paroxetine

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.

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:

May ↑ risk of suicide attempt/ideation, especially during early treatment or dose adjustment; this risk appears to be greater in adolescents or children
;
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 ↑ 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: Safety and effectiveness not established in children;
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, ↓appetite, abdominal pain, dyspepsia, flatulence, taste disturbances, vomiting, weight loss

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

Hemat: BLEEDING

Metab: ↑appetite, weight gain

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 (NMS), paresthesia, SUICIDAL THOUGHTS/BEHAVIORS, syncope, tremor

Resp: cough

Misc: chills, fever, SEROTONIN SYNDROME, yawning

Interactions ⬆ ⬇

Drug-drug:

MAO inhibitors may result in serious, potentially fatal reactions; wait ≥2 wk after stopping MAO inhibitor before initiating paroxetine; wait ≥2 wk after stopping paroxetine before starting MAO inhibitors.
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).
Pimozide or thioridazine may ↑ risk of QT interval prolongation and torsades de pointes; concurrent use contraindicated.
May ↑ levels and risk of toxicity of other antidepressants, phenothiazines, class Ic antiarrhythmics, risperidone, atomoxetine, theophylline, and quinidine; concurrent use should be undertaken with caution.
Cimetidine may ↑ levels and risk of toxicity.
Phenobarbital and phenytoin may ↓ levels and effectiveness.
May ↓ the effectiveness of digoxin and tamoxifen.
May ↑ 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, may ↑ 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 ): 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.

Renal Impairment

PO (Adults ): Paxil or Paxil CR: 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).

Hepatic Impairment

PO (Adults ): Paxil or Paxil CR: 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).

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 suspension orange flavor: 10 mg/5 mL
Paroxetine mesylate capsules : 7.5 mg

Assessment ⬆ ⬇

Monitor appetite and nutritional intake. Weigh weekly. Notify health care provider 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 ↑ in adults ≤24 yr. After starting therapy, young adults should be seen by health care provider face-to-face at least weekly for 4 wk, then every other wk for next 4 wk, then at 12 wk, and then on advice of health care provider thereafter.
Assess for signs and symptoms of serotonin syndrome (confusion, delirium, agitation, coma, dilated pupils, tachycardia, hyperthermia, shivering, hyperreflexia, muscle rigidity, hypertension, vomiting, diarrhea, seizures). ↑ risk of serotonin syndrome with concurrent use of other serotonergic drugs (SSRIs, SNRIs, triptans); discontinuation may be required.
Monitor for signs and symptoms of NMS (hyperpyrexia, muscle rigidity, seizures, altered mental status, evidence of autonomic instability [irregular HR or BP, tachycardia, diaphoresis, cardiac arrhythmia]). If signs/symptoms of NMS occur, discontinue paroxetine.
Assess for rash or signs/symptoms of SJS periodically during therapy (fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis). If SJS suspected, discontinue therapy and provide supportive care.
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 provider if patient demonstrates significant ↑ in anxiety, nervousness, or insomnia.
OCD: Assess 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 periodically during therapy.
Premenstrual Dysphoria: Assess symptoms of premenstrual distress before starting and during therapy.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Assess sodium levels at baseline and then after 3–4 wk in high-risk patients (> 65 yr, previous history of antidepressant-induced hyponatremia, low body weight, concurrent use of thiazides or other hyponatremia-inducing agents).
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 cannot be substituted with paroxetine (Paxil or Paxil CR) or generic paroxetine.
- Periodically reassess dose and continued need for therapy.
During administration and when preparing tablets, wear double chemotherapy gloves, protective gown, and hair and shoe covers. Respiratory (N95) protection and eye/face protection are needed if there is risk of patient vomiting or spitting up. Single chemotherapy gloves are appropriate if handling and administering intact tablets from a unit-dose package. Health care providers who are actively trying to conceive, who are pregnant or may become pregnant, and who are breastfeeding should avoid handling paroxetine.
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 ⬆ ⬇

Explain the purpose and side effects of paroxetine. Instruct patient to take 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 provider 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.
Emphasize the importance of follow-up exams to monitor progress. Encourage patient participation in psychotherapy to improve coping skills.
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 provider 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.
Advise patient and caregivers to immediately notify health care provider if symptoms of serotonin syndrome occur.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider 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 >2 wk.
Advise patient to notify health care provider if headache, weakness, nausea, anorexia, anxiety, or insomnia persists.
Inform patient that paroxetine may cause symptoms of sexual dysfunction. In men, ejaculatory delay or failure, ↓ libido, and erectile dysfunction may occur. In women, may result in ↓ libido and delayed or absent orgasm. Advise patient to notify health care provider if symptoms occur.
Rep: Advise women of reproductive potential to notify health care provider immediately if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Use in the month before delivery has been associated with an ↑ in the risk of postpartum hemorrhage. Infants exposed to paroxetine during 1st trimester have ↑ 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, or 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/.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