Last Updated on February 19, 2017 by Dr.Derek Fhisher
Most popular brand: Arava
Active ingredient: Leflunomide
Available dosage forms: 10, 20 mg
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Leflunomide general information
Leflunomide was designed especially for rheumatoid disease. Gold salts have been put to use for more than 50 years in curing rheumatoid disease. I’ll talk about the major impacts on the body here. Chronic disease places increased demands on a kid’s body and makes a need for extra calorie intake.
Crico-arytenoid joint involvement within the larynx can result in hoarseness and vocal cord collapse. Care is required during intubation along with the anaesthetist have to be aware of the complication. For instance, slower growth might occur within the jaw on account of arthritis within the TMJ (temporomandibular joint). This is usually to be done to be able to escape to some extent the harmful unwanted side effects of toxins within the commercial medicines.
There is a variety of ailments proven to be brought about by smoking. Because there are different kinds of arthritis, affecting young and old, the individual should heed your physician for advice about what to do, what things to take, what things to eat, what things to avoid, etc.. It’s because some therapies may be good for somebody with rheumatoid arthritis, however it’s not good for those with osteoarthritis. Some medicines may be harmful to someone with this specific variety of arthritis, but these may be rather useful for somebody with a different form of arthritis. RA mainly impacts the joints and it’ll make them stiff, painful, swollen and from time to time, unstable and deformed, but it could also lead to fatigue and you couuld have problems with your heart as well as your eyes. Here are a few organic methods to treat rheumatoid arthritis.
Considerations have to be made regarding each individual’s individual reactions to side results and contraindications of varied arthritis drugs. Medication doses ought to be adjusted regularly as the little one grows to be sure the appropriate dosages are used. These drugs are frequently used together with NSAIDs. It truly is known to become an allergic reaction to particular medicines or particular allergic diseases. You must call the physician if symptoms appear suddenly, or if they’re accompanied by means of a fever or rash. Due to their many unwanted side effects, glucocorticoids must be utilized with caution.
Biological agents are a new category of medications made from synthetic proteins. There are a number of RA medications which are compatible with breast-feeding. They ought to be taken only under a doctor’s advice together with other medications. Have to be taken a few weeks to determine if helping control pain as well as inflammation. That is why someone should continually need vitamins, healthful food regimen, adequate and normal exercise, and clean environment. Side effects can consist of skin rash, mouth sores, kidney complications, a minimal blood count or anemia.
Treatment aims not to care for pain and inflammation except to blunt the destructive course of action.” These medications might be used to take care of children with arthritis and relevant conditions. Treatment for RA can likewise involve occupational as well as physical therapy. Along with exercises, physical therapists too can employ various other treatments including heat along with ice therapy, including massage. It can decrease pain and boost function. Any synovium-lined structure could be involved like tendon sheaths and bursae.
There are many common misconceptions about arthritis. Before addressing the issue, it’s good to grasp some basic guidelines about the thyroid. The diagnosis of rheumatoid disease may be hard and various other conditions ought to be considered. This is actually the complete list of all probable symptoms of the syndrome. They don’t have an impact on the underlying disease. Joint problems can eventually become a leading long-term symptom.
There are contraindications. Before taking consult your doctor.
The commercial name abroad (abroad) – Afiancen, Arabloc, Artrilab, Cleft, Filartros, Inmunoartro, Lara, Lefluar, Lefno, Lefra, Lisifen, Lunava, Repso, Rumalef.
All immunosuppressants and antirheumatic products base here.
All the drugs used in rheumatology, here.
Ask a question or leave a review about the medicine (please do not forget to specify the name of the drug in the body of the message) here.
Preparations containing Leflunomide (Leflunomide, ATC (ATC) code L04AA13):
Common forms of release (more than 100 proposals in Moscow pharmacies)
Arava (leflunomide original) – the official instruction manual. Prescription drug information is intended only for healthcare professionals!
Clinico – pharmacological group:
Basic antirheumatic drug.
Mode of action
Basic antirheumatic drug. It has antiproliferative, immunomodulatory (immunosuppressant) and anti-inflammatory effect. The active metabolite of leflunomide A771726 inhibits enzyme degidroorotat – dehydrogenase and has antiproliferative effects. A771726 in vitro inhibits mitogen-induced proliferation and DNA synthesis of T – lymphocytes. The antiproliferative activity A771726 appears on – apparently, at the level of pyrimidine biosynthesis, since the addition of cell culture eliminates the inhibitory effect of uridine metabolite A771726. Using radioisotope ligands shown that selectively binds A771726 degidroorotat dehydrogenase enzyme, which accounts for its property to inhibit this enzyme and lymphocyte proliferation at G1 phase. Lymphocyte proliferation is one of the key stages in the development of rheumatoid arthritis.
