Arava, 30 pcs., 20 mg, film-coated tablets
Arava should only be prescribed to patients 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 have previously received other basic drugs for the treatment of rheumatoid arthritis, which have hepato- and hematotoxic effects. The active metabolite of leflunomide, A771726, has a long half-life, usually ranging from 1 to 4 weeks. Due to the long half-life of leflunomide's active metabolite, A771726, serious adverse effects (e.g., hepatotoxicity, hematoxicity, or allergic reactions, see below) may occur or persist even if leflunomide treatment is discontinued. In this case, a “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 complete “washing” procedure is mandatory. Therefore, if such cases of toxicity occur or when switching to another basic drug (for example, methotrexate) after treatment with leflunomide, it is necessary to carry out a washout procedure (see below). Liver reactions Because the active metabolite of leflunomide, A771726, is protein bound and eliminated through hepatic metabolism and bile secretion, it is expected that plasma levels of A771726 may be increased in patients with hypoproteinemia. Arava is contraindicated in patients with severe hypoproteinemia or impaired liver function. (see section "Contraindications".). Rare cases of severe liver damage, in some cases fatal, have been reported during treatment with leflunomide. Most of these cases were observed during the first six months of treatment. Although the causal relationship of these adverse events to leflunomide has not been established, and in most cases there were several additional suspicious factors, strict adherence to treatment monitoring recommendations 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 once every 6 to 8 weeks. There are the following recommendations for adjusting the dosage regimen or discontinuing the drug, depending on the severity and persistence of the increase in ALT levels. If ALT is confirmed to be 2-3 times the upper limit of normal, reducing the dose from 20 mg to 10 mg per day may allow leflunomide to be continued, provided that this indicator is carefully monitored. If 2-3 times the upper limit of normal ALT persists, or if there is a confirmed rise in ALT levels greater than 3 times the upper limit of normal, leflunomide should be discontinued and a washout procedure should be initiated. Due to possible additive hepatotoxic effects, it is recommended to avoid alcohol intake during treatment with leflunomide. Hematological reactions A complete clinical blood count, including determination of the leukocyte formula and platelet count, should be performed before starting treatment with leflunomide, as well as every 2 weeks during the first 6 months of treatment and then every 6-8 weeks. In patients with pre-existing anemia, leukopenia and/or thrombocytopenia, as well as in patients with impaired bone marrow function or at risk of developing such disorders, the risk of hematological disorders increases. If this type of phenomenon occurs, a “washing” procedure should be used to reduce the level of A771726 in the blood plasma. If serious hematological reactions, including pancytopenia, occur, discontinue Arava and any other concomitant drug that suppresses bone marrow hematopoiesis and initiate a washout procedure. Concomitant use with other treatments There is currently no information available regarding the concomitant use of leflunomide with antimalarial drugs used in rheumatology (for example, chloroquine and hydroxychloroquine), intramuscular or oral gold preparations, D-penicillamine, azathioprine and other immunosuppressive drugs (except methotrexate). The risk associated with the prescription of complex therapy, especially with long-term treatment, is unknown. Since this type of therapy can lead to the development of additive or even synergistic toxicity (for example, hepato- or hematotoxicity), combinations of this drug with other basic drugs (for example, methotrexate) are not advisable. Switching to other treatments Because leflunomide has a long shelf life in the body, switching to another disease-modifying drug (eg, methotrexate) without an appropriate washout may increase the potential for additional risks even long after switching (eg, kinetic interactions, organ toxicity). . Likewise, recent treatment with hepatotoxic or haematoxic drugs (eg methotrexate) may result in an increased incidence of adverse events, so when starting treatment with leflunomide, it is necessary to carefully consider 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 necrolysis have been reported in patients receiving leflunomide. If skin and/or mucosal reactions occur, you should stop taking Arava and any other related drug and immediately begin a washout procedure. It is necessary to achieve complete elimination of the drug from the body. In such cases, re-prescribing the drug is contraindicated. Infections It is known that drugs like leflunomide, which have immunosuppressive properties, make patients more susceptible to various types of infections, including opportunistic infections (infections caused by fungi and microorganisms that can cause infections only in conditions of decreased immunity). Infectious diseases that arise are usually severe and require early and intensive treatment. If a severe infection occurs, it may be necessary to interrupt leflunomide treatment and initiate a washout procedure. Tuberculin-positive patients should be closely monitored due to the risk of reactivation of tuberculosis. Respiratory tract reactions Rare cases of interstitial pulmonary disease have been reported during leflunomide therapy. Symptoms such as cough and dyspnea may be a reason to stop taking leflunomide. Blood pressure Blood pressure levels should be monitored before starting treatment with leflunomide and periodically after starting it. Interactions Caution should be exercised when prescribing drugs 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 the father's sperm) when using leflunomide in men. Experimental data in this direction have not been carried out. To minimize the possible risk, men planning to have a child should stop taking leflunomide and use cholestyramine 8 g 3 times a day for 11 days or 50 g of powdered activated carbon 4 times a day for 11 days.
