DRPIS MO Valpakine 500mg Comp GAS VERSET2016
DRPIS MO Valpakine 500mg Comp GAS VERSET2016
DRPIS MO Valpakine 500mg Comp GAS VERSET2016
– CCDS v21
Bolivia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala ,Haiti,
Honduras, Paraguay
MONOGRAFÍA
VALPAKINE® 500 mg
Valproato sódico
Comprimidos recubiertos gastrorresistentes
COMPOSICIÓN
Cada comprimido recubierto gastrorresistente contiene:
Valproato sódico…………………………….........................................….. 500 mg
Excipientes: núcleo: Povidona (K90), Silicato de calcio, Talco, estearato de
magnedio, agua purificada. Revestimiento: Povidona (K 30), Macrogol 400,
Almidón de maíz, Talco, Dióxido de titanio, óxido férrico amarillo, agua purificada,
acetato ftalato de celulosa, dietilftalato.
INDICACIONES
En el adulto: En monoterapia o en combinación con otro tratamiento
antiepiléptico:
- Tratamiento de las epilepsias generalizadas: crisis clónicas, tónicas, tónico-
clónicas, ausencias, crisis mioclónicas, atónicas y síndrome de Lennox-Gastaut.
- Tratamiento de las epilepsias parciales: crisis parciales con o sin
generalización secundaria.
En ciertos casos Valpakine puede ser una opción apropiada para las mujeres
con potencial de quedar embarazadas, bajo los requisitos de una elección
informada, basada en una evaluación muy cuidadosa, por el paciente
conjuntamente con su médico de todos los elementos relevantes (ver
advertencias y precauciones).
CARACTERÍSTICAS FARMACOLÓGICAS/PROPIEDADES
FARMACODINÁMICAS
Valproate – CCDS v21
Bolivia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala ,Haiti,
Honduras, Paraguay
PROPIEDADES FARMACOCINÉTICAS
Posología
Posología promedio en 24 horas:
• Lactante y niño: 30mg/kg (de preferencia se utilizará la forma de solución
bebible de 200mg/mL).
• Adolescente y adulto: 20 a 30 mg/kg (de preferencia se utilizará la forma de
comprimidos de 500 mg)
• Ancianos (≥65 años): 15 a 20 mg/kg.
Modo de administración
Vía oral.
CONTRAINDICACIONES
• Hepatitis aguda o crónica
• Antecedente familiar o del paciente de hepatitis severa, especialmente
relacionada con medicamentos
• Antecedentes de hipersensibilidad al valproato de sodio o los componentes de
la formulación
• Porfiria hepática
Los pacientes con trastornos mitocondriales causados por mutaciones en el
gen nuclear que codifica para la enzima mitocondrial polimerasa γ (POLG,
por ejemplo el síndrome Alpers-Huttenlocher) y en niños menores de 2 años
con sospecha de tener un trastorno POLG relacionado. (Ver Advertencias).
Pacientes con trastornos del ciclo de la urea (Ver Precauciones).
ADVERTENCIAS
- Condiciones de aparición:
Excepcionalmente se ha reportado daño hepático grave resultando algunas
veces mortal. La experiencia indica que la mayoría de los pacientes en riesgo,
especialmente en casos de tratamiento anticonvulsivante múltiple, son infantes y
niños menores de 3 años de edad con trastornos convulsivos graves,
particularmente aquellos con lesión cerebral, retardo mental y/o enfermedad
metabólica congénita o degenerativa.
Después de la edad de 3 años, el riesgo se reduce significativamente y
disminuye progresivamente con la edad.
En la mayoría de los casos, estos daños hepáticos ocurrieron durante los
primeros 6 meses de tratamiento.
- Signos sugestivos:
Los síntomas clínicos son esenciales para el pronto diagnóstico. En particular,
deben ser tomados en consideración las siguientes condiciones que pueden
preceder a la ictericia, especialmente en pacientes con riesgo:
- Síntomas inespecíficos, habitualmente de aparición repentina, tales como
astenia, anorexia, letargia, somnolencia, que en ocasiones se asocian con
vómitos repetidos y dolor abdominal.
- En pacientes con epilepsia, recurrencia de convulsiones.
Los pacientes (o sus familiares en caso de niños), deben ser informados de
notificar inmediatamente a un médico si ocurre cualquiera de estos signos.
Deben realizarse inmediatamente exámenes incluyendo examen clínico y
evaluación biológica de las funciones hepáticas.
Valproate – CCDS v21
Bolivia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala ,Haiti,
Honduras, Paraguay
- Detección:
Las pruebas de función hepáticas deben ser realizadas antes de iniciar el
tratamiento y luego periódicamente durante los 6 primeros meses de tratamiento.
Entre los exámenes habituales, las más significativas son las pruebas que
reflejan la síntesis de las proteínas y especialmente el índice de protrombina. La
confirmación de un índice de protrombina anormalmente bajo, particularmente
en asociación con otras anormalidades biológicas (reducción significativa del
fibrinógeno y de los factores de coagulación, incremento del nivel de bilirrubina,
elevación de las transaminasas) requiere la interrupción del tratamiento con
Valpakine. Como medida de precaución y en caso de que sean administrados
concomitantemente, los salicilatos también debe ser descontinuados debido a
que utilizan la misma vía metabólica.
Pancreatitis
La terapia con Valproato solo se debe continuar después de que un médico con
experiencia en el manejo de la epilepsia o del trastorno bipolar, reevalúe los
beneficios y riesgos del tratamiento con Valproato.
Agentes Carbapenémicos
Agravamiento de convulsiones
PRECAUCIONES
Las pruebas hepáticas deben ser realizadas antes del inicio del tratamiento (ver
Contraindicaciones), y periódicamente durante los 6 primeros meses
especialmente en pacientes en riesgo (ver Advertencias). Como con la mayoría
de medicamentos antiepilépticos, se puede observar un ligero incremento de las
enzimas hepáticas, especialmente al inicio del tratamiento, que son transitorias y
aisladas.
Se recomienda en estos pacientes realizar investigaciones biológicas más
amplias (incluyendo índice de protrombina), se puede considerar un ajuste de
dosis cuando sea apropiado y se debe repetir las pruebas cuando sea necesario.
Se recomienda realizar pruebas hematológicas (recuento de células sanguíneas,
incluyendo recuento de plaquetas y tiempo de sangrado), antes de iniciar el
tratamiento o antes de la cirugía, y en caso de hematomas o hemorragias
espontáneas.
Aunque se han observado trastornos inmunes sólo en casos excepcionales
durante la administración de Valpakine, debe sopesarse el beneficio potencial de
Valpakine frente al riesgo potencial en pacientes con lupus eritematoso
sistémico.
Cuando se sospeche de una deficiencia enzimática del ciclo de la urea, se debe
realizar exámenes metabólicos antes del tratamiento debido al riesgo de
hiperamonemia por valproato. Ver contraindicaciones
Se debe advertir a los pacientes del riesgo de la ganancia de peso al inicio del
tratamiento y se debe adoptar estrategias adecuadas para minimizar este riesgo
(ver Reacciones adversas).
INTERACCIONES
- Litio
Valpakine no tiene ningún efecto sobre las concentraciones plasmáticas de litio.
- Fenobarbital
Valpakine incrementa las concentraciones plasmáticas de fenobarbital. Se
recomienda un monitoreo clínico especialmente durante los primeros 15 días del
tratamiento con reducción inmediata de las dosis de fenobarbital en caso de
sedación y determinación del nivel plasmático de fenobarbital cuando sea
oportuno.
- Primidona
Valpakine incrementa los niveles plasmáticos de primidona. Se recomienda un
monitoreo clínico especialmente al inicio del tratamiento combinado ajustando la
dosis cuando sea necesario.
