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
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
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 …
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:
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
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.
Actions of the GABAB agonist, - -baclofen, on neurones in deep dorsal horn of the rat spinal cord in vitro. Pain Physician ; 18 4 : E—E Dispense in a light-resistant container. 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 Keywords: Baclofen, spasticity, toxicity, withdrawal. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Usual maintenance dose: Children and Adolescents: Intrathecal: to 2, mcg daily Berweck ; the manufacturer provides the following:. Dosing options include simple continuous dosing, variable hour flex dosing, or regularly scheduled boluses. Lancet ; : — Agabio R, Colombo G. Publication types Review. Benzodiazepines and cyproheptadine 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. J Clin Pharmacol ; 54 5 : — CBD What you need to know CBD cannabidiol is a chemical found in the Cannabis sativa plant, which is being investigated for its potential health benefits. Prolonged intrathecal baclofen withdrawal syndrome. Inconsistent results have been reported with baclofen use for the treatment of nystagmus Averbuch-Heller , Comer , Dieterich West J Emerg Med ; 13 4 : — 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. Arch Phys Med Rehabil ; 80 12 : — In this study, authors reported that baclofen was more effective than placebo in reducing alcohol consumption to low-risk levels. 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. Procter Gamble Pharmaceuticals. Entreprises Importfab Inc. Boxed Warning Abrupt withdrawal injection : 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. J Neurosurg ; 83 : — Mechanism of action 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. Ann Neurol ; 17 2 : — Ghanavatian S, Derian A. Ongoing withdrawal may lead to hallucinations, delirium, seizures, and muscle rigidity. Gastroenterology ; 1 : 7— Indian J Pharmacol ; 41 2 : 89— Front Neurosci ; 8 : You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine. Low-dose propofol infusion for controlling acute hyperspasticity after withdrawal of intrathecal baclofen therapy. BMJ Case Rep ; 13 : e System Baclofen toxicity Baclofen withdrawal General Hypothermia, death Pruritus, hyperthermia, multisystem organ failure, death Psychiatric Hallucinations, agitation, mania, catatonia Hallucinations, anxiety, paranoia, delusions Neurological Hyporeflexia, tremor, confusion, impaired memory, lethargy, somnolence, seizures, encephalopathy, coma Hyperreflexia, tremor, paresthesias, headache, altered mental status, delirium, seizures Cardiovascular Conduction abnormalities, prolonged QTc interval, autonomic dysfunction: bradycardia, tachycardia, hypotension, hypertension Acute reversible cardiomyopathy, cardiac arrest, autonomic dysfunction: bradycardia, tachycardia, hypotension, hypertension Respiratory Respiratory failure Respiratory failure Gastrointestinal Nausea, vomiting Nausea, vomiting, diarrhea Musculoskeletal Hypotonia Hypertonia, rhabdomyolysis. Baclofen overdose with cardiac conduction abnormalities: case report and review of the literature. Hypotension, hypotonia, bradycardia, and respiratory depression are expected signs of baclofen toxicity, although the clinical presentation can vary dramatically. Hyporeflexia, tremor, confusion, impaired memory, lethargy, somnolence, seizures, encephalopathy, coma. Free E-newsletter Subscribe to Housecall Our general interest e-newsletter keeps you up to date on a wide variety of health topics. Overall, doses must be carefully titrated to achieve relief of withdrawal symptoms because there is no direct conversion from intrathecal to oral baclofen dosing. Sign up now. Specific movement of esophagus during transient lower esophageal sphincter relaxation in gastroesophageal reflux disease. Gastroenterol Res Pract ; : Performing a thorough history and physical is critical. For example, elevations in serum creatinine kinase, potassium, and creatinine levels can alert clinicians to the development of rhabdomyolysis that can occur with baclofen withdrawal syndrome. Does not require refrigeration. J Child Neurol ; 29 4 : — 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. Assessment should occur within 24 hours of a dose change. Dexmedetomidine for acute management of intrathecal baclofen withdrawal. Inpatients should be assessed at least every 24 hours and receive rehabilitation. Recently, baclofen has been administered as an off-label treatment for alcohol use disorder AUD. A novel approach to avoid baclofen withdrawal when faced with infected baclofen pumps.
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. Oral: Refer to adult dosing; use with caution. If benefits are not observed, withdraw the drug slowly. Oral: Note: Dose-related side effects eg, sedation may be minimized by slow titration; lower initial doses than described below 2. There is limited published data in infants and children; the following is a compilation of small prospective studies Goyal ; Milla ; Scheinberg and one large retrospective analysis of baclofen use in children Lubsch Note: To minimize dose-related side effects eg, sedation , lower initial doses eg, 2. Children 2 to 7 years: Limited data available: Oral: Initial: 2. Intrathecal: 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. Note: A 25 mcg initial screening dose may be considered in very small pediatric patients. Dose titration following pump implant: Children and Adolescents: After positive response to screening dose, a maintenance intrathecal infusion can be administered via an implanted intrathecal pump.