Seroxat

/ GSK

It is recommended that Paroxetine is administered once daily in the morning with food. The tablet should be swallowed whole.
Depressive disorder
Adults: The recommended dose is 20 mg daily. 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 according to the patient’s response. As with all antidepressant drugs, dosage should be reviewed and adjusted if necessary within 2 to 3 weeks of initiation of therapy and thereafter as judged clinically appropriate. Patients with depression should be treated for a sufficient period to ensure that they are free from symptoms. This period may be several months.
Obsessive compulsive disorder
Adults: The recommended dose is 40 mg daily. Patients should start on 20 mg and the dose can be increased weekly in 10 mg increments. Some patients will benefit from having their dose increased up to a maximum of 60 mg/day. Patients with OCD should be treated for a sufficient period to ensure that they are free from symptoms. This period may be several months or even longer.
Panic disorder
Adults: The recommended dose is 40 mg daily. Patients should be started on 10mg/day and the dose increased weekly in 10 mg increments according to patient’s response. Some patients may benefit from having their dose increased up to a maximum of 60 mg/day. A low initial starting dose is recommended to minimise the potential worsening of panic symptomatology, which is generally recognised to occur early in the treatment of this disorder.Patients with panic disorder should be treated for a sufficient period to ensure that they are free from symptoms. This period may be several months or even longer.
Social Phobia
Adults: 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.
Generalised Anxiety Disorder
Adults: 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.
Post-traumatic stress disorder
Adults: 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.
General Information
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.
Populations
Elderly: Increased plasma concentrations of paroxetine occur in elderly subjects, but the range of concentrations overlaps with that observed in younger subjects. Dosing should commence at the adult starting dose and may be increased up to 40 mg daily.
Children and adolescents (<18 years): Paroxetine is not indicated for use in children or adolescents aged <18 years.
Renal/hepatic impairment: Increased plasma concentrations of paroxetine occur in patients with severe renal impairment (creatinine clearance less than 30 ml/min) or in those with hepatic impairment. Therefore, dosage should be restricted to the lower end of the dosage range.

Treatment of (in adults):
– Major Depressive Disorder
– Obsessive Compulsive Disorder (OCD)
– Panic Disorder with and without agoraphobia
– Social Anxiety Disorders/Social phobia
– Generalised Anxiety Disorder
– Post-Traumatic Stress Disorder

Known hypersensitivity to paroxetine and excipients. Paroxetine should not be used in combination with monoamine oxidase (MAO) inhibitors (including linezolid, an antibiotic which is a reversible non-selective MAO inhibitor and methylthioninium chloride (methylene blue)) or within 2 weeks of terminating treatment with MAO inhibitors. Likewise, MAO inhibitors should not be introduced within 2 weeks of cessation of therapy with paroxetine. 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.

Treatment with paroxetine should be initiated cautiously two weeks after terminating treatment with an irreversible MAOI or 24 hours after terminating treatment with a reversible MAO inhibitor. Dosage of paroxetine should be increased gradually until an optimal response is reached.
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 paroxetine 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.
Close supervision of patients and in particular those at high risk should accompany medicinal product 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 paroxetine has been associated with the development of akathisia, which is characterized 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. In patients who develop these symptoms, increasing the dose may be detrimental.
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 medicinal products. As these syndromes may result in potentially life-threatening conditions, treatment with paroxetine should be discontinued if such events 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: As with all antidepressants, paroxetine should be used with caution in patients with a history of mania. Paroxetine should be discontinued in any patient entering a manic phase.
Renal/hepatic impairment: Caution is recommended in patients with severe renal impairment or in those with hepatic impairment.
Diabetes: In patients with diabetes, treatment with an SSRI may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted. Additionally, there have been studies suggesting that an increase in blood glucose levels may occur when paroxetine and pravastatin are co-administered.
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 medicinal product should be discontinued in any patient who develops seizures.
Electroconvulsive therapy (ECT): There is little clinical experience of the concurrent administration of paroxetine with ECT.
Glaucoma As with other SSRIs, paroxetine can cause mydriasis and should be used with caution in patients with narrow angle glaucoma or history of glaucoma.
Cardiac Conditions: The usual precautions should be observed in patients with cardiac conditions.
QT Prolongation: Cases of QT interval prolongation have been reported during the post-marketing period.
Paroxetine should be used with caution in patients with a (family) history of QT interval prolongation, concomitant use of anti-arrhythmic medications or other medications that may potentially prolong QT interval, relevant pre-existing cardiac disease such as heart failure, ischaemic heart disease, heart block or ventricular arrhythmias, bradycardia, and hypokalaemia or hypomagnesemia.
Hyponatraemia: Hyponatraemia has been reported rarely, predominantly in the elderly. Caution should also be exercised in those patients at risk of hyponatraemia e.g. from concomitant medications and cirrhosis. The hyponatraemia generally reverses on discontinuation of paroxetine.
Haemorrhage: There have been reports of cutaneous bleeding abnormalities such as ecchymoses and purpura with SSRIs. Other haemorrhagic manifestations e.g. gastrointestinal and gynaecological haemorrhage have been reported. Elderly patients may be at an increased risk for non-menses related events of bleeding
SSRIs/SNRIs may increase the risk of postpartum haemorrhage.
Caution is advised in patients taking SSRIs concomitantly with oral anticoagulants, medicinal products known to affect platelet function or other medicinal products that may increase risk of bleeding (e.g. atypical antipsychotics such as clozapine, phenothiazines, most TCAs, acetylsalicylic acid, NSAIDs, COX-2 inhibitors) as well as in patients with a history of bleeding disorders or conditions which may predispose to bleeding.
Interaction with tamoxifen: Paroxetine, a potent inhibitor of CYP2D6, may lead to reduced concentrations of endoxifen, one of the most important active metabolites of tamoxifen. Therefore, paroxetine should whenever possible be avoided during tamoxifen treatment.
Withdrawal symptoms seen on discontinuation of paroxetine treatment: Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt. The occurrence of withdrawal symptoms is not the same as the drug being addictive or dependence producing.
The risk of withdrawal symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction.
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 two weeks, though in some individuals they may be prolonged (two-three 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.
Sexual dysfunction: SSRIs may cause symptoms of sexual dysfunction. There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation of SSRIs.
See prescribing information for full details.

