Paroxetine Hydrochloride

• Social anxiety disorder

Paroxetine  is indicated in: Major Depressive Disorder Obsessive Compulsive Disorder Panic Disorder Social Anxiety Disorder Generalized Anxiety Disorder Posttraumatic Stress Disorder.

N/A

Concomitant use in patients taking either monoamine oxidase inhibitors (MAOIs) or thioridazine is contraindicated. This is contraindicated in patients with a hypersensitivity to Paroxetine.

The efficacy of Paroxetine is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5 HT). Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. In vitro radioligand binding studies indicate that paroxetine has little affinity for muscarinic, alpha1, alpha2, beta adrenergic, dopamine (D2), 5-HT1, 5 HT2 and histamine (H1)-receptors; antagonism of muscarinic, histaminergic and alpha1-adrenergic receptors has been associated with various anticholinergic, sedative and cardiovascular effects for other psychotropic drugs. Because the relative potencies of paroxetine’s major metabolites are at most 1/50 of the parent compound, they are essentially inactive.

Food/antacids: The absorption and pharmacokinetics of Paroxetine are not affected by food or antacids.Tryptophan: As with other 5-HT re uptake inhibitors, animal studies indicate that an interaction between Paroxetine and Tryptophan may occur, resulting in a ‘serotonin syndrome’ suggested by a combination of agitation, restlessness and gastrointestinal symptoms including diarrhoea. Drug metabolizing enzyme inducers /inhibitors: The metabolism and pharmacokinetics of Paroxetine may be affected by drugs, which induce or inhibit hepatic drug metabolizing enzymes. When Paroxetine is to be coadministered with a known drug metabolizing inhibitor, consideration should be given to using doses at the lower end of the range. No initial dosage adjustment of Paroxetine is considered necessary when it is to be co-administered with known drug metabolizing enzyme inducers. Any subsequent dosage adjustment should be guided by clinical effect (tolerabilityand efficacy).Alcohol: Although Paroxetine does not increase the impairment of mental and motor skill caused by alcohol, the concomitant use of Paroxetine and alcohol in depressed patients is not advised.Haloperidol/amylobarbitone/oxazepam: Experience in a limited number of healthy subjects has shown that Paroxetine did not increase the sedation and drowsiness associated with haloperidol, amylobarbitone or oxazepam when given in combination.MAOls: As with other 5-HT re uptake inhibitors, animal studies indicate that an interaction between Paroxetine and monoamine oxidase (MAO) inhibitors may occur.Lithium: Since there is little clinical experience, and there have been reports of interaction of lithium with other 5-HT re-uptake inhibitors, the concurrent administration of Paroxetine and lithium should be undertaken with caution.Lithium levels should be monitored. Phenytoin / anticonvulsants: Co-administration of Paroxetine and phenytoin is associated with decreased plasma concentrations of Paroxetine and increased adverse experiences. Co-administration of Paroxetine with other anticonvulsants may also be associated with an increased incidence of adverse experiences.Warfarin: Preliminary data suggest that there may be a pharmacodynamic interaction between Paroxetine and warfarin, which may result in increased bleeding in the presence of unaltered prothrombin times. Paroxetine should therefore be administered with great caution to patients receiving oral anticoagulants.

Major depressive disorder: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance and other male genital disorders.Obsessive compulsive disorder: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence and abnormal ejaculation.Panic disorder: Asthenia, sweating, decreased appetite, decreased libido , tremor, abnormal ejaculation, female genital disorders and impotence.Social anxiety disorder: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, decreased libido, yawn, abnormal ejaculation, female genital disorders and impotence.Generalised anxiety disorder: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, decreased libido, somnolence, tremor, sweating and abnormalejaculation.Post-traumatic stress disorder: Asthenia, sweating nausea, dry mouth, diarrhoea, decreased appetite, somnolence, decreased libido, abnormal ejaculation, female genital disorders and impotence.

This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Labor and Delivery: The effect of Paroxetine on labor and delivery in humans is unknown.Nursing Mothers: Like many other drugs, Paroxetine is secreted in human milk, and caution should be exercised when Paroxetine hydrochloride is administered to a nursing woman.

Cardiac conditions: Paroxetine does not produce clinically significant changes in blood pressure, heart rate and ECG. Nevertheless, as with all psychoactive drugs, caution is advised when treating patients with cardiac conditions.Epilepsy: As with other antidepressants, Paroxetine should be used with caution in-patients with epilepsy.Seizures: Overall, the incidence of seizures is < 0.1% in patients treated with Paroxetine. Paroxetine should be discontinued in any patient who develops seizures.ECT: There is little clinical experience of concurrent administration of Paroxetine with ECT.Ability to drive/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.Discontinuation of Treatment with Paroxetine: Recent clinical trials supporting the various approved indications of Paroxetine employed a taper phase regimen, rather than an abrupt discontinuation of treatment. The taper phase regimen used in GAD and PTSD clinical trials involved an incremental 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 1 week before treatment was stopped.

Dosage for Elderly or Debilitated, and Patients with Severe Renal or Hepatic Impairment: The recommended initial dose is 10 mg/day for elderly patients, debilitated patients, and/or patients with severe renal or hepatic impairment. Increases may be made if indicated. Dosage should not exceed 40 mg/day.