Seroxat

Central Nervous System , Drugs / September 22, 2016

Class: Central Nervous System
Dosage Form: Tablets
Description: Antidepressant serotonergic agent
Stock: Available
Manufacturer: GlaxoSmithKline (GSK)

Composition:

Paroxetine hydrochloride…………12.5 and 25 mg

Properties:

Pharmacodynamics
Paroxetine is a potent and selective inhibitor of serotonin (5 hydroxytryptamine, 5-HT) re-uptake and its antidepressant action and efficacy in the treatment of OCD and panic disorder is thought to be related to its specific inhibition of serotonin re-uptake in brain neurons.
Paroxetine is chemically unrelated to the tricyclic, tetracyclic and other available antidepressants.
The principal metabilites of paroxetine are polar and conjugated products of oxidation and methylation, which are readily cleared. In view of their lack of pharmacological activity, it is most unlikely that they contribute to the therapeutic effects of Seroxat.
Long-term treatment with Seroxat has shown that antidepressant efficacy is maintained for periods of at least one year.
In a placebo-controlled trial, the efficacy of Seroxat in the treatment of panic disorder has been maintained for at least one year.

Pharmacokinetics
Paroxetine is well absorbed after oral dosing and undergoes first-pass metabolism.
The elimination half-life is variable but is generally about one day. Steady state systemic levels are attained by seven to 14 days after starting treatment and pharmacokinetics do not appear to change during long-term therapy.

Indications:

Seroxat is indicated in treatment of:

  • Symptoms of depressive illness of all types including reactive and severe depression and depression accompanied by anxiety. Following an initial satisfactory response, continuation with Seroxat therapy is effective in preventing relapse of depression.
  • Symptoms and prevention of relapse of Obsessive Compulsive Disorder (OCD)
  • Symptoms and prevention of relapse of Panic Disorder with or without agoraphobia.
  • Social Anxiety Disorder/Social Phobia

Contraindicatons:

Seroxat is contraindicated in:

 

  • Known hypersensitivity to Seroxat
  • Monoamine Oxidase Inhibitors (MAOIs): As with most anti-depressants, Seroxat should not be used in combination with MAOIs or within two weeks of terminating treatment with MAOIs. Thereafter treatment should be initiaited cautiously and dosage increased gradually util optimal response is reached. MAOIs should not be introduced within two weeks of cessation of therapy with Seroxat.
  • History of Mania: As with all anti-depressants, Seroxat should be used with caution in patients with a history of mania.
  • Oral anticoagulants: Seroxat should be administered with great caution to patients receiving oral anticoagulants (see ‘Interactions’).
  • Tryptophan: As adverse experiences have been reported when tryptophan was administered with another selective serotonin re-uptake inhibitor (SSRI), Seroxat should not be used in combination with tryptophan medication (‘see Interactions’).
  • Cardiac Conditions: As with all psychoactive drugs, caution is advised when treating patients with cardiac conditions.
  • Epilepsy: As with other antidepressants, Seroxat should be used with caution in patients with epilepsy.
  • Seizures: Overall, the incidence of seizures is <0.1% in patients treated with Seroxat. Seroxat should be discontinued in any patients who develops seizures.
  • Glaucoma: As with other SSRIs, Seroxat infrequently caused mydriasis and should be used with caution in patients with narrow angle galucoma.
  • Electroconvulsive therapy (ECT): There is little clinical experience of the concurrent administration of Seroxat with ECT. However, there have been rare reports of prolonged ECT-induced seizures and/or secondary seizures in patients on SSRIs.
  • Neuroleptics: Seroxat should be used with caution in patients already receiving  neuroleptics, since symptoms suggestive of Neuroleptic Malignant Syndrome have been reported with this combination.
  • Worsening depression, suicidal ideation and the possibility of suicide is inherent in patients suffering from depressive illness. Patients should therefore be closely monitored during treatment until significant remission occurs.
  • Hyponataraemia has been reported rarely, predominantly in the elderly. The hyponatraemia generally reverses on discontinuation of paroxetine.
  • Seroxat suspension contains methyl and propyl parahydroxybenzoate.
  • Skin and mucous membrane bleeding has been reported following treatment with Seroxat. Seroxat should therefore be used with caution in patients concomitantly treated with drugs that give an increased risk of bleeding, and in patients with a known tendency for bleeding or those with predisposing conditions.

