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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(pa ROKS e teen)
Generic Available (U.S.)
Yes: Excludes suspension, tablet (mesylate)
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Paxil CR®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088676.pdf
Pexeva®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088684.pdf
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of major depressive disorder (MDD); treatment of panic disorder with or without agoraphobia; obsessive-compulsive disorder (OCD); social anxiety disorder (social phobia); generalized anxiety disorder (GAD); post-traumatic stress disorder (PTSD); premenstrual dysphoric disorder (PMDD)
Use: Unlabeled/Investigational
May be useful in eating disorders, impulse control disorders, self-injurious behavior; vasomotor symptoms of menopause; treatment of depression and obsessive-compulsive disorder (OCD) in children; treatment of mild dementia-associated agitation in nonpsychotic patients
Pregnancy Risk Factor
D
Pregnancy Considerations
Due to adverse events observed in human studies, paroxetine is classified as pregnancy category D. Paroxetine crosses the placenta. The risk of cardiovascular and other congenital malformations may be higher with paroxetine than with other antidepressants. Nonteratogenic effects in the newborn following SSRI exposure late in the third trimester include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo- or hypertonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor. An increased risk of low birth weight, lower Apgar scores, and blunted behavioral response to pain for a prolonged period after delivery has also been reported. Exposure to SSRIs after the twentieth week of gestation has been associated with persistent pulmonary hypertension of the newborn (PPHN). Adverse effects may be due to toxic effects of the SSRI or drug withdrawal due to discontinuation. The long-term effects of in utero SSRI exposure on infant development and behavior are not known.Due to pregnancy-induced physiologic changes, women who are pregnant may require increased doses of paroxetine to achieve euthymia. Women treated for major depression and who are euthymic prior to pregnancy are more likely to experience a relapse when medication is discontinued as compared to pregnant women who continue taking antidepressant medications. The ACOG recommends that therapy with SSRIs or SNRIs during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary healthcare provider, and pediatrician. The ACOG also recommends that therapy with paroxetine be avoided during pregnancy if possible and that fetuses exposed in early pregnancy be assessed with a fetal echocardiography. If treatment during pregnancy is required, consider tapering therapy during the third trimester in order to prevent withdrawal symptoms in the infant. If this is done and the woman is considered to be at risk of relapse from her major depressive disorder, the medication can be restarted following delivery, although the dose should be readjusted to that required before pregnancy. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (Yonkers, 2009).
Lactation
Enters breast milk/use caution (AAP rates “of concern”; AAP 2001 update pending)
Breast-Feeding Considerations
Paroxetine is excreted in breast milk and concentrations in the hindmilk are higher than in foremilk. Paroxetine has not been detected in the serum of nursing infants and adverse events have not been reported. The manufacturer recommends that caution be exercised when administering paroxetine to nursing women.
The long-term effects on development and behavior have not been studied; therefore, one should prescribe paroxetine to a mother who is breast-feeding only when the benefits outweigh the potential risks.
Contraindications
Hypersensitivity to paroxetine or any component of the formulation; use with or within 14 days of MAO inhibitors; concurrent use with thioridazine or pimozide
Warnings/Precautions
Boxed warnings:
• Suicidal thinking/behavior: See “Major psychiatric warnings” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Major psychiatric warnings:
• [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Paroxetine is not FDA approved for use in children.
• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants (for any indication) should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.
• May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Paroxetine is not FDA approved for the treatment of bipolar depression.
Concerns related to adverse effects:
• Akathisia: Inability to remain still due to feelings of agitation or restlessness has been observed with paroxetine and other SSRIs. Usually occurs within the first few weeks of therapy.
• Anticholinergic effects: Has low potential for sedation and anticholinergic effects relative to cyclic antidepressants; however among the SSRI class these effects are relatively higher.
• Bleeding risk: May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin, NSAIDs, warfarin or other anticoagulants. Bleeding related to SSRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.
• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.
