Daklinza Side Effects Linked to Cases of Liver Failure

Recent warnings issued by Japanese health regulators suggest that side effects of the recently introduced hepatitis C drug Daklinza may increase the risk liver failure. 

Daklinza (daclatasvir) is a Bristol-Myers Squibb drug that was just approved in the United States in July, for treatment of patients with chronic hepatitis C genotype 3. It is a 12-week course of once-per-day oral tables that are believed to have a 96% chance of successfully curing patients who have not experienced cirrhosis.

The regimen costs $63,000 for a 12 week treatment program, and it must be used with Sovaldi in the U.S., a Gilead hepatitis drug that costs $84,000 for 12 weeks. The high cost of $1,750 per day for the two pills, has drawn fire from critics as being excessive, so the potential safety concerns raise further concerns.

This week, the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) ordered new label warnings (PDF, translation required) on Daklinza and another similar drug that is not approved in the United States, Sunvepra (asunaprevir). The warnings indicate that patients may experience a sudden decrease in liver function that could result in liver failure from Daklinza or Sunvepra.

Daklinza has been available in Japan longer than the U.S., and the PMDA warns that those treated with the drug have reported decreased albumin levels, prolonged prothrombin time, hepatic encephalopathy and hepatic failure.

The Japanese regulators have received at least 37 reports of decreased liver function from Daklinza and Sunvepra users, including one death report. While liver problems are frequently associated with hepatitis C, Japanese investigators have been unable to rule out a causal relationship between the drugs and the liver problems in 21 of those cases.

The Phase III study provided by Bristol-Myers Squibb to the FDA, known as ALLY-3, looked at only 152 patients with chronic hepatitis C genotype 3 and found no treatment-related serious adverse events, and no discontinuations due to adverse events. Bristol-Myers Squibb has indicated that the most frequent side effects of Daklinza were headache, fatigue, nausea and diarrhea.