Baclofen toxicity

Chen KS, Bullard MJ, Chien YY, Lee SY. Baclofen toxicity in patients with severely impaired renal function. Ann Pharmacother 1997 31(ll) 1315-20. 

Seyfert S, Kraft D, Wagner K. Baclofen-Dosis bei Haemodialyse und Niereninsuffizienz. [Baclofen toxicity during intermittent renal dialysis.] Nervenarzt 1981 52(10) 616-17. 

A man developed baclofen toxicity when given ibuprofen. 

An isolated report describes a man taking baclofen 20 mg three times a day, who developed baclofen toxicity (confusion, disorientation, bradycardia, blurred vision, hypotension and hypothermia) after taking 8 doses of ibuprofen 6(X) mg three times daily. It appeared that the toxicity was caused by ibuprofen-induced acute renal impairment leading to baclofen accumulation. Renal impairment is a relatively rare adverse effect of ibuprofen. The general importance of this interaction is likely to be very small. There appears to be no information about baclofen and other NSAIDs, and little reason for avoiding concurrent use. 

Dahlin PA, Geoi e J. Baclofen toxicity associated with declinii renal clearance after ibiq>ro-fen. DrugIntellCUnPharm (1984) 18, 805-8. 

Severe renal impairment may cause baclofen toxicity. Patients with renal insufficiency or those ungerdoing hemodialysis require a reduced dose. 

Baclofen GABAb agonist, facilitates spinal inhibition of motor neurons Pre- and postsynaptic inhibition of motor output Severe spasticity due to cerebral palsy, mulitple sclerosis, stroke Oral, intrathecal Toxicities Sedation, weakness... 

As 70% of baclofen is excreted unchanged in the urine (29), accumulation and overdosage of baclofen can occur in patients with end-stage renal disease. Confusion, drowsiness, and coma after standard doses have been reported (30). In addition, abdominal pain was a common adverse effect of baclofen in patients with severe renal insufficiency (31). Toxic reactions characterized by a psychotic syndrome and myoclonus have also been reported (32). Patients with severely impaired renal function typically present with altered consciousness after very small doses of baclofen (31). Symptoms of overdose may resolve after hemodialysis (30,31). 

Toxicity The sedation produced by diazepam is significant but milder than that produced by other sedative-hypnotic drugs at doses that induce equivalent muscle relaxation. Baclofen produces less sedation than diazepam. Dantrolene causes significant muscle weakness but less sedation than either diazepam or baclofen. Tizanidine may cause drowsiness and hypotension. 

Various drugs have been used to treat muscle spasm. Most compounds in this group act as simple sedative-hypnotic agents and produce skeletal muscle relaxation indirectly. The drugs commonly used as skeletal muscle relaxants are listed in Table 11-53. Carisoprodol (Soma ) and baclofen have been abused as recreational drugs. I. Mechanism of toxicity... 

Twelve patients with parkinsonism on levodopa plus a dopa-decarboxylase inhibitor were additionally given baclofen. The eventual baclofen dosage was intended to be 90 mg daily, but the adverse effects were considerable (visual hallucinations, a toxic confusional state, headaches, nausea) so that only 2 patients reached this dosage, and 2 patients withdrew because they could not tolerate these adverse effects. The mean dosage for those who continued was 45 mg daily. Rigidity was aggravated by an average of 46% and functional capacity deteriorated by 21%. ... 

Not understood. The toxicity seen appears to be an exaggeration of the known adverse effects of baclofen. 

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