Arthritis Drug Leflunomide (ARAVA) Linked to Japanese Deaths from Lung Disease

Aventis, manufacturer of the widely prescribed arthritis drug leflunomide (ARAVA) said that five Japanese patients have died after taking its drug to treat arthritis and that it has asked doctors to take further precautions before prescribing the medication.

Sixteen people developed interstitial pneumonia, a debilitating lung condition, after taking the drug. Five of them, aged between 57 and 71, subsequently died, according to the company. The company has warned doctors not to prescribe the drug to patients with respiratory problems, a history of interstitial pneumonia or lung problems. It will further advise that X-rays be conducted on any patient who is to receive the drug for the first time.

“We were aware of the side effects ... but we did not imagine such a frequency. We will promptly investigate whether the drug was responsible,” Aventis Pharma Japan’s Vice President Masaki Noguchi said.

Since its launch in Japan last September, some 3,400 people had taken the drug, which is used to treat rheumatoid arthritis — a chronic illness that can result in inflammation of the joints, stiffness, loss of movement and sometimes deformity.

Overseas, the drug has been administered to some 400,000 people and 80 people have developed interstitial pneumonia, according to the company. Arava was put on the market in 1998 in the U.S. and has since been made available in 72 countries. In 2002, Arava world-wide sales came to $300 million, according to a company statement.

Public Citizen’s Health Research Group has been trying to get the FDA to ban this drug because of liver toxicity and because it appears to cause hypertension. We first warned readers in the December 2001 Worst Pills, Best Pills News that leflunomide was a Do Not Use drug because it causes life-threatening liver toxicity. In March 2002, we petitioned the Food and Drug Administration (FDA) asking that leflunomide immediately be removed from the market because of this liver toxicity (see Worst Pills, Best Pills News June 2002). In our petition we noted that from when the drug was first marketed in the U.S. in late September 1998 through September 2001, leflunomide had been associated with at least 130 severe liver adverse reactions including 56 hospitalizations and 22 deaths, two of whom were patients in their twenties. For 12 of these deaths, leflunomide-induced liver toxicity appears to be the most plausible explanation.

What You Can Do

As we have previously advised Worst Pills, Best Pills News readers, DO NOT USE leflunomide.