paroxetine

BEERS REMS

Paxil, Paxil CR, Pexeva

Treatment of the following disorders:
- Major depressive disorder,
- Panic disorder.

Paxil, Pexeva

Treatment of the following disorders:
- Obsessive compulsive disorder (OCD),
- Generalized anxiety disorder.

Paxil, Paxil CR

Social anxiety disorder.

Paxil

Post-traumatic stress disorder (PTSD).

Paxil CR

Premenstrual dysphoric disorder.

Paroxetine mesylate (7.5–mg capsule)

Moderate to severe vasomotor symptoms associated with menopause

Action ⬆ ⬇

Inhibits neuronal reuptake of serotonin in the CNS, thus potentiating the activity of serotonin; has little effect on norepinephrine or dopamine; mechanism for benefit in treating vasomotor symptoms unknown.

Therapeutic effects:

Antidepressant action.
Decreased frequency of panic attacks, OCD, or anxiety.
Improvement in manifestations of PTSD.
Decreased dysphoria prior to menses.
Decreased vasomotor symptoms in postmenopausal women

Pharmacokinetics ⬆ ⬇

Absorption: Completely absorbed following oral administration. Controlled-release tablets are enteric-coated and control medication release over 4–5 hr.

Distribution: Widely distributed throughout body fluids and tissues, including the CNS; cross the placenta and enter breast milk.

Protein Binding: 95%.

Metabolism/Excretion: Highly metabolized by the liver, primarily by the CYP2D6 isoenzyme; the CYP2D6 isoenzyme exhibits genetic polymorphism; ∼7% of population may be poor metabolizers and may have significantly ↑ paroxetine concentrations and an ↑ risk of adverse effects. 2% excreted unchanged in urine.

Half-Life: 21 hr.

Time/Action Profile ⬆ ⬇

(antidepressant action)

ROUTE	ONSET	PEAK	DURATION
PO	1–4 wk	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent use of MAO inhibitors or MAO-inhibitor-like drugs (linezolid or methylene blue);
Concurrent use of thioridazine or pimozide;
Lactation: Lactation.

Use Cautiously in:

Risk of suicide (may ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment);
History of mania;
History of seizures;
History of bipolar disorder;
Angle-closure glaucoma;
Severe renal impairment;
Severe hepatic impairment;
OB: Use during the 1st trimester may be associated with an risk of cardiac malformations—consider fetal risk/maternal benefit; use during the 3rd trimester may result in neonatal serotonin syndrome requiring prolonged hospitalization, respiratory and nutritional support;
Pedi: May risk of suicide attempt/ideation especially during early treatment or dose adjustment; may be greater in children and adolescents (safety and effectiveness in children/adolescents not established);
Geri: Appears on Beers list. May worsen or cause syndrome of inappropriate antidiuretic hormone (SIADH) secretion and/or hyponatremia in older adults. Use with caution in older adults and closely monitor sodium concentrations when starting therapy or dose.

Adv. Reactions/Side Effects ⬆ ⬇

CV: chest pain, edema, hypertension, palpitations, postural hypotension, tachycardia, vasodilation

Derm: sweating, photosensitivity, pruritus, rash, STEVENS-JOHNSON SYNDROME (SJS)

EENT: blurred vision, pharyngitis, rhinitis

Endo: SIADH

F and E: hyponatremia

GI: constipation, diarrhea, dry mouth, nausea, abdominal pain, dyspepsia, flatulence, taste disturbances, vomiting

GU: ↓libido, delayed/absent orgasm, ejaculatory delay/failure, erectile dysfunction, genital disorders, infertility, urinary disorders, urinary frequency

Hemat: BLEEDING

Metab: ↓/↑ appetite, weight gain/loss

MS: back pain, bone fracture, myalgia, myopathy

Neuro: anxiety, dizziness, drowsiness, headache, insomnia, weakness, agitation, amnesia, confusion, depression, emotional lability, hangover, impaired concentration, malaise, NEUROLEPTIC MALIGNANT SYNDROME, paresthesia, SUICIDAL THOUGHTS, syncope, tremor

