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content:vigabatrin [2020/02/23 18:15] – [Dosage and titration] icnacontent:vigabatrin [2022/04/30 11:32] (current) – changed pubmed syntax administrator@icnapedia.org
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 ===== Clinical applications ===== ===== Clinical applications =====
   * initial treatment of choice for infantile (epileptic) spasms   * initial treatment of choice for infantile (epileptic) spasms
-  * used cautiously in the treatment of patients with intractable focal seizures that have failed to respond to all other appropriate AED combinations and surgical procedures[(:cite:kramer2002>Kramer G, Wohlrab G. Vigabatrin. In: Shorvon S, Perucca E, Engel JJr, eds. The treatment of epilepsy (3nd edition). Oxford: Willey- Blackwell, 2009:699-712)][(:cite:19230067>{{pubmed>19230067}})]+  * used cautiously in the treatment of patients with intractable focal seizures that have failed to respond to all other appropriate AED combinations and surgical procedures[(:cite:kramer2002>Kramer G, Wohlrab G. Vigabatrin. In: Shorvon S, Perucca E, Engel JJr, eds. The treatment of epilepsy (3nd edition). Oxford: Willey- Blackwell, 2009:699-712)][(:cite:19230067>{{pmid>19230067}})]
  
 ===== Dosage and titration ===== ===== Dosage and titration =====
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 ===== Adverse drug reactions ===== ===== Adverse drug reactions =====
   * **Visual field defects**   * **Visual field defects**
-    * high prevalence of visual field defects occurring in around one-third of patients (adults and children) treated with vigabatrin[(:cite:15122710>{{pubmed>15122710}})][(:cite:9468717>{{pubmed>9468717}})] +    * high prevalence of visual field defects occurring in around one-third of patients (adults and children) treated with vigabatrin[(:cite:15122710>{{pmid>15122710}})][(:cite:9468717>{{pmid>9468717}})] 
-    * also produces retinal electrophysiological changes in nearly all patients.[(:cite:2667602>{{pubmed>2667602}})][(:cite:9203252>{{pubmed>9203252}})][(:cite:12588920>{{pubmed>12588920}})]+    * also produces retinal electrophysiological changes in nearly all patients.[(:cite:2667602>{{pmid>2667602}})][(:cite:9203252>{{pmid>9203252}})][(:cite:12588920>{{pmid>12588920}})]
     * Visual field loss resulting from vigabatrin is not usually reversible     * Visual field loss resulting from vigabatrin is not usually reversible
     * visual acuity, colour vision and the loss of amplitude on the electroretinogram may be reversible in patients with minimal or no visual field loss     * visual acuity, colour vision and the loss of amplitude on the electroretinogram may be reversible in patients with minimal or no visual field loss
-    * there is some evidence that visual field defects remain stable with continuous treatment. It is, therefore, feasible to continue treatment with vigabatrin in these cases, provided visual field monitoring is performed regularly[(:cite:19845417>{{pubmed>19845417}})]+    * there is some evidence that visual field defects remain stable with continuous treatment. It is, therefore, feasible to continue treatment with vigabatrin in these cases, provided visual field monitoring is performed regularly[(:cite:19845417>{{pmid>19845417}})]
     * the mechanism of vigabatrin-induced visual field defects are probably due to reversible oedema of the myelin in the optic nerves, retinal cone system dysfunction or both.     * the mechanism of vigabatrin-induced visual field defects are probably due to reversible oedema of the myelin in the optic nerves, retinal cone system dysfunction or both.
   * Other ADRs include sedation, dizziness, headache, ataxia, paraesthesiae, memory, cognitive and behavioural disturbances, weight gain and tremor   * Other ADRs include sedation, dizziness, headache, ataxia, paraesthesiae, memory, cognitive and behavioural disturbances, weight gain and tremor
-  * there is no evidence of idiosyncratic ADRs.+  * there is no evidence of idiosyncratic ADRs 
 +  * movement disorders including dystonia, dyskinesia, and hypertonia have been reported in patients treated for infantile spasms.
  
 ===== Mechanism of action ===== ===== Mechanism of action =====
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   * Visual field defects have virtually eliminated vigabatrin from common clinical practice except for infantile spasms   * Visual field defects have virtually eliminated vigabatrin from common clinical practice except for infantile spasms
   * Visual field defects may not be clinically detectable. Therefore, patients should be monitored with perimetry prior to and every 6 months during vigabatrin treatment.   * Visual field defects may not be clinically detectable. Therefore, patients should be monitored with perimetry prior to and every 6 months during vigabatrin treatment.
-  * Electrophysiological testing is considered to be more accurate than perimetry for the direct vigabatrin effect on the outer retina[(:cite:12588920>{{pubmed>12588920}})].The manufacturers provide a procedure for testing children. +  * Electrophysiological testing is considered to be more accurate than perimetry for the direct vigabatrin effect on the outer retina[(:cite:12588920>{{pmid>12588920}})].The manufacturers provide a procedure for testing children. 
-  * Aggravation of seizures: vigabatrin is a pro-absence agent which aggravates absence seizures and provokes absence status epilepticus[(:cite:9371946>{{pubmed>9371946}})].This alone would prohibit use of vigabatrin in IGEs with absences.+  * Aggravation of seizures: vigabatrin is a pro-absence agent which aggravates absence seizures and provokes absence status epilepticus[(:cite:9371946>{{pmid>9371946}})].This alone would prohibit use of vigabatrin in IGEs with absences.
   * Vigabatrin, may also exaggerate atypical absences (such as those occurring in Lennox–Gastaut syndrome) and myoclonic seizures (such as those occurring in progressive or non-progressive myoclonic epilepsies).   * Vigabatrin, may also exaggerate atypical absences (such as those occurring in Lennox–Gastaut syndrome) and myoclonic seizures (such as those occurring in progressive or non-progressive myoclonic epilepsies).
  
