Five patients who used Aventis Pharma Ltd.’s Arava rheumatoid arthritis drug have died of pneumonia over the past four months since the drug was launched in Japan, the pharmaceutical company said Tuesday.
Eleven other users of the drug, generically known as leflunomide, have developed interstitial pneumonia, according to the Japanese unit of the Franco-German pharmaceutical giant.
The Tokyo-based subsidiary called for doctors to refrain from prescribing the drug to patients who previously suffered from interstitial pneumonia or lung fibrosis, or exhibit respiratory symptoms like coughing.
Aventis Pharma said it has monitored 3,400 users of the drug since its launch in Japan in September and started receiving reports about the pneumonia in late October.
It has thus far confirmed just the five deaths, reports of which started coming in Jan. 6. The victims ranged in age from 57 to 71. In two of the cases, doctors attributed the cause of death to the drug, but the relationship between the drug and the remaining three deaths is unknown, the firm said.
Because there is a chance the deaths resulted from interaction with other drugs or other illnesses, the drugmaker said it would convene its safety evaluation committee Saturday to study the five cases in greater depth.
The Health, Labor and Welfare Ministry approved Arava for use last April based on overseas clinical trial data, without conducting a “phase three” trial in Japan, which tests if the drug works in large numbers of patients and is the last step before a drug can be approved for regular use, Aventis Pharma said.
In place of conducting clinical tests in Japan, Aventis was required to implement an “all patients surveillance” on the first 3,000 patients to obtain data on the drug’s safety and effectiveness. During this program, the drug was provided only to medical institutions that consented to the monitoring program.
Arava was put on the market in Europe and the United States in 1998 and grossed 31.9 billion yen in 2002 global sales.
Overseas, some 80 users of the drug have reportedly developed interstitial pneumonia, but no deaths have been reported, the firm said.