Resp: cough, yawning

Misc: chills, fever, SEROTONIN SYNDROME

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with MAO inhibitors may result in serious, potentially fatal reactions (wait at least 2 wk after stopping MAO inhibitor before initiating paroxetine; wait at least 2 wk after stopping paroxetine before starting MAO inhibitors).
Concurrent use with MAO-inhibitor-like drugs, such as linezolid or methylene blue may ↑ risk of serotonin syndrome; concurrent use contraindicated; do not start therapy in patients receiving linezolid or methylene blue; if linezolid or methylene blue need to be started in a patient receiving paroxetine, immediately discontinue paroxetine and monitor for signs/symptoms of serotonin syndrome for 2 wk or until 24 hr after last dose of linezolid or methylene blue, whichever comes first (may resume paroxetine therapy 24 hr after last dose of linezolid or methylene blue)
Concurrent use with pimozide or thioridazine may ↑ risk of QT interval prolongation and torsades de pointes; concurrent use contraindicated.
May ↓ metabolism and ↑ effects of certain drugs that are metabolized by the liver, including other antidepressants, phenothiazines, class IC antiarrhythmics, risperidone, atomoxetine, theophylline, and quinidine. Concurrent use should be undertaken with caution.
Cimetidine↑ blood levels.
Phenobarbital and phenytoin may ↓ effectiveness.
Concurrent use with alcohol is not recommended.
May ↓ the effectiveness of digoxin and tamoxifen.
↑risk of bleeding with NSAIDs, aspirin, clopidogrel, prasugrel, ticagrelor, dabigatran, apixaban, edoxaban, rivaroxaban, or warfarin.
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SNRIs, fentanyl, lithium, buspirone, tramadol, meperidine, methadone, amphetamines, and triptans, ↑ risk of serotonin syndrome

Drug-Natural Products:

↑risk of serotonergic side effects including serotonin syndrome with St. John’s wort, SAMe, and tryptophan.

Route/Dosage ⬆ ⬇

Depression

PO (Adults ): 20 mg as a single dose in the morning; may ↑ by 10 mg/day at weekly intervals (not to exceed 50 mg/day). Controlled-release tablets: 25 mg once daily initially. May ↑ at weekly intervals by 12.5 mg (not to exceed 62.5 mg/day).
PO Geriatric Patients or Debilitated Patients): 10 mg/day initially; may be slowly ↑ (not to exceed 40 mg/day). Controlled-release tablets: 12.5 mg once daily initially; may be slowly ↑ (not to exceed 50 mg/day).

Obsessive Compulsive Disorder

PO (Adults ): 20 mg/day initially; ↑ by 10 mg/day at weekly intervals up to 40 mg (not to exceed 60 mg/day).

Panic Disorder

PO (Adults ): 10 mg/day initially; ↑ by 10 mg/day at weekly intervals up to 40 mg (not to exceed 60 mg/day). Controlled-release tablets: 12.5 mg/day initially; ↑ by 12.5 mg/day at weekly intervals (not to exceed 75 mg/day).

Social Anxiety Disorder

PO (Adults ): 20 mg/day. Controlled-release tablets: 12.5 mg/day initially; may ↑ by 12.5 mg/day weekly intervals (not to exceed 37.5 mg/day).

Generalized Anxiety Disorder

PO (Adults ): 20 mg once daily initially; ↑ by 10 mg/day at weekly intervals (not to exceed 50 mg/day).

Post-Traumatic Stress Disorder

PO (Adults ): 20 mg/day initially; may ↑ by 10 mg/day at weekly intervals (not to exceed 50 mg/day).

Premenstrual Dysphoric Disorder

PO (Adults ): Controlled-release tablets: 12.5 mg once daily throughout menstrual cycle or during luteal phase of menstrual cycle only; may ↑ to 25 mg/day after 1 wk.

Menopausal Vasomotor Symptoms

PO (Adults ): 7.5 mg once daily at bedtime.

Hepatic Impairment

PO (Adults ):
Paxil, Paxil CR, or Pexeva:
Severe hepatic impairment: 10 mg/day initially; may slowly ↑ (not to exceed 40 mg/day). Controlled-release tablets: 12.5 mg once daily initially; may slowly ↑ (not to exceed 50 mg/day).

Renal Impairment

PO (Adults ):
Paxil, Paxil CR, or Pexeva:
Severe renal impairment: 10 mg/day initially; may slowly ↑ (not to exceed 40 mg/day). Controlled-release tablets: 12.5 mg once daily initially; may slowly ↑ (not to exceed 50 mg/day).

