Leflunomide

Leflunomide

Leflunomide is a useful disease modifying drug in the armamentarium for treatment of Rheumatoid arthritis. It is relatively faster acting than Sulfasalazine and even Methotrexate if a loading dose is used. Its effect is generally evident by 4-6 weeks and maximizes by 4-6 months of treatment. The drug is a long acting one and remains in the body for a long-time even after discontinuation. Therefore, in case of serious side effects (see below) a wash out procedure is necessary (see below). The side effects known to occur with this drug are Diarrhea particularly where a loading dose is used. For this reason a lot of Rheumatologists have now discontinued the practice of using a loading dose and start with a dose of 10 to 20 mg per day in which case the chances of loose motions have reduced but the time to take effect has now increased. Now a 20 mg per day dose would take longer to show benefit and may be as long as 2 months sometimes a little longer also. It can be taken at any time of the day, on empty stomach or after meals   Though there is no recommendation in the medical literature on this, Leflunomide has been used in combination with methotrexate in cases of aggressive Rheumatoid arthritis. This often results in better control of the arthritis but with a higher incidence of side effects.   Skin rashes can occur with this drug and patients are advised to discontinue this drug the moment they begin to experience generalized itching or a rash. Hypertensive patients are advised to watch their blood pressure as this drug can sometimes be responsible for increased blood pressure. This drug is metabolized by the liver and can sometimes cause hematologic abnormalities hence periodic monitoring of blood tests is mandatory. For the first 6 months frequent blood counts, liver function tests and creatinine levels need to be checked. Thereafter the duration can be increased slightly if the drugs is well tolerated. One adverse effect to watch for is signs of tingling, numbness or even burning sensation in the lower limbs while on this drug. Should this occur, the drug needs to be discontinued immediately. One complaint that we face very often is significant hair loss while on this drug. Since Rheumatoid arthritis affects women more than men this complaint assumes a lot of significance and may require the dose to be reduced or the drug to be changed. A hypersensitivity phenomenon may cause Progressive cough with breathlessness which is a rare but serious complication and requires urgent measures.   The drug has adverse effect on the developing fetus and therefore pregnancy and lactation should be strictly avoided while on the drug and for 2 years on its discontinuation, unless a wash out is employed and its blood levels are checked and found to be safe. Unfortunately blood levels are not checked in India and hence we need to go by the guidelines of following the wash out period and waiting for two years. There have been cases in the literature where successful pregnancies have occurred with normal children where the duration was shorter than 2 years however the literature is sketchy on this point and one cannot use this as a norm. Any inadvertent pregnancy while on the drug needs to be terminated. Hence this drug should be avoided in child bearing age. Wash-out procedures (any one can be used)

  1. Cholestyramine 8gm of three times/d x 11 days
  2. Activated charcoal 50gm four times daily x 11 days.

Symptoms to watch for & report

  • Oral ulcers
  • Intolerance( nausea, vomiting, hair loss etc)
  • Persistent (> 4-5 days) cough and breathlessness – report immediately

§ Abnormal blood tests – report immediately NOTE: You should always get instructions & follow up advice of your rheumatologist. leflunomide should not be taken without regular supervision of a rheumatologist .