Sativex

What it is

Sativex is a pump actuated metered dose aerosol oromucosal spray containing nabiximols extracted from Cannabis sativa L. leaf and flower, delivering 27 mg delta-9-tetrahydrocannabinol (THC) and 25 mg cannabidiol (CBD) per millilitre, with lesser amounts of other cannabinoids totalling 56 mg of cannabinoids per millilitre. Sativex is supplied as a solution in a spray container and is for use as an oromucosal spray only. Each 100 microlitre spray contains 2.7 mg THC and 2.5 mg CBD.

Approved indications

— Treatment for symptom improvement in patients with moderate to severe spasticity due to multiple sclerosis (MS) who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity related symptoms during an initial trial of therapy.

Dosing overview

Treatment must be assessed by a neurologist or rehabilitation physician before commencing, and patients must be reassessed after 4 weeks of treatment. Patients who do not show clinically significant improvement in spasticity on reassessment should not continue Sativex. Treatment must be initiated and supervised by a specialist neurologist or rehabilitation physician with expertise in treating patients with spasticity due to multiple sclerosis. A titration period is required to reach optimal dose, with the number and timing of sprays varying between patients. Patients may gradually increase the dose by one spray per day, up to a maximum of 12 sprays per day, until they achieve optimum symptom relief. There should be at least a 15 minute gap between sprays, and the maximum number of consecutive sprays must not exceed 7 within a 3 hour period. The median dose in clinical trials for patients with multiple sclerosis was eight sprays per day. Doses must not exceed 12 sprays in any 24-hour period. Sativex is not recommended for use in children or adolescents below 18 years of age due to lack of safety and efficacy data.

Key safety warnings

The maximum recommended dose of Sativex should not be exceeded. High doses of Sativex increase the risk of serious psychiatric adverse events including psychosis, hallucinations, delusions, and homicidal and suicidal ideation. Mild or moderate dizziness is commonly reported, most frequently occurring in the first few weeks of treatment. Alterations in pulse rate and blood pressure have been observed following initial dose introduction. Fainting episodes have been observed with use of Sativex, and use of Sativex is not recommended in patients with serious cardiovascular disease. Psychiatric adverse events including disorientation, depression, euphoric mood, and dissociation occurred more frequently in patients given Sativex than in those given placebo in clinical trials. Approximately 10% more patients given Sativex experienced a psychiatric adverse event than those given placebo. Patients with a personal or family history of psychotic illness should not receive Sativex. Patients with a history of depression should be closely monitored and Sativex discontinued if clinically significant worsening of symptoms occurs on therapy. In a few cases a causal association between Sativex administration and suicidal ideation could not be ruled out. In this circumstance, Sativex should be stopped immediately and the patient monitored until the symptom has completely resolved. There is a risk of an increase in incidence of falls in patients whose spasticity has been reduced and whose muscle strength is insufficient to maintain posture or gait. In addition to an increased risk of falls, the CNS adverse reactions of Sativex could potentially have an impact on various aspects of personal safety, such as with food and hot drink preparation.

Contraindications

Sativex is contraindicated in patients with hypersensitivity to cannabinoids or to any of the excipients. Sativex is contraindicated in patients with any known or suspected history or family history of schizophrenia, or other psychotic illness; history of severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition. Sativex is contraindicated in patients who are breast feeding in view of the considerable levels of cannabinoids likely in maternal breast milk and the potential adverse developmental effects in infants.

PBS listing

Information regarding PBS listing is not provided in the available source documents.

Regulatory history

Sativex was first listed on the Australian Register of Therapeutic Goods on 26 November 2012 under ARTG registration 181978. The TGA approved Sativex on 26 November 2012 for symptom improvement in patients with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement during an initial trial of therapy.