Antiepileptics. Fatty acid derivatives
Brand names: Depakote ER, Depakote, Depakene, Stavzor, Depacon
Updated · Methodology
First line
For typical absence seizures in children and adolescents, valproate and ethosuximide are first-line. Comparative RCTs (Glauser 2010) showed similar efficacy; ethosuximide has better cognitive profile and is used for isolated absences. Valproate is preferred when generalized tonic-clonic seizures coexist.
Sources
ICD-10: G40.7 · ICD-11: 8A61.21
First line
Valproate is used for acute mania in bipolar disorder and maintenance therapy. CG185 and RANZCP 2022 list valproate as a first-line option for acute mania alongside lithium and atypical antipsychotics. Efficacy in mania is comparable to lithium per meta-analyses. Not used in women of reproductive age without strict indications.
In women of reproductive age with bipolar disorder, valproate is not used except in cases of intolerance or ineffectiveness of alternatives and under strict contraception.
Sources
ICD-10: F31 · ICD-11: 6A60
First line
Valproic acid is first-line antiepileptic for generalised epilepsy (tonic-clonic, absence, myoclonic seizures) and effective in focal seizures. ILAE 2017 and SEN recommend as first choice in men and postmenopausal women. In women of childbearing age imposed strict restriction since 2018 due to high teratogenic risk (mandatory pregnancy prevention programme).
Sources
ICD-10: G40 · ICD-11: 8A6Z
First line
Valproate is first-line for idiopathic generalized epilepsy in men and postmenopausal women. NG217 and ILAE consider valproate the most effective drug for generalized tonic-clonic, myoclonic seizures, and juvenile myoclonic epilepsy. Effective in 70–80% of patients. In women of reproductive age, prescribed only when alternatives are unsuitable and Pregnancy Prevention Programme is strictly followed.
In women of reproductive age, prescription is allowed only within a Pregnancy Prevention Programme (annual signed informed consent, mandatory effective contraception, pregnancy testing).
Sources
ICD-10: G40.3 · ICD-11: 8A61
Second line
Valproate is included in international guidelines (/AHS, EHF) as a drug with proven efficacy in episodic migraine prophylaxis. Reduces attack frequency by 50% in some patients. Used when first-line agents (beta-blockers, topiramate, anti-CGRP monoclonal antibodies) are ineffective or intolerable. Not used in women of reproductive age due to teratogenicity.
ICD-10: G43.9 · ICD-11: 8A80.Z
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Use of valproate in women of reproductive age without strict contraception and without compelling indication is not supported by international regulators. 2018 and MHRA Pregnancy Prevention Programme require annual signed informed consent, mandatory effective contraception, and regular pregnancy testing. Valproate is among the most teratogenic antiepileptics: neural tube defect risk approximately 10%, average IQ reduction of 7–10 points in offspring.
This block reiterates the Pregnancy Prevention Programme information and is essential to prevent inappropriate prescribing without proper procedures.
ICD-10: F41.9 · ICD-11: 6B0Z
Enhances GABAergic transmission, blocks sodium channels, inhibits T-type calcium channels. Used for generalized epilepsy, absences, bipolar disorder, migraine prophylaxis. Category X teratogen: neural tube defects and IQ reduction in the fetus – contraindicated in pregnancy and in women of reproductive age without reliable contraception.
Boxed warning
FDA triple boxed warning: 1) Hepatotoxicity, especially in children under 2 and with polytherapy – risk of fatality. 2) Teratogenicity: valproate is not used in women of reproductive age for conditions other than epilepsy if alternatives exist. 3) Pancreatitis. EMA 2018 introduced a Pregnancy Prevention Programme: annual informed consent, mandatory effective contraception, pregnancy testing.
