The precise mechanism of action of baclofen as a muscle relaxant and antispasticity agent is not fully understood. Baclofen inhibits both monosynaptic and polysynaptic reflexes at the spinal level, possibly by decreasing excitatory neurotransmitter release from primary afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect. Baclofen is a structural analog of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), an may exert its effects by stimulation of the GABAB receptor subtype. Baclofen when introduced directly into the intrathecal space permits effective CSF concentrations to be achieved with resultant plasma concentrations 100 times less than those occurring with oral administration. In people, as well as in animals, baclofen has been shown to have general CNS depressant properties as indicated by the production of sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression.

• GABLOFEN is a gamma-aminobutyric acid (GABA) ergic agonist indicated for use in the management of severe spasticity of cerebral or spinal origin in adult and pediatric patients age 4 years and above. • GABLOFEN should be reserved for patients unresponsive to oral baclofen therapy, or those who experience intolerable central nervous system side effects at effective doses. • Patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via an implantable pump. • Spasticity due to traumatic brain injury: wait at least one year after injury before considering GABLOFEN therapy.

• GABLOFEN is intended for use by the intrathecal route in single bolus test doses (via spinal catheter or lumbar puncture) and, for chronic use in the Medtronic SynchroMed® II Programmable Pump or other pumps labeled for intrathecal administration of GABLOFEN; Refer to the pump manufacturer's manual and follow the specific instructions and precautions for programming the pump and/or refilling the reservoir. • Screening: Patients who do not respond to a 100 mcg intrathecal bolus should not be considered for an implanted pump for chronic infusion. • Dose Titration: Spasticity may be necessary to sustain upright posture and balance in locomotion or may be useful to obtain optimal function and care.

• The most common adverse reactions in patients with spasticity of spinal origin were somnolence, dizziness, nausea, hypotension, headache, convulsions and hypotonia. • The most common adverse reactions in patients with spasticity of cerebral origin were agitation, constipation, somnolence, leukocytosis, chills, urinary retention and hypotonia.

• Hypersensitivity to baclofen. • Do not use GABLOFEN for intravenous, intramuscular, subcutaneous or epidural administration.

• Do not directly inject GABLOFEN into the pump catheter access port, as this may cause a life-threatening overdose. • Potential for contamination due to non-sterile external surface of prefilled syringe. • Potentially life-threatening CNS depression, cardiovascular collapse, and/or respiratory failure; Resuscitative equipment and trained staff must be available during screening, dose titration, and refills. • Overdose may cause drowsiness, lightheadedness, dizziness, somnolence, respiratory depression, seizures, rostral progression of hypotonia, and loss of consciousness progressing to coma. • Possible exacerbation of psychotic disorders, schizophrenia or confusional states.