Life-Threatening Respiratory Depression: Concomitant use of pms-BACLOFEN with opioids may result in respiratory depression, profound sedation, syncope, and death.
Limit dosages and durations to the minimum required.
Follow patients for signs and symptoms of respiratory depression and sedation.
Abrupt Drug Withdrawal: Following abrupt withdrawal of baclofen, delirium, visual and auditory hallucinations, convulsion (status epilepticus), dyskinesia, confusional state, psychotic disorder, mania or paranoia, anxiety with tachycardia and sweating, insomnia, rhabdomyolysis and worsening of spasticity have occurred. Therefore, except for serious adverse reactions, the dose should be reduced slowly when the drug is discontinued (over a period of approximately 1-2 weeks).
For the intrathecal formulation of baclofen, it has been reported that clinical characteristics of withdrawal may resemble autonomic dysreflexia, malignant hyperthermia, neuroleptic-malignant syndrome, or other conditions associated with a hypermetabolic state or widespread rhabdomyolysis.
Neonatal Withdrawal: Drug withdrawal reactions including, irritability, high-pitched crying, tremor, hypertonicity, excessive sucking, disordered sleep, hyperthermia, mottling, and postnatal convulsions have been reported in neonates after intrauterine exposure to oral baclofen. Neonates with risk of intrauterine exposure to pms-BACLOFEN should be carefully monitored for the development of signs consistent with withdrawal. If clinical manifestations of withdrawal develop, non-pharmacologic measures should be considered (for instance, minimizing sensory or environmental stimulation, maintaining temperature stability, increasing the frequency of feeds). Initiation of pharmacotherapy may be considered in neonates with moderate to severe signs of withdrawal to prevent further complications (see Use in Pregnancy & Lactation).
Neurologic: Respiratory Depression: Baclofen has been associated with central nervous system (CNS) depression including sedation, somnolence, loss of consciousness, as well as serious cases of respiratory depression. Patients with compromised respiratory function, respiratory or neurological disease, renal impairment and the elderly are at higher risk of experiencing these severe adverse effects. Concomitant use of CNS depressants with baclofen is also a contributing factor.
Concomitant Use with Opioids: Concomitant use of opioids with baclofen potentiates the risk of respiratory depression, profound sedation, syncope, and death. Patients who require concurrent treatment with opioids or other CNS depressants should be observed carefully for signs and symptoms of CNS depression, and the dose of baclofen or opioid should be reduced accordingly.
Psychomotor Impairment: Baclofen may be associated with adverse effects such as dizziness, sedation, somnolence and visual impairment (see Adverse Reactions), which may impair the patient's reaction. Patients experiencing these adverse reactions should be advised to refrain from driving or using machines. Patients should also be cautioned that the central nervous system effects of baclofen may be additive to those of alcohol and other CNS depressants.
Renal Impairment: After oral baclofen dosing, severe neurological outcomes and symptoms of overdose including clinical manifestations of toxic encephalopathy (e.g., confusion, hallucination, somnolence, depressed level of consciousness and coma) have been reported in patients with renal impairment. Patients with renal impairment should be closely monitored for prompt diagnosis of early signs and/or symptoms of toxicity (e.g., somnolence, lethargy) (see Overdosage). Caution should be exercised while administering pms-BACLOFEN in patients with renal impairment because baclofen is primarily excreted unchanged through the kidneys. In patients dependent on dialysis, a particularly low dose of pms-BACLOFEN should be selected (i.e., approximately 5 mg daily). Unscheduled hemodialysis may be considered a treatment option in cases of severe baclofen toxicity as hemodialysis has been reported to effectively remove baclofen from the body, alleviate clinical symptoms of overdose and shorten the recovery time in these patients.
End Stage Renal Failure: pms-BACLOFEN should be administered to end stage renal failure patients only if the expected benefits are considered acceptable, given potential risks.
Concomitant medications that may impact renal function: Particular caution is required when combining baclofen to drugs or medicinal products that can significantly impact renal function. Renal function shall be closely monitored and pms-BACLOFEN daily dosages adjusted accordingly to prevent baclofen toxicity (see Interactions).
Stroke: Baclofen has not significantly benefited patients with stroke. These patients have also shown poor tolerability to the drug.
Epilepsy: Extreme caution should be exercised in patients with epilepsy or a history of convulsive disorders. In such patients, the clinical state and electroencephalogram should be monitored at regular intervals during therapy, as deterioration in seizure control and EEG has been reported occasionally in patients taking baclofen.