Tramadol gets rejected by FDA owing to safety concerns

USA: The US Food and Drug Administration (FDA) has issued a complete response letter ("CRL") regarding the New Drug Application ("NDA") for Avenue Therapeutics' IV tramadol. The CRL stated that although the pivotal Phase 3 clinical trials demonstrated statistically significant outcomes for all of the primary and many secondary endpoints, the FDA has determined that it cannot approve the application in its present form.

Intravenous (IV) tramadol is meant for the management of adults with moderate to moderately severe pain in a medically supervised healthcare setting.

The CRL stated that the NDA could not be approved in its current form because IV tramadol, which is intended to treat patients in acute pain who require an opioid, is not safe for the intended patient population. Specifically, if a patient requires an analgesic between the first dose of IV tramadol and the onset of analgesia, a rescue analgesic would be needed. The likely choice would be another opioid, which would result in opioid "stacking" and increase the likelihood of opioid-related adverse effects. Other than this potential safety concern, the FDA did not identify a safety signal in Avenue's clinical development program. In addition, the CRL stated that the FDA requires an adequate terminal sterilization validation prior to NDA approval, which is planned for later this quarter.