Paroxetine (Brand Names Seroxat, Paraxyl) is available as immediate-release and extended-release formulations. It is used in the treatment of unipolar depression with predominant anxiety.

Paroxetine Uses:

• Generalized anxiety disorder (immediate release):

  • Treatment of generalized anxiety disorder.

• Major depressive disorder (unipolar) (immediate and extended-release):

  • Treatment of unipolar major depressive disorder.

• Obsessive-compulsive disorder (immediate-release):

  • Obsessions and compulsions treatment in patients with obsessive-compulsive disorder.

• Panic disorder (immediate and extended-release):

  • Treatment of panic disorder, with or without agoraphobia.

• Posttraumatic stress disorder (immediate-release):

  • Treatment of posttraumatic stress disorder.

• Premenstrual dysphoric disorder (extended-release):

  • Treatment of premenstrual dysphoric disorder.

• Social anxiety disorder (immediate and extended-release):

  • Social anxiety disorder, also called social phobia.

• Vasomotor symptoms of menopause (immediate release; 7.5 mg capsule):

  • Moderate to severe vasomotor symptoms associated with menopause.

• Off Label Use of Paroxetine in Adults:

  • Body dysmorphic disorder
  • Premature ejaculation

Paroxetine Dose in Adults

Note:

• Dose:
  • In patients sensitive to side effects, some experts suggest a lower starting dose of 5 to 10 mg once a day (immediate-release) or 12.5 mg once a day (extended-release) and gradual adjustment in increments of no more than 10 mg (immediate-release) or 12.5 mg (extended-release), particularly in patients suffering from anxiety who are more sensitive to overstimulation effects e.g, anxiety, insomnia with antidepressants.
• Dosage forms:
  • Paroxetine is available as IR and ER formulations; both formulations are dosed once a day but are not interchangeable on a mg to mg basis. Where dosing for the ER formulation is not provided for an indication, may convert between formulations using equivalence shown in the dosing conversions section below.

Paroxetine Dose in the treatment of Body dysmorphic disorder (off-label):

Dosing recommendations based on expert opinion:

• Immediate release:

  • Oral: Initial: 20 mg once a day;
  • may increase the dose gradually based on response and tolerability in increments of 20 mg per day at intervals of every 2 to 3 weeks to a usual dose of 60 mg per day;
  • doses up to 100 mg per day may be necessary for some patients for optimal response, typically under specialist care.
  • Note: An adequate trial for assessment of effect in body dysmorphic disorder is 12 to 16 weeks, including maximum tolerated doses for at least 3 to 4 of those weeks.

Paroxetine Dose in the treatment of Generalized anxiety disorder:

• Immediate release:

  • Oral: Initial: 10 mg once a day;
  • may increase the dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week up to 50 mg/day.

Paroxetine Dose in the treatment of major unipolar depressive disorder:

• Immediate-release:

  • Oral: Initial: 20 mg once a day;
  • may increase the dose based on response and tolerability in increments of 10 to 20 mg/day at intervals ≥1 week to a maximum of 50 mg/day.

• Extended-release:

  • Oral: Initial: 25 mg once a day;
  • may increase the dose based on response and tolerability in increments of 12.5 mg per day at intervals ≥1 week to a maximum of 62.5 mg per day.

Paroxetine Dose in the treatment of Obsessive-compulsive disorder:

• Immediate release:

  • Oral: Initial: 20 mg once every day;
  • may increase the dose based on response and tolerability in increments of 10 mg per day at intervals of more than 1 week up to a recommended dose of 40 to 60 mg/day;
  • The maximum dose: 60 mg per day.
• Note: An adequate trial for assessment of effect in obsessive-compulsive disorder is considered for ≥6 weeks at the maximum tolerated dose.

Paroxetine Dose in the treatment of Panic disorder:

• Immediate-release:

  • Oral: Initial: 10 mg once every day for 3 to 7 days;
  • may increase the dose based on response and tolerability in increments of 10 mg per day at intervals ≥1 week up to a usual dose of 20 to 40 mg per day;
  • The maximum dose: 60 mg/day.

• Extended-release:

  • Oral: Initial: 12.5 mg once every day; may increase the dose based on response and tolerability in increments of 12.5 mg per day at intervals ≥1 week up to a maximum of 75 mg/day.

Paroxetine Dose in the treatment of Posttraumatic stress disorder:

• Immediate-release:

  • Oral: Initial: 20 mg once a day;
  • may increase the dose based on response and tolerability in increments of 10 to 20 mg/day at intervals ≥1 week up to 60 mg/day.

Paroxetine Dose in the treatment of Premature ejaculation (off-label):

• Immediate release:

  • Oral: Initial: 10 mg once daily;
  • may increase the dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week to the usual dosage of 20 mg/day.
  • Some patients may require up to 40 mg/day for the optimal response;
  • some experts suggest 3- to 4-week titration intervals.

