Special Warning : אזהרת שימוש

4.4     Special warnings and precautions for use
The following special warnings and precautions apply to the therapeutic class of SSRIs (Selective Serotonin Re-uptake Inhibitors).

Paediatric population
Cipralex should not be used in the treatment of paediatric population Suicide related behaviours (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among the paediatric population treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in the paediatric population concerning growth, maturation and cognitive and behvaioural development are lacking.


Paradoxical anxiety


Some patients with panic disorder may experience increased anxiety symptoms at the beginning of treatment with antidepressants. This paradoxical reaction usually subsides within two weeks during continued treatment.
A low starting dose is advised to reduce the likelihood of an anxiogenic effect (see section 4.2).

Seizures
Escitalopram should be discontinued if a patient develops seizures for the first time, or if there is an increase in seizure frequency (in patients with a previous diagnosis of epilepsy). SSRIs should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy should be closely monitored.

Mania
SSRIs should be used with caution in patients with a history of mania/hypomania. SSRIs should be discontinued in any patient entering a manic phase.

Diabetes
In patients with diabetes, treatment with an SSRI may alter glycaemic control (hypoglycaemia or hyperglycaemia). Insulin and/or oral hypoglycaemic dosage may need to be adjusted.

Suicide/suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which Cipralex is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta analysis of placebo controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old. Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Akathisia/psychomotor restlessness
The use of SSRIs/SNRIs has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.

Hyponatraemia
Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported rarely with the use of SSRIs and generally resolves on discontinuation of therapy. Caution should be exercised in patients at risk, such as the elderly, or patients with cirrhosis, or if used in combination with other medications which may cause hyponatraemia.

Haemorrhage
There have been reports of cutaneous bleeding abnormalities, such as ecchymoses and purpura, with SSRIs.
SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections 4.6, 4.8). Caution is advised in patients taking SSRIs, particularly in concomitant use with oral anticoagulants; with medicinal products known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory medicinal products (NSAIDs), ticlopidine and dipyridamole) and in patients with known bleeding tendencies.

ECT (electroconvulsive therapy)
There is limited clinical experience of concurrent administration of SSRIs and ECT; therefore caution is advisable.


Serotonin syndrome
Caution is advisable if escitalopram is used concomitantly with medicinal products with serotonergic effects such as triptans (including sumatriptan), opioids (including tramadol), and tryptophan.
In rare cases, Serotonin syndrome has been reported in patients using SSRIs concomitantly with serotonergic medicinal products. A combination of symptoms, such as agitation, tremor, myoclonus and hyperthermia, may indicate the development of this condition.
If this occurs, treatment with the SSRI and the serotonergic medicinal product should be discontinued immediately and symptomatic treatment initiated.


St. John´s Wort
Concomitant use of SSRIs and herbal remedies containing St. John´s Wort (Hypericum perforatum) may result in an increased incidence of adverse reactions (see section 4.5).

Discontinuation symptoms seen when stopping treatment
Discontinuation symptoms when stopping treatment are common, particularly if discontinuation is abrupt (see section 4.8). In clinical trials adverse events seen on treatment discontinuation occurred in approximately 25% of patients treated with escitalopram and 15% of patients taking placebo.

The risk of discontinuation symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. Generally these symptoms are mild to moderate, however, in some patients they may be severe in intensity.
They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose.
Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that escitalopram should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient’s needs (see “Discontinuation symptoms seen when stopping treatment”, section 4.2).

Sexual dysfunction
Selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section 4.8). There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation of SSRIs/SNRI.

Coronary heart disease
Due to limited clinical experience, caution is advised in patients with coronary heart disease (see section 5.3).

QT interval prolongation
Escitalopram has been found to cause a dose-dependent prolongation of the QT interval. Cases of QT interval prolongation and ventricular arrhythmia including torsade de pointes have been reported during the post- marketing period, predominantly in patients of female gender, with hypokalaemia, or with pre-existing QT interval prolongation or other cardiac diseases (see sections 4.3, 4.5, 4.8, 4.9 and 5.1).

Caution is advised in patients with significant bradycardia; or in patients with recent acute myocardial infarction or uncompensated heart failure.

Electrolyte disturbances such as hypokalaemia and hypomagnesaemia increase the risk for malignant arrhythmias and should be corrected before treatment with escitalopram is started.

If patients with stable cardiac disease are treated, an ECG review should be considered before treatment is started.

If signs of cardiac arrhythmia occur during treatment with escitalopram, the treatment should be withdrawn and an ECG should be performed.

Angle-Closure Glaucoma
SSRIs including escitalopram may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure and angle-closure glaucoma, especially in patients pre-disposed. Escitalopram should therefore be used with caution in patients with angle- closure glaucoma or history of glaucoma.

Excipients
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

Effects on Driving

4.7     Effects on ability to drive and use machines
Although escitalopram has been shown not to affect intellectual function or psychomotor performance, any psychoactive medicinal product may impair judgement or skills. Patients should be cautioned about the potential risk of an influence on their ability to drive a car and operate machinery.