PO Baclofen Rx Dosing & Concentration o Initial dose & titration o Simple continuous vs. Flex Intrathecal baclofen pharmacokinetics Onset of action . o Bolus 0.5-1hr o Continuous infusion 6-8hrs Peak effect o Bolus ~4 hrs o Continuous infusion 24-48hrs ... If oral baclofen relieves symptoms:
Feb 17, 2020 · Note: Lower initial doses (5 to 10 mg/day) and more frequent titration intervals (every 3 days) have also been described (Milla 1977). Higher maximum daily doses (up to 200 mg/day) have been described in some patients in a retrospective review, usually the …
DOSING SCHEDULE FOR BACLOFEN 10 MG TABLETS Insert Date Morning NoonEveningDaily Dose Start 001 tablet10 mg After 5-7 days 0 1 tablet 1 tablet 20 mg After 5-7 days 1 tablet 1 tablet 1 tablet 30 mg After 5-7 days 1 tablet 1 tablet 2 tablets 40 mg After 5-7 days 1 tablets 2 tablets 2 tablets 50 mg After 5-7 days 2 tablets 2 tablets 2 tablets 60 mg
Jun 03, 2021 · For persistent or chronic hiccups, oral baclofen dosing starts with an initial dose of 5–10 mg, administered three times a day and titrating up to a maximum dose of 45 mg/day. 37 For muscle spasms or musculoskeletal pain, oral baclofen dosing starts with an initial dose of 5–10 mg, administered —one to three times a day as needed. 2Cited by: 1
Oral antispasmodics can be weaned, one drug at a time beginning with oral baclofen after ITB begins. Assessment should occur within 24 hours of a dose change. For adults, daily dose increases may be 5% to 15% once every 24 hours for cerebral-origin spasticity and 10% to …Cited by: 23
Best practices for intrathecal baclofen therapy: screening test. Gastroenterol Res Pract ; : References in languages other than English and unpublished reports were not included. While there are no published studies evaluating the comparative effectiveness of pharmacologic agents for baclofen withdrawal, best practice guidelines recommend benzodiazepines and cyproheptadine as first-line adjuncts to ITB for the management of ITB withdrawal. BMJ Case Rep ; : Indian J Nephrol ; 22 3 : — Biomed Res Int ; : Baclofen and alcohol use disorders: breakthrough or great white elephant? Effective management requires the prompt cessation of baclofen administration and supportive measures to ensure adequate circulatory and respiratory function until the toxic effects of the drug subside. This is only a brief summary of general information about this medicine. Mix while adding Simple Syrup, NF in incremental proportions to almost mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add a sufficient quantity of vehicle to make mL. Do not freeze or heat sterilize. Adv Pharmacol ; 58 : 19— Baclofen has proven to be a valuable pharmacologic agent for patients with spasticity. Keep from freezing. Baclofen may be a useful alternative when other treatments have failed. There have been several cases of baclofen overdose described in the literature with notable variation in dosing thresholds and clinical presentations. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. Ghanavatian S, Derian A. Oral: Note: Dose-related side effects eg, sedation may be minimized by slow titration; lower initial doses than described below 2. Baclofen toxicity should be considered in the setting of hypotonia and flaccid paralysis, while spasticity and hyperreflexia are more commonly encountered with baclofen withdrawal. Clin Transl Gastroenterol ; 9 : Leo RJ, Baer D. Drug information provided by: IBM Micromedex. Br J Psychiatry ; : — The anticholinergic effects of cyproheptadine can be additive with other anticholinergics. Volume of distribution: Pediatric patients age range: 2 to 17 years: Oral: Highly variable: 1. Keating GM. Note: This is not a comprehensive list of all side effects. Gut ; 50 1 : 19— In general, withdrawal from oral baclofen is most often associated with the development of mild symptoms, while withdrawal from ITB is more likely to present with