- Fenitoína
Valpakine disminuye la concentración plasmática total de fenitoína. Valpakine
aumenta la concentración de la forma libre de fenitoína con posibles síntomas
de sobredosis (Valpakine desplaza fenitoina de su sitio de unión en las proteínas
plasmáticas y reduce el catabolismo hepático). Se recomienda un monitoreo
Valproate – CCDS v21
Bolivia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala ,Haiti,
Honduras, Paraguay
- Carbamazepina
Se ha reportado toxicidad clínica cuando valproato fue co-administrado con
carbamazepina debido a que el valproato puede potenciar los efectos tóxicos de
la carbamazepina. Se recomienda un monitoreo clínico especialmente al inicio
del tratamiento combinado ajustando la dosis cuando sea necesario.
- Lamotrigina
Valpakine reduce el metabolismo de lamotrigina e incrementa la vida media de
lamotrigina cerca del doble. Esta interacción puede conducir a un incremento en
la toxicidad de lamotrigina en particular erupciones cutáneas serias. Por
consiguiente, se recomienda el monitoreo clínico y la dosis debe ser ajustada
(disminución de la dosis de lamotrigina) cuando sea necesario.
- Zidovudina
El Valproato puede elevar la concentración plasmática de zidovudina
conduciendo a un incremento de la toxicidad de zidovudina.
- Felbamato
El Valproato puede disminuir el aclaramiento promedio del felbamato hasta en
un 16%.
- Olanzapina
El ácido valproico puede disminuir la concentración plasmática de Olanzapina.
- Rufinamida
El ácido valproico puede llevar al incremento del nivel plasmático de Rufinamida.
Este incremento es dependiente de la concentración del ácido valproico. Tener
precaución, en particular, con los niños ya que el efecto es mayor en esta
población.
- Propofol
El ácido valproico puede dar lugar a un aumento del nivel sanguíneo de propofol.
Cuando se coadministra con valproato, se debe considerar una reducción de la
dosis de propofol.
Nimodipina
El tratamiento concomitante de nimodipina con ácido valproico puede aumentar
la concentración plasmática de la nimodipina en 50%.
-Los niveles de metabolitos del ácido valproico pueden aumentar por el uso
concomitante con Fenitoína o Fenobarbital. Los pacientes tratados con estos
dos medicamentos deben ser cuidadosamente controlados por signos y
síntomas de hiperamonemia.
- Se debe realizar una estricta vigilancia del índice de protrombina en caso del
uso concomitante de la vitamina K dependiente del factor anticoagulante.
- Inhibidores de proteasa
Valproate – CCDS v21
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- Colestiramina
La colestiramina puede llevar a la disminución del nivel plasmático del valproato
cuando se administran concomitantemente.
· Otras interacciones
EMBARAZO
Malformaciones congénitas
En humanos: La información disponible sugiere una mayor incidencia de
malformaciones menores o mayores incluyendo, particularmente, defectos del
tubo neural, defectos cráneofaciales, malformación de las extremidades,
malformaciones cardiovasculares, hipospadias y anomalías múltiples que
Valproate – CCDS v21
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Honduras, Paraguay
Hay datos que muestran que los niños expuestos al Valproato en el útero están
en mayor riesgo de sufrir alteraciones de la gama del autismo (riesgo estimado:
3 a 5 veces mayor), incluyendo el autismo en la infancia.
Valproate – CCDS v21
Bolivia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala ,Haiti,
Honduras, Paraguay
Los datos limitados sugieren que los niños expuestos al Valproato en el útero
tienen mayor probabilidad de desarrollar síntomas del trastorno por déficit de
atención con hiperactividad (ADHD por sus siglas en inglés).
FERTILIDAD
En mujeres que utilizan Valproato se ha reportado amenorrea, ovarios
poliquísticos e incremento de los niveles de testosterona (Ver Reacciones
adversas). La administración de Valproato también puede afectar la fertilidad en
hombres (Ver Reacciones adversas). Los reportes de caso indican que las
alteraciones de fertilidad son reversibles después de interrumpir el tratamiento.
Valproate – CCDS v21
Bolivia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala ,Haiti,
Honduras, Paraguay
LACTANCIA
La excreción del valproato en la leche materna es escasa, con una
concentración del 1% al 10% de los niveles séricos maternos. Se puede
considerar la lactancia materna con base en la literatura y la experiencia clínica,
teniendo en cuenta el perfil de seguridad de Valpakine y especialmente los
trastornos hematológicos.
REACCIONES ADVERSAS
Investigaciones
- Rara: disminución de los factores de coagulación (al menos uno), pruebas
anormales de coagulación (tales como prolongación del tiempo de protrombina,
tiempo de tromboplastina activado parcial prolongado, tiempo de trombina
prolongado, INR prolongado), (vea las secciones de Precauciones y Embarazo),
deficiencia de biotina/ deficiencia de biotinidasa.
Trastornos gastrointestinales
- Muy Frecuente: náuseas.
- Frecuente: vómitos, trastorno gingival (principalmente hiperplasia gingival),
estomatitis, dolor abdominal superior, diarrea.
- Poco frecuente: Pancreatitis, algunas veces mortal.
Trastornos endocrinos
- Poco frecuente: Síndrome de Secreción inapropiada de la Hormona
Antidiurética, hiperandrogenismo (hirsutismo, virilismo, acné, alopecia de patrón
masculino, y / o aumento de andrógenos).
- Rara: hipotiroidismo.
Trastornos vasculares
-Frecuente: hemorragia.
- Poco frecuente: vasculitis.
Trastornos hepatobiliares
-Frecuente: daño hepático.
Trastornos psiquiátricos
-Frecuente: estados confusionales, alucinaciones, agresión*, agitación*,
problemas de atención*.
-Rara: Comportamiento anormal*, hiperactividad psicomotora*, problemas de
aprendizaje*.
Valproate – CCDS v21
Bolivia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala ,Haiti,
Honduras, Paraguay
SOBREDOSIS
Signos y síntomas
Signos de sobredosis aguda masiva generalmente incluyen coma con hipotonía
muscular, hiporreflexia, miosis y deterioro de la función respiratoria, acidosis
metabólica, hipotensión y colapso/shock circulatorio.
Las muertes han ocurrido como consecuencia de una sobredosis masiva, no
obstante, por lo general el resultado es favorable.
Tratamiento
El manejo hospitalario de la sobredosis debe ser sintomático: se puede usar
lavado gástrico hasta 10 a 12 horas después de la ingestión, vigilancia cardio-
respiratoria.
En algunos casos aislados se ha utilizado con éxito Naloxona.
En caso de sobredosis masiva, la hemodiálisis y hemoperfusión se han utilizado
satisfactoriamente.
PRESENTACIONES
Caja de 20 y 40 comprimidos.
CONDICIONES DE ALMACENAMIENTO
Conservar a una temperatura no mayor a 30°C
IMP./DIST. Por:
Valproate – CCDS v21
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Honduras, Paraguay
Bolivia: Quimiza Ltda – Q.F. Dra. Jenny Flores. Venta bajo receta médica.
ESTRUCTURA
REFERENCIAS BIBLIOGRÁFICAS
1 CO “Paediatric data on bipolar disorder” (A. Giudicelli, dated 03-Dec-08)
2 CO: valproate -use of valproate in pregnant women (GPE-CL-2014-00594)
3 CO: valproate: residus in stools, C. Janiak-Bolzinger and K. Pearson, 12 March 2014 (GPE-CL-2014-00107)
4 DOSS M, et al. Drug safety in porphyria: risks of valproate and metoclopramide. The Lancet 1981, July 11, 91
5 SUZUKI A et al. Acute intermittent porphyria and epilepsy: safety of clonazepam. Epilepsia 1992; 33(1):108-111
6 McGUIRE G.M. and al. Effects of sodium valproate on hem biosynthesis in man: implication for seizure management in the porphyric patient. Eur.J.Clin.Invest.
1988; 18: 29-32.