Very common: Nausea, sexual dysfunction.
Common: Increases in cholesterol levels, decreased appetite, somnolence, insomnia, agitation, abnormal dreams (including nightmares), dizziness, tremor, headache, blurred vision, yawning, constipation, diarrhoea, vomiting, dry mouth, sweating, asthenia, body weight gain.
See prescribing information for full details.

Serotonergic medicinal products: As with other SSRIs, co-administration with serotonergic medicinal products may lead to an incidence of 5-HT associated effects. Caution should be advised and a closer clinical monitoring is required when serotonergic medicinal products (such as L-tryptophan, triptans, tramadol, linezolid, methylthioninium chloride (methylene blue), SSRIs, lithium, pethidine, buprenorphine, and St. John’s Wort – Hypericum perforatum – preparations) are combined with paroxetine. Caution is also advised with fentanyl used in general anaesthesia or in the treatment of chronic pain. Concomitant use of paroxetine and MAOIs is contraindicated because of the risk of serotonin syndrome.
Pimozide: Increased pimozide levels of on average 2.5 times have been demonstrated in a study of a single low dose pimozide (2 mg) when co-administered with 60 mg paroxetine. Due to the narrow therapeutic index of pimozide and its known ability to prolong QT interval, concomitant use of pimozide and paroxetine is contraindicated.
Medicinal products that prolong the QT interval: The risk of QTc prolongation and/or ventricular arrhythmias (e.g. TdP) may be increased with concomitant use of other medicinal products which prolong the QTc interval (e.g. some antipsychotics). Concomitant use of thioridazine and paroxetine is contraindicated, because, as with other medicinal products which inhibit the hepatic enzyme CYP450 2D6, paroxetine can elevate plasma levels of thioridazine which can prolong QT interval.
Drug metabolising enzymes: 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 paroxetine doses at the lower end of the range.
No initial dosage adjustment is considered necessary when the medicinal product is to be co-administered with known drug metabolising enzyme inducers (e.g. carbamazepine, rifampicin, phenobarbital, phenytoin) or with fosamprenavir/ritonavir. Any paroxetine dosage adjustment (either after initiation or following discontinuation of an enzyme inducer) should be guided by clinical effect (tolerability and efficacy).
Neuromuscular Blockers: SSRIs may reduce plasma cholinesterase activity resulting in a prolongation of the neuromuscular blocking action of mivacurium and suxamethonium.
Fosamprenavir/ritonavir: Co-administration of fosamprenavir/ritonavir 700/100 mg twice daily with paroxetine 20 mg daily in healthy volunteers for 10 days significantly decreased plasma levels of paroxetine by approximately 55%. The plasma levels of fosamprenavir/ritonavir during co-administration of paroxetine were similar to reference values of other studies, indicating that paroxetine had no significant effect on metabolism of fosamprenavir/ritonavir. There are no data available about the effects of long-term co-administration of paroxetine and fosamprenavir/ritonavir exceeding 10 days.
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.
CYP2D6 inhibitory potency of paroxetine: As with other antidepressants, including other SSRIs, paroxetine inhibits the hepatic cytochrome P450 enzyme CYP2D6. Inhibition of CYP2D6 may lead to increased plasma concentrations of co-administered medicinal products metabolised by this enzyme. It is not recommended to use paroxetine in combination with metoprolol when given in cardiac insufficiency, because of the narrow therapeutic index of metoprolol in this indication.
Pharmacokinetic interaction between CYP2D6 inhibitors and tamoxifen, showing a 65-75% reduction in plasma levels of one of the more active forms of tamoxifen, i.e. endoxifen, has been reported in the literature. Reduced efficacy of tamoxifen has been reported with concomitant usage of some SSRI antidepressants in some studies. As a reduced effect of tamoxifen cannot be excluded, co-administration with potent CYP2D6 inhibitors (including paroxetine) should whenever possible be avoided.
Alcohol: As with other psychotropic medicinal products patients should be advised to avoid alcohol use while taking paroxetine.
Oral anticoagulants: A pharmacodynamic interaction between paroxetine and oral anticoagulants may occur. Concomitant use of paroxetine and oral anticoagulants can lead to an increased anticoagulant activity and haemorrhagic risk. Therefore, paroxetine should be used with caution in patients who are treated with oral anticoagulants.
NSAIDs and acetylsalicylic acid, and other antiplatelet agents:
Concomitant use of paroxetine and NSAIDs/acetylsalicylic acid can lead to an increased haemorrhagic risk. Caution is advised in patients taking SSRIs, concomitantly with oral anticoagulants, medicinal products known to affect platelet function or increase risk of bleeding (e.g. atypical antipsychotics such as clozapine, phenothiazines, most TCAs, acetylsalicylic acid, NSAIDs, COX-2 inhibitors) as well as in patients with a history of bleeding disorders or conditions that may predispose to bleeding.
Pravastatin: An interaction between paroxetine and pravastatin has been observed in studies suggesting that co-administration of paroxetine and pravastatin may lead to an increase in blood glucose levels. Patients with diabetes mellitus receiving both paroxetine and pravastatin may require dosage adjustment of oral hypoglycaemic agents and/or insulin.
See prescribing  information for full details.