• Serotonin syndrome (SS)/neuroleptic malignant syndrome (NMS)-like reactions: SS and NMS-like reactions have occurred with serotonin/norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) when used alone, and particularly when used in combination with serotonergic agents (eg, triptans) or antidopaminergic agents (eg, antipsychotics). The diagnosis of SS can be made using the Hunter Serotonin Toxicity Criteria (Dunkley, 2003). Identification and differentiation of SS (eg, tremor, myoclonus, agitation) and more severe NMS-like reactions (eg, hyperthermia, muscle rigidity, autonomic instability, mental status changes) can be complex; monitor patients closely for either syndrome. Discontinue treatment (and any concomitant serotonergic and/or antidopaminergic agents) immediately if signs/symptoms arise.
• Sexual dysfunction: May cause or exacerbate sexual dysfunction.
• SIADH and hyponatremia: SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported rarely (including severe cases with serum sodium <110 mmol/L), predominately in the elderly. Volume depletion and/or concurrent use of diuretics likely increases risk.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease; paroxetine has not been systemically evaluated in patients with a recent history of MI or unstable heart disease.
• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed.
• Narrow-angle glaucoma: May cause mydriasis which can exacerbate narrow angle glaucoma.
• Renal impairment: Use with caution in patients with renal impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed.
• Seizure disorder: Use with caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism.
Concurrent drug therapy issues:
• Agents which lower seizure threshold: Concurrent therapy of paroxetine with these drugs may increase the risk of seizure.
• Anticoagulants/Antiplatelets: Use caution with concomitant use of NSAIDs, ASA, or other drugs that affect coagulation; the risk of bleeding may be potentiated.
• CNS depressants: Use caution with concomitant therapy.
• MAO inhibitors: Potential for severe reaction when used with MAO inhibitors; autonomic instability, coma, death, delirium, diaphoresis, hyperthermia, mental status changes/agitation, muscular rigidity, myoclonus, neuroleptic malignant syndrome features, and seizures may occur. Concurrent use with paroxetine is contraindicated.
• Serotonin syndrome/NMS-like reactions: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans), agents which reduce paroxetine's metabolism, or antidopaminergic agents (including antipsychotics). Concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
• Thioridazine and pimozide: Potential for QTc prolongation and arrhythmia; concurrent use of paroxetine with either of these agents is contraindicated.
Special populations:
• Elderly: Use caution in elderly patients; risk of hyponatremia and other adverse events may be increased.
• Pediatrics: Safety and efficacy in children have not been established.
• Pregnancy: Avoid use in the first trimester.
Other warnings/precautions:
• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.
• Withdrawal syndrome: May cause dysphoric mood, irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. Upon discontinuation of paroxetine therapy, gradually taper dose. If intolerable symptoms occur following a decrease in dosage or upon discontinuation of therapy, then resuming the previous dose with a more gradual taper should be considered.
Adverse Reactions
Frequency varies by dose and indication. Adverse reactions reported as a composite of all indications.