7 CO: valproate Use in patients with mitochondrial diseases, C. Janiak-Bolzinger, 17 July 2014 (GPE-CL-2014-00053)
8 CO: valproate and patients with urea cycle disorders, C. Janiak-Bolzinger, 30 June 2014 (GPE-CL-2014-00136)
9 DECKERS C.L.P. and al. Adverse effects in epilepsy therapy. Wait and see or go for it? Acta Neurol.Scand.1997; 95 : 248-252
10 PELLOCK J.M. & WILLMORE J. A rational guide to routine blood monitoring in patients receiving antiepileptic drugs. Neurology 1991; 41 : 961-964
11 WYLLIE E. & WYLLIE R. Routine laboratory monitoring for serious adverse effects of antiepileptic medications: the controversy. Epilepsia; 32 (Suppl.5 : S574-
S579
12 LEVY RH et al. Valproic acid, absorption, distribution, and excretion. Antiepileptic drugs 1995 ; (48) :605-619
13 CO AEDs and suicidality (M. Brunet) LRC 18Sep08
14 Final SPC and PIL wording agreed by the PhVWP in January 2010: Valproic acid and interactions with carbapenems
15 CO: valproate Use in patients with mitochondrial diseases, C. Janiak-Bolzinger, 17 July 2014 (GPE-CL-2014-00053)
16 CO : Valproate and aggravated convulsion/paradoxical convulsion. C. Meidinger, 29 February 2016 (GPE-CL-2015-00652)
17 LOISEAU P. Altérations plaquettaires au cours du traitement des épilepsies par le valproate de sodium. Nouv.Presse Med.1981; 10 (46) : 3789-3790
18 DRORY et al. Hypersensitivity vasculitis and systemic lupus erythematosus induced by anticonvulsants. Clinical Neuropharmacology 1993; 16(1): 19-29
19 BLECK et al. Possible induction of systemic lupus erythematosus by valproate. Epilepsia 1990 ; 31:343-345
20 CASTRO-GAGO M. et al. Effects of valproic acid on the urea cycle and carnitine metabolism. Int.Pediatr. 1990; 5 (1): 54-57
21 HONEYCUTT D. et al. Heterozygote ornithine transcarbamylase deficiency presenting as symptomatic hyperammonemia during initiation of valproate therapy.
Neurology 1992; 42: 666-668
22 HORIUCHI M. et al. Carbamoylphosphate synthetase deficiency in an adult: deterioration due to administration of valproic acid. J.Inher.Metab.Dis. 1993; 16: 39-
45
23 LEAO M. Valproate as a cause of hyperammonemia in heterozygotes with ornithine-transcarbamylase deficiency. Neurology 1995; 45: 593-594
24 MORGAN H.B. & SWAIMAN K.F. Diagnosis of argininosuccinic aciduria after valproic acid-induced hyperammonemia. Neurology 1987; 37 (5): 886-887
25 Clinical overview “Rhabdomyolysis” (A. Coulon, dated 03June 2013)
26 Reasoned statement “valproate alcohol intake” (C. Janiak-Bolzinger, dated 17-Feb-2011)
27 BARRY M. & FEELY J. Enzyme induction and inhibition. Pharmac.Ther.1990; 48 (1): 71-94
28 BLAISE F.D. & BOURGEOIS M.D. Pharmacologic interactions between valproate and other drugs. Am.J.Med. 1988; 84 (Sup ;1A): 29-33
29 BRODIE M.J. Drug interactions in epilepsy. Epilepsia 1992 ; 33 (Suppl.1): S13-S22
30 LEPPIK I.E. & WOLFF D.L. Antiepileptic medications interactions. Epilepsy 1993; 11 (4): 905-921
31 LEVY R.H. & KOCH K.M. Drug interactions with valproic acid. Drugs 1982; 24: 543-556
Valproate – CCDS v21
Bolivia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala ,Haiti,
Honduras, Paraguay
32 LEVY R.H. & SHEN D.D. Valproic acid: absorption, distribution, and excretion. Antiepileptic Drugs 1995; 4th ed. 605-619
33 PISANI F. Influence of co-medication on the metabolism of valproate. Pharm.Weekbl. 1992; 14 (3A): 108-113
34 PISANI F. and al. Clinically relevant anti-epileptic drug interactions. J.Intern.Med.Res. 1990; 18 (1): 1-135
35 QUINN D.I. & DAY R.O. Drug interactions of clinical importance. Drug safety1995 ; 12 (6): 393-452
36 RAMBECK B. and al. Pharmacokinetic interactions of the new antiepileptic drugs. Clin.Pharmacokinet. 1996 ; 31 (4): 309-324
37 SCHEYER R.D. and al. Valproic acid. Interactions with other drugs. Antiepileptic Drugs 1995; Fourth Edition: 621-631
38 ZACCARA G. and al. Clinical pharmacokinetics of valproic acid. Clin.Pharmacokin. 1988; 15 (6): 367-389
39 COSTELLO L.E. & SUPPES T. A clinically significant interaction between clozapine and valproate. J.Clin.Psychopharmacol.1995, 15 (2): 139-141
40 FU C. et al. Valproate / nortriptyline interaction. J.Clin.Psychopharmacol. 1994 ; 14 (3): 205-206
41 SHELLY R.K. Fatal pharmacokinetic interaction involving amitryptiline combined with valproate and clozapine. Ir.J.Psych.Med.1998; 15 (3): 113-114
42 CORRIGAN F.M. Sodium valproate augmentation of fluoxetine or fluvoxamine effects. Biol.Psychiatry 1992; 31: 1172-1183
43 ANDERSON et al. Lorazepam valproate interaction: studies in normal subjects and isolated perfused rat liver. Epilepsia 1994, 35(1): 221-225
44 CALVO et al. Differential effects of valproic acid on the serum protein binding of lorazepam and diazepam. Int J. Clin. Pharm. Res 1986, VI(3): 213-215
45 DHILLON et al. Valproic acid and diazepam interaction in vivo. Br.J.clin.Pharmac. 1982 13, 553-560
46 JOSEPH A.B. & WROBLEWSKI B.A. Potentially serum concentrations of desipramine after discontinuation of valproic acid. Brain Injury 1993 ; 7 (5): 463-465
47 F. PISANI and al. Valproic acid - Amitriptyline interaction in man. Ther.Drug Monitor. 1986; 8: 382-383
48 BENAZZI F. Dagerous interaction with nefazodone added to fluoxetine, desipramine, venlafaxine, valproate and clonazepam combination therapy.
J.Psychopharmacol.1997; 11 (2) : 190-191
49 CRUZ-FLORES S. and al. Valproic toxicity with fluoxetine therapy. Missouri Med. 1995 ; 92 (6): 297-298
50 DROULERS A. and al. Decrease of valproic acid concentration in the blood when coprescribed with fluoxetine. J.Clin.Psychopharmacol. 1997; 17 (2): 139-140
51 SOVNER R. & DAVIS J.M. A potential drug interaction between fluoxetine and valproic acid. J. Clin. Psychopharmacol. 1991; 11 (6): 389
52 ANDERSEN B.B. and al. No influence of the antidepressant paroxetine on carbamazepine, valproate and phenytoin. Epilepsy Res. 1991; 10: 201-204
53 JOHN L. and al. Serotonine syndrome associated with nefadozone and paroxetine. Ann.Emerg.Med.1997; 29: 287-289
54 PEAK D.A. Toxic effects of nefadozone. Ann.Emerg.Med.1997; 30: 550-551
55 KETTER T.A. and al. Carbamazepine but not valproate induces bupropion metabolism. J.Clin.Psychopharmacol. 1995; 15: 327-333
56 POPLI A.P. Bupropion and anticonvulsant drug interactions. Ann ;Clin.Psychiatry 1995; 7 (2): 99-101
57 CENTORRINO F. and al. Serum concentrations of clozapine and its major metabolites: effects of co-treatment with fluoxetine or valproate. Am.J.Psychiatry
1994; 151 (1): 123-125
58 FINLEY P. & D.WARNER. Potential impact of valproic acid therapy on clozapine disposition. Biol. Psychiatry 1994; 36: 487-488
59 KANDO J.C. and al. Concurrent use of clozapine and valproate in affective and psychotic disorders. J.Clin.Psychiatry 1994; 55 (6): 255-257
60 SUPPES T. & RUSH A.J. Medication optimization during clozapine treatment. J.Clin.Psychiatry 1996; 57 (7): 307-308
61 WIRSHING W.C. and al. Hepatic encephalopathy associated with combined clozapine and divalproex sodium treatment. J.Clin.Psychopharmacol. 1997; 17 (2):
120-121
62 ISHIZAKI T. and al. The effects of neuroleptics (haloperidol and chlorpromazine) on the pharmacokinetics of valproic acid in schizophrenic patients.
