XET 20 Paroxetine Hydrochloride 20mg Film-Coated Tablet 1's

Adults: Depression: Depression of all types, including reactive and severe depression and depression accompanied by anxiety. Paroxetine is indicated for the prevention of relapse and also recurrence of further depressive episodes. In the treatment of depressive disorders, Paroxetine exhibits comparable efficacy to standard antidepressants. In general, improvement in patients starts after one week but does not become superior to placebo until the second week of therapy.
Paroxetine, in addition to its significant antidepressant effects, also improves associated symptoms of anxiety. There is also some evidence that Paroxetine may be of therapeutic value in patients who have failed to respond to standard therapy.
Morning dosing with Paroxetine does not have any detrimental effect on either the quality or duration of sleep. Moreover, patients are likely to experience improved sleep as they respond to Paroxetine therapy.
Where it is clinical practice to co-prescribe short-acting hypnotics with antidepressants, no additional adverse events have been recorded.
Paroxetine is effective in improving depression and suicidal ideation concurrently during the first few weeks of therapy.
Long term treatment with Paroxetine has shown that efficacy is maintained for periods of at least one year.
Obsessive Compulsive Disorder: Paroxetine is indicated for the treatment of Obsessive Compulsive Disorder (OCD).
In a placebo-controlled trial, the efficacy of Paroxetine in the treatment of OCD has been maintained for at least 1 year.
Panic Disorder: Paroxetine is indicated for the treatment of Panic Disorder with and without agoraphobia.
The combination of Paroxetine and cognitive-behavioural therapy has been shown to be significantly more effective than cognitive-behavioural therapy alone in the treatment of Panic Disorder.
In a placebo-controlled trial, the efficacy of Paroxetine in the treatment of Panic Disorder has been maintained for up to 1 year.
Social Anxiety Disorder/Social Phobia: Paroxetine has been shown to be effective in the treatment of Social Anxiety Disorder/Social Phobia.
Generalised Anxiety Disorder: Paroxetine has been shown to be effective in the treatment of Generalised Anxiety Disorder. In a placebo-controlled trial, the efficacy of Paroxetine in the treatment of Generalised Anxiety Disorder has been maintained for up to 32 weeks.
Post-traumatic Stress Disorder: Paroxetine has been shown to be effective in the treatment of Post-traumatic Stress Disorder.
All indications: Children and adolescents (<18 years).
Paroxetine is not indicated for use in children or adolescents aged <18 years.
Controlled clinical studies in children and adolescents with major depressive disorder failed to demonstrate efficacy, and do not support the use of Paroxetine in the treatment of depression in this population.
The safety and efficacy of Paroxetine in children aged <7 years has not been studied.

 

Paroxetine should be administered once daily with food, preferably in the morning. The tablet(s) should be swallowed rather than chewed.
Depression: The recommended dose is 20 mg/day. Some patients not responding to a 20 mg dose may benefit from dose increases, in 10 mg/day increments, up to a maximum of 50 mg/day. The dosage should be reviewed and adjusted within 2 to 3 weeks of initiation of therapy and thereafter as deemed clinically appropriate. Any changes in dosage should occur at intervals of at least one week.
Obsessive Compulsive Disorder (OCD): The recommended dose is 40 mg/day. Patients should start on an initial dose of 20 mg/day and the dose can then be increased in weekly 10 mg/day increments. Doses up to a maximum of 60 mg/day may benefit some patients.
Panic Disorder: The recommended dose is 40 mg/day. Patients should begin treatment at a dose of 10 mg/day with the dose being adjusted in weekly 10 mg/day increments according to their individual response. Doses up to a maximum of 60 mg/day may benefit some patients.
Social Anxiety Disorder/Social Phobia: The recommended dose is 20 mg/day. Some patients not responding to a 20 mg dose may benefit from having dose increases in 10 mg increments as required, up to a maximum of 50 mg/day according to the patients response. It is generally recommended that a course of antidepressant drug treatment should continue for a sufficient period to ensure the patient is free from symptoms. This period may be several months for depression but can be longer for OCD and Panic Disorder.
Generalised Anxiety Disorder: The recommended dose is 20 mg daily. Some patients not responding to a 20 mg dose may benefit from having dose increases in 10 mg increments as required, up to a maximum of 50 mg/day according to the patient's response.
Posttraumatic Stress Disorder: For the majority of patients, the recommended starting and maintenance dose is 20 mg daily. However, some patients not responding to a 20 mg dose may benefit from having dose increases in 10 mg increments as required, up to a maximum of 50 mg/day according to the patient's response.
The use of Paroxetine beyond 12 weeks has not been investigated in clinical trials.
Use in Elderly: Increased plasma concentrations of Paroxetine occur in elderly subject. But the range of concentration overlaps those observed in younger subjects. Dosing should begin with the adult starting dose and may be increased by weekly 10 mg/day increments up to 40 mg/day, according to the patient's response.
Use in Children and Adolescent Patients (under 18 years of age): Paroxetine should not be used in patients under 18 years of age.
Renal/Hepatic Impairment: Increased plasma concentrations of Paroxetine occur in patients with renal impairment (creatinine clearance <30 mL/min) or severe hepatic impairment. Dosages should be restricted to the lower end of the dosage range.
Discontinuation of Paroxetine: As with other psychoactive medications, abrupt discontinuation should generally be avoided. The taper phase regimen used in recent clinical trials involved a decrease in the daily dose by 10 mg/day at weekly intervals. When a daily dose of 20 mg/day was reached, patients were continued on this dose for one week before treatment was stopped. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.

