PROP Answers Questions Raised About Opioid Label Changes
PPM: One of the requested changes was to limit the duration of opioid prescriptions to 90 days. What does this mean—75 days of opioid therapy, and then 15 days to taper a patient off opioids? What about patients who have chronic pain (defined as pain lasting more than 90 days)? What is the PROP panel’s recommendation for managing these cases?
Dr. Kolodny: The requested label changes will not prohibit prescribing of opioids beyond 90 days or interfere in any way with clinical decision-making. This question indicates a misunderstanding of the petition and of the FDA’s regulatory role. The petition is not asking the FDA to impose strict limits on opioid prescribing. The FDA does not have the authority to regulate the practice of medicine. The FDA regulates drug companies, not doctors.
We are requesting that a 90-day duration of use be added to the label so that prescribers will be informed that daily use beyond 90 days has not been proven safe and effective. We are also interested in this change because it will prohibit drug companies from advertising long-term use of opioids for common chronic conditions. Presently, drug companies are able to get away with promoting long-term use of opioids because the current label is too broad.
PPM: What is the rationale for limiting the dose to a 100-mg morphine equivalent dose (MED)? Opioid response may vary depending on genetic polymorphisms and patient-specific physiologic differences. What about patients who have been safely and effectively maintained on higher opioid doses?
Dr. Kolodny: As explained above, our requested label changes will not interfere with clinical decision-making. If a clinician believes that a patient requires high doses of opioids, the clinician is permitted to prescribe above 100 mg MED.
It is true that individuals can vary in their response to opioids. But this is also true for other medications that have a suggested upper dose limit on their FDA-approved label. We believe that opioids, which can be especially dangerous when high doses are taken, should also have an upper dose limit listed on their label.
The 100 mg dose limit was selected because recent studies indicate that there is a significantly increased risk of overdose in chronic pain patients who are prescribed doses that exceed 100 mg MED.
PPM: If passed, would physicians be at risk for malpractice if they prescribed these medications off-label?
Dr. Kolodny: Prescribing medications off-label is very common and is not considered to be malpractice. At times, off-label use of a product is considered to be a standard of care. Off-label prescribing of medications is very common and is not considered inappropriate.
PPM: Would insurance companies cover such uses?
Dr. Kolodny: Insurance companies generally do not link their coverage decisions to a medication’s FDA-approved label. They tend to be more concerned with paying for an expensive medication when less expensive alternatives are available than they are with a medication’s approved indications. There are even examples of insurance companies preferring an off-label medication when it’s less expensive. For example, some companies prefer Neurontin over Lyrica for fibromyalgia, even though Neurontin is off-label for fibromyalgia and Lyrica is on-label.
PPM: Cancer versus non-cancer pain: How does the peripheral and central nervous system know that the painful etiology is cancer or non-cancer related? Are cancer patients more deserving of pain treatment than non-cancer patients?
Dr. Kolodny: We agree with concerns about lumping together diverse conditions into a single category defined as chronic non-cancer pain. The overly broad categories of “cancer pain” and “non-cancer pain” include diverse conditions that may respond differently to opioids and concerns about risks of long-term use apply in both populations. However, precedent does exist at the FDA for making a distinction between pain from cancer and pain from all other causes. For example, the FDA limits on-label use of transmucosal fentanyl products to breakthrough pain from cancer. With the exception of transmucosal fentanyl products, the current on-label indication on all opioid analgesics is non-specific. This allows drug companies to promote opioids for all types of pain, including pain from conditions where some experts recommend against opioid use, like fibromyalgia. Our requested label changes would close this loophole and create an incentive for drug companies to conduct long-term studies on treatment of different types of pain. If we continue to allow drug companies to promote long-term opioids for conditions where use has not been proven safe and effective, overprescribing is likely to continue unabated and needed research will not be carried out.