Paroxetine Dose in the treatment of Premenstrual dysphoric disorder:

• Note: Some experts prefer selective serotonin reuptake inhibitors (SSRIs) other than paroxetine for this use.

• Continuous daily dosing regimen:

  • Immediate release (off-label):

    • Oral: Initial: 10 mg once every day; increase to the usual effective dose of 20 mg once a day over the first month;
    • in a subsequent menstrual cycle, a further increase to 40 mg per day may be required in some patients for optimal response.

  • Extended-release:

    • Oral: Initial: 12.5 mg once every day; increase to usual effective dose of 25 mg once a day over the first month; in a subsequent menstrual cycle, a further increase to 50 mg/day (based on equivalent IR dose) may be necessary for some patients for an optimal response.

• Intermittent regimens:

  • Luteal phase dosing regimen:

    • Immediate release (off-label):

      • Oral: Initial: 10 mg once a day during the luteal phase of the menstrual cycle only (ie, beginning therapy 14 days before the anticipated onset of menstruation and continued to the onset of menses);
      • over the first month, it may increase to the usual effective dose of 20 mg once daily during the luteal phase;
      • in a subsequent menstrual cycle, a further increase to 30 mg/day during the luteal phase may be necessary for some patients for optimal response.

    • Extended-release:

      • Oral: Initial: 12.5 mg once a day during the luteal phase of the menstrual cycle only (ie, beginning therapy 14 days before the anticipated onset of menstruation and continued to the onset of menses);
      • over the first month, may increase to usual effective dose of 25 mg once a day during the luteal phase;
      • in a subsequent menstrual cycle, a further increase to 37.5 mg/day (based on equivalent IR dose) during the luteal phase may be necessary for some patients for optimal response.

  • Symptom-onset dosing regimen (off-label):

    • Immediate release: Oral: Initial: 10 mg once a day from the day of symptom onset until a few days after the start of menses; over the first month, may increase the dose based on response and tolerability up to 20 mg/day;
    • in a subsequent menstrual cycle, a further increase to 30 mg per day may be necessary for some patients for optimal response.

Paroxetine Dose in the treatment of Social anxiety disorder:

• Immediate-release:

  • Oral: Initial: 10 mg once every day;
  • may increase the dose based on response and tolerability in increments of 10 mg per day at intervals ≥1 week to a maximum of 60 mg per day.

• Extended-release:

  • Oral: Initial: 12.5 mg once every day;
  • may increase the dose based on response and tolerability in increments of 12.5 mg per day at intervals ≥1 week up to a maximum of 37.5 mg/day (manufacturer's labeling).
  • Note: Doses up to 75 mg per day (based on equivalent IR dose) may be required in some patients for optimal response.

Paroxetine dose as alternative agent in the treatment of Vasomotor symptoms of menopause:

• Note: Non-hormonal alternative in patients unable or not willing to take estrogen.

• Immediate release :

  • Capsule: Oral: 7.5 mg once a day at bedtime.
  • Tablet (off-label): Oral: 10 to 20 mg once a day at bedtime.

• Extended-release (off-label):

  • Oral: 12.5 to 25 mg once a day at bedtime.

• Dosing conversions:

  • Immediate-release 10 mg is equivalent to the extended-release of 12.5 mg.

• Discontinuation of therapy:

  • When discontinuing antidepressant treatment that has lasted for more than 21 days, gradually taper the dose e.g, over 2 to 4 weeks of time in order to reduce withdrawal symptoms and detect reemerging symptoms.
  • Reasons for a slower titration (eg, over 4 weeks) include the use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, or high doses of antidepressants.
  • If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate.
  • Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months.
  • Evidence supporting ideal taper rates is limited.

• Switching antidepressants:

  • Evidence for ideal antidepressant inter-converting strategies is limited; strategies include cross-titration (i.e gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly stopping the first antidepressant drug and then starting the new antidepressant at an equivalent dose or at lower dose and increasing it gradually).
  • Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches but is contraindicated when switching to or from an MAOI.
  • A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs) when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects.
  • When choosing the switch strategy, consider the risk of discontinuation symptoms, the potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired.

• Switching to or from an MAOI:

  • Allow 14 days to elapse between discontinuing an MAOI and initiation of paroxetine.
  • Allow 14 days to elapse between discontinuing paroxetine and initiation of an MAOI.

Paroxetine Dose in Childrens

Paroxetine dose in the treatment of Obsessive-compulsive disorder (OCD):

• Children and Adolescents 7 to 17 years:

  • Oral: Initial: 10 mg once a day;
  • titrate every 7 to 14 days in 10 mg/day increments;
  • The maximum daily dose: 60 mg/day.

Paroxetine Dose in the treatment of Social anxiety disorder:

• Children and Adolescents 8 to 17 years:

  • Oral: Initial: 10 mg once a day; titrate at intervals of at least 7 days in 10 mg/day increments;
  • The maximum daily dose: 50 mg/day.

