Nabiximols (Sativex) is a purified form of Cannabis extracted from whole-plant Cannabis sativa L. Cannabis species. It is available as a buccal spray for pain management.

Nabiximols (Sativex) Uses:

Note: It is not approved in the US

• Multiple sclerosis:

  • Use as an adjunctive treatment in adults with MS for the symptomatic relief of neuropathic pain and of spasticity that does not respond to other therapy

• Pain:

  • Use as an adjunctive treatment in adults with advanced cancer with moderate-to-severe pain at the highest tolerated dose of strong opioid therapy

Nabiximols (Sativex) Dose in Adults

Nabiximols (Sativex) Dose in the treatment of Spasticity/ neuropathic pain associated with multiple sclerosis (MS) and Cancer pain:

Nabiximols (Sativex) Buccal Spray:

• One spray in the morning and one spray in the afternoon or evening initially (maximum initial dose: 2 sprays on day one)

• Titration and individualization:

  • Dosage is titrated by the patient himself.
  • 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 every day.
  • Most patients require ≤12 sprays daily.
  • limited experience available with the 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.

Nabiximols (Sativex) Dose in Childrens

Not indicated in children.

Pregnancy Risk Category: X

• Contraindicated for use during pregnancy in women with childbearing potential who are not using reliable contraception and men planning to start a family.
• There have been reports of reproductive toxicities associated with cannabinoids. Animal studies have shown that cannabinoids may cause spermatogenesis and fetal development problems.
• For the duration of treatment, and for three months after discontinuation, women with childbearing potential or males capable of causing pregnancy should use reliable contraception.

Nabiximols use during breastfeeding:

• Breastfeeding is contraindicated

Nabiximols (Sativex) Dose in Kidney Disease:

No dosage adjustments provided in the manufacturer’s labeling (has not been studied). Use cautiously.

Nabiximols (Sativex) Dose in Liver disease:

No dosage adjustments provided in the manufacturer’s labeling (has not been studied). Use cautiously.

Common Side Effects of Nabiximols (Sativex):

• Central Nervous System:

  • Dizziness
  • Drowsiness
  • Fatigue Gastrointestinal: Nausea

Less Common Side Effects Of Nabiximols (Sativex):

• Cardiovascular:

  • Hypotension
  • Palpitations
  • Syncope
  • Tachycardia

• Central Nervous System:

  • Confusion
  • Vertigo
  • Disorientation
  • Disturbance In Attention
  • Depression
  • Equilibrium Disturbance
  • Headache
  • Insomnia
  • Intoxicated Feeling
  • Panic Attack
  • Euphoria
  • Hallucination
  • Depersonalization
  • Dysarthria
  • Falling
  • Feeling Abnormal
  • Lethargy
  • Amnesia
  • Malaise
  • Memory Impairment
  • Paranoia
  • Suicidal Ideation

• Gastrointestinal:

  • Vomiting
  • Diarrhea
  • Xerostomia
  • Dysgeusia
  • Glossalgia
  • Oral Candidiasis
  • Anorexia
  • Constipation
  • Dental Discoloration
  • Oral Mucosa Changes
  • Oral Mucosa Ulcer
  • Abdominal Pain
  • Increased Appetite
  • Stomatitis

• Genitourinary:

  • Urinary Retention
  • Hematuria

• Hepatic:

  • Abnormal Hepatic Function Tests

• Neuromuscular & Skeletal:

  • Weakness

• Ophthalmic:

  • Blurred Vision

• Respiratory:

  • Throat Irritation

Contraindications to Nabiximols (Sativex):

• Hypersensitivity to cannabinoids and propylene glycol, alcohol, peppermint oil or any other ingredient of the formulation
• Serious cardiovascular disease, including arrhythmias, severe hypertension and ischemic heart diseases, can occur.
• History of schizophrenia or other psychotic disorders
• Women with childbearing potential that aren't using a reliable contraceptive method
• Men who want to start a family
• Pregnancy
• Breastfeeding
• Children under 18 years old

Warnings and precautions

• Irritation of the buccal mucosa

  • It can cause irritation to the buccal mucosa
  • Do not give in to soreness or inflammation.
  • Inspect oral mucosa regularly.

