Antiepileptics Pregnancy: Avoid unless clearly necessary — limited data; register with UK Epilepsy and Pregnancy Register; seizure control is paramount — discuss risk vs benefit

Cannabidiol

Brand names: Epidiolex

Adult dose

Dose: 2.5 mg/kg twice daily starting dose; increase to 5 mg/kg twice daily after 1 week; max 10 mg/kg twice daily

Route: Oral

Frequency: Twice daily with food (same amount of fat-containing food each time)

Max: 10 mg/kg twice daily (20 mg/kg/day)

Take with food — consistent fat content improves bioavailability. Shake oral solution before use. When stopping, reduce dose gradually over at least 1 week. Store in original bottle.

Paediatric dose

Dose: 2.5 mg/kg twice daily starting mg/kg

Route: Oral

Frequency: Twice daily

Max: 10 mg/kg twice daily

Licensed from age 2 years for Dravet syndrome and Lennox-Gastaut syndrome; purified plant-derived cannabidiol (not cannabis); seek specialist paediatric neurology opinion

Dose adjustments

Renal

No dose adjustment required

Hepatic

Mild impairment: no adjustment. Moderate impairment: start at lower dose and titrate slowly. Severe impairment: avoid — significantly increased exposure

Paediatric weight-based calculator

Patient weight (kg)

Licensed from age 2 years for Dravet syndrome and Lennox-Gastaut syndrome; purified plant-derived cannabidiol (not cannabis); seek specialist paediatric neurology opinion

Clinical pearls

Mechanism: not fully understood — cannabidiol (CBD) is a phytocannabinoid that does NOT bind significantly to CB1 or CB2 cannabinoid receptors; potential mechanisms include modulation of T-type calcium channels, GPR55, TRPV1, glycine receptors, and adenosine uptake; desensitises voltage-gated sodium channels
Dravet syndrome (NEJM 2017): cannabidiol vs placebo in Dravet — 39% reduction in convulsive seizure frequency vs 13% placebo; first drug to show efficacy specifically in Dravet syndrome
Lennox-Gastaut syndrome (NEJM 2018): cannabidiol vs placebo — significant reduction in drop attack frequency; licensed for LGS in addition to Dravet
MHRA 2019: first licensed cannabis-derived medicinal product in UK — licensed for seizures associated with Dravet syndrome and LGS as adjunctive therapy in patients 2 years and above; NICE TA614 recommends both indications
LIVER MONITORING CRITICAL: baseline LFTs before starting; at 1, 3, and 6 months; then every 6 months; immediately if symptoms (nausea, vomiting, jaundice, dark urine); if ALT above 3× ULN — reduce dose or stop; if above 5× ULN — stop immediately
MHRA 2021: updated guidance — when used with valproate, monthly LFT monitoring recommended; hepatotoxicity is significantly more common and severe in the valproate combination

Contraindications

Known hypersensitivity to cannabidiol or sesame oil (vehicle in Epidiolex)
Severe hepatic impairment

Side effects

Hepatotoxicity — MOST IMPORTANT: raised ALT/AST in 16%; severe hepatocellular injury reported; LFT monitoring mandatory (especially with valproate)
Somnolence and sedation
Diarrhoea
Decreased appetite and weight loss
Infections (upper respiratory tract)
Suicidal ideation (antiepileptic class effect)

Interactions

Valproate (CRITICAL — additive hepatotoxicity; risk of severe liver injury increases significantly with coadministration; monitor LFTs monthly if combined)
Clobazam (cannabidiol inhibits CYP2C19 — increases norclobazam active metabolite by 3-fold; may increase sedation and other clobazam effects; reduce clobazam dose if needed)
Stiripentol (inhibits CYP2C19 and CYP3A4 — reduces cannabidiol metabolism; interaction if used together in Dravet syndrome)
CNS depressants (additive sedation)

Monitoring

LFTs — baseline, at 1, 3, 6 months, then 6-monthly (monthly if combined with valproate)
Seizure diary (frequency and severity — especially drop attacks and convulsive seizures)
Weight and appetite
Sedation and cognitive effects
Suicidal ideation

Reference: BNFc; BNF 90; Dravet trial NEJM 2017;376(21):2011-2020; LGS trial NEJM 2018;378(20):1888-1897; NICE TA614; MHRA 2019; MHRA 2021 DSU (hepatotoxicity). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Pathways