Celecoxib
Severe
Textbook-cited
Valproate toxicity (tremor, sedation, hepatotoxicity).
Avoid concurrent use; use paracetamol as substitute
Source: KDT 7e · p949
Drug reference
Valproate
Broad-spectrum antiepileptic / mood stabiliser (valproate sodium / sodium valproate) · Antiepileptic
Also known as Valproic Acid, Sodium Valproate, Divalproex Sodium
START
Epilepsy 600 mg/day divided, titrate by 200 mg q3 days; mania ~20–30 mg/kg/day
TYPICAL MAX
~2.5 g/day (≈60 mg/kg/day)
STOP IF
Hepatotoxicity (lethargy/jaundice/↑LFTs), pancreatitis, hyperammonaemic encephalopathy, pregnancy (non-epilepsy)
WATCH
Baseline + periodic LFTs (esp. first 6 months), amylase/lipase if abdominal pain, ammonia if encephalopathy, platelets, pregnancy-prevention programme
CDSCO approvedJan AushadhiNPPA price-controlledATC N03AG01
KDIGO 2024 + manufacturer label
- ONSET
- 2h · absorption
- PEAK
- 3h · Cmax (IR)
- t½
- 13h · plasma t½
- DURATION
- 12h · BID interval
EXCRETION
Hepatic glucuronidation/oxidation; renal metabolites
route + CYP
INTERACTIONS
12 major
SEVERE in our sources
PREGNANCY
Contraindicated for migraine and bipolar; in epilepsy only if no effective alternative — highest-risk AED (NTDs, ~10% major malformations, reduced IQ); pregnancy-prevention programme mandatory
FDA category + note
Top interactionssee all 12 →
- CelecoxibSevereTextbook-citedKDT 7e · p949
- DiclofenacSevereTextbook-citedKDT 7e · p949
- IbuprofenSevereTextbook-citedKDT 7e · p949
- IndomethacinSevereTextbook-citedKDT 7e · p949
Available in India
17 branded formulations. Look up specific brands in the Drugs workspace.
Jan Aushadhi — generic available at GoI pharmacies
Mechanism
Increases brain GABA (GABA-transaminase inhibition), blocks voltage-gated sodium and T-type calcium channels and has histone deacetylase inhibition — broad anticonvulsant, antimanic and migraine-prophylactic activity.
Indications
Generalised and focal epilepsy (incl. absence, myoclonic, tonic-clonic)Bipolar disorder — acute mania/maintenanceMigraine prophylaxis
Dosing
- Adult
- Epilepsy: 600 mg/day in 1–2 divided doses, increase by 200 mg every 3 days to 1–2 g/day (max 2.5 g/day). Mania: 750 mg/day or ~20–30 mg/kg, titrate to response/levels.
- Pediatric
- 10–15 mg/kg/day titrated to 25–40 mg/kg/day (specialist).
- Renal adjustment
- No specific adjustment (free fraction may rise — interpret levels with caution).
- Hepatic adjustment
- Contraindicated in significant hepatic dysfunction.
- Geriatric
- Lower dose; reduced clearance, sedation, hyponatraemia.