J.Clin.Psychopharmacol. 1984; 4 (5): 254-261
63 BALDASSANO C.F. & GHAEMI S.N. Generalized edema with risperidone / Divalproex sodium treatment. J.Clin.Psychiatr.1996; 57: 9
64 LAUTERBACH E.C. Catatonia-like events after valproic acid with risperidone and sertraline. NNBN 1998; 11: 157-163
65 COCKS A. and al. The effects of clobazam on the blood levels of sodium valproate. RSM Int.Congr.Symp.Ser. 1993; 74: 155-157
66 LAEGREID L. and al. Benzodiazepine amplification of valproate teratogenic effects in children of mothers with absence epilepsy. Neuropediatrics 1993; 24 : 88-
92
67 MIRELES R. & LEPPIK E. Valproate and clonazepam in patients with intractable epilepsy. Epilepsia 1985; 26 (2): 122-126
68 WATSON W.A. Interaction between clonazepam and sodium valproate. N.Engl.J.Med.1979; 300 (12): 678-679
69 Granneman GR., Schneck DW., Cavanaugh JH., Witt GF. J. Clin Psychiatry 57:5, May 1996.
70 BOURGEOIS B.F. Pharmacologic interactions between valproate and drugs. Am.J.Med. 1988; 84 (1A): 29-33
71 BRUNI J. Valproic acid and plasma levels of primidone and derived phenobarbital. J.Can.Sci.neurol. 1981; 8 (1): 91-92
72 HOFFMAN A. & HABIB G. Valproic acid intensifies the depressant action of phenobarbital and ethanol by a pharmacodynamic mechanism. J.Pharm.Sci. 1994;
83 (5): 733-735
73 YUKAWA E. and al. The effect of concurrent administration of sodium valproate on serum levels of primidone and its metabolite phenobarbital.
J.Clin.Pharm.Ther. 1989; 14 (5) : 387-392
74 MONKS A. & RICHENS A. Effect of single doses of sodium valproate on serum phenytoin levels and protein binding in epileptic patients.
Clin.Pharmacol.Ther.1980; 27 (1): 89-95
75 PERRUCA E. et al. Interaction between phenytoin and valproic acid: plasma protein binding and metabolic effects. Clin.Pharmacol.Ther.1980; 28 (6): 779-789
76 RIVA R. et al. Time-dependent interaction between phenytoin and valproic acid. Neurology 1985; 35 (4): 510-515
77 KERR B. and al. Inhibition of human liver microsomal epoxide hydrolase by valproate and valpromide. In vitro / in vivo correlation. Clin.Pharmacol.Ther. 1989;
46: 82-93
78 KODAMA Y. and al. Evaluation of equations for unbound serum concentration prediction of carbamazepine-10, 11-epoxide in polytherapy pediatric patients with
epilepsy. J.Pharm.Sci. 1995; 84 (7): 835-839
79 McKEE P.J.W. and al. Variability and clinical relevance of the interaction between sodium valproate and carbamazepine in epileptic patients. Epilepsy Res. 1992;
11: 193-198
80 MEIJER J.W.A. and al. Possible hazard of valpromide-carbamazepine combination therapy in epilepsy. Lancet 1984; 1(8380): 802
81 PACIFICI G.M. Valpromide-carbamazepine and risk of teratogenicity. Lancet 1985; 1 (8425): 397-398
82 PANESAR S.K. The effect of carbamazepine on valproic acid disposition in adult volunteers. Br.J.Clin.Pharmac.1989; 27 (3): 323-328
83 PERUCCA E. and al. In vivo inhibition of epoxide hydrolase by valpromide and valproic acid. Acta Pharmacol.Toxicol. 1986; 59 (5): 111
84 PISANI F. and al. Sodium valproate and valpromide: differential interactions with carbamazepine in epileptic patients. Epilepsia 1986; 27 (5): 548-552
85 SVINAROV D.A. & PIPPENGER C.E. Valproic acid-carbamazepine interaction: is valproic acid a selective inhibitor of epoxide hydrolase? Ther.Drug Monitor.
1995; 17 (3): 217-220
86 Clinical Overview “Interaction with lamotrigine” (C. Janiak-Bolzinger; dated 17-Feb-2011)
87 ERIKSSON A.S. et al. Pharmacokinetic interactions between lamotrigine and other epileptic drugs in children with intractable epilepsy. Epilepsia 1996; 37 (8):
769-773
88 MANASCO P. et al. Skin rash associated with Lamictal: incidence, time to onset, risk factors. Epilepsia 1996; 37 (Supp.5): 164
89 PISANI F. et al. Interaction of lamotrigine with sodium valproate. Lancet 1993; 341: 1224
90 SCHLUMBERGER E. et al. Lamotrigine in treatment of 120 children with epilepsy. Epilepsia 1994; 35 (2): 359-367
91 YUEN A.W.C. et al. Sodium valproate acutely inhibits lamotrigine metabolism. J.Clin.Pharmac. 1992; 33 (5): 511-513
92 VEGGIOTTI P. and al. Lamotrigine in infantile spasms. Lancet 1994; 344 (8933): 1375-1376
93 VUKELIC D. and al. Lamotrigine and toxic epidermal necrolysis. Dermatology 1997; 195 (3): 307
94 WADELIUS M. and al. Lamotrigine and toxic epidermal necrolysis. Lancet 1996; 348: 1041
95 VPA CO Lamotrigine (N. Rabault) LRC 03Oct05
96 LERTORA J.J.L. et al. Pharmacokinetic interaction between zidovudine and valproic acid in patients infected with human immunodeficiency virus.
Clin.Pharmacol.Ther. 1994; 56 (3): 272-278
97 ROBERTSON-DALLAS S. et al. New drug interactions with zidovudine. Pharmacotherapy 1997; 17 (6): 1198-1209
98 Clinical Overview “Interaction valproate acid and felbamate” (S. Fabre-Decourt; dated 25-jan-2011)
99 CO: valproate interaction with olanzapine, A.Lin and C. Hamelin, 23 Jun 2014 (GPE-CL-2014-00490)
100 CO: valproate Interaction with rufinamide, C. Favennec-Meidinger, 02 Dec 2014 (GPE-CL-2014-00901)
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101 BERNUS I. et al. Effect of felbamate on the plasma protein binding of valproate. Clin.Drug Invest. 1995; 10 (5): 288-295
102 HOOPER W.D. et al. Effect of felbamate on valproic acid disposition in healthy volunteers: inhibition of oxidation. Epilepsia 1996; 37 (1): 91-97
103 WAGNER M.L. et al. The effect of felbamate on valproic acid disposition. Clin.Pharmacol.Ther. 1994; 56: 494-502
104 McCONNELL H. and al. Neuropsychiatric side effects related to treatment with felbamate. J.Neuropsy. 1996; 8 (3): 341-346
105 CO: valproate Hyperammonemia – Phenobarbital, A. Villoing, C. Favennec-Meidinger, K. Pearson, 15 Dec 2014 (GPE-CL-2014-00788)
106 CO: valproate Hyperammonemia – Phenytoin, C. Favennec-Meidinger, K. Pearson, 15 Dec 2014 (GPE-
107 JALLON P. Aggravation d'une épilepsie par la prise de méfloquine. Boll.Lega.It.Epil.1988; 62/63: 229
108 O’BRYAN J. Malaria prophylaxis: more data required. Pharm.J. 1994; 252: 425
109 DASGUPTA A. & JACQUES M. Reduced in vitro displacement of valproic acid from protein binding by salicylate in uremic sera compared with normal sera.
