Baclofen Toxicity in Kidney Disease

Wolf, Erin; Kothari, Niraj R.; Roberts, J. K.; Sparks, Matthew A.

doi:10.1053/j.ajkd.2017.07.005

Cited by 32 publications

(29 citation statements)

References 42 publications

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“…It is possible that she may be sensitive to baclofen. The patients with mild, moderate and severe renal impairment require adjustment of baclofen dose by 40%, 60% and 70%, respectively; and in critically ill patients would require further dose adjustment 5…”

Section: Discussionmentioning

confidence: 99%

Baclofen encephalopathy: uncommon side effect of a common drug

Sachan

Singh

Kalita

et al. 2020

Postgraduate Medical Journal

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Section: Discussionmentioning

confidence: 99%

Baclofen encephalopathy: uncommon side effect of a common drug

Sachan

Singh

Kalita

et al. 2020

Postgraduate Medical Journal

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“…Baclofen toxicity has previously been described with overdose in adults 8,9 and children, [10][11][12] as well as in adults with renal dysfunction. [5][6][7] The main adverse events described were CNS depression and decreased LOC, hypotonia, respiratory depression, bradycardia, hypertension, or hypotension. Some of these patients recovered spontaneously, while others required clearance of the drug by dialysis.…”

Section: Discussionmentioning

confidence: 99%

Baclofen Toxicity in Children With Acute Kidney Injury: Case Reports and Review of the Literature

Mishaal

Lanphear

Armarnik

et al. 2020

Child Neurology Open

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Baclofen is a medication used for tone management in cerebral palsy. Although it acts mainly at the spinal cord level, it can cause central nervous system adverse reactions at higher doses. Baclofen is mainly eliminated by renal excretion and there have been reports on adverse events when used in adults with renal impairment; however, there are no consensus guidelines as to the dose adjustments required due to renal impairment. The authors describe 2 children with acute kidney injury (AKI) and systemic side effects with initiation of oral baclofen, which was started for treatment of dystonia/spasticity in the recovery phase of their kidney injury. Following the initiation of the drug, they both had decreased level of consciousness and respiratory difficulties, which warranted discontinuation of the drug. These cases highlight the need for reduced initial dose, slow titration, and close monitoring when initiating baclofen treatment in children with AKI.

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“…It's noticeable that during a baclofen overdose an increase of T1/2 is not always observed ( 32 ). In such situation, which may lead to comatose, severe respiratory depression and neurotoxicity, hemodialysis has been effective in reversing baclofen toxicity if the patient had a renal insufficiency ( 33 ). A gastro-intestinal decontamination with activated charcoal can also be proposed to avoid a persistent intestinal absorption related to a reduced gastro-intestinal mobility or a pharmacobezoar ( 34 ).…”

Section: Metabolism and Eliminationmentioning

confidence: 99%

Pharmacokinetic Studies of Baclofen Are Not Sufficient to Establish an Optimized Dosage for Management of Alcohol Disorder

2018

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Several clinical randomized trials have evaluated the interest of baclofen in patients with alcohol use disorder. Depending on the study design and the inclusion criteria, the results vary from enthusiastic to pessimistic. However, all researchers and practitioners agree that they observe a wide variability in the therapeutic responses. If some patients exhibit a clinical response at low doses, ~40 mg daily, others require doses higher than 300 mg. Before multiplying new other clinical trials, it is required to better understand the reason of this variability. Several mechanisms may be responsible for providing different effects with an identical daily dose. Especially, each pharmacokinetic step, absorption, distribution, metabolism, and elimination may lead to a different exposure after an identical dose. Absorption may imply a saturation process limiting the bioavailability (F) of baclofen in some patients. In such a situation, food, or drug-drug interaction can change the absorption rate of the drug modifying the maximum concentration (Cmax) and area under the curve (AUC). Distribution and brain penetration across the blood-brain barrier may depend of a specific transporter. These transporters are subject to genetic polymorphism and drug-drug interaction. Finally, elimination may be increased by a specific secretion pathway. This review describes all available pharmacokinetic data on these different pharmacokinetics steps aiming to identify the source of variability of baclofen in patients with alcohol use disorder.

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Baclofen Toxicity in Kidney Disease

Cited by 32 publications

References 42 publications

Baclofen encephalopathy: uncommon side effect of a common drug

Baclofen encephalopathy: uncommon side effect of a common drug

Baclofen Toxicity in Children With Acute Kidney Injury: Case Reports and Review of the Literature

Pharmacokinetic Studies of Baclofen Are Not Sufficient to Establish an Optimized Dosage for Management of Alcohol Disorder

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