>10%:
Central nervous system: Somnolence (15% to 24%), insomnia (11% to 24%), headache (17% to 18%), dizziness (6% to 14%)
Endocrine & metabolic: Libido decreased (3% to 15%)
Gastrointestinal: Nausea (19% to 26%), xerostomia (9% to 18%), constipation (5% to 16%), diarrhea (9% to 12%)
Genitourinary: Ejaculatory disturbances (13% to 28%)
Neuromuscular & skeletal: Weakness (12% to 22%), tremor (4% to 11%)
Miscellaneous: Diaphoresis (5% to 14%)
1% to 10%:
Cardiovascular: Vasodilation (2% to 4%), chest pain (3%), palpitation (2% to 3%), hypertension (≥1%), tachycardia (≥1%)
Central nervous system: Nervousness (4% to 9%), anxiety (5%), agitation (3% to 5%), abnormal dreams (3% to 4%), concentration impaired (3% to 4%), yawning (2% to 4%), depersonalization (up to 3%), amnesia (2%), chills (2%), emotional lability (≥1%), vertigo (≥1%), confusion (1%)
Dermatologic: Rash (2% to 3%), pruritus (≥1%)
Endocrine & metabolic: Orgasmic disturbance (2% to 9%), dysmenorrhea (5%)
Gastrointestinal: Appetite decreased (5% to 9%), dyspepsia (2% to 5%), flatulence (4%), abdominal pain (4%), appetite increased (2% to 4%), vomiting (2% to 3%), taste perversion (2%), weight gain (≥1%)
Genitourinary: Genital disorder (male 10%; female 2% to 9%), impotence (2% to 9%), urinary frequency (2% to 3%), urinary tract infection (2%)
Neuromuscular & skeletal: Paresthesia (4%), myalgia (2% to 4%), back pain (3%), myoclonus (2% to 3%), myopathy (2%), myasthenia (1%), arthralgia (≥1%)
Ocular: Blurred vision (4%), abnormal vision (2% to 4%)
Otic: Tinnitus (≥1%)
Respiratory: Respiratory disorder (up to 7%), pharyngitis (4%), sinusitis (up to 4%), rhinitis (3%)
Miscellaneous: Infection (5% to 6%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Acute renal failure, adrenergic syndrome, akinesia, alkaline phosphatase increased, allergic reaction, anaphylaxis, anemias (various), angina pectoris, angioedema, aphasia, aphthous stomatitis, arrhythmias (atrial and ventricular), arthrosis, asthma, behavioral disturbances (various), bilirubinemia, bleeding time increased, blood dyscrasias, bloody diarrhea, bradycardia, bronchitis, bulimia, BUN increased, bundle branch block, cardiospasm, cataract, cellulitis, cerebral ischemia, cerebrovascular accident, cholelithiasis, colitis, congestive heart failure, creatine phosphokinase increased, deafness, dehydration, delirium, diabetes mellitus, drug dependence, dyskinesia, dysphagia, dyspnea, dystonia, ecchymosis, eclampsia, electrolyte abnormalities, emphysema, erythema, exfoliative dermatitis, extrapyramidal syndrome, fecal impactions, fungal dermatitis, gamma globulins increased, gastroenteritis, glaucoma, goiter, Guillain-Barré syndrome, hallucinations, hematemesis, hematoma, hemorrhage, hemoptysis, hepatic necrosis, hepatitis, hypercholesteremia, hyper-/hypoglycemia, hyper-/hypothyroidism, hypotension, ileus, intestinal obstruction, jaundice, ketosis, lactic dehydrogenase increased, liver function tests abnormal, low cardiac output, lung fibrosis, lymphadenopathy, meningitis, MI, migraine, myelitis, myocardial ischemia, neuroleptic malignant syndrome, neuropathy, osteoporosis, pancreatitis, pancytopenia, peptic ulcer, peritonitis, phlebitis, pneumonia, platelet count abnormalities, pulmonary edema, pulmonary embolus, pulmonary hypertension, seizure, sepsis, serotonin syndrome, status epilepticus, suicidal tendencies, syncope, tetany, thrombophlebitis, thrombosis, tongue edema, torsade de pointes, toxic epidermal necrolysis, vasculitic syndrome
Metabolism/Transport Effects
Substrate of CYP2D6 (major); Inhibits CYP1A2 (weak), 2B6 (moderate), 2C9 (weak), 2C19 (weak), 2D6 (strong), 3A4 (weak)
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification
Alcohol (Ethyl): May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors. Risk D: Consider therapy modification
Alpha-/Beta-Blockers: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Alpha-/Beta-Blockers. Risk C: Monitor therapy
Analgesics (Opioid): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antidepressants (Serotonin Reuptake Inhibitor/Antagonist): Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Antidepressants (Serotonin Reuptake Inhibitor/Antagonist). This may cause serotonin syndrome. Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy
Aprepitant: May decrease the serum concentration of PARoxetine. PARoxetine may decrease the serum concentration of Aprepitant. Risk C: Monitor therapy
Asenapine: May increase the serum concentration of PARoxetine. Risk C: Monitor therapy
Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Atomoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (adult doses -- patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. Risk D: Consider therapy modification
Beta-Blockers: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Beta-Blockers. Exceptions: Acebutolol; Atenolol; Betaxolol; Betaxolol (Ophthalmic); Betaxolol (Systemic); Bisoprolol; Carteolol; Carteolol (Ophthalmic); Esmolol; Labetalol; Levobunolol; Metipranolol; Nadolol; Penbutolol; Sotalol. Risk C: Monitor therapy
