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:

  • Usage as an additional therapy for individuals with MS to address symptoms of neuropathic pain and spasticity that do not improve with existing treatments.

• 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:

• First, apply one spray each in the morning and afternoon or evening (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 Children

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:

There are no dosage modifications listed on the manufacturer's label (has not been studied). Use with caution.

Nabiximols (Sativex) Dose in Liver disease:

There are no dosage modifications listed on the manufacturer's label (has not been studied). Use with caution.

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.
  • Individuals who have a history of drug or alcohol misuse ought to exercise caution.

• 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

  • Patients with severe renal impairment have not yet been tested with it  Use caution.

• 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:

• Put the vial vertically in your mouth and spray. Many areas below the tongue and on the inside of the cheeks should get the spray.
  On the first day of therapy, provide one spray in the morning (between waking and noon) and one in the afternoon or evening (between 4 and 6 pm).
• You should wait at least 15 minutes between sprays for consecutive titrations. Sprays, however, must to be spaced out evenly throughout each day for initial titration.

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.