Am.J.Clin.Pathol. 1994; 101 (3): 349-353
110 ORR J.M. et al. Interaction between valproic acid and aspirin in epileptic children: serum protein binding and metabolic effects. Clin.Pharmacol.Ther.1982; 31
(5): 642-649
111 GRIMALDI R. et al. In vivo plasma protein binding interaction between valproic acid and naproxen. Eur.J.Drug Metab.Pharmacokin. 1984; 9 (4): 359-363
112 GUTHRIES SK., et al. Hypothesized interaction between valproic acid and warfarin. J. Clin Psychopharmacol. 1995, 15(2) 138-139
113 WEBSTER L.K. et al. Effect of cimetidine and ranitidine on carbamazepine and sodium valproate pharmacokinetics. Eur.J. Clin. Pharmacol. 1984; 27 (3): 341-
343
114 GOPAUL S.V. et al. A case study of erythromycin interaction with valproic acid. Pharm.Res. 1996; 13 (9): S-434
115 REDINGTON K. et al. Erythromycin and valproate interaction. Ann.Intern.Med.1992; 116 (10): 877-878
116 Von ROSENSTIEL N.A. & ADAM D. Macrolide antibacterials. Drug interactions of clinical significance. Drug Safety 1995; 13 (2): 105-122
117 DE TURCK BJ, et al.Lowering of plasma valproic acid concentrations during concomitant therapy with meropenem and amikacin. J Antimicrob Chemother.
1998 Oct;42(4): 563-4
118 YAMAGATA T, et al. Panipenem-betamipron and decreases in serum valproic acid concentration. The Drug Monit. 1998 Aug;20(4): 396-400
119 NAGAI K, et al. Decrease in serum levels of valproic acid during treatment with a new carbapenem, panipenem/betamipron. J Antimicrob Chemother. 1997
Feb;39(2): 295-6
120 SANDER JW et al. Epilepsy and comorbidity: infections and antimicrobials usage in relation to epilepsy management. Acta Neurol Scand 2003;108(Suppl 180):
16-22
121 VPA CO Interaction between valproate and rifampicin (M. Brunet) LRC 18Sept08
122 CO: Interaction between valproate and protease inhibitors (lopinavir / ritonavir), F. Perrouin, K.Pearson, C. Janiak-Bolzinger, 10 Sep 2014 (GPE-CL-2014-
00234)
123 CO: valproate Interaction with cholestyramine, A. Villoing, K.Pearson, C. Janiak-Bolzinger, 11 Sep 2014 (GPE-CL-2014-00416)
124 CO: Valproate: Acetazolamide-hyperammonaemia, P. Fitas, 14 Mar 2014 (GPE-CL-2014-00072)
125 VPA CO Interaction between valproate and topiramate (M. Brunet) LRC 18Sept 08
126 Clinical overview “Interaction quetiapine (leucopenia) (A. Lachinsky, dated 10-Dec-13)
127 CRAWFORD. The lack of effect of sodium Valproate on the pharmakocinetic of oral steroids. Contraception 1986, 33(1): 23-9
128 MATTSON et al. Use of oral contraceptives by women with epilepsy 1986 JAMA 256 : 238-240
129 VPA CO Mother and fetus (A.Giudicelli) LRC 03Oct05
130 FRIED S et al. Malformation rates in children of women with untreated Epilepsy. A metanalysis. Drug Safety 2004: 27(3): 197-202
131 SAMREN EB et al. Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European propective study of human teratogenesis
associated with maternal epilepsy. Epilepsia 1997;38(9): 981-90
132 WIDE K et al. Major malformations in infants exposed to antiepileptic drugs in utero with emphasis on carbamazepine and valproic acid: a nation-wide,
population-based register study. Acta Paediatr 2004;93: 174-6
133 ARPINO C. et al. Teratogenic effects of antiepileptic drugs: use of an international database on malformations and drug exposure (MADRE). Epilepsia
2000;41(11): 1436-43
134 CHADWICK D. Managing epilepsy in women: special considerations. Update, Sep. 2001
135 CRAWFORD P, APPLETON R, BETTS T, DUNCAN J, GUTHRIE E, MORROW J, The woman with epilepsy guidelines development group. Best practice
guidelines for the management of women with epilepsy. Seizure, 1999; 8(4): 201-217
136 DEAN JCS, HAILEY H, MOORE SJ, LLOYD DJ, TURNPENNY PD, LITTLE J. Long term health and neurodevelopment in children exposed to antiepileptic
drugs before birth. J Med Genet, 2002; 39: 251-259
137 WIDE K, WINBLADH B, TOMSON T, SARS-ZIMMER K, BERGGREN E. Psychomotor development and minor anomalies in children exposed to
antiepileptic drugs in utero: a prospective population-based study. Dev Med Child Neurol, 2000; 42: 87-92
138 TETTENBORN B, GENTON P POLSON D. Epilpesy and women's problems: An update. Epileptic disord 2002; 4(suppl2): SI11-9
139 Clinical overview “valproate and Hypospadias” (C. Janiak and A. Coulon, dated 25-jun-2012)
140 Clinical overview “valproate and incidence for congenital malformations” (A. Coulon and C. Janiak-Bolzinger, dated 25-Jun-2012)
141 ADAB N, JACOBY A, SMITH D, CHADWICK D. Additional educational needs in children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry
2001; 70: 15-21
142 THISTED E, EBBESEN F. Malformations, withdrawal manifestations, and hypoglycaemia after exposure to valproate in utero. Arch Dis Child 1993;69: 288-
291
143 MOORE SJ, TURNPENNY P, QUINN A, et al. A clinical study of 57 children with fetal anticonvulsant syndromes. J Med Genet 2000; 37: 489-497
144 LINDHOUT D, MEINARDI H, MEIJER JW, NAU H. Antiepileptic drugs and teratogenesis in two consecutive cohorts: changes in prescription policy
paralleled by changes in pattern of malformations. Neurology 1992;42(4 Suppl 5): 94-110
145 HÄTTIG H, HELGE H, STEINHAUSN H-C. Infants of epileptic mothers: developmental scores at 18 months. In Wolf P, Dam M, Janz D, Dreifuss FE
(editors). Advances in Epileptology Vol. 16. New York: Raven Press 1987: 579-581
146 CEROVAC-COSIC N, JOVIC N, VRANJESEVIC D. Neurological development of infants born to mothers with juvenile myoclonic epilepsy (JME). Epilepsia
1998;39(Suppl 2): 21
147 OHTSUKA Y, SILVER K, LOPES-CENDES I, et al. Effect of antiepileptic drugs on psychomotor development in offspring of epileptic mothers. Epilepsia
1999;40(Suppl 2): 296
148 MAWER G, CLAYTON-SMITH J, COYLE H, KINI U. Outcome of pregnancy in women attending an outpatient epilepsy clinic: adverse features associated
with higher doses of sodium valproate. Seizure 2002;11: 512-518
149 GAILY E, KANTOLA-SORSA E, HIILESMAA V, et al. Normal intelligence in children with prenatal exposure to carbamazepine. Neurology 2004;62: 28-32
150 ADAB N, KINI U, VINTEN J, AYRES J, BAKER G, CLAYTON-SMITH J, COYLE H, FRYER A, GORRY J, GREGG J, MAWER G, NICOLAIDES P,
PICKERING L, TUNNICLIFFE L, CHADWICK DW. The longer-term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry 2004;75:
1575-1583
151 JAMES FH, FAIRGRIEVE S, LYNCH SA, JACKSON MJ. Prospective study of development of infants born to mothers with epilepsy. J Neurol Neurosurg
Psych 2002;72: 135
152 BETTS T, FOX C. Proactive pre-conception counselling for women with epilepsy-is it effective? Seizure. 1999 Sep;8(6):322-7
153 BAVOUX F. and al. Neonatal fibrinogen depletion caused by sodium valproate. Ann.Pharmacother. 1994; 28: 1307
154 MAJER R.V. & GREEN P.J. Neonatal afibrinogenaemia due to sodium valproate. Lancet 1987; 2: 740-741
155 STAHL M.M.S. and al. Thrombocytopenia purpura and anemia in a breast-fed enfant whose mother was treated with valproic acid. J.Pediatr.1997; 130: 1001-
1003
156 Clinical overview “valproate and coagulation factors factors decrease” (C. Janiak and A. Coulon, dated 25-jun-2012)
157 Clinical overview “Neonatal hypoglycaemia” (C. Janiak-Bolzinger and A. Coulon, dated 17-Feb-2011)
158 Clinical overview “valproate and hypothyroidism” (A. Coulon, dated 25-Jun-2012)
159 Clinical overview “Neonatal withdrawal syndrome” (‘A. Coulon, dated 03-Jun-13)
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Honduras, Paraguay
160 VPA CO Lactation (N. Rabault) LRC 03Oct05
161 CO ADRs (M. Luong) LRC 18Sep08