Pregnancy: Some epidemiological studies suggest an increased risk of congenital malformations, particularly cardiovascular (e.g. ventricular and atrial septum defects) associated with the use of paroxetine during the first trimester. The mechanism is unknown. The data suggest that the risk of having an infant with a cardiovascular defect following maternal paroxetine exposure is less than 2/100 compared with an expected rate for such defects of approximately 1/100 in the general population.
Paroxetine should only be used during pregnancy when strictly indicated. The prescribing physician will need to weigh the option of alternative treatments in women who are pregnant or are planning to become pregnant. Abrupt discontinuation should be avoided during pregnancy.
Observational data indicated an increased risk (less than 2-fold) of postpartum haemorrhage following SSRI/SNRI exposure within the month prior to birth.
Neonates should be observed if maternal use of paroxetine continues into the later stages of pregnancy, particularly the third trimester.
Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may have an increased risk of persistent pulmonary hypertension of the newborn (PPHN). The observed risk was approximately five cases per 1000 pregnancies. In the general population one to two cases of PPHN per 1000 pregnancies occur.
Lactation: Small amounts of paroxetine are excreted into breast milk. In published studies, serum concentrations in breast-fed infants were undetectable (<2 nanograms/mL) or very low (<4 nanograms/mL), and no signs of drug effects were observed in these infants. Since no effects are anticipated, breast-feeding can be considered.
See prescribing  information for full details.

Symptoms and Signs: A wide margin of safety is evident from available overdose information on paroxetine. Experience of paroxetine in overdose has indicated that, in addition to those symptoms mentioned under ‘Adverse Reactions’, fever, blood pressure changes, involuntary muscle contractions, anxiety and tachycardia have been reported. Patients have generally recovered without serious sequelae even when doses of up to 2000 mg have been taken alone. Events such as coma or ECG changes have occasionally been reported and, very rarely a fatal outcome, but generally when paroxetine was taken in conjunction with other psychotropic drugs, with or without alcohol.
Treatment: No specific antidote is known. The treatment should consist of those general measures employed in the management of overdose with any antidepressant. Where Supportive care with frequent monitoring of vital signs and careful observation is indicated. Patient management should be as clinically indicated, or as recommended by the national poisons centre, where available.

Storage: Do not store above 30°C. Store in the original package in order to protect from light.