• Discontinuation of therapy:

  • Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms. Evidence supporting ideal taper rates is limited.
  • APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively.
  • In addition to long-term treated patients, WFSBP guidelines recommend tapering over 4 to 6 months.
  • If intolerable withdrawal symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate.

Paroxetine use with an MAO inhibitor - recommendations:

• Switching to or from an MAO inhibitor intended to treat psychiatric disorders:

  • Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of paroxetine.
  • Allow 14 days to elapse between discontinuing paroxetine and initiation of an MAO inhibitor intended to treat psychiatric disorders.

• Use with other MAO inhibitors (linezolid or IV methylene blue):

  • Do not initiate paroxetine in patients receiving linezolid or IV methylene blue; consider other interventions for a psychiatric condition.
  • If urgent treatment with linezolid or IV methylene blue is required in a patient already receiving paroxetine and potential benefits outweigh potential risks, discontinue paroxetine promptly and administer linezolid or IV methylene blue.
  • Monitor for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first.
  • May resume paroxetine 24 hours after the last dose of linezolid or IV methylene blue.

Pregnancy Risk Factor D/X

• Pregnancy Implications Paroxetine crosses over the placenta.
• A higher risk of teratogenic effects including cardiovascular defects may be linked to maternal use of paroxetine and other SSRIs. However, there is limited information.
• The newborn may experience nonteratogenic effects from SSRI/SNRI late in the third trimester.
• These include respiratory distress, seizures, temperature instability and feeding difficulties, as well as hypoglycemia or hypotonia, hypo-, hypertonia, hyperreflexia and jitteriness.
• Symptoms could be caused by toxicity of SSRIs/SNRIs, or a discontinuation syndrome. This may also be consistent with serotonin syndrome that is associated with SSRI treatment.
• SSRIs have also been linked to persistent pulmonary hypertension in the newborn (PPHN).
• We don't know the long-term effects of in utero SSRIs on infant behavior and development.
• Some pharmacokinetic parameters for paroxetine could be affected by pregnancy-induced physiological changes
• The maternal CYP2D6 gene also has an impact on paroxetine plasma levels during pregnancy.
• If the benefits of treatment are not justified, discontinue paroxetine treatment or switch to an antidepressant. Women who plan to become pregnant should consider other options.
• ACOG recommends that treatment with SSRIs and SNRIs during pregnancy is individualized.
• Treatment of depression during pregnancy should include the clinical expertise of the mental healthcare provider, obstetrician and primary care provider.
• ACOG recommends that paroxetine therapy be avoided during pregnancy, if at all possible, and that any fetuses who are exposed to it in the early stages of pregnancy be evaluated with fetal echocardiography.
• Other guidelines state that paroxetine should never be administered to pregnant women.
• According to the American Psychiatric Association, the risks associated with medication treatment must be weighed against other treatment options.
• Paroxetine should not be used as a first-line treatment for pregnant women.
• People who have stopped taking antidepressant medication during pregnancy or who are at high risk of postpartum depression can resume their medications after delivery.
• The ACOG and APA have developed treatment algorithms for women with depression before and during pregnancy.
• Paroxetine is not recommended for pregnant women because it does not treat menopausal vasomotor signs.

Use of paroxetine while breastfeeding

• Breast milk contains paroxetine.
• The relative infant dose (RID), of paroxetine, is 5.6%. This was calculated using the highest concentration of breast milk and compared with a maternal weight-adjusted dose of 50 mg/day.
• When the RID is less than 10%, breastfeeding is generally acceptable.
• Some sources mention that breastfeeding is only recommended if the RID for psychotropic drugs is less than 5%.
• The RID of paroxetine is calculated using a milk content of 255.3ng/mL. This gives an estimated daily infant dose of 0.04 mg/kg/day.
• This milk concentration was achieved after maternal administration of 50 mg/day paroxetine.
• Linear correlation exists between milk and maternal plasma concentrations.
• Some infants breastfed with paroxetine had serum levels that were detectable.
• Breastfed infants who were exposed to SSRIs, including paroxetine, have shown constant crying, insomnia, poor weight gain, restlessness, lethargy and lethargy.
• Mothers who use psychotropic medication should monitor their infants daily for any changes in sleep, feeding, behavior, or neurodevelopment.
• Pregnancy may be delayed if a mother uses an SSRI.
• If the product is to be administered to a nursing woman, it is recommended that caution be taken.
• Paroxetine can be used to initiate an antidepressant treatment in a breastfeeding woman. However, other agents are possible if the woman needs long-term therapy or wishes to have another child.
• If there are no contraindications, women who have been successfully treated with paroxetine in pregnancy can continue to breastfeed if they have not had any other complications.