162 Clinical overview “Frequencies of adverse drug reactions” (L. Delfau and C. Janiak-Bolzinger; dated 31-May-2011)
163 Clinical overview “valproate addendum Frequencies” (L. Delfau and C. Janiak-Bolzinger; dated 06-Jun-2012)
164 Clinical overview “Valproate and adverse reactions frequency Addendum (C. Janiak-Bolzinger, dated 10-Dec-13)
165 BRICHARD B. et al. Haematological disturbances during long-term valproate therapy. Eur. J. Pediatr. 1994; 153 (5): 378-380
166 DELGADO M.R. et al. Thrombocytopenia secondary to high valproate levels in children with epilepsy. J.Child Neurol. 1994; 9 (3): 311-314
167 FAWCETT R.G. Dose-related thrombocytopenia and macrocytic anemia associated with valproate use in bipolar disorder. J.Clin.Psychiatry 1997; 58 (3): 125
168 GANICK D.J. et al. Severe hematologic toxicity of valproic acid: a report of four patients. Am.J.Pediatr.Hemato.Oncol. 1990; 12 (1): 80-85
169 MAY R.B. & SUNDER T.R. Hematologic manifestations of long-term valproate therapy. Epilepsia 1993; 34 (6): 1098-1101
170 RAJANTIE J. et al. Fatal pancytopenia during high-dose valproate monotherapy. Eur.J.Pediatr. 1992; 151: 619-620
171 WATTS R.G. et al. Clinical and laboratory observations. Valproic acid-induced cytopenias: evidence for a dose-related suppression of hematopoiesis. J.Pediatr.
1990; 117 (3): 495-499
172 BALLABAN-GIL K. and al. Complications of the ketogenic diet (thrombocytopenia ; increase in liver function tests). Epilepsia 1998; 39 (7): 744-748
173 CO Bone marrow failure/aplasia/pure red cell (M. Brunet) LRC 18Sep08
174 CO Agranulocytosis (M. Brunet) LRCSep08
175 Clinical overview “valproate and macrocytosis/macrocytotic anaemia” (A. Coulon; dated 25-Jun-2012)
176 BRENINGSTALL G.N. & CICH J.A. Pseudo valproate-induced hypofibrinogenemia. Pediatr.Neurol. 199; 14 (4): 345
177 ANDERSON G.D. et al. Lack of bleeding complications in patients undergoing cortical surgery while receiving valproate therapy. Epilepsia 1996; 37 (suppl.5):
169
178 GIDAL B.E. et al. Valproate-mediated disturbances of hemostasis: relationship to dose and plasma concentration. Neurology 1994; 44: 1418-1422
179 KREUZ W. et al. Valproate therapy induces von Willebrand disease type I. Epilepsia 1992; 33 (1): 178-184
180 LOISEAU et al. Sodium valproate, platelet dysfunction and bleeding. Epilepsia 1981, 22: 141-146
181 WINTER S.L. et al. Perioperative blood loss: the effect of valproate. Ped.Neurol. 1996; 15 (1): 19-22
182 Clinical overview” Biotin deficiency” (C.Janiak-Bolzinger, dated 10-Dec-13)
183 Clinical overview “Valproate and Extrapyramidal disorder” (C. Janiak-Bolzinger; dated 17-Feb-2011)
184 Clinical overview “valproate and cognitive disorders” (C. Janiak-Bolzinger; dated 25-Jun-2012)
185 Clinical overview ”valproate and headache” (E. Zalmover; dated 25-Jun-2011)
186 Clinical overview “valproate and nystagmus” (A. Coulon and C. Janiak-Bolzinger; dated 25-Jun-2012)
187 CO: valproate Dizziness, C. Meidinger and R. Goyal, 16 Dec 2014 (GPE-CL-2014-00947)
188 CO: valproate: ADR Frequency - addendum n°3, A. Lachacinski and C. Favennec-Meidinger, 15 Dec 2014 (GPE-CL-2014-00941)
189 ALVAREZ-GOMEZ MJ, et al. Parkinsonian syndrome in childhood after sodium valproate administration. Clin Neuropharmacol. 1993 Oct;16(5): 451-5
190 DEL REAL FRANCIA MA, et al. [Parkinsonism induced by sodium valproate]. Neurologia. 1995 Nov;10(9): 381-3
191 FROOMES PR, et al. A reversible parkinsonian syndrome and hepatotoxcity following addition of carbamazepine to sodium valproate. Aust N Z J Med. 1994
Aug;24(4): 413-4
192 ONOFRJ M, et al. Reversible parkinsonism induced by prolonged treatment with valproate. J Neurol. 1998 Dec;245(12): 794-6
193 PARK-MATSUMOTO YC, et al. [Valproate induced parkinsonism]. No To Shinkei. 1998 Jan; 50(1): 81-4. Review
194 WILS V, et al. Extrapyramidal syndrome due to valproate administration as an adjunct to lithium in an elderly manic patient. Int J Geriatr Psychiatry. 1997
Feb;12(2): 272
195 SASSO E, et al.Reversible valproate-induced extrapyramidal disorders. Epilepsia 1994 Mar-Apr;35(2): 391-3
196 ZWAN A VAN DER. Transitory Parkinson syndrome and tremor after application of sodium valproate. Ned. Tijdschr.Geneeskd. 1989 ;24: 1230-1232
197 HERRANZ JL et al. Side effects of valproate in monotherapy controlled by plasma levels: a study in 88 pediatric patients. Epilepsia 1982;23: 203-14
198 JEAVONS PM et al. Sodium valproate in treatment of epilepsy. Br Med J 1974;2: 584-6
199 JEAVONS PM et al. Treatment of generalized epilepsies of childhood and adolescence with sodium valproate ('Epilim'). Develop Med Child Neurol 1977;19: 9-
25
200 BARNES SE et al. Sodium valproate in the treatment of intractable childhood epilepsy. Develop Med Child Neurol 1975;17: 175-81
201 HAIGH D et al. The treatment of childhood epilepsy with sodium valproate. Develop Med Child Neurol 1975;17: 743-8
202 VINING E et al. Valproate sodium in refractory seizures. Am J Dis Child 1979;133: 274-6
203 SCHMIDT D. Adverse effects of valproate. Epilepsia 1984;25(Suppl. 1): S44-S49
204 Clinical overview ”valproate and paraesthesia” (C. Cohen; dated 15-Nov-2011)
205 ARMON C. et al. Valproate-induced dementia and Parkinsonism: prevalence in an actively ascertained epilepsy clinic population. Neurology 1991; 41: p.1162
206 DEHLING et al. Reversible dementia after VPA therapy. Epilepsia 1990, 31(2): 218-231
207 GUERRINI R. et al. Reversible pseudoatrophy of the brain and mental deterioration associated with valproate treatment. Epilepsia 1998; 39(1): 27-32
208 MCLACHLAN. Pseudoatrophy of the brain with valproic acid monotherapy. Can J Neurol Sci, 1987, 14(3): 294-296
209 PAPAZIAN O. et al. Reversible dementia and apparent brain atrophy during valproate therapy. Ann.Neurol.1995; 38: 687-691
210 SCHONDIENST et al. Cerebral and cerebellar atrophy caused by valproate? 4 case report Epilepsia 1990, 31(2): 227
211 ZARET et al. Reversible valproic acid-induced Dementia: a case report Epilepsia 1986, 27(3): 234-240
212 BEVERSDORF D. et al. Vaproate-induced encephalopathy treated with carnitine in adult. J.Neurol.Neurosurg.Psych. 1996; 61 (2): 211
213 BRODIE M.J. Antiepileptic Drugs. N. Engl. J. Med. 1996; 334 (3): 168-175
214 DREIFUSS et al. Valproic acid toxicity. Antiepileptic drugs 4th Edition Raven press 1995, 641-645
215 DUARTE J. et al. Valproate-induced coma: case report and literature review. Ann.Pharmacother. 1993; 27: 582-583
216 EZE E. et al. Hyperammonemia and coma developed by a woman treated with valproic acid for affective disorder. Psych. Services 1998; 49: 1358-1359
217 SETTLE E.C. Valproic acid-associated encephalopathy with coma. Am.J.Psychiatr. 1995; 152 (8)
218 AGUGLIA U. and al. Negative myoclonus during valproate-related stupor. Electroencephal.Clin.Neurophysiol. 1995; 94 (2): 103-108
219 BAUER J. Seizure-inducing effects of antiepileptic drugs: a review. Acta.Neurol.Scand. 1996; 94: 367-377
220 De TOLEDO J.C. and al. Status epilepticus associated with the combination of valproic acid and clomipramine. Ther.Drug Monitor. 1997; 19: 71-73
221 MacDONALD J.T. Breakthrough seizure following substitution of Depakine capsules (Abbott) with a generic product. Neurology 1987; 37: p.1885
222 STECKER M.M. & KITA M. Paradoxical response to valproic acid in a patient with a hypothalamic hamartoma. Ann.Pharmacother.1998; 32 (11): 1168-1172
223 STEINHOFF B.J. & STODIECK S.R.G. Temporary abolition of seizure activity by flumazenil in a case of valproate-induced non-convulsive status epilepticus.
