including interstitial pneumonia), with a possible fatal outcome.
- metabolic disorders
Frequent: increased creatine phosphokinase (CPK)
Infrequent: hypokalemia, hyperlipidemia, hypophosphatemia.
Rare: elevated levels of lactate dehydrogenase (LDH)
Frequency unknown: hypuricemia
- Nervous system
Frequent: headache, dizziness, paresthesia.
Infrequent: Anxiety.
Very rare: peripheral neuropathy
- Musculoskeletal system
Frequent: tenosynovitis.
Infrequent: tendon rupture
- Skin and
derivatives Frequent: increased hair loss, eczema, rash (including maculopapular rash), itching, dry skin.
Infrequent: urticaria
Very rare: toxic epidermal necrolysis (Lyell syndrome), erythema multiforme, Stevens-Johnson syndrome.
- The immune system
Frequent: mild allergic reactions.
Very rare: serious anaphylactic / anaphylactoid reactions, vasculitis, including cutaneous necrotic vasculitis.
- Infections and infestations
Rare: the development of severe infections, including opportunistic infections, and sepsis, which can be fatal.
The number of possible infections (in particular, rhinitis, bronchitis, and pneumonia) may increase.
- Hematopoietic system and lymphatic system
Frequent: leukopenia (white blood cells> 2000 / μl).
Infrequent: anemia, mild thrombocytopenia (platelets <100,000 / μl).
Rare: pancytopenia (probably due to antiproliferative action), leukopenia (white blood cells <2000 / μl), eosinophilia.
Very rare: agranulocytosis.
recent, concomitant or subsequent use of potentially myelotoxic agents may be associated with a greater risk of hematologic effects.
- Hepato-biliary system
Frequent: increased activity of hepatic transaminases (especially alanine aminotransferase (ALT)), less commonly gamma-glutamyl transpeptidases (GGT) and alkaline phosphatase (ALP), hyperbilirubinemia.
Rare: hepatitis, jaundice / cholestasis.
Very rare: severe liver damage, such as liver failure, acute liver necrosis, which can be fatal
- General changes in
Frequent: anorexia, weight loss (usually minor), asthenia.
- From the reproductive system: Frequency unknown: slight decrease in sperm concentration, the total number of sperm and their motility
- From the side of the kidneys and urinary tract: Frequency unknown: renal failure
- Other
The risk of developing malignant, especially lymphoproliferative diseases, increases with the use of some immunosuppressive drugs.
Drug Interactions
An increase in adverse events may occur with the recent or concomitant use of hepatotoxic (including alcohol) or hematotoxic and immunosuppressive drugs or when these drugs are started after treatment with leflunomide without the “washing” procedure (see “Special Instructions”).
No pharmacokinetic interaction between leflunomide (10–20 mg per day) and methotrexate (10–25 mg per week) was found in patients with rheumatoid arthritis.
Patients taking leflunomide are advised not to give colestyramine or activated charcoal, as this leads to a rapid and significant decrease in plasma concentration of A771726 (active metabolite of leflunomide). Believed that this is due to a violation of A771726 recirculation in the liver and small intestine and / or a violation of its gastrointestinal dialysis.
If the patient is already taking non-steroidal anti-inflammatory drugs (NSAIDs) and / or corticosteroids, they can continue to be taken after the start of treatment with leflunomide.
Enzymes involved in the metabolism of leflunomide and its metabolites are not exactly known. An in vivo study of its interaction with cimetidine (a non-specific inhibitor of cytochrome P450) showed the absence of a significant interaction. After the concomitant administration of a single dose of leflunomide to subjects receiving multiple doses of rifampicin (a non-specific cytochrome P450 inducer), 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.
In vitro studies have shown that A771726 inhibits the activity of cytochrome P4502C9 (CYP2C9). In clinical trials, there were no problems with the combined administration of leflunomide and NSAIDs metabolized by CYP2C9. With extreme caution,
leflunomide should be given along with other non-NSAID drugs metabolized by CYP2C9, such as phenytoin, warfarin and tolbutamide. An increase in prothrombin time has been reported with the simultaneous administration of leflunomide and warfarin.
In a study in which leflunomide was given to healthy female volunteers together with three-phase oral contraceptives containing 30 μg of ethinyl estradiol, no decrease in the contraceptive effect of the tablets was found, and the pharmacokinetics of A771726 completely fell within the prescribed range.
Currently, there is no information on the combined use of leflunomide with antimalarial drugs used in rheumatology (for example, chloroquine and hydroxychlorin), Au preparations (IM or oral), D-penicillamine, azathioprine and other immunosuppressive drugs (with the exception of methotrexate ) There is no known risk associated with complex therapy, especially with prolonged 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 (for example, methotrexate) are undesirable. Recent concomitant or subsequent use of potentially myelotoxic agents may be associated with a greater risk of hematologic effects. Immunosuppressants increase the risk of developing infections, as well as malignant, especially lymphoproliferative diseases.
Vaccination
There is no clinical evidence regarding the efficacy and safety of vaccination in patients treated with leflunomide. However, vaccination with live vaccines is not recommended. The long half-life of Arava should be considered when planning vaccination with a live vaccine after discontinuing Arava.
overdose Symptoms of
Chronic overdose has been reported in patients receiving leflunomide at doses up to 5 times the recommended daily dose, as well as reports of acute overdose in adults and children. In most cases, the development of undesirable effects was not reported. Emerging adverse events were comparable to the safety profile of leflunomide. The most commonly observed undesirable effects were diarrhea, abdominal pain, leukopenia, anemia, and elevation of liver function tests.
Treatment
In case of overdose or toxicity, it is recommended to take cholestyramine or activated charcoal to accelerate the body's cleansing.
Cholestyramine, taken by three healthy volunteers orally at
8 g three times a day for 24 hours, reduced blood plasma levels of A771726 by about 40% after 24 hours and by 49-65% after 48 hours.
It is shown that the introduction of activated carbon (powder, orally or via a gastric tube (50 g every 6 hours during the day) reduced the concentration of the active metabolite A771726 in plasma by 37% after 24 hours and by 48% after 48 hours.
These "laundering" procedures can be repeated on a clinical basis.
Studies with hemodialysis and HAPD (chronic outpatient peritoneal dialysis) indicate that A771726, the major metabolite of leflunomide, is unable to be excreted by dialysis.
Storage Conditions
Do not store above 25 ° C.
Shelf life
3 years.
Deystvuyushtee substance
Leflunomide
Sanofi-Aventis, France
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