 

Drug Interactions:

The following interactions are to be noted:

 

  • Monoamine Oxidase Inhibitors (MAOIs): As with most anti-depressants, Seroxat should not be used in combination with MAOIs or within two weeks of terminating treatment with MAOIs. Thereafter treatment should be initiaited cautiously and dosage increased gradually util optimal response is reached. MAOIs should not be introduced within two weeks of cessation of therapy with Seroxat.
  • Tryptophan: As adverse experiences have been reported when tryptophan was administered with another selective serotonin re-uptake inhibitor (SSRI), Seroxat should not be used in combination with tryptophan medication (‘see Interactions’).
  • Oral anticoagulants: Seroxat should be administered with great caution to patients receiving oral anticoagulants (see ‘Interactions’).
  • Neuroleptics: Seroxat should be used with caution in patients already receiving  neuroleptics, since symptoms suggestive of Neuroleptic Malignant Syndrome have been reported with this combination.
  • Food/antacids: The absorption and pharmacokinetics of Seroxat are not affected by food or antacids.
  • MAOIs/tryptophan/other SSRIs: Co-administration with serotonergic drugs (e.g. MAOIs, tryptophan, other SSRIs) may lead to high incidence of serotonin-associated effects. Symptoms have included agitiation, confusion, diaphoresis, hallucinations, hyper-reflexia, mycoclonus, shivering, tachycardia and tremor.
  • Drug metabolizing enzyme inducers/inhibitors:The metabolism and pharmacokinetics of Seroxat may be affected by drugs which incude or inhibit hepatic drug metabolising enzymes. When Seroxat is to be co-administered with a known drug metabolising inhibitor, consideration should be given to using doses at the lower end of the range. No initial dosage adjustment of Seroxat is considered necessary when it is to be co-adminiseterd with known drug metabolising enzyme inducers. Any subsequent dosage adjustment should be guided by clinical effect (tolerability and efficacy).
  • Alcohol: Although Seroxat does not increase the impairment of mental and motor skills caused by alcohol, the concomitant use of Seroxat and alcohol in patient is not advised.
  • Haloperidol/amylobarbitone/oxazepam: Experience in a limited number of healthy subjects has shown that Seroxat did not increase the sedation and drowsiness associated with haloperidol, amylobarbitone or oxazepam when given in combination.
  • Lithium: Studies in depressed patients stabilised on lithium have not demonstrated any pharmacokinetic interaction between Seroxat and lithium. However, since experience is limited, the concurrent administration of Seroxat and lithium should be undertaken with caution. Lithium levels should be monitored.
  • Phenytoin/anticonvulsants: Co-administration of Seroxat with phenytoin is associated with decreased plasma concentrations of paroxetine adn increased adverse experiences. No initial dosage adjustment of Seroxat is considered necessary when these drugs are co-administered; any subsequent dosage adjustement should be guided by clinical effect. Co-administration of Seroxat with other anticonvulsants may also be associated with an increased incidence of adverse experiences.
  • Warfarin/ora anticoagulants: A pharmacodynamic interaction between Seroxat and warfarin may exist. This may result in changes in the prothrombin time and increased bleeding. Seroxat should therefore be administered with great caution to patietnts receiving oral anticoagulants.
  • Tricyclic antidepressants: The effects of the concomitant administration of Seroxat with tricylic antidepressants have not been studied. The concomintant use of Seroxat with these drugs should therefore be approached with caution.
  • Procyclidine: Seroxat can significantly increase the plasma levels of procyclidine. The dose of procylcidine should be reduced if anticholinergic effects are seen.
  • P450 isoenzymes: As with other antidepressants, including other SSRIs, paroxetine inhibits hepatic cytochrome P450 enzyme CYP2D6. Inhibition of CYP2D6 may lead to increased plasma concentrations of co-administered drugs metabloised by this enzyme. These include certain tricyclic antidepressants (e.g. amitriptyline, nortriptyline, imipramine and desipramine), phenothiazine neruoleptics (e.g. perphenazine and thioridazine) and type 1C antiarrhythmics (e.g. propafenone and flecainide).

 

Side Effects:

In controlled clinical trials the most commonly observed adverse events associated with the use of Seroxat were: nausea, somnolence, sweating, tremor, asthenia, dry mouth, insomnia, sexual dysfunction (including impotence and ejaculation disorders) dizziness, constipation, diarrhea and decreased appetite. Adverse experiences may decrease in intensity and frequency with continued treatment and do not generally lead to cessation of therapy.
In addition, during clinical use of Seroxat there have been reports of the following:

