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. Cannabinoids enter breast milk in considerable amounts.

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: Bi-exponential 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)

Contraindication/Precautions

Contraindicated in:

• Allergy/hypersensitivity to cannabinoids, propylene glycol or peppermint oil;
• Serious cardiovascular disease, including ischemic heart disease, arrhythmias, poorly controlled hypertension or severe heart failure;
• History of schizophrenia/psychoses;
• Patients of reproductive potential who are not using reliable contraception;
• Sore/inflamed mucosa (may alter absorption);
• OB:  Pregnancy (avoid use);
• Lactation: Avoid breastfeeding (cannabinoids enter breast milk in considerable amounts);
• Pedi:  Safety and effectiveness not established.

Use Cautiously in:

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

Adverse Reactions/Side Effects

CNS: dizziness, fatigue, confusion, depression, disorientation, drowsiness, euphoria, hallucinations, psychotic reactions, suicidal ideation, weakness

CV: hypertension, palpitations, tachycardia, postural hypotension

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

GU: urinary retention (↑ in cancer patients)

Local: application site irritation

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 inhibits the CYP450 enzyme system; may ↑ effects of  amitriptyline,  alfentanil,  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. If unacceptable effects occur, temporarily discontinue and restart at a lower # of sprays/day or use longer intervals between sprays. Titrate to optimal maintenance dose (usual range 4–8 sprays/day, usually not more than 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 patient's pain level before and after cannabidiol.

Implementation

• Prime pump before first 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.
• Administer one spray 2 times/day, in morning and in evening, on first 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 first day, increase 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 at least 15 min.

Patient/Family Teaching

• Caution patient to use medication as directed.
• Instruct patient on correct spray technique. Instruct patient to rotate sites in the mouth between the tongue and buccal locations.
• Instruct 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.
• Inform 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.
• Caution patient to avoid alcohol while taking cannabidiol.
• Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

• Decrease in pain.
• Decrease in muscle spasticity.