severe, life-threatening withdrawal syndrome. Alcohol Clin Exp Res ; 34 11 : — Baclofen as add-on to standard psychosocial treatment for alcohol dependence: a randomized, double-blind, placebo-controlled trial with 1 year follow-up. Ackland GL, Fox R. Froestl W. Cyproheptadine for intrathecal baclofen withdrawal. Efficacy and safety of oral baclofen in the management of spasticity: a rationale for intrathecal baclofen. Introduction: Intrathecal baclofen ITB therapy aims to reduce spasticity and provide functional control. Takotsubo cardiomyopathy as a reversible complication of intrathecal baclofen withdrawal. Baclofen withdrawal syndrome most commonly occurs in the setting of ITB administration and is most effectively treated with re-initiation or supplementation of baclofen dosing. Lioresal: 0. Arch Phys Med Rehabil ; 84 : — Note: To minimize dose-related side effects eg, sedation , lower initial doses eg, 2. Dispense in a light-resistant container. JAMA ; : — Intrathecal baclofen for severe spinal spasticity. J Clin Pharmacol ; 54 5 : — Oral indications include management of reversible spasticity associated with spinal cord injury and multiple sclerosis. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. View more articles. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Efficacy, tolerability, and safety of low-dose and high-dose baclofen in the treatment of alcohol dependence: a systematic review and meta-analysis.
Abrupt discontinuation of intrathecal baclofen, regardless of the cause, has resulted in sequelae that include high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, which in rare cases has advanced to rhabdomyolysis, multiple organ-system failure, and death. Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. Advise patients and caregivers of the importance of keeping scheduled refill visits and educate them on the early symptoms of baclofen withdrawal. Give special attention to patients at apparent risk eg, spinal cord injuries at T-6 or above, communication difficulties, history of withdrawal symptoms from oral or intrathecal baclofen. Consult the technical manual of the implantable infusion system for additional postimplant clinician and patient information. Excipient information presented when available limited, particularly for generics ; consult specific product labeling. Lioresal: 0. Inhibits the transmission of both monosynaptic and polysynaptic reflexes at the spinal cord level, possibly by hyperpolarization of primary afferent fiber terminals, with resultant relief of muscle spasticity. Oral: Rapid; absorption from the GI tract is thought to be dose dependent; in pediatric patients age range: 2 to 17 years with cerebral palsy, absorption from GI tract highly variable and delayed reported time lag: 0. Volume of distribution: Pediatric patients age range: 2 to 17 years: Oral: Highly variable: 1. Intrathecal bolus: 30 minutes to 1 hour; Continuous infusion: 6 to 8 hours after infusion initiation. Peak effect: Intrathecal bolus: 4 hours effects may last 4 to 8 hours ; Continuous infusion: 24 to 48 hours. Oral: Management of reversible spasticity associated with multiple sclerosis or spinal cord lesions. Limitations of use: Patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via an implantable pump. For spasticity of spinal cord origin, chronic infusion via an implantable pump should be reserved for patients unresponsive to oral baclofen therapy, or those who experience intolerable CNS side effects at effective doses. Patients with spasticity due to traumatic brain injury should wait at least one year after the injury before consideration of long term intrathecal baclofen therapy. In a randomized, placebo-controlled study in patients with alcoholic liver disease, treatment with baclofen significantly improved the proportion of patients who achieved and maintained alcohol abstinence Addolorato Based on the American