A771726 simultaneously inhibits the expression of receptors for Interleukin – 2 (CB – 25) and core antigens Ki – 67 and PCNA, cell cycle-related.
The therapeutic effect of leflunomide was shown in several animal models of autoimmune diseases including rheumatoid arthritis.
Leflunomide decreases the symptoms and slow the progression of joint damage, with the active form of rheumatoid arthritis and psoriatic arthritis.
The therapeutic effect is usually seen after 4 – 6 weeks and may increase in the future, for 4 – 6 months.
Absorption and distribution
When ingestion absorbed from 82% to 95% of the drug. Leflunomide can be taken with food. Leflunomide is rapidly converted to its active metabolite A771726 (primary metabolism in the intestinal wall and metabolism in the “first pass” through the liver). In plasma, urine or feces were seen only trace amounts of unchanged leflunomide. The sole determining metabolite A771726 is responsible for the basic properties of the drug in vivo.
After a single dose of the dose Cmax A771726 determined after 1 – 24 hours. From – for a very long T1 / 2 of A771726 (approximately 2 weeks) used a loading dose of 100 mg per day for 3 – days. This has allowed to quickly reach an equilibrium state plasma concentrations of A771726. Without a loading dose to achieve Css would require a 2 – month drug. In studies with multiple assignment A771726 drug pharmacokinetic parameters were dose-dependent within the dose range of 5 to 25 mg. In these studies, the clinical effect was closely related to the plasma concentration of A771726 and a daily dose of leflunomide. At a daily dose of 20 mg the mean plasma concentration of A771726 at equilibrium have the value of 35 pg / ml.
In a rapid plasma A771726 binding to albumin. Unbound fraction of A771726 is about 0.62%. Binding of A771726 more variable and somewhat reduced in patients with rheumatoid arthritis or chronic renal failure.
Leflunomide is metabolised to one primary (A771726) and several secondary metabolites, including 4 – trifluorometilalanin. The biotransformation of leflunomide to A771726 and subsequent metabolism of A771726 are controlled by several enzymes, and occur in microsomal and other cellular, fractions. Interaction studies with cimetidine (non-specific inhibitor of cytochrome P450) and rifampicin (non-specific inducer of cytochrome P450) showed that in vivo CYP – enzymes involved in the metabolism of leflunomide only marginally.
Removing A771726 from the body and is characterized by slow clearance of 31 ml / h. Leflunomide is excreted in the feces (probably due to biliary excretion) and in the urine. T1 / 2 is about two weeks.
Pharmacokinetics in special clinical situations
The pharmacokinetics of A771726 in patients on chronic ambulatory peritoneal dialysis is similar to that in healthy volunteers.
A more rapid elimination of A771726 observed in patients on hemodialysis, which is not connected with the extraction of drug in the dialysate and displacing it from its association with the protein. Although A771726 clearance is increased to about 2 times the final T1 / 2 is similar to that in healthy individuals, as simultaneously increasing Vd.
Data on the pharmacokinetics of the drug in patients with hepatic insufficiency are absent.
The pharmacokinetics in patients under 18 years have not been studied.
In elderly patients (65 years and older) pharmacokinetic data correspond roughly to the middle age group.
Indications for use of the drug Arava ®
- as a reference drug for the treatment of adult patients with active rheumatoid arthritis to reduce the symptoms and delay the development of structural damage of joints;
- the active psoriatic arthritis.
The use of the drug should begin under the supervision of a physician who is experienced in the treatment of rheumatoid arthritis and psoriatic arthritis.
In rheumatoid arthritis, early treatment drug administered in a loading dose of 100 mg (100 mg tablet form) 1 time per day for 3 days. However, exclusion of the use of a loading dose may decrease the risk of adverse reactions (especially on the part of the digestive tract and effect on the activity of liver enzymes in the blood). The recommended maintenance dose is 20 mg 1 time per day. When you receive a maintenance dose of 20 mg 1 time per day just from the beginning of treatment (that is, without receiving a loading dose) efficacy in rheumatoid arthritis is not decreased. In case of poor tolerability of 20 mg may reduce the dose to 10 mg 1 time a day (in the form of tablets of 10 mg or 20 mg).
When psoriatic arthritis in the early treatment of drug administered in a loading dose of 100 mg 1 time per day for 3 days. The maintenance dose is 20 mg 1 time a day.