Paroxetine Dose in Kidney disease:

• CrCl 30 to 60 mL/minute:

  • There are no dosage adjustments provided in the drug manufacturer's labeling; however, plasma concentration maybe 2 times that seen in normal function.

• Severe impairment (CrCl <30 mL/minute):

  • Mean plasma concentration is ~4 times that seen in normal function.

• Immediate-release:

  • Initial: 10 mg/day;
  • Increase the dose if needed by 10 mg/day increments at intervals of at least 1 week;
  • The maximum dose: 40 mg/day.

• Extended-release:

  • Initial: 12.5 mg/day;
  • Increase the dose if needed by 12.5 mg/day increments at intervals of at least 1 week;
  • The maximum dose: 50 mg/day.

Paroxetine Dose in Liver disease:

Note: In hepatic dysfunction, plasma concentration maybe 2 times that seen in normal function.

• Mild to moderate impairment:

  • There are no dosage adjustments provided in the drug manufacturer's labeling.

• Severe impairment:

  • Immediate-release:
    • Initial: 10 mg/day; increase if needed by 10 mg/day increments at intervals of at least 1 week;
    • The maximum dose: 40 mg/day.
  • Extended-release:
    • Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week;
    • The maximum dose: 50 mg/day.

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Frequency varies by dose and indication. Adverse reactions reported as a composite of all indications.

Common Side Effects of Paroxetine:

• Central Nervous System:

  • Drowsiness
  • Insomnia
  • Headache
  • Dizziness

• Dermatologic:

  • Diaphoresis

• Endocrine & Metabolic:

  • Decreased Libido

• Gastrointestinal:

  • Nausea
  • Xerostomia
  • Constipation
  • Diarrhea

• Genitourinary:

  • Ejaculatory Disorder

• Neuromuscular & Skeletal:

  • Weakness
  • Tremor

Less Common Side Effects Of Paroxetine:

• Cardiovascular:

  • Vasodilation
  • Chest Pain
  • Palpitations
  • Hypertension
  • Tachycardia

• Central Nervous System:

  • Nervousness
  • Anxiety
  • Fatigue
  • Agitation
  • Paresthesia
  • Abnormal Dreams
  • Lack Of Concentration
  • Yawning
  • Depersonalization
  • Myoclonus
  • Amnesia
  • Chills
  • Emotional Lability
  • Vertigo
  • Confusion
  • Myasthenia

• Dermatologic:

  • Skin Rash
  • Pruritus

• Endocrine & Metabolic:

  • Weight Gain

• Gastrointestinal:

  • Decreased Appetite
  • Dyspepsia
  • Flatulence
  • Abdominal Pain
  • Nausea And Vomiting
  • Increased Appetite
  • Vomiting
  • Dysgeusia

• Genitourinary:

  • Male Genital Disease
  • Female Genital Tract Disease
  • Impotence
  • Orgasm Disturbance
  • Dysmenorrhea
  • Urinary Frequency
  • Urinary Tract Infection

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Myalgia
  • Back Pain
  • Myopathy
  • Arthralgia

• Ophthalmic:

  • Blurred Vision
  • Visual Disturbance

• Otic:

  • Tinnitus

• Respiratory:

  • Dyspnea
  • Pharyngitis
  • Sinusitis
  • Rhinitis

Contraindications to Paroxetine:

• Use concurrently with, or within 14 days after, MAOIs to treat psychiatric disorders
• Initiation of patients receiving linezolid IV or methyleneblue IV treatment;
• Use pimozide and thioridazine in conjunction
• hypersensitivity to paroxetine and any component of the formulation
• Pregnancy

Warnings and precautions

• Akathisia

  • Paroxetine, and other SSRIs, can cause agitation or restlessness which causes inability to stay still. This usually occurs within the first few days of therapy.

• Anticholinergic effects

  • Low potential for sedation or anticholinergic effects in comparison to cyclic antidepressants. However, these effects are higher among the SSRI classes.

• Bleeding Risk:

  • Use of aspirin, NSAIDs or warfarin together with other anticoagulants may cause platelet aggregation to be impaired. This can increase the risk of bleeding.
  • Bleeding due to SSRI usage has been reported in a variety of situations, from minor bruising to epistaxis to life-threatening hemorhage.

• Depression in the CNS:

  • This can lead to central nervous system depression which may in turn affect mental or physical abilities.
  • Patients should be counseled when they are required to perform tasks such as operating machinery or driving.

• Fractures

  • Antidepressant treatment has been shown to be associated with bone fractures.
  • If an antidepressant-treated person experiences unresolved bone pain, tenderness, swelling or bruising, it is worth looking into the possibility of a fragility injury.

• Ocular effects

  • Mild pupillary dilation may occur, which could lead to a brief episode of narrow-angle vision in those who are susceptible.
  • Patients who have not had an Iridectomy performed for narrow-angle Glaucoma Risk Factors should be evaluated.

