Arava

Arava (leflunomide) is a medicine used to treat rheumatoid arthritis (RA) and other inflammatory joint diseases. It belongs to a class of drugs known as desmethyl azothiomidines (DMARDs), which are used to suppress the immune system and reduce inflammation in the joints.

The active ingredient leflunomide is a pyrimidine synthesis inhibitor, which means it acts on immune system cells that play a role in the development of joint inflammation in rheumatoid arthritis. Arava helps slow the progression of the disease, reduce inflammation, reduce pain and improve joint function.

The drug is available in the form of tablets for oral administration. It is usually taken daily, but the dosage and dosage schedule may vary depending on your doctor's recommendations and the severity of your illness.

Indications Arabs

1. Rheumatoid Arthritis: The drug is used to reduce inflammation in the joints, reduce pain and improve joint function in patients with rheumatoid arthritis.

Arava may also sometimes be used to treat other inflammatory conditions, such as psoriatic arthritis and inflammatory bowel disease arthritis, but this decision is made on a case-by-case basis by your doctor.

Release form

Arava is usually available in tablet form for oral administration.

Pharmacodynamics

Leflunomide, the active ingredient in Arava, has anti-inflammatory and immunomodulatory properties, which allows it to effectively treat rheumatoid arthritis (RA) and other inflammatory diseases.

The principal action of leflunomide is associated with its ability to inhibit the activity of the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme plays an important role in the synthesis of pyrimidine nucleotides necessary for cell division, including lymphocytes. Blocking DHODH results in decreased production of pyrimidine nucleotides, which inhibits cell division and activation of immune cells such as lymphocytes.

As a result of the use of leflunomide, the immune response and inflammation are suppressed, which helps reduce inflammatory processes in the joints and reduce the symptoms of rheumatoid arthritis.

It should be noted, however, that the exact mechanism of action of leflunomide in the treatment of rheumatoid arthritis is not fully understood, and some of its effects may also be related to other mechanisms, including antioxidant and anti-inflammatory properties.

Pharmacokinetics

• Absorption: Leflunomide is well absorbed from the gastrointestinal tract after oral administration. Maximum plasma concentration is usually achieved after 6-12 hours.
• Bioavailability: The bioavailability of leflunomide is approximately 80-90%.
• Distribution: Leflunomide has a large volume of distribution, which means that it is widely distributed throughout the tissues of the body. It binds strongly to plasma proteins.
• Metabolism: The main route of metabolism of leflunomide is hydrolysis, which results in the formation of the active metabolite - terephthalamide. This metabolite also has anti-inflammatory activity.
• Excretion: The main mechanism for excretion of leflunomide from the body is the biliary tract. It is excreted in the form of metabolites in the feces, and also in small quantities through the kidneys.
• Half-life: The half-life of leflunomide from the body is long, approximately 14-18 days.

Dosing and administration

• Dosage: The generally recommended starting dose of leflunomide is 100 mg per day. This can be taken as one leflunomide tablet (100 mg) daily.
• Taken with food: Leflunomide is usually taken with food as this may help reduce possible gastrointestinal side effects.
• Dosage regimen: An increased dose may be used at the beginning of treatment (usually 100 mg for three days), followed by a standard maintenance dose.
• Maintenance dose: After the initial increased dose, leflunomide is taken at a dose of 20 mg daily. However, the dosage may be adjusted according to your doctor's recommendations.
• Monitoring: It is important to regularly monitor the patient's condition, including checking liver function and other indicators, to assess the effectiveness of treatment and prevent possible side effects.
• Duration of treatment: The duration of treatment and dosage regimen are determined by your doctor depending on the severity of the disease and individual response to treatment.

Use Arabs during pregnancy

• Fetotoxicity and teratogenicity:

  • Leflunomide has demonstrated teratogenic and fetotoxic effects in animal studies, causing developmental defects and fetal death (Brent, 2001). In one mouse study, leflunomide caused multiple external, skeletal, and visceral abnormalities in fetuses (Fukushima et al., 2007).

