Cannabidiol

Indications

Cannabidiol is used for: Indicated for seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS)

Adult Dose

Seizures Indicated for seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) 2.5 mg/kg PO BID initially; after 1 week, dose may be increased to maintenance dose of 5 mg/kg BID If 5 mg/kg BID tolerated and further seizure reduction required, patient may benefit from a dosage increase up to a maximum recommended maintenance dosage of 10 mg/kg BID (ie, 20 mg/kg/day) Increasing to 10 mg/kg BID may be achieved by increased weekly increments of 2.5 mg/kg BID, as tolerated If a more rapid titration from 10 mg/kg/day to 20 mg/kg/day is warranted, the dosage may be increased no more frequently than every other day Administration of the 20-mg/kg/day dosage resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10 mg/kg/day, but with an increase in adverse reactions Hepatic impairment Mild (Child-Pugh A): No dose adjustment required Moderate-to-severe (Child-Pugh B or C): Dosage adjustment recommended, including slower titration Moderate Starting dose: 1.25 mg/kg BID Maintenance dose: 2.5 mg/kg BID Maximum dose: 5 mg/kg BID Severe Starting dose: 0.5 mg/kg BID Maintenance dose: 1 mg/kg BID Maximum dose: 2 mg/kg BID

Child Dose

Seizures Indicated for seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients aged ?2 yr <2 years: Safety and efficacy not established >2 years 2.5 mg/kg PO BID initially; after 1 week, dose may be increased to maintenance dose of 5 mg/kg BID If 5 mg/kg BID tolerated and further seizure reduction required, patient may benefit from a dosage increase up to a maximum recommended maintenance dosage of 10 mg/kg BID (ie, 20 mg/kg/day) Increasing to 10 mg/kg BID may be achieved by increased weekly increments of 2.5 mg/kg BID, as tolerated If a more rapid titration from 10 mg/kg/day to 20 mg/kg/day is warranted, the dosage may be increased no more frequently than every other day Administration of the 20-mg/kg/day dosage resulted in somewhat greater reductions in seizure rates than the recommended maintenance dosage of 10 mg/kg/day, but with an increase in adverse reactions

Renal Dose

Administration

Contra Indications

Hypersensitivity to cannabidiol or any of the ingredients in the product

Precautions

Can cause somnolence and sedation that is dose-related; clobazam and other CNS depressants, including alcohol, may potentiate this adverse effect; monitor for somnolence and sedation and advise patients not to drive or operate machinery until they have gained sufficient experience on drug to gauge whether it adversely affects their ability to safely drive or operate machinery Antiepileptic drugs (AEDs), including cannabidiol, increase risk of suicidal thoughts or behavior in patients taking these drugs for any indication; patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior

Pregnancy-Lactation

Pregnancy There are no available data regarding use in pregnant women Animal data Administration of cannabidiol to pregnant animals produced evidence of developmental toxicity (increased embryofetal mortality in rats and decreased fetal body weights in rabbits decreased growth, delayed sexual maturation, long-term neurobehavioral changes, and adverse effects on the reproductive system in rat offspring) at maternal plasma exposures similar to (rabbit) or greater than (rat) that in humans at therapeutic doses Lactation There are no data on the presence of cannabidiol or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production

Interactions

Coadministration with other CNS depressants, including alcohol, may increase risk of sedation and somnolence Effect of other drugs on cannabidiol Moderate or strong CYP3A4 or CYP2C19 inhibitors: Consider cannabidiol dose reduction Strong CYP3A4 or CYP2C19 inducers: Consider cannabidiol dose increase Coadministration of cannabidiol and valproate increases the incidence of liver enzyme elevations; discontinuation or reduction of cannabidiol and/or concomitant valproate should be considered CYP1A2 and CYP2B6 substrates may also require dose adjustment

Side Effects

Side effects of Cannabidiol : >10% Infections, all (40-41%) Somnolence (23-25%) Infection, other (21-25%) Decreased appetite (16-22%) Diarrhea (9-20%) Transaminases elevated (8-16%) Rash (7-13%) Fatigue, malaise, asthenia (11-12%) Infection, viral (7-11%) Insomnia (5-11%) 1-10% Irritability, agitation (5-9%) Pneumonia (5-8%) Sedation (3-6%) Anger, aggression (3-5%) Decreased weight (3-5%) Gastroenteritis (4%) Hypoxia, respiratory failure (3%) Infection, fungal (1-3%)

Mode of Action

Purified cannabidiol (CBD); the exact mechanism by which CBD produces its anticonvulsant effects is unknown Cannabidiol is a structurally novel anticonvulsant; it does not appear to exert its anticonvulsant effects through CB1 receptors, nor through voltage-gated sodium channels CBD may exert a cumulative anticonvulsant effect, modulating a number of endogenous systems including, but not limited to, neuronal inhibition (synaptic and extrasynaptic GABA channels), modulation of intracellular calcium (TRPV, VDAC, GPR55), and possible anti-inflammatory effects (adenosine)