• Serotonin syndrome

  • Serotonin syndrome (SS), which can be life-threatening, has been reported with serotonergic drugs (eg SSRIs, SNRIs), especially when combined with other serotonergic medications (eg triptans TCAs, fentanyls, lithium, tramadol and buspirone), or drugs that interfere in the metabolism of serotonin.
  • Pay attention to signs of SS in patients.
    • Mental status changes (eg: agitation, hallucinations and delirium, coma).
    • autonomic instability (eg tachycardia or labile blood pressure, diaphoresis)
    • Neuromuscular changes (eg, tremors, rigidity and myoclonus);
    • GI symptoms (eg nausea, vomiting, diarrhea)
    • Seizure
  • If you notice signs/symptoms of serotonin disorder, stop taking any serotonergic agents and discontinue all treatment immediately.

• Sexual dysfunction

  • This may lead to or exacerbate sexual dysfunction.

• SIADH and Hyponatremia

  • SIADH has been developed in association with SSRIs as well as SNRIs.
  • Hyponatremia is a rare condition, especially in elderly people.
  • Risk is likely to increase if volume depletion or concurrent use of diuretics occurs.

• Cardiovascular disease

  • Patients with heart disease should be cautious.
  • Patients with unstable heart disease or recent MI have not had their paroxetine systemically evaluated.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious; plasma concentrations and clearance are decreased, so a lower dose may be necessary.

• Hypomania and mania:

  • This may lead to psychosis in some patients, or a shift towards mania or hypomania among patients with bipolar disorder.
  • Patients with bipolar disorder must be treated in a multi-disciplinary team. Patients with depressive symptoms need to be evaluated for bipolar disorder.
  • For the treatment of bipolar disorder, Paroxetine has not been approved by the FDA.

• Renal impairment

  • Patients with impaired renal function should be cautious. Plasma concentrations and clearance are decreased, so a lower dose may be necessary.

• Seizure disorder

  • Patients with a history of seizure disorders or conditions that predispose to seizures, such as brain damage or addiction, should be cautious.