• Recommendations for use:

  • The American College of Rheumatology (ACR) recommends stopping leflunomide at least 24 months before conception. In case of pregnancy while taking leflunomide, a washout procedure with cholestyramine is recommended to accelerate the elimination of the drug (Alothman et al., 2023).

• Human studies:

  • A study of 289,688 pregnant women in Montreal found no significant increase in the risk of major congenital anomalies, prematurity, low birth weight, or spontaneous abortion in women who took leflunomide during pregnancy (Bérard et al., 2017). li>
  • Other studies have also shown that leflunomide was not associated with a significant increase in the risk of congenital anomalies when the washout procedure was followed (Chambers et al., 2010).

• Practical guide:

  • Women taking leflunomide and planning pregnancy are advised to discontinue the drug and undergo a washout procedure with cholestyramine to minimize the risk of teratogenic effects. In case of unintended conception while taking leflunomide, it is important to consult a doctor and consider a washout procedure (Casanova Sorní et al., 2005).

Contraindications

• Pregnancy and lactation: Leflunomide may cause harm to the fetus and is therefore absolutely contraindicated during pregnancy. Also, the drug is not recommended during breastfeeding.
• Serious liver disorders: In the presence of severe liver disease, leflunomide should be used with caution or avoided altogether.
• Serious renal impairment: The drug should also be used with caution in patients with severe renal impairment.
• Serious infections: The use of leflunomide may increase the risk of developing infections, especially in patients with concomitant conditions associated with impaired immune system.
• Hypersensitivity to leflunomide or other components of the drug: Any known hypersensitivity is a contraindication to the use of the drug.
• Acute or chronic alcoholic pathology: Leflunomide can cause liver damage, so its use in alcoholic pathology requires special caution.
• Acute infectious diseases: During an acute infection, leflunomide is usually temporarily suspended due to possible suppression of the immune system. Systems.

Side effects Arabs

• Increased risk of infections: Taking leflunomide may increase the risk of developing infections because it affects the immune system.
• Increased fatigue: Fatigue and weakness may be some of the most common side effects of taking leflunomide.
• Diarrhea: Some patients may experience diarrhea while taking leflunomide.
• Elevated liver enzymes: Leflunomide may cause elevated liver enzymes in the blood, which may indicate liver damage.
• Decreased appetite and changes in taste preferences: Some patients may experience a decrease in appetite or changes in taste preferences while taking leflunomide.
• Elevated blood creatinine levels: Leflunomide may cause increased blood creatinine levels, which may be a sign of impaired kidney function.
• Increased blood pressure: Some patients may experience increased blood pressure while taking leflunomide.
• Sleep disorders: Some patients may experience sleep disturbances such as insomnia or excessive sleepiness.

Overdose

• Increased side effects of the drug, such as nausea, vomiting, diarrhea, fatigue and others.
• Increased activity of liver enzymes, which may indicate liver damage.
• Changes in blood pressure, heart rate and other cardiovascular responses may occur.

Interactions with other drugs

• Teratogenic drugs: Leflunomide may enhance the teratogenic effects of other drugs. Therefore, the use of leflunomide concomitantly with drugs such as methotrexate is contraindicated, especially in pregnant women.
• Drugs metabolized through cytochrome P450: Leflunomide may affect the activity of cytochrome P450 enzymes, which may lead to changes in the concentration of other drugs in the blood. This may be important when used together with drugs such as warfarin, phenytoin, theophylline, etc.
• Immunosuppressants: Concomitant use of leflunomide with other immunosuppressants, such as cyclosporine or tacrolimus, may enhance their therapeutic effect and increase the risk of infections.
• Drugs that cause hepatotoxicity: Concomitant use of leflunomide with other drugs that can cause hepatotoxicity, such as methotrexate or dapsone, may increase the risk of liver damage.
• Drugs that cause hematologic disturbances: Concomitant use of leflunomide with other drugs that may cause hematologic disturbances, such as methotrexate or anticoagulants, may increase the risk of bleeding or other disturbances.