Class: SSRI Paroxetine Hydrochloride
- Tablets 10 mg
- Tablets 20 mg
- Tablets 30 mg
- Tablets 40 mg
- Suspension, oral 10 mg per 5 mL
- Tablets, controlled-release 12.5 mg
- Tablets, controlled-release 25 mg
- Tablets, controlled-release 37.5 mg
- Tablets 10 mg
- Tablets 20 mg
- Tablets 30 mg
- Tablets 40 mg
CO Paroxetine (Canada)
Sandoz Paroxetine (Canada)
Blocks reuptake of serotonin, enhancing serotonergic function.
Completely absorbed. Steady state is 10 days (hydrochloride; immediate release [IR]), 13 days (mesylate), 2 wk (controlled release [CR]). C max is 61.7 ng/mL (hydrochloride; IR), 81.3 ng/mL (mesylate), 30 ng/mL (CR). T max is 5.2 h (hydrochloride; IR), 8.1 h (mesylate), 6 to 10 h postdose (CR). Food increased AUC 6% and C max 29%, while T max decreased from 6.4 h postdosing to 4.9 h.
Distributes throughout the body, including CNS; only 1% remains in plasma. Protein binding is 93% to 95%.
Extensive first-pass metabolism in liver by CYP-450 2D6. Principal metabolites are polar and conjugated products of oxidation and methylation.
64% of dose excreted in urine (2% as parent compound, 62% as metabolites); 36% excreted in feces (mostly as metabolites). The t ½ is 21 h (hydrochloride; IR), 33.2 h (mesylate), 15 to 20 h (CR).
1 to 4 wk (antidepressant effects).
Special PopulationsRenal Function Impairment
Mean plasma concentrations increased approximately 4 times, with CrCl below 30 mL/min. Plasma concentrations increased 2-fold with CrCl 30 to 60 mL/min. Reduce dose in these patients.Hepatic Function Impairment
2-fold increase in plasma concentrations; dose reduction may be necessary.Elderly
Minimum concentrations were 70% to 80% greater. Reduce initial dosage.
Indications and Usage
Major depressive disorder (MDD); panic disorder; social anxiety disorder (except Pexeva ).IR only
Obsessive-compulsive disorder (OCD); generalized anxiety disorder (GAD) (except Pexeva ); posttraumatic stress disorder (PTSD) (except Pexeva ).CR only
Premenstrual dysphoric disorder (PMDD).
Concomitant use in patients taking MAOIs, pimozide, or thioridazine; hypersensitivity to paroxetine or any of the inactive ingredients.
Dosage and AdministrationGAD/PTSD
PO 20 mg/day as a single dose with or without food, usually in the morning. May increase dose by 10 mg/day at intervals of 7 days. Usual range is 20 to 50 mg/day.MDD
PO 20 mg/day initially; may increase by 10 mg/day at intervals of at least 7 days (max, 50 mg/day). Administer as single daily dose, usually in morning.CR
PO 25 mg/day as a single dose, usually in the morning (usual dose range, 25 to 62.5 mg/day). May increase dose in increments of 12.5 mg/day at intervals of at least 7 days (max, 62.5 mg/day).OCD
PO 20 mg/day initially; recommended dose is 40 mg/day. May increase dose by 10 mg/day at intervals of at least 7 days (max, 60 mg/day). Administer as single daily dose, usually in morning.Panic Disorder
PO 10 mg/day initially; recommended dose is 40 mg/day. May increase dose by 10 mg/day at intervals of at least 7 days (max, 60 mg/day). Administer as single daily dose, usually in morning.CR
PO 12.5 mg/day as a single dose, usually in the morning. May increase dose in increments of 12.5 mg/day at intervals of at least 7 days (max, 75 mg/day).PMDD
PO 12.5 mg/day initially, usually in the morning; change doses at intervals of at least 7 days; usual range is 12.5 to 25 mg/day. May be administered either daily throughout the menstrual cycle or limited to the luteal phase of the menstrual cycle.Social Anxiety Disorder
PO 20 mg/day as a single daily dose, usually in the morning. Usual range is 20 to 60 mg/day.CR
PO 12.5 mg initially, usually in the morning. Usual range is 12.5 to 37.5 mg/day. May increase dose in increments of 12.5 mg/day at intervals of at least 7 days (max, 37.5 mg/day).Dosage Adjustment in Elderly, Debilitated, or Severe Renal or Hepatic Function Impairment
PO 10 mg/day initially; do not exceed 40 mg/day.CR
PO 12.5 mg/day initially; do not exceed 50 mg/day.