College of Gastroenterology ACG for Alcoholic Liver Disease and American Association for the Study of Liver Diseases AASLD guidelines for the management of adult patients with ascites due to cirrhosis , baclofen may be used to reduce alcohol craving and consumption in patients with ascites due to alcoholic liver disease. Data from a meta-analysis and a controlled trial support the use of baclofen for gastroesophageal reflux disease GERD ; baclofen was associated with reductions in the number of reflux episodes and rate of transient lower esophageal sphincter relaxations in patients with GERD. Evidence from a limited number of small controlled and noncontrolled trials and several case reports suggests that baclofen may be effective in resolving or reducing symptoms in patients with chronic hiccups due to various causes. Baclofen may be a useful alternative when other treatments have failed. Inconsistent results have been reported with baclofen use for the treatment of nystagmus Averbuch-Heller , Comer , Dieterich It is unclear why some patients with nystagmus benefit from baclofen therapy and others do not. However, given the lack of a definitive symptomatic treatment for this disease, a therapeutic trial of baclofen may be warranted before more invasive or risky approaches such as botulinum toxin injections or surgery are attempted. Limited evidence from a small, double-blind, crossover trial suggests baclofen is beneficial for trigeminal neuralgia Fromm Based on the European Academy of Neurology guideline on trigeminal neuralgia , baclofen is recommended based on limited evidence as monotherapy or as an adjunct for trigeminal neuralgia when first-line agents are not effective or tolerated EAN [Bendtsen ]. Oral: Initial: 5 mg 3 times daily; may increase by 5 mg per dose every 3 days ie, 5 mg 3 times daily for 3 days, then 10 mg 3 times daily for 3 days, etc. Do not exceed 80 mg daily 20 mg 4 times daily. Screening dose: Initial: 50 mcg for 1 dose; following initial administration, observe patient for 4 to 8 hours. If response is inadequate, may give 75 mcg as a second screening dose 24 hours after the first screening dose; observe patient for 4 to 8 hours. If response is still inadequate, may repeat a final screening dose of mcg given 24 hours after the second screening dose. Dose titration following pump implant: After positive response to screening dose, a maintenance intrathecal infusion can be administered via an implanted intrathecal pump. Most patients have been adequately maintained on 90 mcg to mcg daily spasticity of cerebral origin or mcg to mcg daily spasticity of spinal cord origin. Note: Dosage adjustments may be required often during the first few months of therapy to adjust for life style changes due to alleviation of spasticity. Maintain lowest dose that produces adequate response. Most patients require gradual increases over time to maintain optimal response. Sudden large requirements for a dose increase may indicate a catheter complication eg, kink, dislodgement. Titrate dose to allow sufficient muscle tone and occasional spasms to optimize activities of daily living, support circulation, and possibly prevent DVT formation. Use extreme caution when filling the pump; follow manufacturer instructions carefully. Following the drug holiday intrathecal baclofen may be resumed at the initial continuous infusion dose. Gastroesophageal reflux disease off-label use : Oral: 10 mg 4 times daily Ciccaglione Hiccups off-label use : Oral: 5 to 10 mg 3 times daily maximum: 75 mg daily in divided doses Guelaud ; Zhang Nystagmus off-label use : Oral: 5 mg 3 times daily; may increase at weekly intervals until optimal response is reached or intolerable adverse effects occur. Dosage range studied: 15 to mg daily in divided doses Cormer ; Dieterich Additional data may be necessary to further define the role of baclofen in the treatment of this condition.
