Children and Adolescents (under 18 years of age): 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. Long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
Clinical Worsening and Suicide Risk: Patients of any age with Major Depressive Disorder may experience worsening of their depression and/or the emergence of suicidal ideation and behaviour (suicidality), whether or not they are taking antidepressive medications, and this risk may persist until significant remission occurs. Patients should be closely monitored, especially at the beginning of therapy or when the dose is changed, until improvement occurs.
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 and/or neuroleptic drugs. As these syndromes may result in potentially life threatening conditions, treatment with Paroxetine should be discontinued if such events (characterised by clusters of symptoms such as hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes including confusion, irritability, extreme agitation progressing to delirium and coma) occur and supportive symptomatic treatment should be initiated. Paroxetine should not be used in combination with serotonin-precursors (such as L-tryptophan, oxitriptan) due to the risk of serotonergic syndrome.
Mania and Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed that treating such an episode with any antidepressant alone may increase the likelihood 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. It should be noted that Paroxetine is not approved for use in treating bipolar depression.
MAO 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.
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.
Paroxetine should be discontinued in any patient who develops seizures.
Electroconvulsive Therapy (ECT): There is little clinical experience of the concurrent administration of Paroxetine with Electroconvulsive Therapy (ECT).
Glaucoma: As with other SSRI, Paroxetine infrequently causes mydriasis and should be used with caution in patients with narrow angle glaucoma.
Renal/hepatic impairment: Caution is recommended in patients with severe renal impairment or in those with hepatic impairment.
Hyponatraemia: Hyponatraemia has been reported rarely, predominantly in the elderly. The hyponatraemia generally reverses on discontinuation of Paroxetine.
Haemorrhage: Bleeding abnormalities of the skin and mucous membranes have been reported with the use of SSRIs (including purpura, haematoma, epistaxis, vaginal bleeding and gastrointestinal bleeding). This risk may be potentiated by concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin or other medicines that affect coagulation. Paroxetine should therefore be used with caution in patients concomitantly treated with medicines that increase the risk of bleeding or in patients with a past history of abnormal bleeding or those with predisposing conditions. Pharmacological gastroprotection should be considered for high risk patients.
Cardiac Conditions: Paroxetine does not generally produce clinically significant changes in blood pressure, heart rate or ECG. Paroxetine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Hence, the usual precautions should be observed in such patients. Like other SSRI, Paroxetine infrequently causes mydriasis and therefore should be used with caution in patients with narrow angle glaucoma.
Information for Patients and Families: Patients and their families should be alerted about the need to monitor for the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania, worsening of depression, and suicidal ideation, especially early during antidepressant treatment. Such symptoms should be reported to the patient's doctor, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
Symptoms seen on discontinuation of Paroxetine treatment in adults: 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 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 Paroxetine should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs.
Symptoms seen on discontinuation of Paroxetine treatment in children and adolescents: Emotional lability including suicidal ideation, suicide attempt, mood changes and tearfulness, nervousness, dizziness, nausea and abdominal pain.
Effect on ability to drive or operate machinery: Although Paroxetine did not cause sedation or interfere with psychomotor performance in placebo-controlled studies in normal subjects, patients should be advised to avoid driving a car or operating hazardous machinery until they are reasonably certain that Paroxetine does not affect them adversely.
Other: Preclinical Safety Data: Toxicology studies have been conducted in rhesus monkeys and albino rats; in both, the metabolic pathway is similar to that described for humans. As expected with lipophilic amines, including tricyclic antidepressants, phospholipidosis was detected in rats. Phospholipidosis was not observed in primate studies of up to one year duration at doses that were 6 times higher than the recommended range of clinical doses.
Carcinogenesis: In two-year studies conducted in mice and rats, Paroxetine had no tumorigenic effect.
Genotoxicity: Genotoxicity was not observed in a battery of in vitro and in vivo tests.
Use in Pregnancy & Lactation: Category C: Paroxetine should not be used during pregnancy, unless the potential benefit outweighs the possible risk. The prescribing physician will need to weigh the option of alternative treatments in women who are pregnant or are planning to become pregnant.
If a decision is taken to discontinue Paroxetine treatment in a pregnant woman, the prescriber should consult Discontinuation
of Paroxetine under Dosage & Administration and Symptoms seen on
discontinuation of Paroxetine treatment in adults previously.
Epidemiological studies have shown infants born to women who had first trimester Paroxetine exposure had an increased risk of cardiovascular malformations.
Neonates should be observed if maternal use of Paroxetine continues into the later stages of pregnancy, because there have been reports of complications in neonates exposed to Paroxetine or other SSRIs late in the third trimester of pregnancy. However, a causal association with drug therapy has not been confirmed. Reported clinical findings have included: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying and somnolence. In some instances the reported symptoms were described as neonatal withdrawal symptoms. In a majority of instances the complications were reported to have arisen either immediately or soon (<24 hours) after delivery.