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cannabidiol (Rx)

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Dosing & Uses

Dosage Forms & Strengths

solution, oral
  • 100mg/mL

Seizures

Indicated for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC)

LGS or DS
  • 2.5 mg/kg PO BID initially; after 1 week, may increase 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
  • Starting dose: 2.5 mg/kg PO BID
  • Increase dose in weekly increments of 2.5 mg/kg BID as tolerated, to recommended maintenance dose of 12.5 mg/kg BID
  • If a more rapid titration is warranted, the dosage may be increased no more frequently than every other day
  • Effectiveness of doses 3 x ULN in presence of elevated bilirubin without alternative explanation are important predictors of severe liver injury and should be evaluated before initiating cannabidiol

Hepatitis (Orphan)

Orphan designation for treatment of autoimmune hepatitis

Orphan sponsor
  • Revive Therapeutics Ltd; 5 Director Court, Suite 105; Vaughan, Ontario; Canada

Huntington Disease (Orphan)

Orphan designation for delta-9-THC and cannabidiol for treatment of Huntington disease

Sponsor
  • MMJ International Holdings; 1895 Preston White Drive, Suite 101; Reston, Virginia 20191

Dosage Forms & Strengths

solution, oral
  • 100mg/mL

Seizures

Indicated for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in patients aged ≥1 yr

Age ≥1 year
LGS or DS
  • 2.5 mg/kg PO BID initially; after 1 week, may increase 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
    • Starting dose: 2.5 mg/kg PO BID
    • Increase dose in weekly increments of 2.5 mg/kg BID as tolerated, to recommended maintenance dose of 12.5 mg/kg BID
    • If a more rapid titration is warranted, the dosage may be increased no more frequently than every other day
    • Effectiveness of doses 3 x ULN in presence of elevated bilirubin without alternative explanation are important predictors of severe liver injury and should be evaluated before initiating cannabidiol

    Absence Epilepsy (Orphan)

    Orphan designation for treatment of childhood absence epilepsy

    Orphan sponsor
    • Insys Development Company, Inc; 1333 South Spectrum Blvd, Suite 100; Chandler, Arizona 85286

    Clinical trials did not include any patients aged >55 yr to determine whether or not they respond differently from younger patients

    In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy

    Interactions

    Interaction Checker
    Contraindicated
    Serious – Use Alternative
    Significant – Monitor Closely
    Minor

    Adverse Effects

    >10% (LGS or DS)

    Infections, all (40-41%)

    Infection, other (21-25%)

    Decreased appetite (16-22%)

    Transaminases elevated (8-16%)

    Fatigue, malaise, asthenia (11-12%)

    Infection, viral (7-11%)

    >10% (TSC)

    Elevated transaminases (25%)

    Decreased appetite (20%)

    1-10% (LGS or DS)

    Irritability, agitation (5-9%)

    Anger, aggression (3-5%)

    Decreased weight (3-5%)

    Hypoxia, respiratory failure (3%)

    Infection, fungal (1-3%)

    1-10% (TSC)

    Gait disturbance (9%)

    Ear infection (8%)

    Decreased weight (7%)

    Decreased platelet count (5%)

    Increased eosinophil count (5%)

    Fatigue, malaise, asthenia (5%)

    Urinary tract infection (5%)

    Warnings

    Contraindications

    Hypersensitivity to cannabidiol or any of the product ingredients

    Cautions

    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

    May cause hypersensitivity reactions (eg, pruritus, erythema, angioedema)

    As with other AEDs, cannabidiol should generally be withdrawn gradually because of the risk of increased seizure frequency and status epilepticus; if withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered

    Therapy can cause weight loss, which may be dose-related

    A decrease in hemoglobin and hematocrit reported with no effect on red blood indices

    Elevation of serum creatinine reported within 2 weeks of initiating therapy that was reversible in healthy adults; mechanism not determined

    Medscape – Seizure dosing for Epidiolex (cannabidiol), frequency-based adverse effects, comprehensive interactions, contraindications, pregnancy & lactation schedules, and cost information.

    PediatricEducation.org™

    Pediatric digital library intended to serve as a source of continuing pediatric education, curated by Donna M. D’Alessandro M.D. and Michael P. D’Alessandro M.D.

    What is the Dosing of CBD Oil?