BusPIRone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of BusPIRone. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Selective Serotonin Reuptake Inhibitors. Specifically those agents metabolized via CYP1A2, 2C, and/or 3A4 isoenzymes. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of CarBAMazepine. Specifically those SSRIs that inhibit CYP3A4 isoenzymes. Risk D: Consider therapy modification
Cimetidine: May decrease the metabolism of Selective Serotonin Reuptake Inhibitors. Risk D: Consider therapy modification
CloZAPine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of CloZAPine. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Collagenase (Systemic): Antiplatelet Agents may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy
CYP2B6 Substrates: CYP2B6 Inhibitors (Moderate) may decrease the metabolism of CYP2B6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
CYP2D6 Substrates: CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk D: Consider therapy modification
Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Darunavir: May decrease the serum concentration of PARoxetine. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy
Desmopressin: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Dextromethorphan: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Dextromethorphan. Risk D: Consider therapy modification
Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Management: When possible, avoid use of drotrecogin within 7 days of use of any IIb/IIIa antagonists, higher dose aspirin (more than 650 mg/day), or use of other antiplatelet agents. Risk D: Consider therapy modification
DULoxetine: PARoxetine may decrease the metabolism of DULoxetine. Risk C: Monitor therapy
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Fosamprenavir: May decrease the serum concentration of PARoxetine. The active metabolite amprenavir is likely responsible for this effect. Risk C: Monitor therapy
Fosaprepitant: PARoxetine may decrease serum concentrations of the active metabolite(s) of Fosaprepitant. Fosaprepitant may decrease the serum concentration of PARoxetine. Risk C: Monitor therapy
Galantamine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Galantamine. Risk C: Monitor therapy
Glucosamine: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Haloperidol: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Haloperidol. Risk C: Monitor therapy
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: Consider therapy modification
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification
Iobenguane I 123: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Lithium: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Lithium. Risk C: Monitor therapy
MAO Inhibitors: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination
Methadone: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Methadone. Fluvoxamine appears to be the only interacting SSRI. Risk D: Consider therapy modification
Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
Metoclopramide: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with selective serotonin reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Risk D: Consider therapy modification
Mexiletine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Mexiletine. Risk D: Consider therapy modification
NSAID (COX-2 Inhibitor): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). Risk D: Consider therapy modification
NSAID (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (Nonselective). NSAID (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of an gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Risk D: Consider therapy modification
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pimozide: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Pimozide. Risk X: Avoid combination
Propafenone: PARoxetine may increase the serum concentration of Propafenone. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
RisperiDONE: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of RisperiDONE. Risk C: Monitor therapy
Salicylates: Antiplatelet Agents may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease the metabolism of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Risk X: Avoid combination
Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Tetrabenazine adult dose should be reduced by 50% when starting a strong CYP2D6 inhibitor. Maximum tetrabenazine adult dose is 50 mg/day when used with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification
Thioridazine: CYP2D6 Inhibitors may decrease the metabolism of Thioridazine. Risk X: Avoid combination
Thrombolytic Agents: Antiplatelet Agents may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
TraMADol: Selective Serotonin Reuptake Inhibitors may enhance the neuroexcitatory and/or seizure-potentiating effect of TraMADol. TraMADol may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk D: Consider therapy modification
Tricyclic Antidepressants: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Tryptophan: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Food: Peak concentration is increased, but bioavailability is not significantly altered by food.
Herb/Nutraceutical: Avoid valerian, St John's wort, SAMe, kava kava.
