ARAVA Film-coated tablet Ref.[8128] Active ingredients: Leflunomide

The treatment should be initiated and supervised by specialists experienced in the treatment of rheumatoid arthritis and psoriatic arthritis.

Alanine aminotransferase (ALT) or serum glutamopyruvate transferase (SGPT) and a complete blood cell count, including a differential white blood cell count and a platelet count, must be checked simultaneously and with the same frequency:

• before initiation of leflunomide,
• every two weeks during the first six months of treatment, and
• every 8 weeks thereafter (see section 4.4).

Posology

In rheumatoid arthritis: leflunomide therapy is usually started with a loading dose of 100 mg once daily for 3 days. Omission of the loading dose may decrease the risk of adverse events (see section 5.1).

The recommended maintenance dose is leflunomide 10 mg to 20 mg once daily depending on the severity (activity) of the disease.

In psoriatic arthritis: leflunomide therapy is started with a loading dose of 100 mg once daily for 3 days.

The recommended maintenance dose is leflunomide 20 mg once daily (see section 5.1). The therapeutic effect usually starts after 4 to 6 weeks and may further improve up to 4 to 6 months. There is no dose adjustment recommended in patients with mild renal insufficiency. No dose adjustment is required in patients above 65 years of age. Paediatric population

Arava is not recommended for use in patients below 18 years since efficacy and safety in juvenile rheumatoid arthritis (JRA) have not been established (see sections 5.1 and 5.2).

Method of administration

Arava tablets are for oral use. The tablets should be swallowed whole with sufficient amounts of liquid. The extent of leflunomide absorption is not affected if it is taken with food.

Symptoms

There have been reports of chronic overdose in patients taking Arava at daily doses up to five times the recommended daily dose, and reports of acute overdose in adults and children. There were no adverse events reported in the majority of case reports of overdose. Adverse events consistent with the safety profile for leflunomide were: abdominal pain, nausea, diarrhoea, elevated liver enzymes, anaemia, leucopenia, pruritus and rash.

Management

In the event of an overdose or toxicity, colestyramine or charcoal is recommended to accelerate elimination. Colestyramine given orally at a dose of 8 g three times a day for 24 hours to three healthy volunteers decreased plasma levels of A771726 by approximately 40% in 24 hours and by 49% to 65% in 48 hours.

Administration of activated charcoal (powder made into a suspension) orally or via nasogastric tube (50 g every 6 hours for 24 hours) has been shown to reduce plasma concentrations of the active metabolite A771726 by 37% in 24 hours and by 48% in 48 hours. These washout procedures may be repeated if clinically necessary.

Studies with both hemodialysis and CAPD (chronic ambulatory peritoneal dialysis) indicate that A771726, the primary metabolite of leflunomide, is not dialysable.

3 years.

Blister: Store in the original package.

Bottle: Keep the bottle tightly closed.

Blister: Aluminium/Aluminium blister. Pack sizes: 30 and 100 film-coated tablets.

Bottle: 100 ml HDPE-wide-necked bottle, with screw cap with integrated desiccant container, containing either 30 or 100 film-coated tablets.

Not all pack sizes may be marketed.

No special requirements for disposal.