According to the AEMPS summary of product characteristics (sections 4.3 and 4.6), valproate is contraindicated in pregnancy for bipolar disorder and, for epilepsy, unless there is no suitable alternative; in women of childbearing potential it may be used only under the Pregnancy Prevention Programme. In a meta-analysis, 11% of children of women with epilepsy exposed to valproate monotherapy in pregnancy had major congenital malformations; up to 30–40% of exposed preschool children had early developmental delays, the risk of autism spectrum disorders is about three times higher, and some studies suggest a higher risk of being small for gestational age. A woman planning a pregnancy should have treatment reassessed by a specialist and switched before conception where possible; a woman who becomes pregnant on valproate should be referred to a specialist immediately. For male patients, the summary advises discussing effective contraception, including for a female partner, during treatment and for at least 3 months after stopping: an observational study found more neurodevelopmental disorders in children of fathers treated with valproate in the 3 months before conception.
Passes into breast milk in small amounts (1–10% of maternal plasma level). LactMed lists valproate as generally compatible with breastfeeding under infant monitoring (sedation, hepatotoxicity, thrombocytopenia).
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Valproate reduces plasma L-carnitine via conjugation with glycine and urinary excretion. Carnitine deficiency is linked to hyperammonemic encephalopathy and hepatotoxicity. When symptoms appear (lethargy, vomiting, altered consciousness) or ammonia rises, measure carnitine level and administer L-carnitine IV (100–200 mg/kg/day) or orally (50–100 mg/kg/day).
Source: FDA: Depakote (divalproex sodium) prescribing information (2022)
6 pairs found. Sorted from critical to minor.
Mechanism
Carbapenems collapse valproic acid levels. The AEMPS meropenem label gives the figure: on concomitant use the blood level of valproate falls by 60–100% within about two days, and the same label states that because of the rapid onset and the depth of the fall the combination is not considered manageable and is therefore avoided. The valproate label repeats this from its own side. The mechanism has two parts: the carbapenem inhibits acylpeptide hydrolase, which converts valproate glucuronide back into the active drug, and speeds distribution of valproate into red cells. Raising the valproate dose does not rescue it: in published cases the level did not return to the therapeutic range while the carbapenem stayed in the regimen.
Symptoms
Loss of seizure control 1–3 days after the first meropenem dose: fits return after months without any, up to clusters and status epilepticus. In a patient taking valproate as a mood stabiliser, mania or an abrupt mood swing appears instead of seizures. The blood valproate level drops below the therapeutic range, sometimes to undetectable, with the dose unchanged and adherence intact. Fever and the infection itself lower the seizure threshold further, so the picture is easily written off as the underlying illness.
Management
The combination is taken apart. If meropenem is needed for a life-threatening infection, the anticonvulsant regimen is rebuilt in advance: a drug with a different mechanism is added (levetiracetam, lacosamide, a benzodiazepine for a short course) and kept through the antibiotic course and for several days after. Where the severity of the infection allows, the antibiotic is switched to a non-carbapenem: a cephalosporin with metronidazole, piperacillin-tazobactam, or a fluoroquinolone by susceptibility. Valproate levels are checked before meropenem starts, at 24–48 hours and after the antibiotic stops: recovery is not instant either, and by then the regimen needs revisiting again. Raising the valproate dose as the only measure does not work and adds toxicity risk once the antibiotic ends.
Sources
Mechanism
Both drugs depress the central nervous system (CNS), and their effects add up. The alprazolam SmPC warns that combining it with antiepileptics increases CNS depression and the risk of respiratory depression, coma and death (alprazolam SmPC). Valproate can also enhance the effect of benzodiazepines (valproic acid SmPC).
Symptoms
Drowsiness, slowed thinking and reactions, impaired coordination. With marked depression: slow, shallow breathing and confusion, up to coma (alprazolam SmPC). In older patients, sedation and muscle weakness increase the risk of falls (alprazolam SmPC).
Management
The alprazolam SmPC requires limiting the dose and duration of co-administration with antiepileptics (alprazolam SmPC; alprazolam label of the US Food and Drug Administration, ). Use alprazolam at the lowest effective dose for the shortest time, no longer than 2–4 weeks; in older patients, start with 0.25 mg two or three times a day and use caution because of sedation, muscle weakness and the risk of falls (alprazolam SmPC). Valproate can enhance the effect of benzodiazepines, so monitor the patient clinically and adjust the dose when needed (valproic acid SmPC). Advise the patient not to drive or operate machinery while taking alprazolam (alprazolam FDA label).