Storage
Suspension: Store at ≤25°C (≤77°F).
Tablet: Store at 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Paroxetine is a selective serotonin reuptake inhibitor, chemically unrelated to tricyclic, tetracyclic, or other antidepressants; presumably, the inhibition of serotonin reuptake from brain synapse stimulated serotonin activity in the brain
Pharmacodynamics/Kinetics
Onset of action: Depression: The onset of action is within a week; however, individual response varies greatly and full response may not be seen until 8-12 weeks after initiation of treatment.
Absorption: Completely absorbed following oral administration
Distribution: Vd: 8.7 L/kg (3-28 L/kg)
Protein binding: 93% to 95%
Metabolism: Extensively hepatic via CYP2D6 enzymes; primary metabolites are formed via oxidation and methylation of parent drug, with subsequent glucuronide/sulfate conjugation; nonlinear pharmacokinetics (via 2D6 saturation) may be seen with higher doses and longer duration of therapy. Metabolites exhibit ~2% potency of parent compound. Cmin concentrations are 70% to 80% greater in the elderly compared to nonelderly patients; clearance is also decreased.
Half-life elimination: 21 hours (3-65 hours)
Time to peak: Immediate release: 5.2 hours; controlled release: 6-10 hours
Excretion: Urine (64%, 2% as unchanged drug); feces (36% primarily via bile, <1% as unchanged drug)
Dosage
Oral:
Children:
Depression (unlabeled use; not recommended by FDA): Initial: 10 mg/day and adjusted upward on an individual basis to 20 mg/day
Obsessive-compulsive disorder (unlabeled use): Initial: 10 mg/day and titrate up as necessary to 60 mg/day
Self-injurious behavior (unlabeled use): 20 mg/day
Social anxiety disorder (unlabeled use): 2.5-15 mg/day
Adults:
Major depressive disorder:
Paxil®, Pexeva®: Initial: 20 mg once daily, preferably in the morning; increase if needed by 10 mg/day increments at intervals of at least 1 week; maximum dose: 50 mg/day
Paxil CR®: Initial: 25 mg once daily; increase if needed by 12.5 mg/day increments at intervals of at least 1 week; maximum dose: 62.5 mg/day
Generalized anxiety disorder (Paxil®, Pexeva®): Initial: 20 mg once daily, preferably in the morning (if dose is increased, adjust in increments of 10 mg/day at 1-week intervals); doses of 20-50 mg/day were used in clinical trials, however, no greater benefit was seen with doses >20 mg.
Obsessive-compulsive disorder (Paxil®, Pexeva™): Initial: 20 mg once daily, preferably in the morning; increase if needed by 10 mg/day increments at intervals of at least 1 week; recommended dose: 40 mg/day; range: 20-60 mg/day; maximum dose: 60 mg/day
Panic disorder:
Paxil®, Pexeva®: Initial: 10 mg once daily, preferably in the morning; increase if needed by 10 mg/day increments at intervals of at least 1 week; recommended dose: 40 mg/day; range: 10-60 mg/day; maximum dose: 60 mg/day
Paxil CR®: Initial: 12.5 mg once daily; increase if needed by 12.5 mg/day at intervals of at least 1 week; maximum dose: 75 mg/day
Premenstrual dysphoric disorder (Paxil CR®): Initial: 12.5 mg once daily in the morning; may be increased to 25 mg/day; dosing changes should occur at intervals of at least 1 week. May be given daily throughout the menstrual cycle or limited to the luteal phase.
Post-traumatic stress disorder (PTSD) (Paxil®): Initial: 20 mg once daily, preferably in the morning; increase if needed by 10 mg/day increments at intervals of at least 1 week; range: 20-50 mg. Limited data suggest doses of 40 mg/day were not more efficacious than 20 mg/day.