Paroxetine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)	May enhance the antiplatelet effect of other Agents with Antiplatelet Properties.
Ajmaline	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Ajmaline	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Ajmaline.
Amphetamines	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Amphetamines.
Anticoagulants	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin.
Antiemetics (5HT3 Antagonists)	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Antipsychotic Agents	Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Apixaban	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely.
Aprepitant	PARoxetine may decrease the serum concentration of Aprepitant. Aprepitant may decrease the serum concentration of PARoxetine.
Aspirin	Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin.
Benzhydrocodone	CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Benzhydrocodone.
Beta-Blockers	Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Beta-Blockers. Exceptions: Acebutolol; Atenolol; Betaxolol (Ophthalmic); Betaxolol (Systemic); Bisoprolol; Carteolol (Ophthalmic); Esmolol; Labetalol; Levobunolol; Metipranolol; Nadolol; Sotalol.
Blood Glucose Lowering Agents	Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents.
Brexanolone	Selective Serotonin Reuptake Inhibitors may enhance the CNS depressant effect of Brexanolone.
BuPROPion	May enhance the adverse/toxic effect of PARoxetine. Specifically, the risk for seizures and serotonin syndrome may be increased.
Cephalothin	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased.
Cimetidine	May increase the serum concentration of PARoxetine.
Clarithromycin	May enhance the adverse/toxic effect of PARoxetine. Clarithromycin may enhance the QTc-prolonging effect of PARoxetine.
CloBAZam	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
CloZAPine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of CloZAPine.
CNS Depressants	May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.
Cobicistat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Collagenase (Systemic)	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased.
CYP2D6 Inhibitors (Moderate)	May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).
Cyproheptadine	May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors.
Dabigatran Etexilate	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.
Darunavir	May decrease the serum concentration of PARoxetine.
Dasatinib	May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Deoxycholic Acid	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased.
Desmopressin	Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin.
Edoxaban	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased.
Fat Emulsion (Fish Oil Based)	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.
Fesoterodine	CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine.
Fosamprenavir	May decrease the serum concentration of PARoxetine. The active metabolite amprenavir is likely responsible for this effect.
Fosaprepitant	PARoxetine may decrease serum concentrations of the active metabolite(s) of Fosaprepitant. Fosaprepitant may decrease the serum concentration of PARoxetine.
Galantamine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Galantamine.
Glucosamine	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
HYDROcodone	CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased.
Ibritumomab Tiuxetan	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding.
Ibrutinib	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.
Imatinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Indoramin	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Indoramin.
Inotersen	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Ioflupane I 123	Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123.
Limaprost	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Lofexidine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Lofexidine.
Lumefantrine	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Metaxalone	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Methylphenidate	May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased.
Metoprolol	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoprolol.
MetyroSINE	May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors.
Multivitamins/Fluoride (with ADE)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Multivitamins/Minerals (with ADEK, Folate, Iron)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Multivitamins/Minerals (with AE, No Iron)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Nebivolol	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol.
Nicergoline	CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased.
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective)	Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors.
Nonsteroidal Anti-Inflammatory Agents (Topical)	May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors.
Obinutuzumab	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
Omega-3 Fatty Acids	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Opioid Agonists	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Panobinostat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Peginterferon Alfa-2b	May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Pentosan Polysulfate Sodium	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents.
Pentoxifylline	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Pravastatin	May enhance the adverse/toxic effect of PARoxetine. Specifically, blood glucose elevations may occur with the combination.
Propafenone	PARoxetine may increase the serum concentration of Propafenone.
Prostacyclin Analogues	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
QuiNINE	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Rivaroxaban	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.
Salicylates	Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result.
Serotonin Modulators	May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid.
Tamsulosin	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tamsulosin.
Tedizolid	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Thiazide and Thiazide-Like Diuretics	Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics.
Thrombolytic Agents	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
Thyroid Products	Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased.
Timolol (Ophthalmic)	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Ophthalmic).
TraMADol	CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of TraMADol. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Strong) may increase the serum concentration of TraMADol.
TraMADol	Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Tricyclic Antidepressants	PARoxetine may enhance the serotonergic effect of Tricyclic Antidepressants. PARoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined.
Tropisetron	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tropisetron.
Valbenazine	CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Valbenazine.
Vitamin E (Systemic)	May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
Vitamin K Antagonists (eg, warfarin)	Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists.
Risk Factor D (Consider therapy modification)
Abiraterone Acetate	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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.
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.
ARIPiprazole	PARoxetine may enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of neuroleptic malignant syndrome may be increased. ARIPiprazole may enhance the serotonergic effect of PARoxetine. This could result in serotonin syndrome. PARoxetine may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose adjustment is recommended, except when used adjunctively for depression. Consult full interaction monograph or aripiprazole prescribing information for complete details.
ARIPiprazole Lauroxil	CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Please refer to the full interaction monograph for details concerning the recommended dose adjustments.
Asenapine	PARoxetine may enhance the QTc-prolonging effect of Asenapine. Asenapine may increase the serum concentration of PARoxetine.
Asunaprevir	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
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.
Bemiparin	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding.
Brexpiprazole	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with a strong CYP2D6 inhibitor, reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a CYP3A4 inhibitor; these recommendations do not apply if treating major depressive disorder.
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. Management: The combination of a selective serotonin reuptake inhibitor and buspirone should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome.
Codeine	CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine.
CYP2D6 Inhibitors (Strong)	May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).
CYP2D6 Substrates (High risk with Inhibitors)	CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Exceptions: Ajmaline; Dapoxetine; Indoramin; Metoprolol; Tamoxifen; Timolol (Ophthalmic); Tropisetron.
Dacomitinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index.
Deutetrabenazine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg, and the maximum single dose of deutetrabenazine should not exceed 18 mg with concurrent use of a strong CYP2D6 inhibitor.
Dextromethorphan	Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Dextromethorphan. Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dextromethorphan. Management: Avoid the concurrent use of dextromethorphan and SSRIs, particularly fluoxetine and paroxetine, when possible. The risk for this interaction may persist for several weeks following discontinuation of fluoxetine or paroxetine.
DOXOrubicin (Conventional)	CYP2D6 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided.
DULoxetine	May enhance the serotonergic effect of PARoxetine. This could result in serotonin syndrome. PARoxetine may increase the serum concentration of DULoxetine. Management: Coadminister with caution. If duloxetine and paroxetine are used in combination, monitor for signs and symptoms of serotonin toxicity/serotonin syndrome, as well as other toxic effects of duloxetine.
Eliglustat	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor.
Enoxaparin	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding.
Gilteritinib	May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Avoid use of this combination if possible. If the combination cannot be avoided, monitor closely for evidence of reduced response to the selective serotonin reuptake inhibitor.
Heparin	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required.
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures.
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.
Linezolid	May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Consider alternatives to this combination whenever possible. If clinically acceptable, wait at least 2 weeks (5 weeks for fluoxetine) after SSRI discontinuation to initiate linezolid.
Linezolid	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely.
Lithium	May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could increase the risk of serotonin toxicity/serotonin syndrome. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome.
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.
Metoclopramide	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoclopramide. Management: Reduce metoclopramide dose to 5 mg 4 times daily (30 minutes before each meal and at bedtime) and limit the maximum daily dose to 20 mg if combined with strong CYP2D6 inhibitors.
Nonsteroidal Anti-Inflammatory Agents (Nonselective)	Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2selective NSAIDs reduce risk. Exceptions: Diclofenac (Topical); Ibuprofen (Topical); Piroxicam (Topical).
Perhexiline	CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required.
Pitolisant	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients receiving strong CYP2D6 inhibitors, initiate pitolisant at 8.9 mg once daily and increase after 7 days to a maximum of 17.8 mg once daily.
Primaquine	CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Primaquine. Management: Monitor for signs and symptoms of possible treatment failure with primaquine in patients who are taking strong CYP2D6 inhibitors. If efficacy of primaquine is compromised, may consider adjusting therapies.
Serotonin Reuptake Inhibitor/Antagonists	Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin Reuptake Inhibitor/Antagonists. This may cause serotonin syndrome. Management: Consider alternatives, and use conservative initial dosing. Monitor patients receiving these combinations for signs/symptoms of serotonin toxicity.
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.
Vortioxetine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with a strong CYP2D6 inhibitor. Following cessation of the strong CYP2D6 inhibitor, the vortioxetine dose should be returned to the normal level.
Risk Factor X (Avoid combination)
Bromopride	May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors.
Dapoxetine	May enhance the adverse/toxic effect of Serotonin Modulators.
Dothiepin	Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dothiepin.
Mequitazine	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mequitazine.
Methylene Blue	Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome.
Methylene Blue	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Monoamine Oxidase Inhibitors	May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid.
Pimozide	Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Pimozide. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs as appropriate.
Pimozide	CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pimozide.
Tamoxifen	CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites.
Thioridazine	CYP2D6 Inhibitors may increase the serum concentration of Thioridazine.
Tryptophan	May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome.
Urokinase	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase.