If both readings therapeutic effect usually appears after 4 weeks and may increase further to 4 – 6 months. Therapy is usually held for a long time.
You do not need dose adjustment for patients older than 65 years.
The currently available is not enough experience to give specific guidance on the dosage regimen in patients with impaired renal function. Note that the active metabolite A771726 Leflunomide has high affinity for proteins.
Patients with impaired hepatic function: recommendations for dose adjustment or cancellation of the drug, depending on the severity or persistence of increased activity of ALT in patients receiving the drug, see “Cautions”.
Determination of the frequency of adverse reactions: very often (> 1/10), often (> 1/100, but < 1/10), rare (> 1/1000, but < 1/100), rare (> 1/10 000, but < 1/1000), very rare (< 1/10, 000), the frequency is unknown (on the basis of the available data to estimate the frequency is not possible).
Cardio – vascular system: often – increased blood pressure.
From the digestive system: often – diarrhea, nausea, vomiting, anorexia, loss of the oral mucosa (eg, aphthous stomatitis, ulceration of the oral mucosa), abdominal pain, increased liver transaminases (especially ALT, at least – GGT and alkaline phosphatase), hyperbilirubinemia; rarely – a violation of taste sensations; rarely – hepatitis, jaundice / cholestasis; very rarely – pancreatitis, severe liver injury such as liver failure, acute hepatic necrosis that may be fatal.
With the respiratory system: rarely – interstitial lung disease (including interstitial pneumonitis), which can be fatal.
On the part of metabolism: often – a slight increase in CPK, weight loss; rarely – hypokalemia, hyperlipidemia weak, insignificant hypophosphatemia; the frequency is unknown – a slight increase in the level of LDH, hypouricemia by urikozuricheskogo effect.
From the nervous system: often – headache, dizziness, paresthesia; rare – anxiety; very rarely – peripheral neuropathy.
From the bone – muscular system: the frequency is unknown – tenosynovitis and tendon rupture (causal relationship to leflunomide treatment has not been established).
Skin and subcutaneous tissue disorders: often – increased hair loss, eczema, itching, dry skin; very seldom – toxic epidermal necrolysis (Lyell’s syndrome), erythema multiforme, Stevens – (could not be determined at present causal relationship to leflunomide treatment, but it can not be ruled out) Johnson; the frequency is unknown – cutaneous lupus erythematosus, pustular psoriasis or worsening of psoriasis.
Allergic reactions: often – easy maculo – papular rash and other types of rash; rarely – urticaria; very rarely – severe anaphylactic / anaphylactoid reactions, vasculitis, including cutaneous necrotizing vasculitis (from – for the underlying disease causal relationship to leflunomide treatment can not be established).
From the hematopoietic system: often – leukopenia (leukocytes> 2000 / L); rarely – anemia, slight thrombocytopenia (platelets < 100 000 = “” – = “” 2000 = “” p = “”>
From the reproductive system: the frequency is unknown – a slight decrease in sperm concentration, total sperm count and their motility.
Infectious and parasitic diseases: seldom – the development of serious infections and sepsis, which can be fatal. Medicinal products with immunosuppressive action can make the patient more susceptible to infections, including opportunistic infections. May slightly increase the incidence of rhinitis, bronchitis and pneumonia.
Benign, malignant and unspecified neoplasms: it is known that when using certain immunosuppressive drugs increases the risk of malignancy, particularly the risk of lymphoproliferative disorders.
Common reactions: often – fatigue.
Contraindications to the use of the drug Arava ®
- violations of the liver;
- severe immunodeficiency (including AIDS);
- The expressed disturbances of bone marrow hematopoiesis, or significant anemia, leucopenia, thrombocytopenia resulting from other causes (other than rheumatoid arthritis and psoriatic arthritis);
- severe, uncontrolled infections;
- renal failure, moderate and severe (from – to the small clinical experience);
- severe hypoproteinemia (including with nephrotic syndrome);
- lactation (breastfeeding);
- childbearing age in women who do not intend or are unable to use reliable methods of contraception during treatment with leflunomide, and then as long as the plasma levels of the active metabolite remains above 0.02 mg / l;
- men intending to conceive a child (they should be warned about the possible adverse effect of leflunomide on the sperm of the future father) (during treatment with leflunomide must use reliable methods of contraception);
- age of the patients at least 18 years of age (lack of efficacy and safety data in this group of patients);
- increased sensitivity to the drug.