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   * Numerous RCTs failed to detect common and serious visual field defects   * Numerous RCTs failed to detect common and serious visual field defects
   * Vigabatrin was used as and adjunctive medication in the treatment of focal epilepsies from 1989, when it was first licensed in Europe. Concern over neuropathological findings of microvacuolisation of white matter in animals caused trials of vigabatrin to be halted in 1983, but trials were resumed when a lack of evidence (including visualevoked responses) for toxicity in humans was found.   * Vigabatrin was used as and adjunctive medication in the treatment of focal epilepsies from 1989, when it was first licensed in Europe. Concern over neuropathological findings of microvacuolisation of white matter in animals caused trials of vigabatrin to be halted in 1983, but trials were resumed when a lack of evidence (including visualevoked responses) for toxicity in humans was found.
-  * Numerous RCTs (mostly of class I and II in the ratings of ‘therapeutic articles’)[(:cite:2006001>{{pubmed>2006001}})][(:cite:9203252>{{pubmed>9203252}})][(:cite:2667602>{{pubmed>2667602}})][(:cite:8952010>{{pubmed>8952010}})][(:cite:8439699>{{pubmed>8439699}})][(:cite:8559421>{{pubmed>8559421}})][(:cite:9022432>{{pubmed>9022432}})][(:cite:10406359>{{pubmed>10406359}})] +  * Numerous RCTs (mostly of class I and II in the ratings of ‘therapeutic articles’)[(:cite:2006001>{{pmid>2006001}})][(:cite:9203252>{{pmid>9203252}})][(:cite:2667602>{{pmid>2667602}})][(:cite:8952010>{{pmid>8952010}})][(:cite:8439699>{{pmid>8439699}})][(:cite:8559421>{{pmid>8559421}})][(:cite:9022432>{{pmid>9022432}})][(:cite:10406359>{{pmid>10406359}})] 
-  * All these studies[(:cite:2006001>{{pubmed>2006001}})][(:cite:9203252>{{pubmed>9203252}})][(:cite:2667602>{{pubmed>2667602}})][(:cite:8952010>{{pubmed>8952010}})][(:cite:8439699>{{pubmed>8439699}})][(:cite:8559421>{{pubmed>8559421}})][(:cite:9022432>{{pubmed>9022432}})][(:cite:10406359>{{pubmed>10406359}})] concluded that vigabatrin was a ‘relatively safe drug with a relatively benign adverse-effect profile’. They all failed to identify vigabatrin-associated irreversible visual field defects.  +  * All these studies[(:cite:2006001>{{pmid>2006001}})][(:cite:9203252>{{pmid>9203252}})][(:cite:2667602>{{pmid>2667602}})][(:cite:8952010>{{pmid>8952010}})][(:cite:8439699>{{pmid>8439699}})][(:cite:8559421>{{pmid>8559421}})][(:cite:9022432>{{pmid>9022432}})][(:cite:10406359>{{pmid>10406359}})] concluded that vigabatrin was a ‘relatively safe drug with a relatively benign adverse-effect profile’. They all failed to identify vigabatrin-associated irreversible visual field defects.  
-  * It was astute clinicians who first reported these serious ADRs[(:cite:9022432>{{pubmed>9022432}})], but even after this report had been published, a class I RCT found vigabatrin to be ‘less effective but better tolerated than carbamazepine’[(:cite:10406359>{{pubmed>10406359}})].Results of proper testing for visual field defects are not given; that the patients did not have abnormalities on visual confrontation testing is not reassuring. When such ADRs come to light, good clinical practice mandates that patients are informed and offered the appropriate testing. Visual field testing performed by a protocol amendment post hoc (after termination of another RCT) showed abnormalities in 10% of vigabatrin-treated patients[(:cite:11051124>{{pubmed>11051124}})].+  * It was astute clinicians who first reported these serious ADRs[(:cite:9022432>{{pmid>9022432}})], but even after this report had been published, a class I RCT found vigabatrin to be ‘less effective but better tolerated than carbamazepine’[(:cite:10406359>{{pmid>10406359}})].Results of proper testing for visual field defects are not given; that the patients did not have abnormalities on visual confrontation testing is not reassuring. When such ADRs come to light, good clinical practice mandates that patients are informed and offered the appropriate testing. Visual field testing performed by a protocol amendment post hoc (after termination of another RCT) showed abnormalities in 10% of vigabatrin-treated patients[(:cite:11051124>{{pmid>11051124}})].
  
 ==== References ==== ==== References ====
  
 ~~REFNOTES~~ ~~REFNOTES~~
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