• Cardiovascular effects: [Canadian boxed warning]

  • Potentially can cause adverse cardiovascular effects such as tachycardia, transient alterations of BP (including orthostatic change), and tachycardia.
  • Patients with unfavorable side effects should be closely monitored and dosed. Precautions should be taken during the perioperative period.
  • Contraindicated for ischemic heart disease and arrhythmias.

• CNS effects: [Canadian Boxed Warning]

  • You may experience dizziness, mood changes, cognitive performance or memory problems, impulsivity and coordination.
  • Negative effects can be dose-related and may vary from patient to patient.
  • You can resolve unwanted effects by reducing doses, increasing intervals between doses or interrupting therapy.
  • If the patient is disoriented or confused, interrupt therapy.
  • It can cause impairment of mental or physical abilities. Patients should be warned about driving or operating machinery that requires mental alertness.

• Genitourinary effects

  • Patients with malignancy are at greater risk of infection and urinary retention. Use caution.

• Substance abuse: [Canadian Boxed Warn]

  • There is a dependency potential.
  • With prolonged use, tolerance, psychological dependence, and physical dependence can occur.
  • Patients who have a history of alcohol or drug abuse should be cautious.

• Hepatic dysfunction

  • It has not been proven safe to use in patients suffering from severe hepatic dysfunction. Be cautious

• Psychosis:

  • Patients with strong family histories of psychosis should avoid cannabinoids.
  • Reports of suicidal ideation, and other symptoms that are associated with depression were made.
  • Patients with psychotic reactions such as suicidal ideation or hallucinations, suicidal thoughts, delusions, hallucinations, disorientation and/or confusion should stop using the medication immediately. Continue monitoring until symptoms resolve completely.

• Renal dysfunction

  • It has not been tested in patients with severe renal dysfunction. Be cautious

• Seizure disorder: [Canadian Boxed Warning]:

  • Patients with seizure disorders should be cautious.

Nabiximols (United States: Not available): Drug Interaction

Monitoring parameters:

• Mental status
• response to pain
• mucosal integrity and inflammation
• signs/symptoms of psychosis and/or suicidal ideation
• signs/symptoms of misuse/abuse

How to administer Nabiximols (Sativex)?

• Only for buccal use.
• Avoid inhaling, do not spray towards the throat or into the nose.
• Spray the spray only on inflamed or sore mucosas.
• Before use, shake the vial and take off protective cap.

Priming:

• The Vial should always be upright and placed in a tissue before first use. After this, you can press the actuator 2 to 3. Until a fine spray appears.
• For subsequent uses, priming shouldn't be necessary.
• Spraying near pets or children is not recommended.

Normal use:

• Spray the vial upright into your mouth. The spray should be directed to various locations below the tongue and on the inside of the cheeks.
• Start therapy by giving 1 spray in morning (between waking and 12 noon) and 1 in afternoon or evening (between 4 and 6 pm) on day 1.
• For subsequent titrations, you should allow at least 15 minutes between sprays. However, for initial titration sprays should be evenly spaced throughout each day.

Mechanism of action of Nabiximols (Sativex):

• It stimulates the cannabinoid receptors CB1 & CB2 in CNS, dorsal root Ganglia, and other areas in the body.
• The cannabinoid-induced pain relief is mediated by the spinal cord and brain's cannabinoid receptors.
• The peripheral CB2 receptors can modulate immune function by cytokine release.

Absorption:

• Rapidly absorbed (within 30 mins) from the buccal mucosa

Distribution:

• Widely distributed, particularly to fatty tissues

Protein binding:

• Extensive

Metabolism:

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

Half-life elimination: Biphasic:

• Initial: 1 to 2 hours
• Terminal: 24 to 36 hours (or longer) secondary to redistribution from fatty tissue

Time to peak, plasma:

• 2 - 4 hours

Excretion:

• As metabolites, urine, and feces

International Brands of Nabiximols:

• Sativex

Nabiximols Brand Names in Pakistan

No Brands Available in Pakistan.