Incivek, Xolair Linked to Severe, Sometimes Deadly Reactions: Report

Nearly a thousand deaths were reported to federal health officials involving drug hypersensitivity reactions over the last year, according to a new report, which suggests that the rate of problems seen with the asthma drug Xolair and the hepatitis C treatment Incivek are high enough to raise questions about whether they should remain on the market.  

On May 7, the Institute for Safe Medication Practices (ISMP) released its QuarterWatch (PDF) report, which monitors adverse event reports submitted to the FDA each quarter and identifies any potential trends seen among the drug side effects.

ISMP indicates that nearly 10% of all serious adverse events reported to the FDA over the past year involved drug hypersensitivity reactions, which was only outnumbered by the reports of nonspecific gastrointestinal ailments experienced after use of medications.

In all, the FDA logged 147,318 cases of serious adverse drug events from March 2012 through March 2013, with 13,042, or 8.9%, of those involving hypersensitivity. About 4,045 hypersensitivity reports resulted in serious injury or death, with at least 966 deaths reported.

ISMP indicates that potential hypersensitivity side effects of Incivek and Xolair raise particular concern, indicating that the hypersensitivity problems “were so frequently reported and severe that this risk should be carefully considered in deciding whether clinical use is appropriate.”

Incivek, manufactured by Vertex, was approved in 2011 for the treatment of hepatitis C in combination with other antiviral drugs. ISMP found that 60% of new users reported developing rashes, with 16% of that group having rashes that covered 50% or more of the body. There were 14 patient deaths reported and 104 cases of severe cutaneous reactions, outnumbering all other drugs.

In December 2012, the FDA issued a warning about the risk of serious skin reactions with Incivek, indicating that the medication has been associated with cases of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), which is a severe reaction that causes the skin to separate from the body and can be fatal.

The FDA required the manufacturers to add a new Incivek black box warning about the possible drug interactions, which is the strongest label warning that can be placed on a prescription medication. The prior label already contained information about the risk of serious skin reactions.

Treatment for SJS and TEN typically involves inpatient care at a hospital Burn Unit, and TEN can be fatal due to organ failure. It can also cause permanent blindness.

The asthma drug Xolair, however, accounted for more cases of anaphylaxis than any other drug reported. The drug was linked to 59 cases of anaphylactic shock.

Xolair already carries a “black box” warning due to the risk of anaphylaxis, which can cause trouble breathing, chest tightness, dizziness, fainting, itching, hives, and swelling of the mouth and throat. The warning indicates that some cases of anaphylaxis happened after the first dose, but patients could take Xolair for more than a year before anaphylaxis symptoms appear.

Xolair, manufactured by Genentech, was approved by the FDA in 2003 for use among adults and children over the age of 12 who suffer from moderate to severe persistent asthma caused by airborne allergens.

In 2009, the FDA warned that it found a disproportionate increase in heart problems linked to Xolair use. Side effects appeared to include ischemic heart disease, arrhythmias, cardiomyopathy, heart failure, pulmonary hypertension, cerebrovascular disorders and problems associated with blood clots, like pulmonary embolism.