France became the first country to support this off-label use of baclofen; the US FDA has not made similar formal statements. Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Baclofen neurotoxicity: a metabolic encephalopathy susceptible to exacerbation by benzodiazepine therapy. Farid R. Restoring the Bacloville trial: efficacy and harms. Substances Muscle Relaxants, Central Baclofen. Baclofen withdrawal syndrome most commonly occurs in the setting of ITB administration and is most effectively treated with re-initiation or supplementation of baclofen dosing. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. Time changes may affect flex dosing. Stability of baclofen, captopril, diltiazem hydrochloride, dipyridamole, and flecainide acetate in extemporaneously compounded oral liquids. Baclofen-induced acute hepatitis in alcohol-dependent patient. Patient history, vital sign abnormalities, and physical examination findings are all important in establishing the diagnosis. Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study. Outcomes of intrathecal baclofen therapy in patients with cerebral palsy and acquired brain injury. Do not take more of it, do not take it more often, or do not take it longer than your doctor ordered. Keywords: Administration and dosage; baclofen; consensus; implantable; infusion pumps; intrathecal baclofen; muscle spasticity; patient care management. This expansion of its use has led to an increase in baclofen-associated complications, which can be especially pronounced in patients with renal or hepatic dysfunction. Abstract Baclofen is an effective therapeutic for the treatment of spasticity related to multiple sclerosis, spinal cord injuries, and other spinal cord pathologies. Oral: Initial: 5 mg 3 times daily; may increase by 5 mg per dose every 3 days ie, 5 mg 3 times daily for 3 days, then 10 mg 3 times daily for 3 days, etc. Baclofen is an agonist for gamma-aminobutyric acid GABA B receptors on pre- and postsynaptic neurons in the central nervous system CNS and peripheral nervous system. Effective management requires the prompt cessation of baclofen administration and supportive measures to ensure adequate circulatory and respiratory function until the toxic effects of the drug subside. Drugs ; 75 : — Am J Crit Care ; 15 6 : — Some experts have suggested the following titration parameters: Children and Adolescents Berweck : Intrathecal:. Use extreme caution when filling the pump; follow manufacturer instructions carefully. Acute intrathecal baclofen withdrawal: a brief review of treatment options. Control of transient lower oesophageal sphincter relaxations and reflux by the GABA B agonist baclofen in patients with gastro-oesophageal reflux disease. J Subst Abuse Treat ; 52 : 24— JAMA ; : — J Toxicol Clin Toxicol ; 41 : 83— GABAB receptor ligands for the treatment of alcohol use disorder: preclinical and clinical evidence. Baclofen and alcohol use disorders: breakthrough or great white elephant? Definitive treatment of baclofen withdrawal syndrome involves urgent restoration of drug delivery, preferably via the same route and dosage as before the interruption. Maternal plasma concentrations following administration of intrathecal baclofen are significantly less than those with oral doses; exposure to the fetus is expected to be limited and adverse neonatal events have not been noted in available reports Morton J Neurogastroenterol Motil ; 19 3 : — Clin Res Hepatol Gastroenterol ; 35 5 : — Pregnancy and breastfeeding during intrathecal baclofen therapy—a case study and review. Baclofen for alcohol use disorder. Neurocrit Care ; 22 : — Acute reversible cardiomyopathy, cardiac arrest, autonomic dysfunction: bradycardia, tachycardia, hypotension, hypertension. Continuous intrathecal baclofen infusion for spasticity of cerebral origin. J Neurosurg ; 79 4 : — Talk to your doctor if you have questions. Its narrow therapeutic window mandates careful dose initiation and monitoring. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. Cangene Biopharma Inc. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine. Do not double doses. Dexmedetomidine for acute baclofen withdrawal. Contraindicated in patients receiving MAOI therapy and in debilitated, elderly patients.