  • Nervous System: Hallucinations, hypomania and restlessness have been reported in addition to Serotonergic Syndrome. As with other SSRIs confusion has also been reported. Occasional reports of extrapyramidal reactions, including orofacial dystonia have been received. Sometimes these have occurred in patients with underlying movement disorders of who were taking neuroleptic medication. There have been rare reports of convulsions. Neuroleptic malignant syndrome (usually in patients on concomitant or recently discontinued neurolpetic medication) has also been reported rarely.
  • Digestive System: There have been reports of vomiting. Elevation of hepatic enzymes has been reported. Hepatic events (such as hepatitis, sometimes associated with jaundice, and/or liver failure) have been reported very rarely. Discontinuation of SEROXAT should be considered if there is prolonged elevation of liver function test results.
  • Skin and appendages: There have been very rare reports of allergic reactions (such as angioedema, urticaria and skin rashes and photosensitivity reactions.
  • Metabolic/endocrine: Hyponatraemia has been reported rarely, predominantly in the elderly and may be associated with the syndrome of inappropriate anti-diuretic hormone secretion (SIADH). The hyponatraemia generally reverses on discontinuation of Seroxat. There have been rare reports of symptoms suggestive of hyperprolactinaemia/galactorrhoea.
  • Cardiovascular: As with other SSRIs, transient changes in blood pressure have been reported, usually in patients with pre-existing hypertension or anxiety. Tachycardia has been reported rarely.
  • Haematological: Rarely, abnormal bleeding, predominantly of the skin and mucous membranes (mostly ecchymosis), has been reported following Seroxat treatment. Thrombocytopenia has been reported rarely.
  • Other: There have been rare reports of acute glaucoma, urinary retention and peripheral edema.

Seroxat is less likely that tricyclic antidepressants to be associated with dry mouth, constipation and somnolence.
Symptoms including dizziness, sensory disturbances (e.g. paraestheisa), anxiety, sleep disturbances (including intense dreams), agitations, tremor, nausea, sweating and confusion have been reported following abrupt discontinuation of Seroxat. They are usually self-limiting and symptomatic treatment is seldom warranted. No particular patient group appears to be at higher risk of these symptoms; it is therefore recommended that when antidepressant treatment is no longer required, gradual discontinuation by dose-tapering or alternate day doing be considered.
Manic reactions have been reported rarely.
Blurred vision has been reported rarely.

Dosage and Administration:

For oral administration.
It is recommended that Seroxat be administered once daily in the morning with food.
The tablets should be swallowed rather than chewed.
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 should be treated for a sufficient period to ensure that they are free from symptoms. This period may be several months for depression and may be even longer for OCD and panic disorder. As with many psychoactive medications, abrupt discontinuation should be avoided (see ‘undesirable effects’).

1. Adults:
a) Depression:

  • The recommended dose is 20 mg daily
  • In some patients it may be necessary to increase the dose
  • This should be done gradually by 10 mg increments to a maximum of 50 mg according to the patient’s response

b) Obsessive Compulsive Disorder:

  • The recommended dose is 40 mg daily
  • Patients should start on 20 mg daily and the dose may be increased weekly in 10 mg increments
  • Some patients will benefit from having their dose increased up to a maximum of 60 mg daily

c) Panic Disorder:

  • The recommended dose is 40 mg daily
  • Patients should be started on 10 mg daily and the dose increased weekly in 10 mg increments according to the patient’s response
  • Some patients may benefit from having their dose increased up to a maximum of 50 mg daily
  • As is generally recognized, there is the potential worsening of a panic symptomatology during early treatment of panic disorder; a low initial starting dose is therefore recommended

d) Social Anxiety Disorder:

  • The recommended dose is 20 mg daily
  • Patients not responding to a 20 mg dose may benefit from dose increases in 10 mg increments as required, up to a maximum of 50 mg /day
  • Dose changes should occur at intervals of at least 1 week.

2. Elderly:

  • Increased plasma concentrations of paroxetine occur in elderly subjects
  • Dosing should commence at the adult starting dose and may be increased weekly in 10 mg increments to a maximum of 40 mg daily according to the patient’s response

3. Children:
The use of Seroxat in children is not recommended as safety and efficacy have not been established in this population.

4. Renal Hepatic Impairment:
Increase plasma concentrations of paroxetine occur in patients with severe renal impairment (creatinine clearance <30 ml/min) or severe hepatic impairment. The recommended dose is 20 mg daily, incremental dosage, if required, should be restricted to the lower end of the range.

Overdosage:

A wide margin if safety is evident from available data. Overdose attempts have been reported in patients who took up to 2000 mg alone or in combination with other drugs, including alcohol. Experience of Seroxat in overdosage has shown symptoms including nausea, vomiting, tremor, dilated pupils, dry mouth, irritability, sweating, somnolence, fever, blood pressure changes, headache, involuntary muscle contractions, agitation, anxiety and tachycardia, but not convulsions.
Events such as coma or ECG changes have occasionally been reported and very rarely a fatal outcome, but generally when Seroxat was taken in conjunction with other psychotropic drugs, with or without alcohol.
No specific antidote is known.
Treatment should consist of those general measures employed in management of overdose with any antidepressant. Early administration of activated charcoal may delay the absorption of Seroxat.

Pregnancy and Lactation:

Although animal studies have not shown any teratogenic or selective embryotoxic effects, the safety of SEROXAT in human pregnancy has not been established and it should not be used during pregnancy or by nursing mothers unless the potential benefit outweighs the possible risk.

Warnings:

Clinical experience has shown that therapy with Seroxat 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.

Packaging:

Pack of 3 strips of 10 tablets each.

Storage:

Store in a dry place at a temperature not exceeding 30°C.

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