Leflunomide

Leflunomide is a drug that causes modification of the immune system while undergoing treatment (this modification or alteration is a part of the treatment so that is why it is also called as immunomodulatory agent) and disease modifying anti-rheumatic agent.


Mechanism of action:
Leflunomide causes inhibition of:

1. Multiplication or propagation of T cells

2. Production of autoantibodies by B cells.

Leflunomide inhibit the enzyme Dihydroorotate dehydrogenase (DHODH). This causes Uridine 5’-monophosphate (UMP) not to be produced.

UMP is essential in two ways:

1. It is an important component of RNA synthesis.

2. It is pioneer in making nucleotide which is composed of thymidine, which is required for DNA synthesis.

As a result there is a cell arrest.

Action:

It is a reversible inhibitor of DHODH. It helps to reduce pain and inflammation and along with this function it also helps to reduce the decay or erosion cause to the bones or any other body parts due to inflammation.

It can be used alone or in combination with other drugs like methotrexate.

Pharmacokinetics:
It is well absorbed orally. Its half life is 13-19 days. The binding of this drug to serum albumin is about more than 85%. It is excreted both through biliary and renal excretion. It readily converts to metabolites and the metabolites are excreted in the urine and feces.

The metabolite which is still effective goes back to do some work. Cholestyramine enhances leflunomide excretion.

Adverse effects:
It may cause headache, diarrhea (loose bowels) and nausea. Alopecia, Weight loss or weight gain and allergic reactions like skin rash are its rare side affects.

Contraindications:
It is contraindicated in pregnancy.

Precautions:
As this drug may cause an increase in liver enzyme level so it must be used with caution in liver diseases.