Leflunomide

BRAND NAMES:

Arava: It contains the active ingredient leflunomide. It is available in the form of tablets used to treat pain relief.

MECHANISM OF ACTION:

Leflunomide is an immunomodulatory oral medication that becomes metabolized in the body to its active form metabolite, also known as teriflunomide. This metabolite acts by inhibiting the mitochondrial enzyme dihydro-orotate dehydrogenase. This action prevents the synthesis of ribonucleotide uridine monophosphate pyrimidine and decreases rUMP levels further activating P53. The activation of P53 restricts the progression of the G1 to S-phase in the cell cycle. This restriction halts the proliferation of activated and autoimmune lymphocytes, promoting anti-inflammatory and immunomodulatory effects.

PHARMACOKINETICS:

Absorption: After administering leflunomide, it is well absorbed, with peak plasma concentrations appearing 6–12 hours later.

Distribution: The average volume of distribution for leflunomide is 0.13 L/kg.

Metabolism: Leflunomide is a prodrug rapidly and nearly completely metabolized after oral administration to its pharmacologically active metabolite. This metabolite is responsible for nearly all of the drug activity in vivo. In vitro data show that leflunomide inhibits dihydroorotate dehydrogenase and has antiproliferative activity.

Elimination: Urine excreted 43% of the radioactivity, while feces eliminated 48%.

PHARMACODYNAMICS:

Leflunomide is a pyrimidine synthesis inhibitor given to adults to treat active rheumatoid arthritis. RA is an auto-immune disease marked by elevated T-cell activity. Activated T-cells, which rely on de novo pyrimidine synthesis, will be more vulnerable to leflunomide dehydrogenase inhibition than other cell types that use the pyrimidine salvage pathway.

ADMINISTRATION:

Leflunomide is available in tablets taken orally. It is typically taken once per day. Leflunomide may alleviate the symptoms of rheumatoid arthritis but does not cure it. Even if you are feeling fine, continue to take leflunomide. Do not stop taking leflunomide without consulting your doctor. Leflunomide tablets must be swallowed with water and may be taken with or without food. It is critical to swallow them whole, not chew or crush them. It's best to take leflunomide at the same time every day.

DOSAGE AND STRENGTH:

Leflunomide is available in the form of tablets having the strengths of 10 mg, 20 mg, and 100 mg.

DRUG INTERACTIONS:

The drug interaction of leflunomide may include

• Painkillers: ibuprofen, naproxen, and aspirin.
• Antidepressants: duloxetine
• Corticosteroids (prednisone)
• Arthritis: celecoxib, azathioprine, meloxicam, methotrexate.
• Anti-malaria- Hydroxychloroquine.

CONTRAINDICATIONS:

Teratogenicity with leflunomide contraindicated its use during pregnancy and warrants discretion in females during childbearing years. Discontinuing leflunomide due to concerns for fetal safety during pregnancy is indicated. The recommendation is that the patient stop leflunomide three months before pregnancy. Leflunomide is also contraindicated in patients with underlying interstitial lung disease and can cause symptoms within three months of starting leflunomide. Leflunomide is contraindicated in severe hepatic impairments due to hepatotoxicity.

SIDE EFFECTS:

Leflunomide may cause side effects.

• Diarrhea
• Vomiting
• Heartburn
• Headache
• Dizziness
• Weight loss
• Back pain
• Muscle pain
• Leg cramps
• Dry skin

Some side effects can be serious. It may include

• Rash with or without fever
• Hives
• Mouth sores
• Itching
• Difficulty breathing
• Chest pain
• Pale skin
• Overdose

Symptoms of overdose may include the following:

• Diarrhea
• Stomach pain
• Extreme tiredness
• Weakness
• Pale skin
• Fast heartbeat
• Shortness of breath

TOXICITY:

Leflunomide toxicity can affect the liver by causing acute drug-induced hepatic injury and affect the pulmonary system through pneumonitis and interstitial lung disease. Pancytopenia can also result from leflunomide toxicity. The treatment goal is the same as drug-induced hepatic injury and drug-induced pneumonitis, which is leflunomide-eliminating cholestyramine treatment.

STORAGE CONDITIONS:

Keep out of the reach of children. Store at room temperature. Protect from moisture and light.