Health News Digest

May 7, 2012

The Dangers Of Going Off-Label With Prescription Drugs

Medical building

By  Michael D. Shaw

Simply put, when your doctor prescribes a drug for some use that is not specifically approved, this is called an “off-label” prescription. It is noted that perhaps 20% of all prescriptions are written for off-label use, and a majority of these uses lack conventional scientific support. On the other hand, in the absence of any approved therapy, innovative off-label use can be beneficial. One easily accepted example would be the use of a drug approved only for adults as a last ditch therapy for a child with the indicated disease.

But what if off-label use is encouraged primarily to save money, when an approved drug does exist for the particular indication? According to the European Alliance for Access to Safe Medicines (EAASM), this is precisely what is happening in the case of pharmaceutical therapy for Neovascular (wet) age-related macular degeneration—a leading cause of blindness in the elderly population of the developed world.

Specifically, this is the matter of off-label use of Avastin® (bevacizumab)—an anti-cancer drug—instead of Lucentis® (ranibizumab injection), approved for the treatment of patients with Neovascular (wet) age-related macular degeneration. (Also known as Wet AMD.)

EAASM issued a report in April, 2011 entitled “When Is a Medicine Not a Medicine?” which examined this issue:

[M]any doctors—instead of using the licensed product—are using a medicine (Avastin®) designed for use in seriously ill cancer patients, to treat patients with age-related blindness. Avastin® is not available in the right dosage and it is not supposed to be injected in the eye. Physicians are deciding themselves upon the “right” dosage, changing the dosage and refilling the product into syringes. Doctors or hospitals sometimes may also decide to store the leftover product (although it is not designed for storage after opening) and use the leftovers on other patients. Such behavior brings with it additional risks of infection or contamination of the product.

Why is this happening? The answer is money. Cost differentials between licensed and unlicensed substitutes can be significant (reflecting the research costs, time and effort to test the safety/efficacy of the medicine and market it, and in part simply because hospitals and doctors carry little of the risk and none of the costs of assessing the long term safety of the product in clinical trials). In this case, “compounding” (breaking up a single dose into several doses) creates considerable cost savings.

For some years, authorities have voiced concerns over the safety and efficacy of Avastin® in this usage. Indeed, hundreds of adverse reactions—including complete vision loss—have been reported. But, the cost factor is always there, and patients can feel the pressure.

The Macular Disease Society, based in the UK, observes that it is unreasonable to burden the patient with the decision of which drug to choose. “If doctors and other experts cannot agree on which drug to use it is not reasonable to expect a patient to decide and we have doubts patients would have the issues properly explained to them.”

That’s one reason why the CATT study (Comparison of Age-related macular degeneration Treatment Trials) was undertaken. The full two year data from this study of 1107 patients with wet AMD has just been released. Among the findings…

  • There is 30% higher risk in overall serious systemic adverse events with Avastin® versus Lucentis®
  • There were significantly more gastrointestinal disorders in patients treated with Avastin® compared to Lucentis®

Further to the matter of “additional risks of infection or contamination of the product”—as highlighted by EAASM—in September, 2011, the US Department of Veterans Affairs decided to restrict the use of bevacizumab (Avastin®) in Wet AMD to one patient dose per vial, following reports of infectious endophthalmitis (an inflammatory condition of the intraocular cavities) caused by contaminated compounded bevacizumab.

Another example of the consequences of going off-label involves the improper use of certain preoperative skin disinfectant products containing alcohol, including various available solutions of chlorhexidine. Bear in mind that approved products such as ChloraPrep® are provided with special applicators, ensuring that only the proper dose will be transferred to the patient’s skin. Inappropriate “bulk” application of chlorhexidine solution has been known to cause operating room fires, given the flammability of alcohol.

While obvious abuses can be cited, going off-label remains a complex issue. After all, the Feds have long held that the FDA does not “practice medicine,” and once a drug is on the market, doctors have been given latitude in how they will prescribe it. The conventional wisdom once proclaimed that the cure to off-label prescribing would be third party payers—especially the government—discouraging reimbursement for such practices. Ironically, as we have seen, what is occurring is just the opposite.

More studies like CATT would surely be helpful.