Paroxetine


Full Prescribing Info
Dosage/Direction for Use

Oral
Major depressive disorder
Adult: As paroxetine hydrochloride/mesilate conventional tab; oral susp: 20 mg daily. Dose may be gradually increased in 10 mg increments at intervals of at least 1 week if response is inadequate. Max: 50 mg daily. As paroxetine hydrochloride modified-release tab: Initially, 25 mg daily, may be increased in 12.5 mg daily increments at intervals of at least 1 week according to individual response. Max: 62.5 mg daily. All doses are given as a single daily dose preferably in the morning.
Elderly: As paroxetine hydrochloride/mesilate conventional tab; oral susp: Max: 40 mg daily. As paroxetine hydrochloride modified-release tab: Initially, 12.5 mg daily, may be increased up to 50 mg daily.
Renal impairment:
CrCl (ml/min)Dosage Recommendation
Severe (<30)Use the lower end of the dosage range.
Hepatic impairment:
Use the lower end of the dosage range.

Oral
Obsessive compulsive disorder
Adult: As paroxetine hydrochloride/mesilate conventional tab; oral susp: Initially, 20 mg daily preferably in the morning, may be gradually increased in 10 mg increments at intervals of at least 1 week according to individual response. Usual maintenance: 40 mg daily. Max: 60 mg daily.
Elderly: As paroxetine hydrochloride/mesilate conventional tab; oral susp: Max: 40 mg daily.
Renal impairment:
CrCl (ml/min)Dosage Recommendation
Severe (<30 )Use the lower end of the dosage range.
Hepatic impairment:
Use the lower end of the dosage range.

Oral
Panic disorder with or without agoraphobia
Adult: As paroxetine hydrochloride/mesilate conventional tab; oral susp: Initially, 10 mg daily, may be gradually increased in 10 mg increments at intervals of at least 1 week according to individual response. Recommended maintenance: 40 mg daily. Max: 60 mg daily. As paroxetine hydrochloride modified-release tab: Initially, 12.5 mg daily, may be increased in 12.5 mg daily increments at intervals of at least 1 week according to individual response. Max: 75 mg daily. All doses are given as a single daily dose preferably in the morning.
Elderly: As paroxetine hydrochloride/mesilate conventional tab; oral susp: Max: 40 mg daily. As paroxetine hydrochloride modified-release tab: Initially, 12.5 mg daily, may be increased up to 50 mg daily.
Renal impairment:
CrCl (ml/min)Dosage Recommendation
Severe (<30)Use the lower end of the dosage range.
Hepatic impairment:
Use the lower end of the dosage range.

Oral
Social anxiety disorder
Adult: As paroxetine hydrochloride conventional tab/oral susp: 20 mg daily. Dose may be gradually increased in 10 mg increments if response is inadequate. Max: 50 mg or 60 mg daily. As paroxetine hydrochloride modified-release tab: Initially, 12.5 mg daily, may be increased in 12.5 mg daily increments at intervals of at least 1 week according to individual response. Max: 37.5 mg daily. All doses are given as a single daily dose preferably in the morning.
Elderly: As paroxetine hydrochloride conventional tab/oral susp: Max: 40 mg daily. As paroxetine hydrochloride modified-release tab: Initially, 12.5 mg daily, may be increased up to 37.5 mg daily.
Renal impairment:
CrCl (ml/min)Dosage Recommendation
Severe (<30)Use the lower end of the dosage range.
Hepatic impairment:
Use the lower end of the dosage range.

Oral
Generalised anxiety disorder
Adult: As paroxetine hydrochloride/mesilate conventional tab; oral susp: 20 mg daily preferably in the morning. Dose may be gradually increased in 10 mg increments at intervals of at least 1 week if response is inadequate. Max: 50 mg daily.
Elderly: As paroxetine hydrochloride/mesilate conventional tab; oral susp: Max: 40 mg daily.
Renal impairment:
CrCl (ml/min)Dosage Recommendation
Severe (<30)Use the lower end of the dosage range.
Hepatic impairment:
Use the lower end of the dosage range.

Oral
Posttraumatic stress disorder
Adult: As paroxetine hydrochloride conventional tab/oral susp: Initially, 20 mg daily preferably in the morning, may be gradually increased in 10 mg increments at intervals of at least 1 week according to individual response. Max: 50 mg daily.
Elderly: As paroxetine hydrochloride conventional tab/oral susp: Max: 40 mg daily.
Renal impairment:
CrCl (ml/min)Dosage Recommendation
Severe (<30)Use the lower end of the dosage range.
Hepatic impairment:
Use the lower end of the dosage range.

Oral
Premenstrual dysphoric disorder
Adult: As paroxetine hydrochloride modified-release tab: Initially, 12.5 mg once daily preferably in the morning, may be increased to 25 mg once daily after an interval of at least 1 week if necessary. Doses may be given either continuously (daily throughout the menstrual cycle) or intermittently (during the luteal phase of the menstrual cycle).
Renal impairment:
CrCl (ml/min)Dosage Recommendation
Severe (<30)Use the lower end of the dosage range.
Hepatic impairment: Use the lower end of the dosage range.