Monitoring parameters:

• Liver and renal function tests (baseline; as clinically indicated);
• serum sodium in at-risk populations (as clinically indicated);
• CBC (as clinically indicated);
• evaluate for suicidal ideation (baseline and with dose changes).

How to administer Paroxetine (Seroxat)?

• Oral: May be administered without regard to meals. Administer preferably in the morning; when used for vasomotor symptoms of menopause, administer at bedtime.
• Do not crush, break, or chew ER or IR film-coated tablets.

Mechanism of action of Paroxetine (Seroxat):

• Paroxetine, which is a selective serotonin-reuptake inhibitor, is chemically unrelated with tricyclic, tripetracyclic or other antidepressants.
• Possibly, the brain's inhibition of serotonin metabolism from the brain synapse stimulated the production of serotonin.

The 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 to 12 weeks after initiation of treatment;
• anti-obsessional and anti-panic effects:
  • Up to several weeks

Absorption:

• Completely absorbed following oral administration

Protein binding:

• 93% to 95%

Metabolism:

• Extensively hepatic via CYP2D6 enzymes; primary metabolites are formed via oxidation and methylation of the 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 the parent compound.
• Cmin concentrations are 70% to 80% greater in the elderly compared to nonelderly patients; clearance is also decreased.

Bioavailability:

• Immediate release tablet and oral suspension have equal bioavailability

Half-life elimination:

• Paxil: 21 hours;
• Paxil CR: 15 to 20 hours;
• Pexeva: 33.2 hours

Time to peak:

• Capsules: Median: 6 hours (range: 3 to 8 hours)
• Immediate-release Tablets and oral suspension: Mean: 5.2 to 8.1 hours
• Controlled release Tablets: 6 to 10 hours

Excretion:

• Urine (64%, 2% as unchanged drug);
• feces (36% primarily via bile, <1% as unchanged drug)

International Brands of Paroxetine:

• Brisdelle
• Paxil
• Paxil CR
• Pexeva
• ACT PARoxetine
• AG-Paroxetine
• APO-PARoxetine
• Auro-PARoxetine
• BIO-PARoxetine
• DOMPARoxetine
• JAMP-PARoxetine
• M-Paroxetine
• Mar-PARoxetine
• MINT-Paroxetine
• MYLANPARoxetine
• NRA-Paroxetine
• NU-PARoxetine
• PARoxetine-10
• PARoxetine-20
• PARoxetine-30
• Paxil
• Paxil CR
• PMS-PARoxetine
• Priva-PARoxetine
• RIVA-PARoxetine
• SANDOZ PARoxetine
• TARO-PARoxetine
• TEVA-PARoxetine
• A-Xat CR
• Afentan
• Arapaxel
• Arketis
• Aropax
• Aropax 20
• Aroxat
• Dapagut
• Daparox
• Depanx
• Deprox
• Deroxat
• Divarius
• Ennos
• Euplix
• Extine
• Harotin 10
• Harotin 20
• Harotin 40
• Loxamine
• Melev
• Olane
• Oxat
• Paluxon
• Pari
• PARI CR
• Parmite
• Paroket
• Parolex
• Paroser
• Paroten
• Parotin
• Parox
• Paroxat
• Paroxil CR
• Paroxin
• Paxan
• Paxetil
• Paxetin
• Paxil
• Paxil CR
• Paxitab
• Paxtine
• Paxxet
• Rexsetin
• Roxet
• Seretran
• Seretran CR
• Seroxat
• Seroxat CR
• Seroxate
• Setine
• Sumiko
• Tagonis
• Tiarix
• Unirox
• Xalexa
• Xandol
• XET
• Xet 20
• Xetanor
• Xetine-P