Social anxiety disorder:
Paxil®: Initial: 20 mg once daily, preferably in the morning; recommended dose: 20 mg/day; range: 20-60 mg/day; doses >20 mg may not have additional benefit
Paxil CR®: Initial: 12.5 mg once daily, preferably in the morning; may be increased by 12.5 mg/day at intervals of at least 1 week; maximum dose: 37.5 mg/day
Vasomotor symptoms of menopause (unlabeled use, Paxil CR®): 12.5-25 mg/day
Elderly:
Paxil®, Pexeva®: Initial: 10 mg/day; increase if needed by 10 mg/day increments at intervals of at least 1 week; maximum dose: 40 mg/day
Paxil CR®; Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week; maximum dose: 50 mg/day
Note: Upon discontinuation of paroxetine therapy, gradually taper dose:
Paxil®, Pexeva®: 10 mg/day at weekly intervals; when 20 mg/day dose is reached, continue for 1 week before treatment is discontinued. Some patients may need to be titrated to 10 mg/day for 1 week before discontinuation.
Paxil CR®: Patients receiving 37.5 mg/day in clinical trials had their dose decreased by 12.5 mg/day to a dose of 25 mg/day and remained at a dose of 25 mg/day for 1 week before treatment was discontinued.
Dosage adjustment in renal impairment: Adults:
Clcr <30 mL/minute: Mean plasma concentration is ~4 times that seen in normal function.
Clcr 30-60 mL/minute: Plasma concentration is 2 times that seen in normal function.
Paxil®, Pexeva®: Initial: 10 mg/day; increase if needed by 10 mg/day increments at intervals of at least 1 week; maximum dose: 40 mg/day
Paxil CR®: Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week; maximum dose: 50 mg/day
Dosage adjustment in severe hepatic impairment: Adults: In hepatic dysfunction, plasma concentration is 2 times that seen in normal function.
Paxil®, Pexeva®: Initial: 10 mg/day; increase if needed by 10 mg/day increments at intervals of at least 1 week; maximum dose: 40 mg/day
Paxil CR®: Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week; maximum dose: 50 mg/day
Administration: Oral
May be administered without regard to meals. Do not crush, break, or chew controlled release tablets.
Monitoring Parameters
Mental status for depression, suicide ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; akathisia
Dietary Considerations
May be taken without regard to meals.
Patient Education
It may take 2-3 weeks to achieve desired results. Take in the morning to reduce the incidence of insomnia (may be taken with or without food). Do not crush, break, or chew controlled release (Paxil CR®) tablets. Avoid alcohol. Maintain adequate hydration unless instructed to restrict fluid intake. You may experience drowsiness, dizziness, lightheadedness, nausea, vomiting, anorexia, dry mouth, or orthostatic hypotension. Report persistent insomnia or excessive daytime sedation; tremors or weakness; chest pain, palpitations, or rapid heartbeat; vision changes; abnormal bleeding; change in affect or thought processes or abnormal dreams; worsening of condition; or suicide ideation.
Geriatric Considerations
Paroxetine is the most sedating and anticholinergic of the selective serotonin reuptake inhibitors. Paroxetine has been shown to be an equally effective antidepressant compared to nortriptyline in patients with ischemic heart disease. However, nortriptyline was associated with a significantly higher rate of adverse cardiac events (sustained increase in heart rate, sinus tachycardia, and asymptomatic increase in ventricular ectopy) compared to placebo. The elderly are more prone to SSRI/SNRI-induced hyponatremia.