Oral
Moderate to severe vasomotor symptoms associated with menopause
Adult: As paroxetine mesilate cap: 7.5 mg once daily preferably at bedtime.

Special Populations:
Pharmacogenomics: Paroxetine is extensively metabolised by CYP2D6 isoenzyme to form glucuronide or sulfate conjugates. CYP2D6 polymorphisms may influence the metabolism, clinical efficacy, and safety of paroxetine. CYP2D6 allele frequencies among individuals of different populations and ethnic backgrounds may be a considering factor that may cause potential uncertainty in genotyping and phenotype predictions. For example, CYP2D6*10 is common in Asians and CYP2D6*17 is common in people of Sub-Saharan African ancestry, while these alleles have considerably lower prevalence in other ethnic groups such as Caucasians of European ancestry. Moreover, Asian populations were also found to carry CYP2D6*14A allele. Thus, the alleles that should be tested may considerably vary for a given population. CYP2D6 ultrarapid metabolisers Carriers of duplications of functional alleles e.g. *1/*1xN, *1/*2xN, *2/*2xN. May have increased paroxetine metabolism as compared with extensive metabolisers, resulting in lower or undetectable plasma levels and increased risk of pharmacotherapy failure. Clinical Pharmacogenetics Implementation Consortium (CPIC) recommends selecting an alternative drug not primarily metabolised or to a lesser extent by CYP2D6 (e.g. citalopram, sertraline). CYP2D6 extensive metabolisers Carriers of 2 normal function alleles, or 2 decreased function alleles, or 1 normal function and 1 no function allele, or 1 normal function and 1 decreased function allele e.g. *1/*1, *1/*2, *1/*4, *1/*5, *1/*9, *1/*41, *2/*2, *41/*41. May have normal paroxetine metabolism. CPIC recommends initiating treatment with the recommended starting dose. CYP2D6 intermediate metabolisers Carriers of 1 decreased function and 1 no function allele e.g. *4/*10, *4/*41, *5/*9. May have reduced paroxetine metabolism as compared with extensive metabolisers, resulting in higher plasma concentrations and increased risk of adverse effects (e.g. insomnia, headache, sexual or gastrointestinal dysfunction). However, CPIC considers initiating treatment with the recommended starting dose. CYP2D6 poor metabolisers Carriers of no functional alleles e.g. *3/*4, *4/*4, *5/*5, *5/*6. May have greatly reduced paroxetine metabolism as compared with extensive metabolisers, resulting in higher plasma concentrations and increased risk of adverse effects (e.g. insomnia, headache, sexual or gastrointestinal dysfunction). CPIC recommends selecting an alternative drug not primarily metabolised by CYP2D6 (e.g. citalopram, sertraline). If paroxetine use is warranted, may consider 50% dose reduction of the recommended initial dose and titrate according to response.
Administration
Paroxetine: May be taken with or without food. May be taken w/ meals to minimise GI upset.
Contraindications
Pregnancy (as paroxetine mesilate cap). Concurrent use with or within 14 days after discontinuation of MAOIs (including linezolid and IV methylene blue). Concomitant use with pimozide, thioridazine.
Special Precautions
Patients with history of suicide-related events or pre-existing suicidal ideation, bipolar disorder, history of mania, pre-existing seizure disorder or conditions predisposing to seizures (e.g. brain damage, alcoholism), narrow-angle glaucoma or history of glaucoma, CV disease (e.g. recent history of MI, unstable heart disease), history of bleeding disorders or other conditions predisposing to bleeding, diabetes mellitus, volume depletion. Paroxetine mesilate cap: Not indicated for the treatment of any psychiatric conditions. Oral susp: Patients with high gastric pH or achlorhydria. Concomitant electroconvulsive therapy. Avoid abrupt withdrawal. Severe renal (CrCl <30 mL/min) and hepatic impairment. Debilitated patients. Elderly. Pregnancy and lactation. CYP2D6 ultrarapid and poor metabolisers. Patient Counselling This drug may impair judgment, thinking or motor skills, if affected, do not drive or operate machinery. Monitoring Parameters Perform pregnancy tests for female patients prior to treatment initiation. Monitor renal function at baseline and as clinically indicated; LFTs, CBC as clinically indicated; serum Na in at-risk patients. Closely monitor for signs and symptoms of serotonin syndrome, clinical worsening, suicidality, or unusual behavioural changes especially at the start of therapy or during dose adjustments.
Adverse Reactions