Paroxetine Brand Names in Pakistan:

Paroxetine 20 mg Tablets
Aiz	Avital Pharma
Aptipar	Aptcure Private Limited
Aroxitin	Everest Pharmaceuticals
Depin	Selmore Agencies
Discerox	Crest Pharmaceuticals
Euopram	Healers Laboratories
Froxtin	Friends Pharma (Pvt) Ltd
Gerox	Glitz Pharma
Harmony	Wilsons Pharmaceuticals
Impika	Wilshire Laboratories (Pvt) Ltd.
Medoxetine	Medera Pharmaceuticals (Pvt) Ltd.
Merit	Xenon Pharmaceuticals (Pvt) Ltd.
Myroxit	Welmark Pharmaceuticals
Nubliss Dispersible	Crest Pharmaceuticals
Obexil	Popular Chemical Works (Pvt) Ltd.
Paraxyl	Consolidated Chemical Laboratories (Pvt) Ltd.
Parinom	Cellgene Pharmaceuticals International
Paromax	Genetics Pharmaceuticals
Parotin	Schazoo Zaka
Parotine	Mediate Pharmaceuticals (Pvt) Ltd
Parotine	Fassgen Pharmaceuticals
Parowin	Orta Labs. (Pvt) Ltd.
Paroxetol	Caraway Pharmaceuticals
Paroxin	Amarant Pharmaceuticals (Pvt)
Paroxin	Amarant Pharmaceuticals (Pvt)
Paroxin	Amarant Pharmaceuticals (Pvt)
Paroxit	Gray`S Pharmaceuticals
Paroxten	Medizan Labs (Pvt) Ltd
Paroxywin	Wns Field Pharmaceuticals
Partin	Alliance Pharmaceuticals (Pvt) Ltd.
Parxet	Bio Labs (Pvt) Ltd.
Parxet	Bio Labs (Pvt) Ltd.
Paxetin	Ferroza International Pharmaceuticals (Pvt) Ltd.
Paxil	Aries Pharmaceuticals (Pvt) Ltd
Peroxa	Organic Pharmaceuticals.
Peroxit	Libra Pharmaceuticals (Pvt) Ltd
Pexeva	Shrooq Pharmaceuticals
Pexot	Helix Pharma (Private) Limited
Pexta	Tg Pharma
Pexus	Nexus Pharma (Pvt) Ltd
Plasare	S.J. & G. Fazul Ellahie (Pvt) Ltd.
Poxet	Medisure Laboratories Pakistan (Pvt.) Ltd.
Progra	Gray`S Pharmaceuticals
Proxetol	Linear Pharma
Pyrotin	Olive Laboratories
Quixet	Albro Pharma
Relenza	Meditech Pharmaceuticals
Roxet	Medicure Laboratories
Rozitin	Pulse Pharmaceuticals
Scots Paroxetine	Scotmann Pharmaceuticals
Seroless	Pharma Health Pakistan (Pvt) Ltd
Seroxat	Glaxosmithkline
Smooth Tabs	Werrick Pharmaceuticals
Taxopar	Mass Pharma (Private) Limited
Twinks	Cherwel Pharmaceuticals (Pvt) Ltd
U-Saprox	Usawa Pharmaceuticals
Unexetin	Tg Pharma
Wixetine	Wilsons Pharmaceuticals
Xintin	Genera Pharmaceuticals
Zaprotin	Swan Pharmaceuticals(Pvt) Ltd

 

Paroxetine 25 mg Tablets
Appease Cr	Everest Pharmaceuticals
Deroxat Cr	Global Pharmaceuticals
Paroxin Cr	Amarant Pharmaceuticals (Pvt)
Raxil	Adamjee Pharmaceuticals (Pvt) Ltd.
Roxet Cr	Medicure Laboratories
Seroxat Cr	Glaxosmithkline
Zara	Shrooq Pharmaceuticals

 

Paroxetine 50 mg Tablets
Tretol	Friends Pharma (Pvt) Ltd

 

Paroxetine 12.5 mg Tablets
Deroxat Cr	Global Pharmaceuticals
Paraxyl Cr	Consolidated Chemical Laboratories (Pvt) Ltd.
Paroxin Cr	Amarant Pharmaceuticals (Pvt)
Pexeva Cr	Shrooq Pharmaceuticals
Raxil	Adamjee Pharmaceuticals (Pvt) Ltd.
Seroxat Cr	Glaxosmithkline

 

Paroxetine 37.5 mg Tablets
Deroxat Cr	Global Pharmaceuticals