1993; 2 (3): 261-265
224 ARMON C. et al. Sensorineural hearing loss: a reversible effect of valproic acid. Neurology 1990; 40: 1896-1898
225 ARMON C. et al. Valproate-induced sensorineural hearing impairment. Epilepsia 1990; 31 (5): 601
226 ASCONAPE J.J. et al. Sensorineural hearing loss associated with the use of valproate. Abst.Am.Neurol.Assoc. 1993; 34 (2): p.263
227 NARITOKU D. et al. Does valproate administration alter auditory threshold? Epilepsia 1992; 33 (3): 109-110
228 SELIGMANN H. and al. Drug-induced tinnitus and other hearing disorders. Drug safety 1996; 14 (3): 198-212
229 Clinical overview “valproate and pleural effusion” (C. Hamelin; dated 25-June 2012)
230 Clinical overview “Vomiting” (C. Janiak-Bolzinger, dated 10-Dec-13),
231 Clinical overview “Gingival disorders” (C. Adamy, C. Janiak-Bolzinger, dated 10-Dec-13)
232 Clinical overview “Stomatitis” (C. Janiak-Bolzinger, dated 10-Dec-13)
233 VPA CO Diarrhoea LRC 05Aug02
234 ASCONAPE J.J et al. Valproate-associated pancreatitis. Epilepsia 1993; 14 (1): 177-183
235 BUZAN R.D. et al. Valproate-associated pancreatitis and cholecystitis in six mentally retarded adults. J. Clin. Psychiatry 1995; 56 (11): 529-532
236 RUNZI et al. Drugs associated pancreatitis: facts and fiction ; Pancreas 1996, 13(1): 100-109
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237 WILMINKT & FRICK T.W. Drug-induced pancreatitis. Drug Safety 1996; 14 (6): 406-423
238 Clinical overview “Tubulointerstitial nephritis/renal failure (A. Coulon, dated 03-Jun-13)
239 EGGER J et al. Effects of valproate in 100 children with special reference to weight. Br Med J 1981;283: 577-81
240 HORITA H. et al. Weight gain and nocturnal enuresis associated with sodium valproate. J Jpn Epilepsy Soc 1990;8(2): 176-8
241 PANAYIOTOPOULOS CP. Nocturnal enuresis associated with sodium valproate. Lancet 1985;1(8440): 980-1
242 CHOONARA IA. Sodium valproate and enuresis. Lancet 1985;1(8440): 1276
243 LANDE M.B. et al. Reversible Fanconi syndrome associated with valproate therapy. J.Pediatr.1993; 123: 320-322
244 LENOIR et al. Valproic acid: a possible cause of a proximal tubular renal syndrome. J.Pediatr 1981, 98(3), 503-504
245 RYAN S.J. et al. Occurrence of renal. Fanconi syndrome in children on valproic acid therapy. J. Epilepsy 1996; 9: 35-38
246 SMITH G.C. et al. Anticonvulsants as a cause of Fanconi syndrome. Nephrol.Dial.Transplant. 1995; 10 (4): 543-545
247 QUINONERO M.A. and al. Sindrome de Fanconi asociado a tratamoento con acido valproico. An.Esp.Pediatr.1995; 42: 71-72
248 FUKUDA Y. and al. Immunologically mediated chronic tubulo-interstitial nephritis caused by valproate therapy. 1996; 72: 328-329
249 HAWKINS E. & BREWER E. Renal toxicity induced by valproic acid. Pediatr.Pathol. 1993; 13: 863-868
250 ISHITSU T. and al. Anticonvulsivant-induced rickets associated with renal tubular acidosis and normal level of serum 1,25-dihydroxyvitamin D.
Am.J.Dis.Child. 1981; 135: 1140-1141
251 KORINTHENBERG and al. Renal tubular dysfunction following treatment with antiepileptic drugs. Eur. J. Pediatr. 1994; 153 (11): 855-858
252 LIN C.Y. & CHIANG H. Sodium valproate-induced interstitial nephritis. Nephron 1988; 48: 43-46
253 WATANABE and al. Chronic tubulo-interstitial nephritis. J.G.S. 1992; 34 (10): 1101-1105
254 CO Angioedema (M. Brunet) LRC 18Sep08
255 CO DRESS (M. Brunet) LRC 18Sep08
256 PLANTIN P, et al. [Drug hypersensitivity syndrome during treatment with valproic acid]. Presse Med. 1995 Nov 11;24(34): 1624
257 CIERNIK IF, et al. Anterior uveitis and the anticonvulsant hypersensitivity syndrome. Arch Intern Med. 1998 Jan 26;158(2): 192
258 HOSSEIN FATEMI S. & CALABRESE J.R. Treatment of valproate-induced alopecia. Ann.Pharmacother. 1995; 29 (12): 1302
259 PILLANS P.I. & WOODS D.J. Drug-associated alopecia. Int.J.Dermatol.1995; 34 (3): 149-158
260 CO: Valproate and nail and nail bed disorders, A. Lin and C. Hamelin, 15 Dec 2014 (GPE-CL-2014-00709)
261 CO Angioedema (M. Brunet) LRC 18Sep08
262 Clinical overview “Hair change” (C. Janiak-Bolzinger, dated 10-Dec-13)
263 GAIST D. et al. Spontaneous reports of drug-induced erythema multiforme, Steven-Johnson syndrome and toxic epidermal necrolysis in Denmark 1968-1991.
