Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Mild or moderate dizziness is commonly reported. This most frequently occurs in the first few weeks of treatment.

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.

Although there is a theoretical risk that there may be an additive effect with muscle-relaxing agents such as baclofen and benzodiazepines, thereby increasing the risk of falls, this has not been seen in clinical trials with Sativex. However, patients should be warned of this possibility.

Women of childbearing potential
Sativex may reduce the effectiveness of hormonal contraceptives (See section 4.5).
Women of childbearing potential must use highly effective contraception while taking Sativex. It is currently unknown whether Sativex may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should use an additional method of contraception for the duration of therapy and for three months after discontinuation of therapy (see sections 4.5 and 4.6).

Pregnancy and lactation: refer to section 4.6.

Patients who have a history of substance abuse, may be more prone to abuse Sativex as well (see section 5.1).

The abrupt withdrawal of long-term Sativex treatment has not resulted in a consistent pattern or time- profile of withdrawal-type symptoms and the likely consequence will be limited to transient disturbances of sleep, emotion or appetite in some patients. No increase in daily dosage has been observed in long-term use, and patient self-reported levels of ‘intoxication’ are low. For these reasons, dependence on Sativex is unlikely.

Adverse reactions have been reported which could be associated with the route of administration of the medicine. Application site type reactions consisted of mainly mild to moderate stinging at the time of application. Common application site reactions include application site pain, oral pain and discomfort, dysgeusia, mouth ulceration and glossodynia. Two cases of possible leukoplakia were observed but neither was confirmed histologically; a third case was unrelated. In view of this, patients who observe discomfort or ulceration at the site of application of the medicine are advised to vary the site of application within the mouth and should not continue spraying onto sore or inflamed mucous membrane. Regular inspection of the oral mucosa is also advised in long-term administration.
If lesions or persistent soreness are observed, medication should be interrupted until complete resolution occurs.

Patients should be advised that if they travel to another country it may not be legal for them to take this medicine into some countries. They should be encouraged to check the legal status before travelling with Sativex.

Excipients
Each actuation contains up to 40 mg of ethanol, equivalent to 50% by volume of ethanol. , that is approximately 480mg per maximal daily dose (for an adult weighing 70 kg) equivalent to around 10 mL of beer or 5mL of wine. The small amount of alcohol in this medicine will not have any noticeable effects.

This medicine contains 52 mg propylene glycol in each 100 microlitre spray 


Effects on Driving

4.7   Effects on ability to drive and use machines

Sativex may produce undesirable effects such as dizziness and somnolence which may impair judgement and performance of skilled tasks. Patients should not drive, operate machinery or engage in any hazardous activity if they are experiencing any significant CNS effects such as dizziness or somnolence. Patients should be aware that Sativex has been known to cause a few cases of loss of consciousness.

This medicine can impair cognitive function and can affect a patient’s ability to drive safely.
Therefore according to the Israeli transport regulations and the narcotics ordinance, driving is forbidden during Sativex use