“Breakthrough” pain, a transitory exacerbation of pain that has been generally stable, can be unpredictable and can escalate rapidly in patients with cancer. Oral opioid agents are not always the answer because they may act too slowly.
A nasal morphine-chitosan solution might be a fast, reliable, convenient way to tame breakthrough pain, say British researchers who conducted a pilot study of the drug combination. The nose offers advantages to enhance drug absorption, because it is a large, highly vascularized surface area and the venous blood drains from the nose directly into the systemic circulation, thus avoiding hepatic first-pass metabolism.
Chitosan, a bioadhesive material that binds to mucous membranes, provides other benefits. Morphine, a hydrophilic drug, is poorly absorbed nasally. Chito-san delays clearance and gives the drug more time to work. Adding chito-san to morphine boosts its nasal bioavailability from 10% to 54%, with a time to maximum concentration of 15 minutes. In contrast, even “immediate-release” morphine can take 20 to 30 minutes to begin relieving pain, with peak analgesia reached after one hour or more.
In the study of 14 patients, the researchers observed 20 episodes of breakthrough pain. The patients were given 5 to 80 mg of nasal morphine-chitosan in addition to their regularly prescribed analgesics. Nearly all of the patients rated the treatment as “good” to “excellent”; two found it only “fair.” Morphine-chitosan acted rapidly, with pain relieved or reduced after only five minutes and with maximal improvement reached after 45 minutes.
Side effects were slight and transient. Four patients reported “severe” taste disturbance, which was apparently dose-related. The most common adverse effect was sedation, reported during 16 episodes.
The researchers suggest that the formulation allows morphine to be given more conveniently, which might benefit patients at home and those who are vomiting or unable to swallow.