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Nabiximols (United States: Not available): Drug information

Nabiximols (United States: Not available): Drug information
(For additional information see "Nabiximols (United States: Not available): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: Canada
  • Sativex
Pharmacologic Category
  • Cannabinoid
Dosing: Adult
Spasticity associated with multiple sclerosis

Spasticity associated with multiple sclerosis: Buccal spray:

Initial: Day 1: One spray in the morning and one spray in the afternoon or evening (maximum initial dose: 2 sprays on first day).

Titration and individualization: Dosage is self-titrated by the patient. After initiation of therapy, the dose may be increased each subsequent day by one spray as needed and tolerated. Usual dosage: 4 to 8 sprays daily. Most patients require ≤12 sprays daily. Experience is limited with dosage of >12 sprays daily, although some patients may require and tolerate higher dosing. Sprays should be evenly distributed over the course of the day during initial titration.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in manufacturer’s labeling (has not been studied). Use with caution.

Dosing: Hepatic Impairment: Adult

Mild impairment: There are no specific dosage adjustments provided in the manufacturer's labeling; use with caution.

Moderate to severe impairment: Use is not recommended.

Dosing: Older Adult

Refer to adult dosing. Use with caution and monitor closely.

Dosing: Adjustment for Toxicity: Adult

If adverse reactions, including intoxication-type symptoms, are noted the dosage should be suspended until resolution of the symptoms; a dosage reduction or extension of the interval between doses may be used to avoid a recurrence of symptoms. Retitration may be required in the event of adverse reactions and/or worsening of symptoms.

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Liquid, Buccal:

Sativex: 27-25 MG/ML (5.5 mL, 10 mL) [contains alcohol, usp, polyethylene glycol (macrogol)]

Product Availability

Not available in the US

Controlled Substance

CDSA-II

Administration: Adult

For buccal use only. Do not inhale, spray into nose or towards throat. Do not apply spray to sore or inflamed mucosa.

Shake vial before use and remove protective cap; replace protective cap following use.

Priming: Vial should be held in an upright position and primed into a tissue prior to the initial use by depression of the actuator 2 to 3 times until a fine spray appears. Priming should not be required for subsequent uses. Do not spray near children, pets, or an open flame.

Normal use: Hold vial in upright position and spray into mouth; spray should be directed at varied sites below the tongue or on the inside of the cheeks, avoiding direction to the pharynx. Initiate therapy by administering 1 spray in the morning (between waking up and 12 noon) and 1 spray in the afternoon or evening (between 4 pm and bedtime) on day 1. With subsequent titration, allow at least 15 minutes between sprays; however, during initial titration, sprays should be evenly spaced throughout the day.

Use: Labeled Indications

Note: Not approved in the United States.

Multiple sclerosis: Adjunctive treatment in adults with multiple sclerosis for the symptomatic relief of spasticity that is nonresponsive to other therapy.

Medication Safety Issues
Safety concerns:

ALERT: Canadian Boxed Warning: Health Canada-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see Cannabidiol monograph.

>10%: Nervous system: Dizziness (25%), fatigue (13%)

1% to 10%:

Cardiovascular: Palpitations (1%), tachycardia (1%)

Gastrointestinal: Anorexia (2%), constipation (2%), diarrhea (6%), dysgeusia (3%), increased appetite (1%), nausea (10%), oral mucosa changes (≤2%; including mucosal exfoliation), oral mucosa ulcer (2%), staining of tooth (2%), upper abdominal pain (1%), vomiting (4%), xerostomia (6%)

Nervous system: Amnesia (1%), balance impairment (3%), confusion (≤4%), depersonalization (2%), depression (3%), disorientation (≤4%), disturbance in attention (4%), drowsiness (8%), dysarthria (2%), euphoria (2%), falling (2%), feeling abnormal (2%), intoxicated feeling (3%), lethargy (2%), malaise (1%), memory impairment (1%), vertigo (7%)

Neuromuscular & skeletal: Asthenia (6%)

Ophthalmic: Blurred vision (2%)

<1%:

Cardiovascular: Hypertension, syncope

Gastrointestinal: Oral mucosa hyperpigmentation, stomatitis

Nervous system: Auditory hallucination, delusion, illusion, visual hallucination

Frequency not defined:

Cardiovascular: Orthostatic hypotension, variable blood pressure (transient)

Nervous system: Drug withdrawal

Miscellaneous: Drug tolerance

Postmarketing:

Gastrointestinal: Oral leukoplakia

Nervous system: Suicidal ideation

Contraindications

Hypersensitivity to cannabinoids or any other component of the formulation; cardiovascular disease (including arrhythmias, severe heart failure, poorly controlled hypertension, and ischemic heart disease); history of schizophrenia or any other psychotic disorder; women of childbearing potential or fertile men who are not using a reliable form of contraception; pregnancy; breastfeeding; children <18 years of age.

Warnings/Precautions

Concerns related to adverse effects:

• Buccal mucosa irritation: May be irritating to the buccal mucosa; avoid administration in an area of soreness or inflammation. Inspect oral mucosa regularly.

• Cardiovascular effects: [Canadian Boxed Warning]: May be associated with adverse cardiovascular effects, including tachycardia and transient alterations in blood pressure (including orthostatic changes). Use is contraindicated in ischemic heart disease, arrhythmias, poorly controlled hypertension, and severe heart failure.

• CNS effects: [Canadian Boxed Warning]: May impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). Use may be associated with changes in mood, cognitive performance, memory, impulsivity, and coordination, as well as an altered perception of reality, particularly with respect to an awareness/sensation of time. Adverse effects are dose-related and vary among patients. Dose reductions, greater intervals between doses, or interrupting therapy may resolve unwanted effects. Interrupt therapy if patient is confused or disoriented. Prescriptions should be written for the minimal amount needed between clinic visits.

Disease-related concerns:

• Substance abuse: [Canadian Boxed Warning]: Potential for dependency exists. Tolerance, psychological, and physical dependence may occur with prolonged use. Use with caution in patients with a history of drug or alcohol abuse.

• Hepatic impairment: Use with caution in mild impairment; use in moderate or severe impairment is not recommended.

• Psychosis: Avoid use in patients with personal or strong familial history of psychosis; symptoms may be aggravated with cannabinoids. Suicidal ideation and other symptoms associated with depression have been reported. Discontinue use immediately in patients experiencing psychotic reactions, suicidal ideation, delusions, hallucinations, disorientation, and/or confusion and monitor until complete resolution of symptoms.

• Renal dysfunction: Use in patients with significant renal dysfunction has not been studied. Use with caution.

• Seizure disorder: [Canadian Boxed Warning]: Use with caution in patients with a history of seizure disorder.

Concurrent drug therapy issues:

• Ethanol/CNS depressants: Concomitant use with ethanol or drugs with sedative, hypnotic, or psychotropic effects may potentiate adverse CNS effects; use caution.

Special populations:

• Older adult: Use with caution in elderly patients. Close monitoring is required.

Dosage form specific issues:

• Ethanol: Formulation contains ethanol; use with caution in alcoholism and/or hepatic dysfunction.

Other warnings/precautions:

• Toxicology screen: Cannabinoids accumulate in body fat and may be detectable in the urine and serum for several weeks following drug discontinuation.

Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP2C9 (major), CYP3A4 (major), UGT1A7, UGT1A9, UGT2B7; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Anticholinergic Agents: May enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Cocaine (Topical): May enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Specifically, concentrations of tetrahydrocannabinol may be increased. Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. Management: Avoid use of the tetrahydrocannabinol/cannabidiol oromucosal spray and strong CYP3A4 inducers when possible. If combined use is necessary, careful titration is recommended, notably within the two weeks following discontinuation of the inducer. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Grapefruit Juice: May increase the serum concentration of Tetrahydrocannabinol and Cannabidiol. Risk X: Avoid combination