- Max dose
- ~2.5 g/day (epilepsy); ~60 mg/kg/day
Pharmacokinetics
Onset
Anticonvulsant over days; antimanic ~1–2 weeks
Peak effect
IR Cmax 1–4 h (formulation-dependent)
Duration
BID dosing (MR once–twice daily)
Half-life
~9–16 h (shorter with enzyme-inducers)
Bioavailability
~90–100%
Protein binding
~80–90% (saturable — free fraction rises at high levels/hypoalbuminaemia/uraemia)
Metabolism
Hepatic (glucuronidation, beta-/omega-oxidation; not CYP-dependent)
Excretion
Renal (metabolites; little unchanged)
Contraindications
- Pregnancy for migraine/bipolar (absolute) and epilepsy unless no alternative (highly teratogenic) — pregnancy prevention programme
- Hepatic disease / significant hepatic dysfunction or family history of severe drug hepatotoxicity
- Mitochondrial disorders (POLG mutations, e.g. Alpers–Huttenlocher)
- Urea cycle disorders
- Known hypersensitivity to valproate
Side effects
Common
Nausea/GI upsetTremorWeight gain, increased appetiteHair thinning/alopeciaSedation/dizziness, thrombocytopenia (dose-related)
Serious
- Hepatotoxicity — potentially fatal (boxed; highest risk <2 years, polytherapy, metabolic disease)
- Teratogenicity — neural tube/major defects + neurodevelopmental impairment (boxed)
- Pancreatitis — including haemorrhagic/fatal (boxed)
- Hyperammonaemic encephalopathy
- Thrombocytopenia/coagulopathy; severe skin reactions (DRESS)
Pregnancy & lactation
Pregnancy
Contraindicated for migraine and bipolar; in epilepsy only if no effective alternative — highest-risk AED (NTDs, ~10% major malformations, reduced IQ); pregnancy-prevention programme mandatory
Lactation
Low milk levels — generally considered compatible with infant monitoring (hepatic/haematologic)
Drug interactions
Diclofenac
Severe
Textbook-cited
Valproate toxicity (tremor, sedation, hepatotoxicity).
Avoid concurrent use; use paracetamol as substitute
Source: KDT 7e · p949
Ibuprofen
Severe
Textbook-cited
Valproate toxicity (tremor, sedation, hepatotoxicity).
Avoid concurrent use; use paracetamol as substitute
Source: KDT 7e · p949
Indomethacin
Severe
Textbook-cited
Valproate toxicity (tremor, sedation, hepatotoxicity).
Avoid concurrent use; use paracetamol as substitute
Source: KDT 7e · p949
Ketorolac
Severe
Textbook-cited
Valproate toxicity (tremor, sedation, hepatotoxicity).
Avoid concurrent use; use paracetamol as substitute
Source: KDT 7e · p949
Mefenamic Acid
Severe
Textbook-cited
Valproate toxicity (tremor, sedation, hepatotoxicity)
Avoid concurrent use; use paracetamol as substitute
Source: KDT 7e · p949
Naproxen
Severe
Textbook-cited
Valproate toxicity (tremor, sedation, hepatotoxicity).
Avoid concurrent use; use paracetamol as substitute
Source: KDT 7e · p949
Piroxicam
Severe
Textbook-cited
Valproate toxicity (tremor, sedation, hepatotoxicity)
Avoid concurrent use; use paracetamol as substitute
Source: KDT 7e · p949
Stiripentol
Severe
Textbook
2- to 3-fold increase in valproate concentrations.
Reduction of doses may be necessary to avoid toxicity. Initiation of adjunctive therapy should be gradual with frequent plasma monitoring.
Source: G&G 14e · p402
Aspirin
Severe
Database
Displacement from protein binding + metabolism inhibition → raised free valproate
Avoid; monitor free valproate/toxicity
Source: Kimi deep-research + Cla · p949
Lamotrigine
Severe
Database
Valproate inhibits lamotrigine glucuronidation → toxicity/severe rash
Halve lamotrigine dose; very slow titration
Source: Kimi deep-research + Cla
Phenytoin
Severe
Database
Marked and sustained increases in free phenytoin.
Measure free rather than total phenytoin.
Related guidelines
Initial monotherapy for newly diagnosed epilepsy
IAN · Neurology · 2023
Migraine — preventive therapy
AAN · Neurology · 2015
Status epilepticus
AAN · Neurology · 2020
Initial monotherapy for newly diagnosed epilepsy
ILAE · Neurology · 2013
Generalised anxiety disorder and panic disorder
NICE · Psychiatry · 2020
Ask House about Valproate
Continue into a citation-backed clinical answer with the drug context already attached.
Sources: KD Tripathi 7e, Goodman & Gilman 14e, Harrison 22e, Katzung·Verified: 2026-05-19 · House clinical team·Cockpit curated: 2026-05-19