Availability ⬆ ⬇

(Generic available)

Paroxetine hydrochloride tablets: 10 mg; 20 mg; 30 mg; 40 mg
Paroxetine hydrochloride controlled-release tablets: 12.5 mg; 25 mg; 37.5 mg
Paroxetine hydrochloride oral suspensionorange flavor: 10 mg/5 mL
Paroxetine mesylate capsules : 7.5 mg
Paroxetine mesylate tablets (Pexeva): 10 mg; 20 mg; 30 mg

Assessment ⬆ ⬇

Monitor appetite and nutritional intake. Weigh weekly. Notify health care professional of continued weight loss. Adjust diet as tolerated to support nutritional status.
Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults ≤24 yr.
Assess for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans).
Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness). Discontinue paroxetine and notify health care professional immediately if these symptoms occur.
Assess for rash periodically during therapy. May cause SJS. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
Assess sexual function before starting paroxetine. Assess for changes in sexual function during treatment, including timing of onset; patient may not report.
Depression: Monitor mental status (orientation, mood, behavior). Inform health care professional if patient demonstrates significant increase in anxiety, nervousness, or insomnia.
OCD: Assess patient for frequency of obsessive-compulsive behaviors. Note degree to which these thoughts and behaviors interfere with daily functioning.
Panic Attacks: Assess frequency and severity of panic attacks.
Social Anxiety Disorder: Assess frequency and severity of episodes of anxiety.
PTSD: Assess manifestations of post-traumatic stress disorder periodically during therapy.
Premenstrual Dysphoria: Assess symptoms of premenstrual distress prior to and during therapy.

Lab Test Considerations:

Monitor CBC and differential periodically during therapy. Report leukopenia or anemia.

Implementation ⬆ ⬇

Do not confuse paroxetine with fluoxetine, duloxetine, or piroxicam. Do not confuse Paxil with Doxil, Plavix, or Trexall.
- Paroxetine mesylate (Pexeva) cannot be substituted with paroxetine (Paxil or Paxil CR) or generic paroxetine.
- Periodically reassess dose and continued need for therapy.
PO: Administer as a single dose in the morning. May administer with food to minimize GI irritation.
Swallow tablets whole. DNC: Do not crush, break, or chew. Shake suspension before administering.
Taper to avoid potential withdrawal reactions.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take paroxetine as directed. Take missed doses as soon as possible and return to regular dosing schedule. Do not double doses. Caution patient to consult health care professional before discontinuing paroxetine. Daily doses should be decreased slowly. Abrupt withdrawal may cause dizziness, sensory disturbances, agitation, anxiety, nausea, and sweating. Advise patient to read Medication Guide before starting and with each Rx refill in case of changes.
May cause drowsiness or dizziness. Caution patient to avoid driving and other activities requiring alertness until response to the drug is known.
Advise patient, family, and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care professional immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior, or if symptoms of serotonin syndrome or neuroleptic malignant syndrome occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications and to avoid alcohol or other CNS-depressant drugs, including opioids during therapy.
Inform patient that frequent mouth rinses, good oral hygiene, and sugarless gum or candy may minimize dry mouth. Saliva substitute may be used. Consult dentist if dry mouth persists for more than 2 wk.
Advise patient to notify health care professional if headache, weakness, nausea, anorexia, anxiety, or insomnia persists.
Inform patient that paroxetine may cause symptoms of sexual dysfunction. In males, ejaculatory delay or failure, decreased libido, and erectile dysfunction may occur. In female patients, may result in decreased libido and delayed or absent orgasm. Advise patient to notify health care professional if symptoms occur.
Rep: Advise females of reproductive potential to notify health care professional immediately if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Use in the month before delivery has been associated with an increase in the risk of postpartum hemorrhage. Infants exposed to paroxetine during 1st trimester have increased risk of congenital malformations, particularly cardiovascular malformations. If used during pregnancy, should be tapered during 3rd trimester to avoid neonatal serotonin syndrome. Monitor infants exposed to paroxetine for excess sedation, restlessness, agitation, poor feeding, poor weight gain, respiratory distress; may risk of persistent pulmonary hypertension of the newborn. Inform patient of pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Register patient by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-researchprograms/pregnancyregistry/antidepressants/.
Emphasize the importance of follow-up exams to monitor progress. Encourage patient participation in psychotherapy to improve coping skills.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