Sources
Mechanism
Valproate inhibits glucuronidation, the main elimination route of lamotrigine, and the lamotrigine half-life nearly doubles (lamotrigine and valproate SmPCs). According to the US Food and Drug Administration () label, lamotrigine concentrations rise slightly more than 2-fold with valproate. The risk of serious lamotrigine rash is higher with a high starting dose, with a fast dose increase and with concomitant valproate (lamotrigine SmPC).
Symptoms
Rash, usually within the first 8 weeks of lamotrigine; nearly all life-threatening cases occur within 2–8 weeks. Severe forms: Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) with fever, swollen lymph nodes, facial oedema and blood, liver and kidney involvement. Fever and swollen lymph nodes can appear before the rash. Children have a higher risk of serious rash than adults.
Management
The labels do not ban the pair, but with valproate lamotrigine follows a separate, lower-dose schedule, and neither the starting dose nor the rate of increase may be exceeded (lamotrigine SmPC). In epilepsy, adults and adolescents from 13 years: 25 mg every other day in weeks 1 and 2, 25 mg/day in weeks 3 and 4, then increases of no more than 25–50 mg every 1–2 weeks to the usual maintenance dose of 100–200 mg/day (lamotrigine SmPC). This schedule applies with valproate even if the patient takes other drugs; in children aged 2–12 the dose is calculated per kilogram of body weight from a separate table (lamotrigine SmPC). In bipolar disorder, when valproate is added to a stable lamotrigine dose, the lamotrigine dose is halved from the first week, for example from 200 to 100 mg/day; the maximum dose with valproate is 200 mg/day (lamotrigine SmPC). The US Food and Drug Administration () valproate label also requires a lower lamotrigine dose. At the first sign of rash, lamotrigine is stopped at once unless the rash is clearly unrelated to it (lamotrigine SmPC).
Sources
Mechanism
Aspirin displaces valproate from albumin binding and suppresses its metabolism. The free valproate fraction rises, raising neurotoxicity risk (tremor, sedation, hyperammonaemia).
Symptoms
Tremor, drowsiness, nausea, confusion. Severe cases: hyperammonaemic encephalopathy. Symptoms appear within 1–2 weeks at high aspirin doses.
Management
Cardioprotective aspirin doses (75–100 mg) are usually acceptable. At high doses, check valproate level at 1 week. For chronic analgesia on valproate: paracetamol.
Sources
Mechanism
Valproate weakly blocks hepatic amitriptyline metabolism; TCA plasma levels may rise. Plus additive sedation.
Symptoms
Worsening anticholinergic symptoms, drowsiness, sedation. Older patients: delirium and fall risk.
Management
Reduce amitriptyline by 25% if needed when combined. In older patients, monitor cognition and fall risk. For neuropathic pain, alternative: gabapentin or pregabalin.
Mechanism
The clozapine SmPC describes the interaction as pharmacodynamic and does not name its mechanism. Clozapine itself lowers the seizure threshold, and the seizure risk rises with the dose (Clozaril label, ). It also causes neutropenia and myocarditis. With valproic acid added, the SmPCs report rare but serious seizures, including in people without epilepsy, and isolated cases of delirium. They also report a higher risk of clozapine-induced neutropenia and myocarditis (clozapine and valproate SmPCs). The drugs do not change each other's blood levels: a study in 11 patients with psychosis found no pharmacokinetic interaction (valproic acid label, FDA).
Symptoms
A seizure, including in a person without epilepsy, confusion and delirium (clozapine SmPC). Signs of neutropenia: fever, sore throat, mouth or throat ulcers, flu-like symptoms, any infection (clozapine SmPC). Signs of myocarditis, most often in the first two months of clozapine treatment: persistent resting tachycardia, palpitations, arrhythmia, chest pain, shortness of breath, rapid breathing, unexplained fatigue, flu-like symptoms (clozapine SmPC).