Additional Information
Paxil CR® incorporates a degradable polymeric matrix (Geomatrix™) to control dissolution rate over a period of 4-5 hours. An enteric coating delays the start of drug release until tablets have left the stomach.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation), postural hypotension, and abnormal taste. Problems with SSRI-induced bruxism have been reported and may preclude their use; clinicians attempting to evaluate any patient with bruxism or involuntary muscle movement, who is simultaneously being treated with an SSRI drug, should be aware of the potential association. Prolonged use may decrease or inhibit salivary flow; normal salivation resumes upon discontinuation. See Effects on Bleeding.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Although caution should be used in patients taking tricyclic antidepressants, no interactions have been reported with vasoconstrictor and paroxetine, a nontricyclic antidepressant which acts to increase serotonin; no precautions appear to be needed
Mental Health: Child/Adolescent Considerations
Depression: Paroxetine was shown to be effective and generally well tolerated in a recent randomized, double-blind, placebo-controlled parallel-design study; 275 adolescents (12-18 years of age) with major depression were randomized to receive paroxetine, imipramine, or placebo; 93 patients (mean age: 14.8 ± 1.6 years) received paroxetine at initial doses of 20 mg/day given in the morning; doses were increased if needed at week 5 to 30 mg/day (given in divided doses) and at weeks 6-8 to 40 mg/day (given in divided doses); 48% of patients remained at the initial starting dose of 20 mg/day; mean optimal daily dose: 28 ± 8.54 mg (Keller, 2001). Paroxetine was shown to be effective and well tolerated in an open label clinical trial in 45 children <14 years of age (mean: 10.7 ± 2 years) with major depression (Rey-Sanchoz, 1997). Doses were initiated at 10 mg/day and adjusted upward on an individual basis with a mean dose of 16.2 mg/day used for an average of 8.4 months. Further studies are needed.
Obsessive-compulsive disorder (OCD): Twenty OCD outpatients 8-17 years of age were treated with daily doses ranging from 10-60 mg/day for 12 weeks (Rosenberg, 1999). A randomized, double-blind, placebo-controlled trial with paroxetine was conducted in 207 pediatric patients (aged 7-17 years) meeting DSM-IV criteria for OCD (Geller et al, 2004). Patients received 10-50 mg/day paroxetine or placebo for 10 weeks and change from baseline of the Children's Yale-Brown Obsessive-Compulsive Scale was assessed as the primary endpoint. In the intent-to-treat population, paroxetine was associated with a significant adjusted mean difference improvement (-3.45; 95% CI: -5.6 to -1.29, p =0.002) compared to placebo. Side effects were generally mild to moderate, with 10% and 3% of paroxetine- and placebo-receiving patients, respectively, discontinuing due to adverse events.
Self-injurious behavior: A 15-year old autistic male with self-injurious behavior was successfully treated with 20 mg/day (Snead, 1994). Further studies are needed.
Social anxiety disorder: A small case series reported the effective use of paroxetine in 5 pediatric patients with social phobia [2 children (7 and 11 years of age) and 3 adolescents (16, 17, and 18 years of age)]; comorbid diagnoses (obsessive compulsive disorder and/or dysthymia) existed in 3 patients; doses were adjusted on an individual basis; the 7-year old was started on 2.5 mg/day and increased to 5 mg/day after 4 weeks; the 11-year old was started on 5 mg/day and the dose was titrated upwards by 5 mg/day increments every 3-4 weeks to 15 mg/day; adolescents were started on 20 mg/day (Mancini, 1999); further studies are needed. In a 16-week trial of pediatric patients (aged 8-17 years) presenting with social anxiety disorder, 163 were randomized to receive paroxetine (10-50 mg/day) and 156 to receive placebo (Wagner et al, 2004). From the intent-to-treat analysis, 77.6% of paroxetine patients responded (achievement of Clinical Global Impression-Improvement score of 1 or 2) compared to 38.3% of placebo patients (odds ratio: 7.02, p <0.001). Adverse events occurred in 5% of paroxetine-receiving patients (twice the placebo rate) and consisted mainly of insomnia, decreased appetite and vomiting.
A recent report described the SSRI discontinuation syndrome in 6 children; the syndrome was similar to that reported in adults (Diler, 2002).
Diler RS and Avci A, “Selective Serotonin Reuptake Inhibitor Discontinuation Syndrome in Children: Six Case Reports,” Current Therapeutic Research, 2002, 63(3):188-97.
Geller DA, Wagner KD, Emslie G, et al, “Paroxetine Treatment in Children and Adolescents with Obsessive-Compulsive Disorder: A Randomized, multicenter, Double-Blind, Placebo-Controlled Trial,” J Am Acad Child Adolesc Psychiatry, 2004, 43(11):1387-96.
