PAXIL contains paroxetine hydrochloride, an SSRI. It is the hydrochloride salt of a phenylpiperidine compound identified chemically as (-)-trans-4R-(4′-fluorophenyl)-3S-[(3′,4’methylenedioxyphenoxy) methyl] piperidine hydrochloride hemihydrate and has the empirical formula of C19H20FNO3•HCl•1/2H2O. The molecular weight is 374.8 (329.4 as free base).
PAXIL Tablets: PAXIL tablets are for oral administration. Each film-coated tablet contains 10 mg, 20 mg, 30 mg, or 40 mg of paroxetine equivalent to 11.1 mg, 22.2 mg, 33.3 mg or 44.4 mg of paroxetine hydrochloride, respectively.
Inactive ingredients consist of dibasic calcium phosphate dihydrate, hypromellose, magnesium stearate, polyethylene glycols, polysorbate 80, sodium starch glycolate, titanium dioxide, and 1 or more of the following: D&C Red No. 30 aluminum lake, D&C Yellow No. 10 aluminum lake, FD&C Blue No. 2 aluminum lake, FD&C Yellow No. 6 aluminum lake.
PAXIL Oral Suspension: PAXIL oral suspension is for oral administration. Each 5 mL contains 10 mg of paroxetine equivalent to 11.1 mg of paroxetine hydrochloride.
Inactive ingredients consist of citric acid (anhydrous), FD&C yellow No. 6, flavorings, glycerin, methylparaben, microcrystalline cellulose and carboxymethylcellulose sodium, polacrilin potassium, propylene glycol, propylparaben, purified water, saccharin sodium, simethicone emulsion and sodium citrate (dihydrate).
INDICATIONS AND USAGE
PAXIL is indicated in adults for the treatment of:
- Major depressive disorder (MDD)
- Obsessive compulsive disorder (OCD)
- Panic disorder (PD)
- Social anxiety disorder (SAD)
- Generalized anxiety disorder (GAD)
- Posttraumatic stress disorder (PTSD)
Mechanism of Action
The mechanism of action of PAXIL in the treatment of MDD, SAD, OCD\, PD, GAD, and PTSD is unknown, but is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5-HT).
DOSAGE AND ADMINISTRATION
Administer PAXIL as a single daily dose in the morning, with or without food.
Shake the oral suspension well before administration.
Table 1: Recommended Daily Dosage of PAXIL in Patients with MDD, OCD, PD, and PTSD
|Indication||Starting Dose||Maximum Dose|
|MDD||20 mg||50 mg|
|OCD||20 mg||60 mg|
|PD||10 mg||60 mg|
|PTSD||20 mg||50 mg|
Recommended Dosage for SAD and GAD
SAD: The starting and recommended dosage in patients with SAD is 20 mg daily. In clinical trials the effectiveness of PAXIL was demonstrated in patients dosed in a range of 20 mg to 60 mg daily. While the safety of PAXIL has been evaluated in patients with SAD at doses up to 60 mg daily, available information does not suggest any additional benefit for doses above 20 mg daily.
GAD: The starting and recommended dosage in patients with GAD is 20 mg daily. In clinical trials the effectiveness of PAXIL in GAD was demonstrated in patients dosed in a range of 20 mg to 50 mg daily. There is not sufficient evidence to suggest a greater benefit to doses higher than 20 mg daily.
In patients with an inadequate response, increase dosage in increments of 10 mg per day at intervals of at least 1 week, depending on tolerability.
Screen for Bipolar Disorder Prior to Starting PAXIL
Prior to initiating treatment with PAXIL or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania.
Recommended Dosage for Elderly Patients, Patients with Severe Renal Impairment, and Patients with Severe Hepatic Impairment
The recommended initial dosage is 10 mg per day for elderly patients, patients with severe renal impairment, and patients with severe hepatic impairment. Dosage should not exceed 40 mg/day.
Switching Patients to or From a Monoamine Oxidase Inhibitor (MAOI)
At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI and initiation of PAXIL. In addition, at least 14 days must elapse after stopping PAXIL before starting an MAOI antidepressant.
Discontinuation of Treatment With PAXIL
Adverse reactions may occur upon discontinuation of PAXIL. Gradually reduce the dosage rather than stopping PAXIL abruptly whenever possible.
PAXIL is contraindicated in patients:
- Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome.
- Taking thioridazine because of risk of QT
- Taking pimozide because of risk of QT prolongation.
- With known hypersensitivity (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome) to paroxetine or any of the inactive ingredients in PAXIL
WARNINGS AND PRECAUTIONS
- Increased risk of suicidal thoughts and behavior in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. PAXIL is not approved for use in pediatric patients.
- Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRI, SNRI, triptans), but also when taken alone. If occurs, discontinue PAXIL and initiate supportive measures.
- Embryofetal and Neonatal Toxicity: Can cause fetal and neonatal harm. Increased risk of cardiovascular malformations with exposure during the first trimester. Exposure in late pregnancy may lead to an increased risk for persistent pulmonary hypertension of the newborn.
- Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, other antiplatelet drugs, warfarin, and other anticoagulant drugs may increase risk.
- Activation of Mania/Hypomania: Screen patients for bipolar disorder.
- Seizures: Use with caution in patients with seizure disorders.
- Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants.
- Sexual Dysfunction: PAXIL may cause symptoms of sexual dysfunction.
MDD: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance, and other male genital disorders.
OCD: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence, and abnormal ejaculation.
PD: Asthenia, sweating, decreased appetite, libido decreased, tremor, abnormal ejaculation, female genital disorders, and impotence.
SAD: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, libido decreased, yawn, abnormal ejaculation, female genital disorders, and impotence.
GAD: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, libido decreased, somnolence, tremor, sweating, and abnormal ejaculation.
PTSD: Asthenia, sweating, nausea, dry mouth, diarrhea, decreased appetite, somnolence, libido decreased, abnormal ejaculation, female genital disorders, and impotence.
|Monoamine Oxidase Inhibitors (MAOIs)|
|Clinical Impact||The concomitant use of SSRIs, including PAXIL, and MAOIs increases the risk of serotonin syndrome.|
|Intervention||PAXIL is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue.|
|Examples||selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue|
|Pimozide and Thioridazine|
|Clinical Impact||Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias.|
|Intervention||PAXIL is contraindicated in patients taking pimozide or thioridazine.|
|Other Serotonergic Drugs|
|Clinical Impact||The concomitant use of serotonergic drugs with PAXIL increases the risk of serotonin syndrome.|
|Intervention||Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of PAXIL and/or concomitant serotonergic drugs.|
|Examples||other SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort|
|Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants)|
|Clinical Impact||The concurrent use of an antiplatelet agent or anticoagulant with PAXIL may potentiate the risk of bleeding.|
|Intervention||Inform patients of the increased risk of bleeding associated with the concomitant use of PAXIL and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio.|
|Examples||aspirin, clopidogrel, heparin, warfarin|
|Drugs Highly Bound to Plasma Protein|
|Clinical Impact||PAXIL is highly bound to plasma protein. The concomitant use of PAXIL with another drug that is highly bound to plasma protein may increase free concentrations of PAXIL or other tightly-bound drugs in plasma.|
|Intervention||Monitor for adverse reactions and reduce dosage of PAXIL or other protein-bound drugs as warranted.|
|Drugs Metabolized by CYP2D6|
|Clinical Impact||PAXIL is a CYP2D6 inhibitor. The concomitant use of PAXIL with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate.|
|Intervention||Decrease the dosage of a CYP2D6 substrate if needed with concomitant PAXIL use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if PAXIL is discontinued.|
|Examples||propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone.|
|Clinical Impact||Concomitant use of tamoxifen with PAXIL may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen|
|Intervention||Consider use of an alternative antidepressant with little or no CYP2D6 inhibition.|
|Clinical Impact||Co-administration of fosamprenavir/ritonavir with PAXIL significantly decreased plasma levels of PAXIL.|
|Intervention||Any dose adjustment should be guided by clinical effect (tolerability and efficacy).|
USE IN SPECIFIC POPULATIONS
Pregnancy Category D: Epidemiological studies have shown that infants exposed to paroxetine in the first trimester of pregnancy have an increased risk of congenital malformations, particularly cardiovascular malformations. If paroxetine is used during pregnancy, or if the patient becomes pregnant while taking paroxetine, advise the patient of the potential hazard to the fetus.
Unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant
Like many other drugs, paroxetine is secreted in human milk. Because of the potential for serious adverse reactions in nursing infants from PAXIL, a decision should be made whether to discontinue nursing infants or to discontinue the drug, taking into account the importance of the drug to the mother.
The safety and effectiveness of PAXIL in pediatric patients have not been established. Effectiveness was not demonstrated in three placebo-controlled trials in 752 PAXIL-treated pediatric patients with MDD.
Renal and Hepatic Impairment
Increased plasma concentrations of paroxetine occur in patients with renal and hepatic impairment. The initial dosage of PAXIL should be reduced in patients with severe renal impairment and in patients with severe hepatic impairment.
The following have been reported with paroxetine tablet overdosage:
- Seizures, which may be delayed, and altered mental status including coma.
- Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation. Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol.
- Serotonin syndrome (patients with a multiple drug overdosage with other proserotonergic drugs may have a higher risk).
Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a paroxetine overdose.