- the patients with interstitial lung disease (increased risk of interstitial lung disease);
- anemia patients, leukopenia, thrombocytopenia and disorders of bone marrow hematopoiesis in history; patients who have recently received or are receiving leflunomide concurrently with drugs with immunosuppressive or gematotoksicheskim action; patients not associated with rheumatoid arthritis, significant deviations from the norm of hematological parameters before the start of treatment with leflunomide (requires frequent hematological control);
- the age of 60 years, the simultaneous use of other neurotoxic medications, and diabetes mellitus (increased risk of developing peripheral neuropathy);
- renal failure mild (creatinine clearance less than 80 mL / min and 50 mL / min) (limited clinical experience).
Use of the drug Arava ® Pregnancy and breastfeeding
Clinical studies evaluating leflunomide in pregnant women have been conducted. However A771726 teratogenic in animals (rats, rabbits), and may have adverse effects on the fetus in humans.
Leflunomide is contraindicated in pregnant women or women of childbearing age who are not using reliable contraception during treatment with leflunomide and some – time after this treatment (waiting period or abbreviated period of “laundering”; see below.). It must be ensured in the absence of pregnancy prior to treatment with leflunomide.
Patients should be informed that as soon as there comes a missed period or if there is another reason to assume pregnancy, they should immediately inform your doctor to do a pregnancy test; in the case of a positive pregnancy test physician should discuss with the patient the possible risk to this pregnancy. It is possible that the rapid decline in the level of the active metabolite in the blood with the help of the drug described below will launch the procedure at the first delay of menses to reduce the risk to the fetus from leflunomide.
When you receive negligence of leflunomide in the I trimester of pregnancy in patients with rheumatoid arthritis with subsequent cancellation of the preparation and conduct of the procedure of “washing” with kolestiraminom (see. Below), significant defects were detected in 5.4% of live births, compared with 4.2% of such in the group of women with rheumatoid arthritis who were not taking leflunomide and 4.2% thereof in a group of healthy pregnant women who were not taking leflunomide.
Women who are taking leflunomide and want to become pregnant, it is recommended to follow one of the following procedures to make sure that the fetus is not exposed to toxic concentrations of A771726 (control concentration below 0.02 mg / l), as According to available data the concentration of the active metabolite in plasma is less than 0.02 mg / L (0.02 mg / ml) suggests a minimum teratogenic risk.
The waiting period
One can expect that A771726 plasma concentration may be higher than 0.02 mg / l for a long period. It is believed that the concentration can be less than 0.02 mg / l in 2 years after stopping the treatment with leflunomide.
The first time A771726 plasma concentration is measured after a two-year waiting period.
After that you need to measure the concentration of A771726 in plasma, at least 14 days.
The procedure of “laundering”
After stopping treatment with leflunomide:
- colestyramine 8 g 3 is assigned for 11 days;
- Alternatively 50 g of charcoal, pulverized, 4 administered for 11 days.
Regardless of the procedure of “washing” it is necessary to inspect two separate tests at intervals of at least 14 days and to wait six weeks from the moment when the concentration of drug in plasma is first recorded below 0.02 mg / l, up to the moment of fertilization .
It is necessary to inform women of childbearing age that should go through 2 years after stopping treatment with leflunomide, before they can try to get pregnant. If a 2 – year waiting period under reliable contraception seems unreasonable, it may be advisable to carry out the procedure of “laundering” as a preventive measure. And cholestyramine and activated charcoal may influence the absorption of oestrogens and progestogens, so reliable oral contraceptives do not provide an absolute guarantee in the period of “money” with cholestyramine or activated charcoal. It is recommended to use alternative methods of contraception.
In experimental animal studies have shown that leflunomide or its metabolites are excreted in breast milk. Therefore, women in period of breast-feeding should not be administered leflunomide.
Depending on the importance of treatment to the mother must decide whether conducted breastfeeding or leflunomide treatment is started, in which breastfeeding should be avoided.
Application for violations of liver function
Do not use this in the human liver.
Application for violations of renal function
Do not use this with moderate or severe renal insufficiency (from – to the small experience of clinical observations). No dose adjustment is required in patients with renal insufficiency, mild patients.
The use in elderly patients
You do not need dose adjustment for patients older than 65 years.
Use in children
It is not recommended to use the drug in children and adolescents under the age of 18 years, as data on efficacy and safety in this group of patients are missing.
The drug Arava ® can be administered only after a thorough medical examination.
Effects on ability to drive vehicles and management mechanisms
of the pharmacies vacation Terms
The drug is released with a prescription.