Hormonal Contraceptives: Tetrahydrocannabinol and Cannabidiol may decrease the serum concentration of Hormonal Contraceptives. Management: Patients taking hormonal contraceptives should use an additional, non-hormonal contraceptive or reliable barrier method during treatment with tetrahydrocannabinol and cannabidiol buccal spray. Risk D: Consider therapy modification

St John's Wort: May decrease the serum concentration of Tetrahydrocannabinol and Cannabidiol. Management: Avoid use of St Johns wort during treatment with tetrahydrocannabinol and cannabidiol when possible. If potential benefits of concurrent use outweigh possible risks, monitor closely for reduced tetrahydrocannabinol/cannabidiol effectiveness. Risk D: Consider therapy modification

Sympathomimetics: Cannabinoid-Containing Products may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the tachycardic effect of Cannabinoid-Containing Products. Blood pressure raising effects and drowsiness may also be enhanced. Risk C: Monitor therapy

Warfarin: Cannabinoid-Containing Products may increase the serum concentration of Warfarin. Risk C: Monitor therapy

Food Interactions

Grapefruit juice may increase the serum concentration of tetrahydrocannabinol and cannabidiol. Management: Avoid grapefruit juice during therapy.

Reproductive Considerations

Cannabinoids have been associated with reproductive toxicity. Patients who may become pregnant or who may father a child should use a reliable form of contraception for the duration of treatment and for 3 months following discontinuation. An additional alternative form of birth control is recommended in patients using hormonal contraception. Use is contraindicated in patients who may become pregnant or who may father a child who are not using reliable contraception.

Pregnancy Considerations

Use is contraindicated during pregnancy.

Breastfeeding Considerations

Cannabinoids are present in breast milk.

Use is contraindicated in patients who are breastfeeding.

Dietary Considerations

Avoid grapefruit juice.

Monitoring Parameters

Mental status; mucosal integrity and inflammation; signs/symptoms of psychosis and/or suicidal ideation; signs/symptoms of misuse/abuse.

Mechanism of Action

Stimulates cannabinoid receptors CB1 and CB2 in the CNS and dorsal root ganglia as well as other sites in the body. Cannabinoid receptors in the pain pathways of the brain and spinal cord mediate cannabinoid-induced analgesia. Peripheral CB2 receptors modulate immune function through cytokine release.

Pharmacokinetics

Absorption: Rapidly absorbed (within 15 minutes) from the buccal mucosa.

Distribution: Widely distributed, particularly to fatty tissues.

Protein binding: THC: ~97%.

Metabolism: Hepatic, via CYP isoenzymes (2C9, 2C19, 2D6 and 3A4) to THC metabolite 11-hydroxy-tetrahydrocannabinol (11-OH-THC, psycho-active) and CBD metabolite 7-hydroxy-cannabidiol.

Half-life elimination: Biphasic:

Initial (plasma; prolonged with higher doses): CBD: ~5 to 9 hours; THC: ~2 to 5 hours.

Terminal: 24 to 36 hours (or longer) secondary to redistribution from fatty tissue.

Time to peak, plasma: 45 to 120 minutes.

Excretion: As metabolites, urine and feces.

Brand Names: International
  • Sativex (AT, AU, BE, CZ, DE, DK, ES, FI, FR, GB, IL, IS, NL, NO, NZ, PL, PT, SE, SK)


For country abbreviations used in Lexicomp (show table)
  1. Berman JS, Symonds C, and Birch R, "Efficacy of Two Cannabis Based Medicinal Extracts for Relief of Central Neuropathic Pain From Brachial Plexus Avulsion: Results of a Randomised Controlled Trial," Pain, 2004, 112(3):299-306. [PubMed 15561385]
  2. Sativex (tetrahydrocannabinol and cannabidiol) [product monograph]. Histon, Cambridge, United Kingdom: GW Pharma Ltd; December 2019.
  3. Wade DT, Makela P, Robson P, et al, "Do Cannabis-Cased Medicinal Extracts Have General or Specific Effects on Symptoms in Multiple Sclerosis? A Double-Blind, Randomized, Placebo-Controlled Study on 160 Patients," Mult Scler, 2004, 10(4):434-41. [PubMed 15327042]
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