New Report Sheds Light on Serious Safety Problems with Anti-Smoking Drug Varenicline (CHANTIX)

A new study citing “multiple safety problems” with the anti-smoking drug varenicline (CHANTIX) is spurring changes in Federal Aviation Administration (FAA) regulations.

The study, released by the Institute for Safe Medication Practices (ISMP) on May 22, 2008, examined case studies of side effects reported to the Food and Drug Administration (FDA) in people using varenicline.

The report finds that the drug’s side effects can range from vision impairment to psychiatric problems. And, according to the report, the organization has “immediate safety concerns about the use of varenicline among persons operating aircraft, trains, buses and other vehicles, or in other settings where a lapse in alertness or motor control could lead to massive, serious injury. … Based on reports of sudden loss of consciousness, seizures, muscle spasms, vision disturbances, hallucinations, paranoia and psychosis, we believe varenicline may not be safe to use in these settings.”

As a result of this report, the FAA, which had seen the report prior to its release, announced that the agency would no longer permit pilots or air traffic controllers to use varenicline, citing potential side effects that could pose a threat to the safe operation of aircraft.

According to the FAA, “approximately 150 pilots and 30 controllers are known to use the medication, although the exact number isn't known. To make sure all pilots and controllers got the word, FAA sent a notice to all registered pilots and controllers. It also alerted all aviation medication examiners across the country and notified major pilot associations and the air traffic controllers union, NATCA.”

Drug has dangerous side effects

ISMP, a nonprofit watchdog group, chose to study varenicline due to the unusually large volume of adverse events reported to the FDA in association with the drug. In the fourth quarter of 2007, the FDA received 988 reports of side effects caused by varenicline, including “serious accidents and falls, potentially lethal cardiac rhythm disturbances, severe skin reactions, acute myocardial infarction, seizures, diabetes, psychosis, aggression and suicide.”

The ISMP report states:

The FDA has recently issued a Public Health Advisory about one of the most marked adverse effects of varenicline, psychiatric symptoms that included “changes in behavior, agitation, suicidal ideation, attempted and completed suicide.” However, the FDA alert provided no information about the numbers of reported neuropsychiatric events among treated smokers. ISMP found the following:

• Psychiatric Adverse Effects. From May 2006 through December 2007, the FDA had received 227 domestic reports of suicidal acts, thoughts or behaviors, 397 cases of possible psychosis and 525 reports of hostility or aggression.

• Accidents and injuries. A total of 173 serious events described accidental injury, including 28 road traffic accidents and 77 falls, some leading to fractures of rib, facial bones, hand, ankle, spine and lower limbs. In these cases a variety of potential causes were identified, including loss of consciousness, mental confusion, dizziness and muscle spasms.

• Vision disturbance. At least 148 reports contained medical terms indicating vision disturbances, including 68 cases described as blurred vision and 26 terms indicating transient or other forms of blindness. This reported effect could also describe a mechanism that could or did contribute to accidents and injuries.

Public Citizen and ISMP are not the only members of the scientific community with serious concerns about varenicline.

In the May 2008 issue of the British Drug and Therapeutics Bulletin, the authors cited their concerns about the reports of psychiatric problems in people who use the drug.

“Given such concerns, marketing claims of a ‘favourable safety and tolerability profile’ are questionable,” the authors wrote.

The large number of adverse reactions in the ISMP study adds new urgency to our previous safety concerns about varenicline. It also highlights the dangerous inadequacy of the response of manufacturer Pfizer and the FDA to the rapidly increasing number of serious, life-threatening adverse events seen with this drug.

In September 2007, we warned Worst Pills, Best Pills News readers not to use varenicline until 2014 because of the inadequate amount of information about its safety and concerns raised by the increased amount of psychiatric adverse events that occurred in the randomized trials preceding its approval. In one of the preapproval studies, 6.8 percent of patients using varenicline had psychiatric side effects as opposed to only 2.4 percent of those given a placebo. The information revealed in this ISMP report reinforces our warning.

FDA should re-label drug

The ISMP study of 173 serious reports of accidents and injuries, including 28 road traffic accidents, calls for a much stronger warning than in the recently revised new labeling and new patient medication guide for the drug (last revised on May 16, 2008).

Varenicline’s new label states that “[p]atients should be advised to use caution driving or operating machinery until they know how quitting smoking with CHANTIX may affect them.” This caution is, in our view, not strong enough.

The inadequacy of the label change is further emphasized by the statement in the label that there were, in clinical trials with varenicline, “frequent” dizziness, disturbances in attention and sensory disturbances. None of these are compatible with safely driving (cars, buses, trains or planes) or operating machinery. Instead, we agree with the advice this week in the Drug and Therapeutics Bulletin that “Patients taking varenicline should, therefore, be advised not to drive or operate machinery [emphasis added] until they know whether the drug will impair their ability to do so.”

In addition to the warning against driving, we also urge that the FDA take further steps to protect the public health by requiring a black-box warning about driving and about adverse psychiatric effects such as suicidal thoughts or actions, depression and agitation and serious adverse skin reactions; requiring Pfizer to immediately send a dear doctor letter warning about these adverse effects; and requiring Pfizer to significantly strengthen the warning language in the label and patient medication guide.

What You Can Do

Patients are advised not to use varenicline until 2014, as there are many other safe, effective smoking cessation options.

Patients who do take varenicline should not drive or operate any machinery until they know whether the drug will impair their ability to do so. The frequent occurrence of dizziness, disturbances in attention and sensory disturbances is not compatible with safe driving.