Thursday, January 15th 2009

By lee johnstone

Off-label drug use puts patients at risk in an alarmingly common rate. Most alarming is that this process is legal. The process involves prescribing pharmaceuticals for purposes for which the drug has never been tested or approved. While original drug approval requires rigorous testing, once approved drug usage is not regulated which allows doctors to prescribe drugs for conditions without research to support the safety or efficacy of such decisions. Off-label drug use is also legal for controlled substances, the most common being Actiq which is approximately 100 times stronger than morphine and intended for opiate tolerant individuals undergoing cancer treatment. The only legal issue is that no drug is allowed to be marketed for its off-label use.

While the United States Food and Drug Association (FDA) has issued warning on specific drugs and the unintended side effects they may have when prescribed off-label, Health Canada is lagging claiming to still be reviewing the data. In Canada, patients are prescribed off-label drugs thousands of times a day, and this practice is growing despite its lack of scientific support. From a total of 423 million prescriptions filled last year by drugstores Canada wide, it’s estimated that a quarter of them, or 89 million prescriptions, were written off-label.

Critics of the practice say that it amounts to an uncontrolled experiment on unsuspecting patients, and that most doctors don’t even know when the drug is being prescribed for a condition it has not been approved to treat. These critics want restrictions on off-label promotion of drugs toughened and some are calling on doctors to get informed consent from patients every time a drug is prescribed off-label, which is not required currently.

Doctors can look up a drug’s indication in drug reference guides, but this is a time consuming process that is likely to be overlooked when doctors are under pressure to see more and more patients. “The worrisome thing is, most doctors don’t know what’s on and what’s off-label use,” said Dr. David Wilkes, professor of medicine at the University of California Davis. “Then somebody tells you at a meeting or in the hallway that, ‘hey, I tried this on a patient and it helped her back pain or her anxiety or hot flashes.’ So you try it. The doctor didn’t say, ‘I tried this drug off-label.’”

Also, off-label drug use is sometimes necessary. In cases where all other approved drugs have failed an off-label drug can be the last resort. For example doctors are using Prozac and other drugs for obesity because there are so few effective alternatives. “If you think of the most common symptoms that people have: pain, nausea, can’t sleep – we have very limited therapies in all of those areas,” said Dr. Anne Holbrook, professor in the department of medicine and director of the division of clinical pharmacology and therapeutics at McMaster University.

Off-label prescribing is often unavoidable. In cases of children’s medications it has been estimated that fewer than 30 per cent of drugs used in children have ever been tested in children.

Drug safety expert Joel Lexchin, professor of medicine at York University, said all drugs carry risks that have to be weighed against the benefits. With certain drugs meant to treat a specific condition, “you figure, okay, the drug does have side effects but overall people [with the condition the drug is meant to treat] are better off using it than not,” said Lexchin. But the weighing of risks may not be the same for those with a different condition. He continued, “off –label prescribing means that, really, the data that you’re using is just no that good a lot of the time, in terms of knowing whether or not what you’re prescribing is the most appropriate medication, or whether the doses are right … Often it’s really a shot in the dark, and the patient(s) may be the guinea pigs.”

During Nov. 2008, researchers published a list of 14 widely prescribed drugs that urgently need to be studied about the safety of their off-label uses. On the list is Seroquel, which is an antipsychotic approved for schizophrenia but widely used to treat bipolar disorder, depression and anxiety. The drug runs $207 US per prescription.

“We are prescribing these [off-label] drugs that are often very, very expensive – it’s rarely a generic drug, it’s always some sort of trade name drug that has been marketed,” Wilkes said.

In 2005, Warner-Lambert, a Pfizer subsidiary, agreed to plead guilty and pay more than $430 million in connection with its illegal promotion of Neurontin in the 1990’s for unapproved uses. Sales reps provided one-on-one pitches to doctors about off-label uses, according to U.S. officials. Doctors were paid to attend expensive dinners, lavish weekends and trips to Florida and Hawaii during which presentations were made about unapproved indications for the drug. 

The U.S. Department of Justice said that the unlawful promotion meant patients who received the drug for unapproved and unproven uses “had no assurance that their doctors were exercising their independent and fully informed medical judgement.”

A defendant in another off-label drug suit is arguing another potential harm of off-label drug use. Their fear is that once the patent protection for a drug commonly used off-label expires, other manufacturers will start making and selling generic versions and they will be aimed to treat the conditions for which the original drug had been deceptively and negligently marketed to treat.

Tags: Dr. Anne Holbrook, Off-label, prescription