Significant: Suicidal thoughts and behaviour, worsening of depression, mania or hypomania, akathisia or psychomotor restlessness, seizures, bleeding abnormalities (e.g. ecchymoses, purpura, epistaxis, haematomas, petechiae), anticholinergic effects, bone fractures, mild pupillary dilation, sexual dysfunction (e.g. impotence, ejaculatory disorder), withdrawal symptoms. Rarely, hyponatraemia (primarily in elders). Cardiac disorders: Sinus tachycardia. Rarely, bradycardia. Ear and labyrinth disorders: Tinnitus. Eye disorders: Blurred vision. Gastrointestinal disorders: Nausea, constipation, dry mouth, vomiting, diarrhoea. General disorders and administration site conditions: Asthenia, fatigue, malaise, lethargy. Investigations: Weight gain, increased cholesterol levels, transient changes in blood pressure. Rarely, elevated hepatic enzymes. Metabolism and nutrition disorders: Decreased appetite. Musculoskeletal and connective tissue disorders: Rarely, myalgia, arthralgia. Nervous system disorders: Headache, dizziness, tremor, impaired concentration. Psychiatric disorders: Insomnia, somnolence, agitation, abnormal dreams, aggression. Renal and urinary disorders: Urinary retention or incontinence. Respiratory, thoracic and mediastinal disorders: Yawning. Skin and subcutaneous tissue disorders: Sweating, rashes, pruritus. Vascular disorders: Postural hypotension.
Potentially Fatal: Serotonin syndrome, neuroleptic malignant syndrome (NMS)-like events, haemorrhage (e.g. gastrointestinal or gynaecological haemorrhage). Rarely, anaphylactoid reactions and angioedema.
Overdosage
Symptoms: Somnolence, dizziness, nausea, tremor, tachycardia, confusion, vomiting, fever, involuntary muscle contractions, ECG changes, mydriasis, convulsions, ventricular dysrhythmias, hypertension, aggressiveness, syncope, hypotension, stupor, bradycardia, dystonia, rhabdomyolysis, hepatic dysfunction, manic reactions, myoclonus, acute renal failure, urinary retention, serotonin syndrome and coma. Management: Symptomatic and supportive treatment. Ensure adequate airway, oxygenation, and ventilation. Administer 20-30 g activated charcoal within a few hours of ingestion to decrease absorption. Frequently monitor cardiac rhythm and vital signs.
Drug Interactions
Increased risk of bleeding with aspirin, NSAIDs including COX-2 inhibitors, oral anticoagulants (e.g. warfarin), atypical antipsychotics (e.g. clozapine). May increase risk of hyponatraemia with diuretics. May increase blood glucose levels with pravastatin. May reduce plasma concentration and efficacy of endoxifen (active metabolite of tamoxifen). May reduce absorption of paroxetine oral susp with antacids, histamine H2-receptor antagonists, PPIs. Decreased plasma levels with fosamprenavir/ritonavir. Increased plasma levels of procyclidine, certain TCAs (e.g. clomipramine, nortriptyline, desipramine), phenothiazines (e.g. perphenazine), risperidone, atomoxetine, certain class 1C antiarrhythmics (e.g. propafenone, flecainide), metoprolol. May increase plasma concentrations with cimetidine.
Potentially Fatal: Increased risk of serotonin syndrome with other serotonergic agents (e.g. triptans, TCAs, fentanyl, lithium, tramadol, pethidine, buspirone, amphetamines, tryptophan) and agents which impair metabolism of serotonin (e.g. MAOIs including linezolid, IV methylene blue). Increased plasma levels of thioridazine and pimozide thus increasing the risk of QTc interval prolongation.
Food Interaction
Increased risk of serotonin syndrome with St. John's wort.
Action
Paroxetine selectively inhibits serotonin reuptake from the brain synapse, thereby stimulating serotonin activity in the brain.
Onset: Depression: Within 1 week; Anti-obsessional and anti-panic effects: Up to several weeks.
Absorption: Readily and completely absorbed from the gastrointestinal tract. Increased peak concentration with food. Time to peak plasma concentration: 5.2-8.1 hours (immediate-release tab, susp); 6 hours (range: 3-8 hours [cap]); 6-10 hours (modified-release tab).
Distribution: Widely distributed throughout body tissues. Crosses placenta and enters breast milk. Volume of distribution: 8.7 L/kg (3-28 L/kg). Plasma protein binding: Approx 93-95%.
Metabolism: Undergoes extensive first-pass metabolism in the liver mainly via oxidation and methylation by CYP2D6 isoenzyme to form polar glucuronide and sulfate conjugates.
Excretion: Mainly via urine (approx 64% as metabolites, 2% as unchanged drug); faeces (approx 36% as metabolites, <1% as unchanged drug). Elimination half-life: Approx 21 hours (immediate release tab); 15-20 hours (modified-release tab).
Storage
Oral: Modified-release tab; cap: Store between 20-25°C. Protect from light and humidity. Conventional tab: Store between 15-30°C. Oral susp: Store ≤25°C.
ATC Classification
N06AB05 - paroxetine ; Belongs to the class of selective serotonin reuptake inhibitors. Used in the management of depression.
Disclaimer: This information is independently developed by CIMS based on paroxetine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to CIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, CIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 CIMS. All rights reserved. Powered by CIMSAsia.com
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