History:

The use of baclofen can be traced back to the 1920s when it was used as a potential antiepileptic drug, and was also found to be safe and effective for reducing spasticity. However, in the 1980s it was determined to be more effective when delivered directly to the central nervous system.  Dr. Tony Yaksh studied the analgesic effects of baclofen when administered intra-spinally to primates in 1981. The intraspinal administration of baclofen for hypertonicity was first studied with rabbits in 1984 by Richard Penn, MD – who ultimately expanded his research to the intrathecal administration of baclofen in humans.

As a drug that is used to manage spasticity in adults and children with spinal cord injuries, baclofen is now also used for conditions such as cerebral palsy and multiple sclerosis. Technological advancements enabled medical professionals to avoid severe side-effects of oral medication, and it was determined that a superior effect on spasticity is attained using intrathecal baclofen.

Michael Saulino MD, PhD has recently published literature pertaining to baclofen trialing and pump management in Intrathecal Drug Delivery for Pain and Spasticity – a book edited by doctors Tim Deer, Sudhir Diwan, and Asokumar Buvanendran.

In the early 1990s, baclofen gained FDA approval for intrathecal administration and in 1992 was approved for administration through the implantable infusion pump.

About Baclofen:

Baclofen is structurally related to gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which acts on GABA-B receptors in the brainstem and dorsal horn of the spinal cord. It reduces muscle tone by suppressing the release of an excitatory neuro-transmitter.

At Hartley Medical, we have extensive experience with baclofen and its intraspinal application – having quantitatively analyzed it for more than twelve years. Treatment with baclofen must take into consideration that the drug has a very small therapeutic window and presents significant withdrawal issues that must be carefully managed.

The product can be compounded in a vast range of concentrations exceeding 4,000 mcg/ml. However, some reports have proposed baclofen’s instability in concentrations exceeding 2,000 mcg/ml. Hartley Medical has expansive knowledge of this drug for intraspinal use and pump administration; particularly in relation to enduring storage within an implantable pump for 60 to 90 days. If you would like to discuss this further, please contact me at questions@hartleymedical.com.

The number of patients treated with baclofen is expanding by approximately 10,000 new patients per year, and the need for intrathecal baclofen therapy is here to stay because it does not cure spasticity – it manages it.

Baclofen in Combination:

Baclofen can be safely compounded with many medicinals such as fentanyl, sufentanil, ziconotide, and more commonly, morphine and hydromorphone. It has a good shelf life and sustained stability within an implantable pump.

A study performed by Donald A. Godwin, PhD, Nae-Hwa Kim, and Robert Zuniga, MD and published in Hospital Pharmacy in 2001 showed baclofen and clonidine to be stable in borosilicate test tubes stored at 37 degrees C for 10 weeks. Although the study was not conducted within an implantable device, the results showed chemical integrity in combination and resistance to degradation attributed to body temperature. The stability and compatibility of baclofen and morphine were studied and published in the International Journal of Pharmaceutics. This study determined that both drugs maintained structure when introduced into an implantable device, stored at body temperature, for 30 days.

Furthermore, in a study published in the March/April 2008 edition of Pain Physician, preclinical data in rats revealed that when baclofen is co-administered with morphine or fentanyl, baclofen exhibits additive nociceptive effects and significantly suppressed retching and vomiting induced by morphine, as well as inhibited place preference elicited by morphine or fentanyl. The study suggests that “potential future combination products of morphine and baclofen [“morphlofen”]) may be of interest.”

For more drug reviews, visit Hartley Medical’s Knowledge Center by clicking here.

Sources:

http://www.baclofen.info/patient-information.htm

http://www.drugs.com/newdrugs/fda-approves-movement-disorder-cns-therapeutics-gablofen-baclofen-severe-spasticity-2435.html

http://www.factsandcomparisons.com/assets/hospitalpharm/sept2001_peer1.pdf

http://www.painphysicianjournal.com/2008/march/2008;11;201-214.pdf