Management
The SmPCs do not forbid the combination: valproate is given with clozapine under close monitoring of both treatments (clozapine and valproate SmPCs). On clozapine the absolute neutrophil count (ANC) is checked weekly for the first 18 weeks, then monthly to the end of the first year. Extra counts are taken after valproic acid is added, especially in the initial period (clozapine SmPC). With an ANC of 1000–1499/mm3 clozapine continues with counts twice a week until the count stabilises; below 1000/mm3 clozapine is stopped at once and never restarted (clozapine SmPC). With fever, sore throat or any infection the ANC is checked immediately (clozapine SmPC). Before valproate starts, a full blood count with platelets and coagulation tests is done (valproate SmPC). With persistent resting tachycardia, chest pain, shortness of breath or flu-like symptoms clozapine is stopped promptly and the patient is referred to a cardiologist. After myocarditis clozapine is not restarted (clozapine SmPC). After a seizure the clozapine dose is reduced and anticonvulsant treatment is started if needed (clozapine SmPC). The seizure risk rises with the dose, so clozapine is started low and increased slowly (Clozaril label, ). No dose adjustment for blood levels is needed, because no pharmacokinetic interaction was found (valproic acid label, FDA).
Sources
Verbatim lines from the interaction sections, in the language of the label
«Medicamentos conjugados con pivalato: Se debe evitar la administración concomitante de valproato y medicamentos conjugados con pivalato (como cefditoreno pivoxilo, adefovir dipivoxil, pivmecilinam y…»AEMPS, section 4.5 · Open on CIMA
«Carbapenemes (panipenem, meropenem, imipenem): La administración de ácido valproico junto con antibióticos del grupo de los carbapenemes ha mostrado niveles disminuidos de ácido valproico, resultando…»AEMPS, section 4.5 · Open on CIMA
«Effects of Co-Administered Drugs on Valproate Clearance: A clinically significant reduction in serum valproic acid concentration has been reported in patients receiving carbapenem antibiotics (for…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Dosage adjustment of amitriptyline/FDA, section 7 · Open on DailyMed
«Anticoagulantes factor dependiente de la vitamina K: En caso de uso concomitante de anticoagulantes dependientes de la vitamina K se debe realizar una estrecha monitorización del tiempo de…»AEMPS, section 4.5 · Open on CIMA
«Effects of Valproate on Other Drugs: In an in vitro study, valproate increased the unbound fraction of warfarin by up to 32.6%. The therapeutic relevance of this is unknown; however, coagulation…»FDA, section 7 · Open on DailyMed
«Productos que contienen estrógenos: El uso concomitante de productos que contienen estrógenos, incluyendo los anticonceptivos hormonales que contienen estrógenos, potencialmente pueden dar lugar a…»AEMPS, section 4.4 · Open on CIMA
«Antipsicóticos, inhibidores de la MAO, antidepresivos y benzodiazepinas: Valproato sódico puede potenciar el efecto de otros psicotrópicos, como antipsicóticos, inhibidores de la MAO, antidepresivos…»AEMPS, section 4.5 · Open on CIMA
«Effects of Valproate on Other Drugs: There is evidence for severe CNS depression, with or without significant elevations of barbiturate or valproate serum concentrations. All patients receiving…»FDA, section 7 · Open on DailyMed
«Antipsicóticos, inhibidores de la MAO, antidepresivos y benzodiazepinas: Valproato sódico puede potenciar el efecto de otros psicotrópicos, como antipsicóticos, inhibidores de la MAO, antidepresivos…»AEMPS, section 4.5 · Open on CIMA
«Carbamazepina: Se ha notificado toxicidad clínica con la administración conjunta de valproato y carbamazepina, ya que valproato puede potenciar los efectos tóxicos de la carbamazepina. Se recomienda…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can…»FDA, section 7 · Open on DailyMed
«Clozapina: El tratamiento concomitante con valproato y clozapina puede aumentar el riesgo de neutropenia y miocarditis inducida por clozapina. Si es necesario el uso concomitante de valproato con…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives: Monitoring of valproate concentrations is recommended (7.1)»FDA, section 7 · Open on DailyMed