- Administer without regard to meals but with food if GI upset occurs.
- CR tablets should be swallowed whole. Do not crush, chew, divide, or break tablets.
- Shake suspension well before measuring dose. Use dosing cup or spoon to measure and administer dose.
Store paroxetine hydrochloride IR tablets, oral suspension, and CR tablets at or below 77°F. Store Pexeva tablets at 59° to 86°F.
Drug Interactions5-HT 1 agonists (eg, naratriptan, sumatriptan, zolmitriptan), linezolid, lithium, macrolide antibiotics (eg, clarithromycin), opioid analgesics (eg, meperidine), other SSRIs, sibutramine, St. John's wort, tramadol, trazodone, tryptophan
Risk of serotonin syndrome may be increased.Alcohol
Causes additive CNS effects; concurrent use is not recommended.Cimetidine
May increase paroxetine concentrations.Cyclosporine
Concentrations of cyclosporine may be elevated, increasing the risk of toxicity.CYP2D6 system
Approach coadministration with other drugs metabolized by CYP-450 2D6 (eg, phenothiazines, risperidone, tricyclic antidepressants, type IC antiarrhythmics) or drugs that inhibit this enzyme (eg, quinidine) with caution.Cyproheptadine
Pharmacologic effects of paroxetine may be decreased or reversed.Digoxin
May decrease digoxin levels.Fosamprenavir, ritonavir
Paroxetine plasma levels may be reduced, decreasing the efficacy.Hemostatic agents (eg, aspirin, NSAIDs, warfarin)
Risk of bleeding (eg, GI bleeding) may be increased.MAOIs
Can cause serious, sometimes fatal reactions. Do not use concomitantly or within 14 days of each other.Phenobarbital, phenytoin
May decrease paroxetine concentration; may reduce phenytoin concentration.Pimozide, thioridazine
Plasma levels may be increased by paroxetine, leading to an increased risk of QTc prolongation, ventricular arrhythmias, and death. Concomitant use is contraindicated.Procyclidine
Reduction of procyclidine dose may be necessary if anticholinergic effects (eg, blurred vision, dry mouth, urinary retention) occur.Protein bound agents
Highly protein bound agents may be displaced by paroxetine or paroxetine may be displaced, increasing plasma levels and the risk of adverse reactions.Sympathomimetics (eg, amphetamine)
Sensitivity of sympathomimetics and risk of serotonin syndrome may be increased.Theophylline
Elevated theophylline levels have occurred with paroxetine. Monitor theophylline levels.Tricyclic antidepressants (eg, amitriptyline)
Metabolism may be inhibited by paroxetine, increasing plasma levels and adverse reactions.Tryptophan
May cause dizziness, headache, nausea, and sweating. Concomitant use is not recommended.Zolpidem
The effect of zolpidem may be increased.
Laboratory Test Interactions
None well documented.
Vasodilation (4%); palpitation (3%); hypertension, tachycardia (at least 1%); vasculitic syndromes (including Henoch-Schönlein purpura), ventricular fibrillation, ventricular tachycardia including torsades de pointes (postmarketing).
Insomnia, somnolence (24%); asthenia (22%); headache (18%); tremor (15%); dizziness (14%); decreased libido (12%); nervousness (9%); anxiety, paresthesia (6%); agitation (5%); abnormal dreams, impaired concentration (4%); depersonalization (3%); amnesia, drugged feeling (2%); confusion (1%); emotional lability, vertigo (at least 1%); extrapyramidal symptoms (including akathisia, bradykinesia, cogwheel rigidity, dystonia, hypertonia, oculogyric crisis), status epilepticus (postmarketing).
Sweating (14%); rash (3%); pruritus (at least 1%); toxic epidermal necrolysis (postmarketing).
Blurred vision (8%); abnormal vision, pharyngitis (4%); rhinitis (3%); tinnitus (at least 1%); laryngismus, optic neuritis (postmarketing).
Nausea (36%); dry mouth (21%); diarrhea (19%); constipation (16%); decreased appetite (9%); dyspepsia (5%); flatulence, increased appetite, taste perversion (4%); vomiting (3%); oropharynx disorder (2%); pancreatitis, trismus (postmarketing).