    Patient Presentation
    An attending physician overheard a resident talking with a father on the telephone in clinic. The parent had asked the resident to give a dosing schedule for over-the-counter cannabidiol (CBD) oil for a 7 year old with attentional issues because the bottle said to consult a physician for children under 12 years of age. The resident discussed that that he could not do this as the preparations varied so much from vendor to vendor and this was not an approved use. The parent was fairly insistent that with the dosing for adults that the resident could “just figure it out,” and give him a dose for his child. The resident said that these preparations are not regulated the way other medications are in the United States and therefore couldn’t give a dosing recommendation. He went on to try to engage the father in discussing why he wanted to give the CBD oil and eventually was able to convince the father to come to clinic to discuss the underlying problems with their regular primary care physician.

    Discussion
    Cannabis sativa makes small fruits which are usually named “seeds” although they are not technically a seed. Hemp oil is derived from the hemp seeds by cold-pressing or other means of macerating or squashing the seeds. Cold pressed oil is high in polyunsaturated fatty acids including various omega-3 and linolenic acids and antioxidants. It is used by some people for its nutritional value and “[a]ccording to an old legend, Buddha (Prince Siddharta Gautama) founder of Buddism, was able to survive eating only one hemp seed each day for six years.” The seeds themselves do not contain any psychoactive compounds (specifically THC or tetrahydrocannabinol) but during processing they can become contaminated with these compounds. The THC impurity concentration is highly variable among different cultivars, processing and storage methods and thermal stress also increases the THC levels. In Europe there are strict limits on THC impurity levels and the oil is recommended to be consumed without heating.

    A review of cannabis can be found here.

    Learning Point
    “…Cultivars used for seed production with a low THC levels generally contain a high concentration of cannabidiol (CBD) which has no THC activity.” An analysis study of cannabinoids in 13 commercial hemp seed oil preparations found that “concentrations of cannabinoids can be extremely variable among different oil varieties.” The authors also state that other methodologies they outline can be used to help determine storage conditions of the oil.

    Medical use of cannabis has been proposed and mainly studied in adult populations. Potential indications include cancer-related nausea, appetite enhancement, neurogenic pain, glaucoma and epilepsy. In pediatrics some of the most common use is for seizures, but also chronic pain and muscle spasms. CBD is the more common form of cannabis used for seizures. Epidiolex® is a liquid cannabis-derived medication, that is FDA approved in the United States for the treatment of patients 2 years and older with Lennox-Gastaut syndrome seizures or Dravot Syndrome. The starting dose is 2.5 mg/kg twice a day orally with increases based on response and side effects.

    Questions for Further Discussion
    1. What is Lorenzo’s oil used for?
    2. What is the legal status of medical cannabis in your location?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
    Information prescriptions for patients can be found at MedlinePlus for these topics: Marijuana and Pregnancy and Substance Abuse.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Citti C, Pacchetti B, Vandelli MA, Forni F, Cannazza G. Analysis of cannabinoids in commercial hemp seed oil and decarboxylation kinetics studies of cannabidiolic acid (CBDA). J Pharm Biomed Anal. 2018;149:532-540. doi:10.1016/j.jpba.2017.11.044

    Samanta D. Cannabidiol: A Review of Clinical Efficacy and Safety in Epilepsy. Pediatr Neurol. March 2019. doi:10.1016/j.pediatrneurol.2019.03.014

    Hoffenberg EJ, McWilliams S, Mikulich-Gilbertson S, Murphy B, Hoffenberg A, Hopfer CJ. Cannabis Oil Use by Adolescents and Young Adults With Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr. 2019;68(3):348-352. doi:10.1097/MPG.0000000000002189

    RxList. Epidiolex (Cannabidiol Oral Solution): Side Effects, Interactions, Warning, Dosage & Uses. https://www.rxlist.com/epidiolex-drug.htm. Accessed June 10, 2019.

    Commissioner of the Federal Drug Administration. Statement from FDA Commissioner Scott Gottlieb, M.D., on new steps to advance agency’s continued evaluation of potential regulatory pathways for cannabis-containing and cannabis-derived products. FDA. http://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-new-steps-advance-agencys-continued-evaluation. Published May 3, 2019. Accessed June 10, 2019.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa

    Patient Presentation An attending physician overheard a resident talking with a father on the telephone in clinic. The parent had asked the resident to give a dosing schedule for over-the-counter cannabidiol (CBD) oil for a 7 year old with attentional issues because the bottle said to consult a physician for children under 12 years of…