«Lamotrigina: Valproato sódico reduce el metabolismo de lamotrigina e incrementa la semivida media de lamotrigina casi dos veces. Esta interacción puede dar lugar a un incremento de la toxicidad de…»AEMPS, section 4.5 · Open on CIMA
«Metotrexato: Algunos informes de casos describen una disminución significativa de los niveles séricos de valproato tras la administración de metotrexato, con aparición de convulsiones. Los…»AEMPS, section 4.5 · Open on CIMA
«Fenobarbital: Valproato sódico incrementa las concentraciones plasmáticas de fenobarbital (debido a la inhibición del catabolismo hepático), con posible aparición de sedación, sobre todo en niños…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can…»FDA, section 7 · Open on DailyMed
«Fenitoína: Valproato sódico reduce la concentración plasmática total de fenitoína. Incrementa la forma libre de fenitoína, dando lugar a posibles síntomas de sobredosis (ácido valproico desplaza a…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can…»FDA, section 7 · Open on DailyMed
«Rifampicina: Rifampicina puede disminuir los niveles en sangre de ácido valproico dando lugar a una falta de efecto terapéutico. Por lo tanto, puede ser necesario un ajuste en la dosis de valproato…»AEMPS, section 4.5 · Open on CIMA
«La administración concomitante de valproato y topiramato o acetazolamida se ha asociado con encefalopatía y/AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Dosage adjustment of amitriptyline/FDA, section 7 · Open on DailyMed
«Effects of Valproate on Other Drugs: Clozapine In psychotic patients (n = 11), no interaction was observed when valproate was co-administered with clozapine.»FDA, section 7 · Open on DailyMed
«Effects of Co-Administered Drugs on Valproate Clearance: Antacids A study involving the co-administration of valproate 500 mg with commonly administered antacids (Maalox, Trisogel, and Titralac - 160…»FDA, section 7 · Open on DailyMed
«Effects of Co-Administered Drugs on Valproate Clearance: Chlorpromazine A study involving the administration of 100 to 300 mg/FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Co-administration of valproate can affect the pharmacokinetics of other drugs (e.g., diazepam, ethosuximide, lamotrigine, phenytoin) by inhibiting their metabolism or protein…»FDA, section 7 · Open on DailyMed
«Cimetidina o eritromicina: Las concentraciones plasmáticas de ácido valproico pueden aumentar (como resultado de la reducción del metabolismo hepático) en caso de uso concomitante con cimetidina o…»AEMPS, section 4.5 · Open on CIMA
«Effects of Co-Administered Drugs on Valproate Clearance: Haloperidol A study involving the administration of 6 to 10 mg/FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Co-administration of valproate can affect the pharmacokinetics of other drugs (e.g., diazepam, ethosuximide, lamotrigine, phenytoin) by inhibiting their metabolism or protein…»FDA, section 7 · Open on DailyMed
«Se han notificado descensos en los niveles sanguíneos del ácido valproico cuando se ha co-administrado con agentes carbapenemes, dando lugar en unos dos días a una disminución de un 60-100% en los…»AEMPS, section 4.5 · Open on CIMA
«Fármacos que pueden aumentar los niveles plasmáticos de la carbamazepina: Dado que el aumento de los niveles plasmáticos de carbamazepina-10,11-epóxido puede producir efectos adversos (p. ej. mareo…»AEMPS, section 4.5 · Open on CIMA
«Se han descrito casos raros pero graves de crisis epilépticas, inclusive en pacientes no epilépticos, y casos aislados de delirio cuando se administró clozapina conjuntamente con ácido valproico…»AEMPS, section 4.5 · Open on CIMA
«Ácido valproico : inhibe el metabolismo hepático de fenobarbital, por lo que pueden aparecer signos de sobredosis al aumentar las concentraciones plasmáticas de fenobarbital, particularmente en…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: Phenytoin, Sodium Valproate, Valproic Acid . The effect of barbiturates on the metabolism of phenytoin appears to be variable. Some investigators report an accelerating effect…»FDA, section 7 · Open on DailyMed
