Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Children and Adolescents (<18 years)
Treatment with antidepressants is associated with an increased risk of suicidal thinking and behaviour in children and adolescents with major depressive disorder and other psychiatric disorders. In clinical trials of paroxetine in children and adolescents, adverse events related to suicidality (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in patients treated with paroxetine compared to those treated with placebo (see 4.8 Undesirable effects). Long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
Clinical worsening and suicide risk in adults
Young adults, especially those with Major Depressive Disorder (MDD), may be at increased risk for suicidal behaviour during treatment with paroxetine. An analysis of placebo controlled trials of adults with psychiatric disorders showed a higher frequency of suicidal behaviour in young adults (prospectively defined as aged 18-24 years) treated with paroxetine compared with placebo (17/776 [2.19%] versus 5/542 [0.92%]), although this difference was not statistically significant. In the older age groups (aged 25-64 years and ≥65 years), no such increase was observed. In adults with MDD (all ages), there was a statistically significant increase in the frequency of suicidal behaviour in patients treated with paroxetine compared with placebo (11/3455 [0.32%] versus 1/1978 [0.05%]; all of the events were suicide attempts).
However, the majority of these attempts for paroxetine (8 of 11) were in younger adults aged 18-30 years.
These MDD data suggest that the higher frequency observed in the younger adult population across psychiatric disorders may extend beyond the age of 24.
Patients with depression may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviours (suicidality) whether or not they are taking antidepressant medications. This risk persists until significant remission occurs. It is general clinical experience with all antidepressant therapies that the risk of suicide may increase in the early stages of recovery.
Other psychiatric conditions for which paroxetine is prescribed can also be associated with an increased risk of suicidal behaviour and these conditions may be co-morbid with MDD.
Additionally, patients with a history of suicidal behaviour or thoughts, young adults, and those patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are at a greater risk of suicidal thoughts or suicide attempts. All patients should be monitored for clinical worsening (including development of new symptoms) and suicidality throughout treatment, and especially at the beginning of a course of treatment, or at the time of dose changes, either increases or decreases.
Patients, ( families and caregivers of patients) should be alerted about the need to monitor for any worsening of their condition (including development of new symptoms) and/or the emergence of suicidal ideation/behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present. It should be recognised that the onset of some symptoms, such as agitation, akathisia or mania, could be related either to the underlying disease state or the drug therapy (see Akathisia and Mania and Bipolar Disorder below; 4.5 Undesirable Effects).
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients who experience clinical worsening (including development of new symptoms) and/or the emergence of suicidal ideation/behaviour, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
Akathisia
Rarely, the use of paroxetine or other SSRIs has been associated with the development of akathisia, which is characterised by an inner sense of restlessness and psychomotor agitation such as an inability to sit or stand still usually associated with subjective distress. This is most likely to occur within the first few weeks of treatment.
Serotonin Syndrome/Neuroleptic Malignant Syndrome
On rare occasions development of a serotonin syndrome or neuroleptic malignant syndrome-like events may occur in association with treatment of paroxetine, particularly when given in combination with other serotonergic drugs (including triptans) , with drugs that impair metabolism of serotonin (including MAOIs), or with antipsychotic or other dopamine antagonists. Symptoms of serotonin syndrome may include mental status changes (eg, agitation, hallucinations, and coma), autonomic instability (eg, tachycardia, labile blood pressure, and hyperthermia), neuromuscular aberrations (eg, hyperreflexia and incoordination), and/or gastrointestinal tract symptoms (eg, nausea, vomiting, and diarrhea). Severe cases can resemble NMS, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms.
A concomitant treatment of depression with MAOIs and Paroxetine is contraindicated.
Parotin-treated patients receiving triptans should be observed closely, particularly during initiation of therapy, dose increases, or the addition of another serotonergic drug.
Concomitant use of Parotin with serotonin precursors (eg, tryptophan) is not recommended. Treatment with Parotin and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately in patients in whom symptoms of serotonin syndrome develop.
Mania and Bipolar disorder
A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone can increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that paroxetine is not approved for use in treating bipolar depression. As with all antidepressants, paroxetine should be used with caution in patients with a history of mania.
Monoamine Oxidase Inhibitors
Treatment with paroxetine should be initiated cautiously at least 2 weeks after terminating treatment with MAO inhibitors and dosage of paroxetine should be increased gradually until optimal response is reached (see Serotonin syndrome/ Neuroleptic Malignant Syndrome, 4.3 4.3 Contraindications and 4.5 Interaction with other medicinal products and other forms of interaction ).
Renal/hepatic impairment
Caution is recommended in patients with severe renal impairment or in those with hepatic impairment. (See 4.2 Posology and method of administration).
Epilepsy: As with other antidepressants, paroxetine should be used with caution in patients with epilepsy.
Seizures: Overall the incidence of seizures is less than 0.1% in patients treated with paroxetine. The drug should be discontinued in any patient who develops seizures.
ECT: There is little clinical experience of the concurrent administration of paroxetine with ECT.
Glaucoma: As with other SSRI's, paroxetine can cause mydriasis and should be used with caution in patients with narrow angle glaucoma.
Hyponatremia: Hyponatraemia has been reported rarely, predominantly in the elderly. The hyponatraemia generally reverses on discontinuation of paroxetine.
Hemorrhage: Skin and mucous membrane bleedings (including gastrointestinal bleeding) have been reported following treatment with paroxetine. Paroxetine should therefore be used with caution in patients concomitantly treated with drugs that give an increased risk for bleeding, and in patients with a known tendency for bleeding or those with predisposing conditions.
Cardiac conditions: The usual precautions should be observed in patients with cardiac conditions.
Symptoms seen on discontinuation of paroxetine treatment in adults:
In clinicals trials in adults, adverse events seen on treatment discontinuation occurred in 30% of patients treated with paroxetine compared to 20% of patients treated with placebo. The occurrence of discontinuation symptoms is not the same as the drug being addictive or dependence producing as with a substance of abuse.
Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including intense dreams), agitation or anxiety, nausea, tremor, confusion, sweating, headache, diarrhoea have been reported. 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 selflimiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that paroxetine should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs (see "Discontinuation of Paroxetine", 4.2 Posology and method of administration).
Symptoms seen on discontinuation of paroxetine treatment in children and adolescents: In clinical trials in children and adolescents, adverse events seen on treatment discontinuation occurred in 32% of patients treated with paroxetine compared to 24% of patients treated with placebo. Events reported upon discontinuation of paroxetine at a frequency of at least 2% of patients and which occured at a rate at least twice that of placebo were: emotional lability (including suicidal ideation, suicide attempt, mood changes and tearfulness), nervousness, dizziness, nausea and abdominal pain (see 4.8 Undesirable effects).

Effects on Driving

4.7 Effects on ability to drive and use machines
Clinical experience has shown that therapy with paroxetine is not associated with impairment of cognitive or psychomotor function. However, as with all psychoactive drugs, patients should be cautioned about their ability to drive a car and operate machinery.
Although paroxetine does not increase the mental and motor skill impairments caused by alcohol, the concomitantuse of paroxetine and alcohol is not advised.