Pharmacoepidemiol.Drug Safety 1996; 5: 79-86
264 ROUJEAU J.C. & STERN R.S. Severe adverse cutaneous reactions to drugs. New Engl.J.Med. 1994; 331 (19): 1272-1285
265 ROUJEAU J.C. et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. New Engl.J.Med. 1995; 333 (24): 1600-1607
266 CO DRESS (M. Brunet) LRC 18Sep08
267 Clinical overview “valproate and osteoporosis and fractures” (C. Janiak-Bolzinger and C. Hamelin; dated 25-Jun-2012)
268 Clinical overview” valproate and lupus erythematosus” (C. Favennec-Meidinger; dated 17-Nov-2011)
269 VPA CO SIADH (M. Brunet) LRC 18Sep08
270 Clinical overview “Hyperandrogenism” (A. Lesaint, H. Arroum, C.jjaniak-Bolzinger, dated 10-Dec-13)
271 VPA CO PCOS LRC 05Aug02
272 BAUER J. and al. Polycystic ovary syndrome in patients with focal epilepsy: a study in 93 women. Epilepsy research 41 (2000) 163-167
273 BAUER J. and al. Reproductive dysfunction in women with epilepsy: recommendations for evaluation and management. J; Neurol. Neurosurg. Psychiatry 2002;
73: 121-125
274 BILO L. and al. Characterization of reproductive endocrine disorders in Women with epilepsy. The Journal of Endocrinology and Metabolism 2001 Vol 86,
No.7: 2950-2956
275 DUNCAN S. Polycystic ovarian syndrome in women with epilepsy: a review. Epilepsia 42 (Suppl.3): 60-65. 2001
276 GENTON P. and al. Controversies in Epilepsy on the association between valproate and polycystic ovary syndrome. Epilepsia, 42(3): 295-304, 2001
277 LUEF G. and al. Polycystic ovaries, obesity and insulin resistance in women with epilepsy: a comparative study of carbamazepine and valproic acid in 105
women. J. Neurol. (2002) 249: 835-841
278 CO: valproate Obesity, C. Janiak- Bolzinger, 25 Nov 2014 (GPE-CL-2014-00608)
279 ALTUNBASAK et al. Asymptomatic hyperammonaemia in children treated with valproic acid. Journal of child Neurology 12 (7): 461-463
280 PATSALOS et al. The prevalence of valproic acid associated hyperammonaemia in patients with intractable epilepsy resident at the chalfont centre for epilepsy.
J Epilepsy 1993 ; 6: 228-232
281 Clinical overview “Myelodysplasic and valproate (C. Hamelin; dated 2012)
282 Clinical overview “valproate and haemorrhage” (C. Janiak-Bolzinger; dated 25-Jun-2012)
283 KAMPER et al.: Cutaneous vasculitis induced by sodium valproate The Lancet 1991, 337(8739): 497-498
284 Clinical overview “Hypothermia”(C. Janiak-Bolzinger, C. Adamy, dated 10-Dec-13)
285 VPA CO Oedema LRC 05Aug02
286 BICKENESE et al. Early childhood hepatocerebral degeneration misdiagnosed as valproate hepatotoxicity. Ann Neurol 1992 , 32: 767-775
287 BRYANT A.E. & DREIFUSS F.E. Valproic acid hepatic fatalities. III. U.S. experience since 1986. Neurology 1996; 46: 465-469
288 DREIFUSS F.E. et al. Valproic acid hepatic fatalities: a restrospective review. Neurology 1987; 37: 379-385
289 DREIFUSS F.E. & LANGER D.H. Hepatic considerations in the use of antiepileptic drugs. Epilepsia 1987; 28(Suppl.2): 523-529
290 DREIFUSS F.E. et al. Valproic acid hepatic fatalities. II. U.S. experience since 1984. Neurology 1989; 39: 201-207
291 KOENIG et al. Severe hepatotoxicity during valproate therapy: an update and report of eight new fatalities. Epilepsia 1994, 35(5): 1005-1015
292 JONES TH. Sodium valproate -induced menstrual disturbances in young woman. Hormone Res 1991, 35: 82-85
293 MARGRAF J.W et al. Amenorrhea following initiation of therapy with valproic acid. Neurology 1981,31: 159
294 Clinical overview “Valproate and Male infertility” (C. Janiak-Bolzinger; dated 17-Dec-2011)
295 VPA CO PCOS LRC 05Aug02
296 BAUER J. and al. Polycystic ovary syndrome in patients with focal epilepsy: a study in 93 women. Epilepsy research 41 (2000) 163-167
297 BAUER J. and al. Reproductive dysfunction in women with epilepsy: recommendations for evaluation and management. J; Neurol. Neurosurg. Psychiatry 2002;
73: 121-125
298 BILO L. and al. Characterization of reproductive endocrine disorders in Women with epilepsy. The Journal of Endocrinology and Metabolism 2001 Vol 86,
No.7: 2950-2956
299 DUNCAN S. Polycystic ovarian syndrome in women with epilepsy: a review. Epilepsia 42 (Suppl.3): 60-65. 2001
300 GENTON P. and al. Controversies in Epilepsy on the association between valproate and polycystic ovary syndrome. Epilepsia, 42(3): 295-304, 2001
301 LUEF G. and al. Polycystic ovaries, obesity and insulin resistance in women with epilepsy: a comparative study of carbamazepine and valproic acid in 105
women. J. Neurol. (2002) 249: 835-841
302 Clinical overview “Hallucination” (C. Jjaniak-Bolzinger, A; Coulon, dated 10-dec-13)
303 Clinical overview “valproate and behavior disorders” (C. Janiak-Bolzinger; dated 25-jun-2012
304 Clinical overview “valproate and psychomotor hyperactivity” (C. Janiak-Bolzinger; dated 25-jun-2012)
305 ISBISTER G et al. Valproate overdose: a comparative cohort study of self-poisonings. Br J Clin Pharmacol. 2003;55(4): 398-404
306 SPILLER H et al. Multicenter case series of valproic acid ingestion: serum concentrations and toxicity. J Toxicol Clin Toxicol. 2000;38(7): 755-60
307 DUMOULIN A et al. Acidosis and hyperlactatemia in acute sodium valproate poisoning. Presse Med. 1997;26(12): 555-7
308 Clinical overview “Hypotension in context of overdose” (B. Martin, C. Janiak-Bolzinger, dated 10-Dec-13)
309 BERTHELOT-MORITZ F. and al. Fatal sodium valproate poisoning. Int.Care Med.1997; 23 (5): 599
310 DUPUIS R.E. and al. Acute valproic acid overdose. Drug Safety 1990; 5 (1): 65-71
Valproate – CCDS v21
Bolivia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala ,Haiti,
Honduras, Paraguay
311 EEG-OLOFSSON O. & LINDSKOG U. Acute intoxication with valproate. Lancet 1982; 1306
312 GARNIER R. & FOURNIER E. Intoxication aiguë par le valproate de sodium. Nouv.Presse Med. 1982; 11 (9): p.678
313 MORROW J.I. & ROUTLEDGE P.A. Poisoning by anticonvulsants. Adv.Drug React.Acute Poisoning Rev. 1989; 8 (2): p.97-109
314 ANDERSEN GO, et al. Life threatening intoxication with sodium valproate. J Toxicol Clin Toxicol. 1995;33(3): 279-84
315 DUPUIS RE, et al. Acute valproic acid overdose. Clinical course and pharmacokinetic disposition of valproic acid and metabolites. Drug Saf. 1990 Jan-Feb;5(1):
65-71
316 PEDERSEN B, et al. Electroencephalographic alterations during intoxication with sodium valproate: a case report. Epilepsia. 1984 Feb;25(1): 121-4
317 Clinical overview “Hypernatraemia” (B. Martin, C. Janiak-Bolzinger, dated 10-Dec-13)
318 MONTERO FJ. Naloxone in the reversal of coma induced by sodium valproate. Ann Emerg Med. 1999 Mar;33(3): 357-8
319 STEIMAN GS, et al. Treatment of accidental sodium valproate overdose with an opiate antagonist. Ann Neurol. 1979 Sep;6(3): 274
320 CO Valproate and overdose (M. Brunet) LRC 18Sep08
321 Clinical overview “valproate and increased ketone body excretion” (C. Favennec-Medinger, dated 25-jun-2012 )