SATIVEX OROMUCOSAL

Sativex is for oromucosal use only. Sativex is intended to be used in addition to the patient’s current anti-spasticity medication. Treatment must be initiated and supervised by a physician with specialist expertise in treating this patient population.

Adults:

Page 2 of 15 The spray container should be shaken before use and the spray should be directed at different sites on the oromucosal surface changing the application site each time the product is used. Patients should be advised that it might take up to 2 weeks to find the optimal dose and that undesirable effects can occur during this time, most commonly dizziness.

These undesirable effects are usually mild and resolve in a few days. However, physicians should consider maintaining the current dose, reducing the dose or interrupting, at least temporarily, the treatment depending on seriousness and intensity.

5). 5).

Titration period:

A titration period is required to reach optimal dose. The number and timing of sprays will vary between patients. The number of sprays should be increased each day following the pattern given in the table below. The afternoon/evening dose should be taken at any time between 4 pm and bedtime.

When the morning dose is introduced, it should be taken at any time between waking and midday. The patient may continue to gradually increase the dose by 1 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. Day Number of sprays in the morning Number of sprays in the evening (Total number of sprays per day) 1 0 1 1 2 0 1 1 3 0 2 2 4 0 2 2 5 1 2 3 6 1 3 4 7 1 4 5 8 2 4 6 9 2 5 7 10 3 5 8 11 3 6 9 12 4 6 10 13 4 7 11 14 5 7 12 Maintenance period: Following the titration period, patients are advised to maintain the optimum dose achieved.

The median dose in clinical trials for patients with multiple sclerosis is eight sprays per day. Once the optimum dose has been achieved, patients may spread the doses throughout the day according to individual response and tolerability.

Re-titration upwards or downwards may be appropriate if there are any changes in the severity of the patient’s condition, changes in their concomitant medication or if troublesome adverse reactions develop. Doses of greater than 12 sprays per day are not recommended.

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. Page 8 of 15 The most commonly reported adverse reactions in the first four weeks of exposure were dizziness, which occurs mainly during the initial titration period, and fatigue.

2). When the recommended dose titration schedule was used, the incidence of dizziness and fatigue in the first four weeks was much reduced. The frequency of adverse events with a plausible relationship to Sativex, from placebo controlled trials in patients with MS, according to System Organ Classes (SOC) are given below (some of these adverse events may be part of the underlying condition).

A single case of ventricular bigeminy has been reported though this was in the context of acute nut allergy. 7. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard

Mild or moderate dizziness is commonly reported. This most frequently occurs in the first few weeks of treatment. Page 4 of 15 Alterations in pulse rate and blood pressure have been observed following initial dose introduction so caution during initial dose titration is essential.

Fainting episodes have been observed with use of Sativex. Use of Sativex is not recommended in patients with serious cardiovascular disease. However, following dosing in healthy volunteers with Sativex up to 18 sprays twice daily, there were no clinically relevant changes in QTc, PR or QRS interval duration, heart rate, or blood pressure.

Until further information is available, caution should be taken when treating patients with a history of epilepsy, or recurrent seizures. Psychiatric symptoms such as anxiety, illusions, changes in mood, and paranoid ideas have been reported during treatment with Sativex.

These are likely to be the result of transient CNS effects and are generally mild to moderate in severity and well tolerated. They can be expected to remit on reduction or interruption of Sativex medication. Disorientation (or confusion), hallucinations and delusional beliefs or transient psychotic reactions have also been reported and in a few cases a causal association between Sativex administration and suicidal ideation could not be ruled out.

In any of these circumstances, 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, particularly in elderly patients, could potentially have an impact on various aspects of personal safety, such as with food and hot drink preparation.

1. • 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 levels of cannabinoids likely in maternal breast milk and the potential adverse developmental effects in infants).