 

Overdosage

Should be taken with food: Preferably taken in the morning. Tab should be swallowed rather than chewed.

Paroxetine is contraindicated in patients with known hypersensitivity to Paroxetine or any of its excipients.
Paroxetine is also contraindicated in patients taking monoamine oxidase inhibitors (MAO).

 

Warnings

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.

 

Use In Pregnancy & Lactation

The most commonly observed adverse effects from the use of Paroxetine were: asthenia, constipation, decreased appetite, diarrhea, dizziness, dry mouth, insomnia, male sexual dysfunction, nausea, somnolence, sweating and tremor.
The following adverse effects have been reported rarely: dizziness, rash, acute glaucoma, urinary retention, peripheral and facial edema, sinus tachycardia, thrombocytopenia, serotonergic syndrome (symptoms may include agitation, confusion, diaphoresis, hallucinations, hyperreflexia, myoclonus, shivering, tachycardia and tremor), symptoms suggestive of hyperprolactinaemia/galactorrhoea and hyponatraemia (predominantly in the elderly).
Elevation of hepatic enzymes has been reported. Serious liver abnormalities have been reported rarely. If there is a prolonged elevation on liver function test, discontinuation of treatment with Paroxetine should be considered.
Blood & lymphatic system disorders: Uncommon: abnormal bleeding, predominantly of the skin and mucous membranes, including purpura, epistaxis, haematomas, vaginal bleeding and gastrointestinal bleeding.
Immune system disorders: Very rare: allergic reactions (including urticaria and angioedema).
Endocrine disorders: Very rare: syndrome of inappropriate anti-diuretic hormone secretion (SIADH).
Metabolism & nutrition disorders: Common: decreased appetite.
Rare: hyponatraemia.
Hyponatraemia has been reported predominantly in elderly patients and is sometimes due to syndrome of inappropriate anti-diuretic hormone secretion (SIADH).
Psychiatric disorders: Common: somnolence, insomnia, agitation.
Uncommon: confusion, hallucinations.
Rare: manic reactions.
Nervous system disorders: Common: dizziness, tremor.
Uncommon: extrapyramidal disorders.
Rare: convulsions, akathisia.
Very rare: serotonin syndrome (symptoms may include agitation, confusion, diaphoresis, hallucinations, hyperreflexia, myoclonus, shivering tachycardia and tremor).
Reports of extrapyramidal disorders including oro-facial dystonia have been received in patients sometimes with underlying movement disorders or who were using neuroleptic medication.
Eye disorders: Common: blurred vision.
Very rare: acute glaucoma.
Cardiac disorders: Uncommon: sinus tachycardia
Vascular disorders: Uncommon: transient increases or decreases in blood pressure.
Transient increases or decreases of blood pressure have been reported following treatment with Paroxetine, usually in patients with pre-existing hypertension or anxiety.

 

The metabolism and pharmacokinetics of Paroxetine may be affected by the induction or inhibition of drug metabolising enzymes.
When Paroxetine is to be co-administered with a known drug metabolising enzyme inhibitor, consideration should be given to using doses at the lower end of the range. No initial dosage adjustment is considered necessary when the drug is to be co-administered with known drug metabolising enzyme inducers (e.g. carbamazepine, rifampicin, phenobarbital, phenytoin). Any subsequent dosage adjustment should be guided by clinical effect (tolerability and efficacy).
Fosamprenavir/ritonavir: Co-administration of fosamprenavir/ritonavir with Paroxetine significantly decreased plasma levels of Paroxetine. Any dose adjustment should be guided by clinical effect (tolerability and efficacy).
Procyclidine: Daily administration of Paroxetine increases significantly the plasma levels of procyclidine. If anti-cholinergic effects are seen, the dose of procyclidine should be reduced.
Anticonvulsants: Carbamazepine, phenytoin, sodium valproate. Concomitant administration does not seem to show any effect on pharmacokinetic/dynamic profile in epileptic patients.
Paroxetine should not be used in combination with thioridazine, because, as with other drugs, which inhibit the hepatic enzyme CYP450 2D6, Paroxetine can elevate plasma levels of thioridazine. Administration of thioridazine alone can lead to QTc interval prolongation with associated serious ventricular arrhythmia such as torsades de pointes, and sudden death.
Paroxetine should not be used in combination with pimozide.

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Antidepressants