Posology : מינונים

4.2    Posology and method of administration

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:
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.
To minimise variability of bioavailability in the individual patient, administration of Sativex should be standardised as far as possible in relation to food intake (see section 4.5). In addition, starting or stopping some concomitant medicinal products may require a new dose titration (see section 4.5).

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          Number of          (Total number in the morning          sprays in the        of sprays per evening                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.

Review by the physician
A thorough evaluation of the severity of spasticity related symptoms and of the response to standard anti-spasticity medication should be performed prior to initiation of treatment. Sativex is only indicated in patients with moderate to severe spasticity that have responded inadequately to other anti- spasticity medication. The patient’s response to Sativex should be reviewed after four weeks of treatment. If a clinically significant improvement in spasticity related symptoms is not seen during 
this initial trial of therapy, then treatment should be stopped. In the clinical trials this was defined as at least a 20% improvement in spasticity related symptoms on a 0-10 patient reported numeric rating scale (see section 5.1). The value of long term treatment should be re-evaluated periodically.

Paediatric population
Sativex is not recommended for use in children or adolescents below 18 years of age.
A randomized placebo-controlled trial was performed in children and adolescents with cerebral palsy or traumatic central nervous system injury and its results regarding efficacy were negative. The data is described in section 5.1.

Elderly
No specific studies have been carried out in elderly patients, although patients up to 90 years of age have been included in clinical trials. However, as elderly patients may be more prone to develop some CNS adverse reactions, care should be taken in terms of personal safety such as preparation of hot food and drinks.

Patients with significant hepatic or renal impairment
No data with multiple dosing are available in subjects with hepatic impairment. Sativex can be administered to patients with mild hepatic impairment without any dose adjustment. Administration to patients with moderate or severe hepatic impairment is not advised due to the lack of information on the potential for accumulation of THC and CBD with chronic dosing (see section 5.2).

There are no studies in patients with impaired renal function. However, in these sub-populations the effects of Sativex may be exaggerated or prolonged. Frequent clinical evaluation by a clinician is recommended in these patient populations (see section 4.4).