Stability and Compatibility of Morphine-Clonidine Admixtures in an Implantable Infusion System

Abstract

Nonopioid analgesics are often coadministered with intrathecal morphine to increase efficacy. The purpose of this study was to evaluate stability and compatibility of morphine-clonidine admixtures with an implantable infusion system that is commonly used to treat pain patients. Infusion systems were filled with admixture and maintained at 37 degrees C for 90 days. Samples were collected monthly. Drug concentrations were determined using stability-indicating, high-performance liquid chromatography. For compatibility testing, individual materials comprising the fluid pathway of the device were immersed in clonidine solution and stored at 37 degrees C for various periods through 64 weeks and mechanical performance evaluated. After 3 months of containment in the infusion system, morphine and clonidine concentrations remained at > or = 94% of the theoretical starting concentrations. All device materials retained acceptable mechanical performance following clonidine exposure. These results demonstrate that morphine and clonidine are stable when combined in aqueous solution maintained at body temperature in an implantable infusion system for at least 3 months.

Abstracts from the 19th Annual North American Neuromodulation Society Meeting (NANS) Las Vegas, NV, USA December 10-13, 2015

“…In both cases reported here, the neuromodulation targets were caudal to the site of the lesion. A similar finding has been reported in the literature (5). DRG stimulation may ameliorate central pain by 1) orthodromic activation of spinocortical tracts to 'close the gate' on the central pain generator and/or by 2) modulation of the presumably-aberrant activity in primary sensory neurons.…”

“…Disclosures Introduction: It is well known that the current distribution at an electrode subjected to a time varying stimulus is non-uniform [1][2][3][4][5]. In most previous studies, the interface was modeled as a constant voltage source applied uniformly across the surface of the electrode or was assumed to be purely capacitive.…”

“…In 6 cases the previously implanted leads (5 percutaneous, 1 surgical plate) were connected to a new generator; while in the others (4, all percutaneous) new leads were used. Scoring tools were: Numeric Rating Scale (NRS) and Satisfaction (1)(2)(3)(4)(5). Patients were also asked if they would recommend the system to a close friend.…”

Current and Future Issues in the development of spinal agents for the management of pain

“…High concentration solutions, extreme pH (e.g.,<3) and formulations or drug combinations may exert effects upon pumping mechanisms. Each manufacturer may have compatibility protocols that require consideration for drugs to be delivered by such devices and literature exists for some agents and agent combinations (see, for example: [473,474]. Given the different mechanics of each pump (e.g., valved vs. peristaltic), compatibility in one pumping system dose not guarantee compatibility in another.…”

Intrathecal drug therapy for long-term pain management

“…If the known solubility of each medication is not exceeded, the likelihood of precipitation is low. 11,19,[104][105][106][107][108][109] However, solubility decreases unpredictably when multiple medications are combined in one solution. Caution should be used when combining multiple drugs at high concentrations.…”