Safety and tolerability
The Sativex clinical program has so far involved over 1500 patients with MS in placebo controlled trials and long-term open label studies in which some patients used up to 48 sprays per day.
Common adverse reactions (1)
The most commonly reported adverse reactions in the first four weeks of exposure were dizziness, which occured mainly during the initial titration period, and fatigue (see Table 2). These reactions are usually mild to moderate and resolve within a few days even if treatment is continued.
When the recommended dose titration schedule was used, the incidence of dizziness and fatigue in the first four weeks was much reduced.
|MedDRa SOC||Very Common
≥ 1/100 to < 1/10
≥ /1000 to < 1/100
|Infections and infestations||Pharyngitis|
|Metabolism and nutrition disorders||Anorexia (including appetite decreased); appetite increased|
|Psychiatric disorders||Depression; disorientation; dissociation; euphoric mood||Hallucination (unspecified, auditory, visual); illusion; paranoia; suicidal ideation; delusional perception*|
|Nervous system disorders||Dizziness||Amnesia; balance disorder; disturbance in attention; dysarthria; dysgeusia; lethargy; memory impairment somnolence||Syncope|
|Eye disorders||Vision blurred|
|Ear and labyrinth disorders||Vertigo|
|Cardiac disorders||Palpitations; tachycardia|
|Respiratory, thoracic and mediastinal disorders||Throat irritation|
|Gastrointestinal disorders||Constipation; diarrhoea; dry mouth; glossodynia; mouth ulceration; nausea; oral discomfort; oral pain; vomiting||Abdominal pain (upper); oral mucosal discolouration*; oral mucosal disorder; oral mucosal exfoliation*; stomatitis; tooth discolouration|
|General disorders and administration site conditions||Fatigue||Application site pain; asthenia; feeling abnormal; feeling drunk; malaise||Application site irritation|
|Injury, poisoning and procedural complaints||Fall|
Drug interactions (1)
During the clinical trials of Sativex, patients remained on their existing medications.
However care should be taken with hypnotics, sedatives and drugs with potential sedating effects as there may be an additive effect on sedation and muscle relaxing effects.
Also, although there has been no greater rate of adverse events in patients already taking anti-spasticity agents when they also take Sativex, care should be taken when co-administering Sativex with anti-spasticity agents, since a reduction in muscle tone and power may occur, leading to a greater risk of falls.
Refer to the SmPC for details of CYP3A4 inhibitor effect and possible digoxin interaction.
Sativex is contraindicated in patients:
- With hypersensitivity to cannabinoids or to any of the excipients.
- 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.
- Who are breast feeding (in view of the considerable likely levels of cannabinoids in maternal breast milk and the potential adverse developmental effects in infants).
NB. Sativex should not be used during pregnancy unless the potential risks to the fetus and/or embryo are considered to be outweighed by the benefit of treatment. Men and women of child-bearing age should take reliable contraceptive precautions for the duration of the treatment and for three months after discontinuation of therapy.
Abuse potential (1)
In a study designed to identify its abuse potential, Sativex at a dose of four sprays taken at one time did not differ significantly from placebo.
People with MS spasticity who take Sativex for prolonged periods do not increase their daily dose, and also do not develop any withdrawal syndrome if the treatment is stopped suddenly. Sativex therefore has limited abuse potential in patients at the recommended dose.
- Sativex Summary of Product Characteristics, 2012.