cannabidiol

REMS

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.

Contraind./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.

Adv. 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

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.

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

Route/Dosage ⬆ ⬇

(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.

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 effects:

Decreased pain and spasticity.

Classifications ⬆ ⬇

Therapeutic Classification: analgesic adjuncts, therapeutic, antispasticity agents

Pharmacologic Classification: cannabinoids

Pharmacokinetics ⬆ ⬇

Absorption: Buccal absorption is slower than inhalation.

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

Metabolism/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.

Canadian Brand Names ⬆ ⬇

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.

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.

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Indications ⬇