«Ácido valproico : la administración conjunta de ácido valproico y acetilsalicílico produce una disminución de la unión a proteínas plasmáticas y una inhibición del metabolismo de ácido valproico.»AEMPS, section 4.5 · Open on CIMA
«Anticonvulsivantes: Si se administra clobazam simultáneamente con anticonvulsivantes (p.ej., fenitoína, ácido valproico) pueden elevarse los niveles plasmáticos de estos medicamentos. Si la dosis de…»AEMPS, section 4.5 · Open on CIMA
«No se ha observado interacción entre gabapentina y fenobarbital, fenitoína, ácido valproico o carbamazepina.»AEMPS, section 4.5 · Open on CIMA
«Medicamentos antiepilépticos: En estudios de interacción lacosamida no afectó significativamente las concentraciones plasmáticas de carbamazepina y ácido valproico. Las concentraciones plasmáticas de…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos antiepilépticos: Los datos de los estudios clínicos, realizados en adultos antes de la comercialización, indican que levetiracetam no influye en las concentraciones séricas de los…»AEMPS, section 4.5 · Open on CIMA
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Valproic acid is evaluated for the following indications with varying evidence strength: Epilepsy (evidence tier A), Generalized epilepsy (evidence tier A), Absence seizures (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of Valproic acid (≥ 1 in 100): Nausea, vomiting, dyspepsia, Weight gain, Tremor, Alopecia, Drowsiness, Elevated liver transaminases (usually asymptomatic). See the Safety section for uncommon and serious reactions.
According to the AEMPS summary of product characteristics (sections 4.3 and 4.6), valproate is contraindicated in pregnancy for bipolar disorder and, for epilepsy, unless there is no suitable alternative; in women of childbearing potential it may be used only under the Pregnancy Prevention Programme. In a meta-analysis, 11% of children of women with epilepsy exposed to valproate monotherapy in pregnancy had major congenital malformations; up to 30–40% of exposed preschool children had early developmental delays, the risk of autism spectrum disorders is about three times higher, and some studies suggest a higher risk of being small for gestational age. A woman planning a pregnancy should have treatment reassessed by a specialist and switched before conception where possible; a woman who becomes pregnant on valproate should be referred to a specialist immediately. For male patients, the summary advises discussing effective contraception, including for a female partner, during treatment and for at least 3 months after stopping: an observational study found more neurodevelopmental disorders in children of fathers treated with valproate in the 3 months before conception.
Passes into breast milk in small amounts (1–10% of maternal plasma level). LactMed lists valproate as generally compatible with breastfeeding under infant monitoring (sedation, hepatotoxicity, thrombocytopenia).
Valproic acid is contraindicated in: Hypersensitivity to valproate; Acute and chronic hepatitis, hepatic insufficiency; Hepatic porphyria; Mitochondrial disorders (POLG mutations); Urea cycle disorders. Full list in the Safety section.
FDA triple boxed warning: 1) Hepatotoxicity, especially in children under 2 and with polytherapy – risk of fatality. 2) Teratogenicity: valproate is not used in women of reproductive age for conditions other than epilepsy if alternatives exist. 3) Pancreatitis. EMA 2018 introduced a Pregnancy Prevention Programme: annual informed consent, mandatory effective contraception, pregnancy testing.
in women of reproductive age, use is strictly limited due to high teratogenicity. Neural tube defects 1–2%, average IQ reduction 7–10 points.
average gain 5–15 kg in the first year. Linked to increased appetite and insulin resistance. Persists in most patients during therapy.
when planning pregnancy, switch to alternatives 1–3 months ahead with concomitant folic acid.
Direct links to regulator labels. Open in a new tab.
Zonisamide, Carbamazepine, Eslicarbazepine acetate, Gabapentin, Levetiracetam, Phenytoin, Lacosamide, Lamotrigine