Keller MB, Ryan ND, Strober M, et al, “Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A Randomized, Controlled Trial,” J Am Acad Child Adolesc Psychiatry, 2001, 40(7):762-72.
Mancini C, Van Ameringen M, Oakman JM, et al, “Serotonergic Agents in the Treatment of Social Phobia in Children and Adolescents: A Case Series,” Depress Anxiety, 1999, 10(1):33-9.
Rey-Sanchez F and Guitierrez-Cassares JR, “Paroxetine in Children With Major Depressive Disorder: An Open Trial,” J Am Acad Child Adolesc Psychiatry, 1997, 36(10):1443-7.
Rosenberg DR, Stewart CM, Fitzgerald KD, et al, “Paroxetine Open-Label Treatment of Pediatric Outpatients With Obsessive-Compulsive Disorder,” J Am Acad Child Adolesc Psychiatry, 1999, 38(9):1180-5.
Snead RW, Boon F, and Presberg J, “Paroxetine for Self-Injurious Behavior,” J Am Acad Child Adolesc Psychiatry, 1994, 33(6):909-10.
Wagner KD, Berard R, Stein MB, et al, “A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Paroxetine in Children and Adolescents With Social Anxiety Disorder,” Arch Gen Psychiatry, 2004, 61(11):1153-62.
Mental Health: Comment
The SSRIs as a class are generally considered to be safe and equally effective. For the management of depression, these drugs display a flat dose-response curve. Allow sufficient dose-response time (6-12 weeks). Differences lie in approved indications, receptor profiles, pharmacokinetics, and cytochrome P450 activity profile. Subtle differences exist in adverse effect profiles. All SSRIs have the potential to cause sexual dysfunction. Among the SSRIs, paroxetine is felt to be the most sedating and anticholinergic. Discontinuation syndromes may be more severe with paroxetine compared to other SSRIs. It also has been associated with more long-term weight gain (Marks, 2008).
Marks DM, Park MH, Ham BJ, et al, "Paroxetine: Safety and Tolerability Issues," Expert Opin Drug Saf, 2008, 7(6):783-94.
Nursing: Physical Assessment/Monitoring
Monitor for clinical worsening and suicide ideation. Taper dosage slowly when discontinuing.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, oral, as hydrochloride [strength expressed as base]:
Paxil®: 10 mg/5 mL (250 mL) [contains propylene glycol; orange flavor]
Tablet, oral, as hydrochloride [strength expressed as base]: 10 mg, 20 mg, 30 mg, 40 mg
Paxil®: 10 mg, 20 mg [scored]
Paxil®: 30 mg, 40 mg
Tablet, oral, as mesylate [strength expressed as base]:
Pexeva®: 10 mg
Pexeva®: 20 mg [scored]
Pexeva®: 30 mg, 40 mg
Tablet, controlled release, enteric coated, oral, as hydrochloride [strength expressed as base]: 12.5 mg, 25 mg, 37.5 mg
Paxil CR®: 12.5 mg, 25 mg, 37.5 mg
Tablet, extended release, enteric coated, oral, as hydrochloride [strength expressed as base]: 12.5 mg, 25 mg
Pricing: U.S. (www.drugstore.com)
Suspension (Paxil)
10 mg/5 mL (250): $189.98
Tablet, 24-hour (PARoxetine HCl)
12.5 mg (30): $102.67
25 mg (30): $105.86
37.5 mg (30): $107.99
Tablet, 24-hour (Paxil CR)
12.5 mg (30): $120.00
37.5 mg (30): $129.99
Tablets (PARoxetine HCl)
10 mg (30): $29.99
20 mg (30): $14.99
30 mg (30): $35.99
40 mg (30): $24.99
Tablets (Paxil)
10 mg (30): $115.99
20 mg (30): $121.99
30 mg (30): $129.99
40 mg (30): $129.99
Tablets (Pexeva)
20 mg (30): $190.98
30 mg (30): $200.98
40 mg (30): $205.00
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International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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