ARAVA TAB. P/P/O 20MG No. 30
Arava should only be prescribed to patients 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 have previously received other basic drugs for the treatment of rheumatoid arthritis, which have hepato- and hematotoxic effects. The active metabolite of leflunomide, A771726, has a long half-life, usually ranging from 1 to 4 weeks. Due to the long half-life of leflunomide's active metabolite, A771726, serious adverse effects (e.g., hepatotoxicity, hematoxicity, or allergic reactions, see below) may occur or persist even if leflunomide treatment is discontinued. In this case, a washout 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 complete laundering procedure is mandatory. Therefore, if such cases of toxicity occur or when switching to another basic drug (for example, methotrexate) after treatment with leflunomide, it is necessary to carry out a washout procedure (see below). Liver reactions Because the active metabolite of leflunomide, A771726, is protein bound and eliminated through hepatic metabolism and bile secretion, it is expected that plasma levels of A771726 may be increased in patients with hypoproteinemia. Arava is contraindicated in patients with severe hypoproteinemia or impaired liver function. (See section Contraindications.). Rare cases of severe liver damage, in some cases fatal, have been reported during treatment with leflunomide. Most of these cases were observed during the first six months of treatment. Although the causal relationship of these adverse events to leflunomide has not been established, and in most cases there were several additional suspicious factors, strict adherence to treatment monitoring recommendations 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 once every 6 to 8 weeks. There are the following recommendations for adjusting the dosage regimen or discontinuing the drug, depending on the severity and persistence of the increase in ALT levels. If ALT is confirmed to be 2-3 times the upper limit of normal, reducing the dose from 20 mg to 10 mg per day may allow leflunomide to be continued, provided that this indicator is carefully monitored. If ALT levels of 2 to 3 times the upper limit of normal persist, or if there is a confirmed rise in ALT levels greater than 3 times the upper limit of normal, leflunomide should be discontinued and a washout procedure should be initiated. Due to possible additive hepatotoxic effects, it is recommended to avoid alcohol intake during treatment with leflunomide. Hematological reactions A complete clinical blood count, including determination of the leukocyte formula and platelet count, should be performed before starting treatment with leflunomide, as well as every 2 weeks during the first 6 months of treatment and then every 6-8 weeks. In patients with pre-existing anemia, leukopenia and/or thrombocytopenia, as well as in patients with impaired bone marrow function or at risk of developing such disorders, the risk of hematological disorders increases. If this type of phenomenon occurs, a washout procedure should be used to reduce the level of A771726 in the blood plasma. If serious hematological reactions, including pancytopenia, occur, discontinue Arava and any other concomitant drug that suppresses bone marrow hematopoiesis and begin a washout procedure. Concomitant use with other treatments There is currently no information available regarding the concomitant use of leflunomide with antimalarial drugs used in rheumatology (for example, chloroquine and hydroxychloroquine), intramuscular or oral gold preparations, D-penicillamine, azathioprine and other immunosuppressive drugs (except methotrexate). The risk associated with the prescription of complex therapy, especially with long-term treatment, is unknown. Since this type of therapy can lead to the development of additive or even synergistic toxicity (for example, hepato- or hematotoxicity), combinations of this drug with other basic drugs (for example, methotrexate) are not advisable. Switching to other treatments Because leflunomide persists in the body for a long time, switching to another disease-modifying drug (eg, methotrexate) without proper washout may increase the possibility of additional risks even long after switching (eg, kinetic interactions, organ toxicity). Likewise, recent treatment with hepatotoxic or haematoxic drugs (eg methotrexate) may result in an increased incidence of adverse events, so when starting treatment with leflunomide, it is necessary to carefully consider 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 necrolysis have been reported in patients receiving leflunomide. If skin and/or mucosal reactions occur, stop taking Arava and any other related drug and immediately begin a washout procedure. It is necessary to achieve complete elimination of the drug from the body. In such cases, re-prescribing the drug is contraindicated. Infections It is known that drugs like leflunomide, which have immunosuppressive properties, make patients more susceptible to various types of infections, including opportunistic infections (infections caused by fungi and microorganisms that can cause infections only in conditions of decreased immunity). Infectious diseases that arise are usually severe and require early and intensive treatment. If a severe infection occurs, it may be necessary to interrupt leflunomide treatment and begin a washout procedure. Tuberculin-positive patients should be closely monitored due to the risk of reactivation of tuberculosis. Respiratory tract reactions Rare cases of interstitial pulmonary disease have been reported during leflunomide therapy. Symptoms such as cough and dyspnea may be a reason to stop taking leflunomide. Blood pressure Blood pressure levels should be monitored before starting treatment with leflunomide and periodically after starting it. Interactions Caution should be exercised when prescribing drugs 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 the father's sperm) when using leflunomide in men. Experimental data in this direction have not been carried out. To minimize the possible risk, men planning to have a child should stop taking leflunomide and use cholestyramine 8 g 3 times a day for 11 days or 50 g of powdered activated carbon 4 times a day for 11 days.