Abnormal ejaculation (28%); ejaculatory disturbance (13%); other male genital disorders (10%); female genital disorders including anorgasmia, impotence (9%); dysmenorrhea (5%); impaired urination, urinary disorder, urinary frequency or hesitancy (3%); UTI (2%); acute renal failure, eclampsia, priapism (postmarketing).
Agranulocytosis, aplastic anemia, bone marrow aplasia, hemolytic anemia, pancytopenia, thrombocytopenia (postmarketing).
Elevated LFTs, liver necrosis, grossly elevated transaminases associated with severe liver dysfunction (postmarketing).
Weight gain (at least 1%); porphyria (postmarketing).
Myalgia (4%); back pain, myoclonus (3%); myopathy (2%); myasthenia (1%); arthralgia (at least 1%); SIADH (postmarketing).
Respiratory disorder (7%); yawning (5%); sinusitis (4%); allergic alveolitis, pulmonary hypertension (postmarketing).
Infection, trauma (6%); abdominal pain (4%); chest pain (3%); chills (2%); anaphylaxis, Guillain-Barré syndrome, neuroleptic malignant syndrome, serotonin syndrome, symptoms of galactorrhea and prolactinemia (postmarketing).
Antidepressants increased the risk of suicidal thinking and behavior in short-term studies in children and adolescents with MDD and other psychiatric disorders. Closely observe patients who are started on therapy for clinical worsening, suicidality, or unusual changes in behavior.
Category D .
Excreted in breast milk. Use with caution.
Safety and efficacy not established.
May increase plasma concentrations of paroxetine; adjust dosage.
May increase plasma concentrations of paroxetine; adjust dosage.
Special Risk Patients
Use with caution in patients with concomitant illness or history of drug abuse or dependence, hypomania, mania, narrow-angle glaucoma, seizure, or suicidal tendencies.
Bleeding episodes have been reported in patients taking psychotropic drugs that interfere with serotonin reuptake.
May occur, especially within the first few weeks of treatment.
Patients with MDD may experience worsening of depression and/or emergence of suicidal ideation and behavior, whether or not they are taking antidepressant medication; risk may persist until significant remission occurs. Monitor patients closely for clinical worsening of depression and suicidal ideation.
Avoid abrupt cessation. Gradually reduce dose. If treatment is to be discontinued or the dose reduced, gradually taper dose and monitor patient for withdrawal symptoms (eg, abnormal skin sensations, agitation, anxiety, dizziness, nausea, sweating). If significant withdrawal symptoms develop, reinstitute previous dosing schedule and attempt a less rapid tapering regimen after patient has stabilized.
Hyponatremia has occurred. Use drug with caution in elderly patients, patients taking diuretics, and volume-depleted patients.
Paroxetine may activate hypomania or mania. Use cautiously in patients with history of mania.
Life-threatening serotonin syndrome may occur, particularly with coadministration of serotonergic drugs.
Confusion, coma, dizziness, nausea, somnolence, tachycardia, tremor, vomiting.
- Advise patient to read the Medication Guide before starting therapy and with each refill.
- Advise patient that medication is usually started at a low dose and then gradually increased until max benefit is obtained.
- Advise patient that medication is usually administered as a single daily dose, preferably in the morning.
- Advise patient to take prescribed dose without regard to meals, but to take with food if stomach upset occurs.
- Instruct patient taking CR tablet to swallow whole and not crush, chew, divide, or break tablet.
- Advise patient using suspension to shake well before measuring dose and use a dosing cup or spoon to measure prescribed dose.
- Advise patient and care giver to be alert for abnormal changes in mood or thinking and to immediately report the following symptoms to health care provider: agitation, anxiety, hostility or aggression, impulsivity, irritability, panic attacks, suicidal thoughts and behavior.
- Inform patient that it may take 1 to 4 wk to note improvement in symptoms and to continue with the prescribed therapy once improvement has been noted.
- Instruct patient to contact health care provider if symptoms do not appear to be getting better, are getting worse, or if the following bothersome side effects occur: changes in sexual function, diarrhea, drowsiness, headache, insomnia, nausea, nervousness, unusual sweating.
- Advise patient that if medication needs to be discontinued, it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
- Advise patient to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
- Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
- Advise patient that drug may impair judgment, thinking, or reflexes, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
Copyright © 2009 Wolters Kluwer Health.
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