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Paroxetine

Pronunciation

Pronunciation: par-OX-e-teen
Class: SSRI Paroxetine Hydrochloride

Trade Names

Paxil
- Tablets 10 mg
- Tablets 20 mg
- Tablets 30 mg
- Tablets 40 mg
- Suspension, oral 10 mg per 5 mL

Paxil CR
- Tablets, controlled-release 12.5 mg
- Tablets, controlled-release 25 mg
- Tablets, controlled-release 37.5 mg

Paroxetine Mesylate

Pexeva
- Tablets 10 mg
- Tablets 20 mg
- Tablets 30 mg
- Tablets 40 mg

Apo-Paroxetine (Canada)
CO Paroxetine (Canada)
Gen-Paroxetine (Canada)
Novo-Paroxetine (Canada)
PMS-Paroxetine (Canada)
ratio-Paroxetine (Canada)
Sandoz Paroxetine (Canada)

Pharmacology

Blocks reuptake of serotonin, enhancing serotonergic function.

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Pharmacokinetics

Absorption

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.

Distribution

Distributes throughout the body, including CNS; only 1% remains in plasma. Protein binding is 93% to 95%.

Metabolism

Extensive first-pass metabolism in liver by CYP-450 2D6. Principal metabolites are polar and conjugated products of oxidation and methylation.

Elimination

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).

Onset

1 to 4 wk (antidepressant effects).

Special Populations

Renal 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).

Contraindications

Concomitant use in patients taking MAOIs, pimozide, or thioridazine; hypersensitivity to paroxetine or any of the inactive ingredients.

Dosage and Administration

GAD/PTSD
Adults IR

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
Adults IR

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
Adults IR

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
Adults IR

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
Adults CR

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
Adults IR

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
IR

PO 10 mg/day initially; do not exceed 40 mg/day.

CR

PO 12.5 mg/day initially; do not exceed 50 mg/day.

General Advice

  • 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.

Storage/Stability

Store paroxetine hydrochloride IR tablets, oral suspension, and CR tablets at or below 77°F. Store Pexeva tablets at 59° to 86°F.

Drug Interactions

5-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.

Adverse Reactions

Cardiovascular

Vasodilation (4%); palpitation (3%); hypertension, tachycardia (at least 1%); vasculitic syndromes (including Henoch-Schönlein purpura), ventricular fibrillation, ventricular tachycardia including torsades de pointes (postmarketing).

CNS

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).

Dermatologic

Sweating (14%); rash (3%); pruritus (at least 1%); toxic epidermal necrolysis (postmarketing).

EENT

Blurred vision (8%); abnormal vision, pharyngitis (4%); rhinitis (3%); tinnitus (at least 1%); laryngismus, optic neuritis (postmarketing).

GI

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).

Genitourinary

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).

Hematologic

Agranulocytosis, aplastic anemia, bone marrow aplasia, hemolytic anemia, pancytopenia, thrombocytopenia (postmarketing).

Hepatic

Elevated LFTs, liver necrosis, grossly elevated transaminases associated with severe liver dysfunction (postmarketing).

Metabolic-Nutritional

Weight gain (at least 1%); porphyria (postmarketing).

Musculoskeletal

Myalgia (4%); back pain, myoclonus (3%); myopathy (2%); myasthenia (1%); arthralgia (at least 1%); SIADH (postmarketing).

Respiratory

Respiratory disorder (7%); yawning (5%); sinusitis (4%); allergic alveolitis, pulmonary hypertension (postmarketing).

Miscellaneous

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).

Precautions

Warnings

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.


Pregnancy

Category D .

Lactation

Excreted in breast milk. Use with caution.

Children

Safety and efficacy not established.

Renal Function

May increase plasma concentrations of paroxetine; adjust dosage.

Hepatic Function

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.

Abnormal bleeding

Bleeding episodes have been reported in patients taking psychotropic drugs that interfere with serotonin reuptake.

Akathisia

May occur, especially within the first few weeks of treatment.

Depression/Suicide

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.

Discontinuation

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

Hyponatremia has occurred. Use drug with caution in elderly patients, patients taking diuretics, and volume-depleted patients.

Mania/Hypomania

Paroxetine may activate hypomania or mania. Use cautiously in patients with history of mania.

Serotonin syndrome

Life-threatening serotonin syndrome may occur, particularly with coadministration of serotonergic drugs.

Overdosage

Symptoms

Confusion, coma, dizziness, nausea, somnolence, tachycardia, tremor, vomiting.

Patient Information

  • 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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