Try out PMC Labs and tell us what you think. Learn More. Baclofen is an effective therapeutic for the treatment of spasticity related to multiple sclerosis, spinal cord injuries, and other spinal cord pathologies. It has been increasingly used off-label for the management of several disorders, including musculoskeletal pain, gastroesophageal reflux disease, and alcohol use disorder. Baclofen therapy is associated with potential complications, including life-threatening toxicity and withdrawal syndrome. These disorders require prompt recognition and a high index of suspicion. While these complications can develop following administration of either oral or intrathecal baclofen, the risk is greater with the intrathecal route. The management of baclofen toxicity is largely supportive while baclofen withdrawal syndrome is most effectively treated with re-initiation or supplementation of baclofen dosing. Administration of other pharmacologic adjuncts may be required to effectively treat associated withdrawal symptoms. This narrative review provides an overview of the historical and emerging uses of baclofen, offers practical dosing recommendations for both oral and intrathecal routes of administration, and reviews the diagnosis and management of both baclofen toxicity and withdrawal. Baclofen was originally developed as an antiepileptic in by Swiss chemist Heinrich Keberle. Both toxicity and withdrawal represent medical emergencies that carry a risk of death. Relevant English language references on baclofen administration, pharmacology, and adverse effects were reviewed. Included references consist of randomized controlled trials, non-randomized trials, expert opinions, commentaries, structured and unstructured reviews, case reports, and package inserts. References in languages other than English and unpublished reports were not included. Literature search was performed using PubMed. Baclofen is an agonist for gamma-aminobutyric acid GABA B receptors on pre- and postsynaptic neurons in the central nervous system CNS and peripheral nervous system. However, GABA B receptors are also found on other neurons throughout the body, including in the CNS and sympathetic nervous system, which can account for the side effects of drowsiness and dizziness. The net result is a reduction in the postsynaptic motor neuron action potential, decreasing spasticity. Baclofen is an effective treatment for spasticity of cerebral or spinal origin. Oral indications include management of reversible spasticity associated with spinal cord injury and multiple sclerosis. Oral baclofen is the most commonly used antispasmodic. Recently, baclofen has been administered as an off-label treatment for alcohol use disorder AUD. There is a high concentration of GABA B receptors in this area of the brain, and it is believed that activation of these receptors inhibits the surrounding dopaminergic pathways, leading to a decrease in dopamine release in response to alcohol consumption with a corresponding reduction in craving. In , Addolorato et al. In , Reynaud et al. The results of this study did not demonstrate a statistically significant superiority of baclofen in the maintenance of abstinence or reduction in alcohol consumption in alcohol-dependent patients. Minozzi et al. The authors did not find any difference between baclofen and placebo and concluded that the evidence regarding the use of baclofen as a first-line treatment for AUD is uncertain. Conversely, a meta-analysis by Pierce et al. A cohort study from the French Health Insurance claims database compared outcomes of adult patients being treated for AUD with oral baclofen and three other approved drugs. Furthermore, there has been expert opinion highlighting a negative benefit:harm ratio for the use of baclofen for this indication. France became the first country to support this off-label use of baclofen; the US FDA has not made similar formal statements. In , Rigal et al. In this study, authors reported that baclofen was more effective than placebo in reducing alcohol consumption to low-risk levels. Serious adverse events, including death, were more frequent with baclofen administration. Notably, there have been concerns related to the data transparency, delay in study publication, primary outcome measure, and modifications to the study protocol. One of the most widely postulated mechanisms for the development of reflux symptoms is excess transient lower esophageal sphincter relaxation TLESR episodes. Table 1 summarizes the pharmacodynamic and pharmacokinetic properties of baclofen administration. Oral baclofen dosing for spasticity starts at an initial dose of 5 mg, administered one to three times daily. There is no consensus on the appropriate dose of oral baclofen for the off-label treatment of AUD, and several dosing regimens are in use. Overall, the daily baclofen dose should be based on safety, tolerability, and individual patient response. Manufacturers do not provide specific dosing adjustment recommendations in patients with renal impairment. Although baclofen is dialyzable in cases of toxicity, it should be avoided in patients with end-stage renal disease requiring hemodialysis. There are no formal recommendations for dosing adjustments in patients with hepatic impairment. As baclofen undergoes only limited hepatic metabolism, it may be a safe treatment option in patients with liver disease. ITB has a different pharmacokinetic and pharmacodynamic profile compared with oral baclofen administration Table 1. Baclofen directly administered into the intrathecal space allows for therapeutic cerebrospinal fluid CSF concentrations to be achieved with plasma concentrations times less than that associated with oral administration. ITB dosing for spasticity begins with a screening test to assess for a positive response, characterized by a reduction in tone, a reduction in spasms, or improved functional capacity. Maintenance ITB infusion dosing is dictated by the response to the initial screening dose. Patient history, vital sign abnormalities, and physical examination findings are all important in establishing the diagnosis.