cannabidiol

General

Canada-Approved Medicine

This monograph describes a medication approved for use in Canada by the Therapeutic Products Directorate, a division of Health Canada’s Health Products and Food Branch. The medication is not approved by the United States Food and Drug Administration; however, a similar formulation carrying a different generic or brand name might be available in the US.

cannabidiol

Pronunciation:
ka-na-bi-dye-ole

delta-9–tetrahydrocannabinol (THC)

Pronunciation:
del-ta nine tet-re-hye-dro-ka-na-bi-nole

Trade Name(s)

Sativex

Ther. Class.

analgesic adjuncts, therapeutic

antispasticity agents

Pharm. Class.

cannabinoids

Indications

Adjunct treatment of spasticity in adults with multiple sclerosis (MS) who have not responded to other therapies.
Analgesic adjunct in the management of neuropathic pain in patients with MS or advanced cancer who have not responded to opioids or other analgesics for severe pain.

Action

Acts on cannabinoid receptors located in pain pathways in the brain, spinal cord, and peripheral nerve terminals.
Has analgesic and muscle relaxant properties.

Therapeutic Effect(s):

Decreased pain and spasticity.

Pharmacokinetics

Absorption: Buccal absorption is slower than inhalation.

Distribution: Highly lipid soluble; distributes and accumulates in fatty tissues.

Metabolism and Excretion: Some first-pass hepatic metabolism occurs; highly metabolized by the CYP450 enzyme system. Metabolites can be stored in fatty tissues and rereleased over time (up to weeks); one metabolite of THC is pharmacologically active (11-hydroxy-THC). Further metabolism occurs in renal and biliary systems.

Half-life: Biexponential half-lives with short initial phases of Cannabidiol: 1.4–1.8 hr; THC: 1.3–1.7 hr; 11-hydroxy-THC: 1.9–2.1 hr; terminal elimination half-life of cannabinoids: 24–26 hr or more.

TIME/ACTION PROFILE (analgesic and antispasticity effects)

ROUTE	ONSET	PEAK†	DURATION
cannabidiol	unknown	1.6–2.8 hr	up to 12 hr
THC	unknown	1.6–2.4 hr	up to 12 hr

†Plasma concentrations peak more quickly when administered under the tongue.

Contraindication/Precautions

Contraindicated in:

Hypersensitivity to cannabinoids, propylene glycol, or peppermint oil;
Serious cardiovascular disease, including ischemic heart disease, arrhythmias, poorly controlled hypertension, or severe HF;
History of schizophrenia/psychoses;
Sore/inflamed mucosa (may alter absorption);
OB: Pregnancy;
Lactation: Lactation;
Pedi: Safety and effectiveness not established in children.

Use Cautiously in:

Epilepsy/recurrent seizures;
Substance use;
Perioperative state (consider possible changes in cardiovascular status);
History of depression/suicide attempt or ideation;
Severe renal impairment;
Cancer patients with urinary tract pathology (↑ risk of urinary tract adverse reactions);
Severe hepatic impairment;
Rep: Women of reproductive potential;
Geri: Use cautiously in older adults.

Adverse Reactions/Side Effects

CV: hypertension, palpitations, postural hypotension, tachycardia

GI: appetite change, constipation, dry mouth, mucosal/teeth discoloration, nausea(↑ in cancer patients), stomatitis

GU: urinary retention (↑ in cancer patients)

Local: application site irritation

Neuro: dizziness, fatigue, confusion, depression, disorientation, drowsiness, dysgeusia, euphoria, hallucinations, psychotic reactions, SUICIDAL THOUGHTS/BEHAVIORS, weakness

Misc: physical dependence, psychological dependence

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

↑ risk of CNS depression with other CNS depressants, including alcohol, some antidepressants, some antihistamines, benzodiazepines, GABA inhibitors, sedative/hypnotics, opioids, and psychotropics/antipsychotics.
Cannabidiol may ↑ levels and risk of toxicity of amitriptyline, fentanyl, and sufentanil.

Drug-Natural Products:

↑ risk of intoxication with other forms of cannabis.

Route/Dosage

Buccal: (Adults): Day 1: One spray in the morning and one in the evening; may ↑ by 1 spray/day on subsequent days. Time between sprays should be ≥15 min. If unacceptable effects occur, temporarily discontinue and restart at a lower number of sprays/day or use longer intervals between sprays. Titrate to optimal maintenance dose (usual range 4–8 sprays/day, usually not >12 sprays/day; higher doses have been used/tolerated). Adjust dose to changes in patient condition.

Availability

Buccal spray contains ethanol (50% v/v), propylene glycol, and peppermint oil: Each mL contains Cannabidiol: 25 mg and THC: 27 mg/mL. Delivers 100 microliters/spray; each spray provides cannabidiol 2.5 mg and THC 2.7 mg

Assessment

Assess spasticity, pain levels, sleep quality, and functional improvement during therapy.
Assess neurological status, gait, and coordination before and during therapy.
Monitor for mood changes and suicidal thoughts or behaviors, especially in those with history of psychiatric illness.
Assess mucosal integrity for stomatitis and mouth ulcers.

Lab Test Considerations:

Monitor liver function tests periodically during therapy.

Implementation

Prime pump before 1st use. Shake vial gently and remove protective cap. Hold vial in an upright position and press firmly and quickly on the actuator 2 or 3 times, until a fine spray appears. Point spray into a tissue, away from patient.
Buccal: Administer one spray 2 times/day, in morning and in evening, on 1st day. Administer under tongue or in buccal area. Rotate sites in mouth to avoid irritation. Effects should be noticed in about 30 min. Do not spray the back of throat or into nose. After 1st day, ↑ dose by 1 spray every 24 hr, spacing doses evenly. No more than 12 doses should be used over a 24-hr period. Space each spray by ≥15 min.

Patient/Family Teaching

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Advise to take as directed.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Advise patient and caregiver if any suicidal thoughts or behaviors occur to notify health care provider immediately.
Educate patient on correct spray technique. Advise patient to rotate sites in the mouth between the tongue and buccal locations.
Advise patient to store unopened bottles in refrigerator. Do not freeze. Keep away from sources of heat such as direct sunlight or flames (product is flammable). Opened bottles may be stored at room temperature. Keep out of reach of children.
Advise patient that any unused contents should be discarded after 28 days. Do not dispose of medications in wastewater (e.g., down the sink or in the toilet) or in household garbage. Consult pharmacist how to dispose of expired or unneeded medication.
Advise patient about the potential for dependency. Tolerance as well as psychological and physical dependence may occur with prolonged use. Use cautiously with a history of drug or alcohol abuse and advise patient to avoid alcohol and other drugs while taking cannabidiol.
Advise patient of impairment to physical or mental abilities and to avoid activities that require mental alertness until response to medication is known.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes