Drug Name

Paxil (Paroxetine)

Generic Name

Paroxetine (par-OX-e-teen)

Looks like

• Paxil 10 mg - oval, yellow, film-coated scored tablets
• Paxil 20 mg - oval, pink, film-coated scored tablets
• Paxil 30 mg - oval, blue, film-coated scored tablets
• Paxil 40 mg - oval, green, film-coated scored tablets

Dosage Form

Tablets

Route Of Administration

ORAL

Imprint Code

Paxil;10 / Paxil;20 / Paxil;30 / Paxil;40

Size

9mm / 11mm / 13mm / 14mm

Alternatives

Anxiety
Lexapro (Escitalopram), Cymbalta (Duloxetine)
Depression
Lexapro (Escitalopram), Cymbalta (Duloxetine) Zoloft (Sertraline), Prozac (Fluoxetine)
Panic Disorder
Zoloft (Sertraline), Prozac (Fluoxetine)
Obsessive Compulsive Disorder
Zoloft (Sertraline), Prozac (Fluoxetine), Celexa (Citalopram)

Drug Uses

Paxil is used to treat depression, obsessive-compulsive disorder, anxiety disorders, post-traumatic stress disorder (PTSD), and premenstrual dysphoric disorder (PMDD).

Drug class

Paxil is an antidepressant in a group of drugs called selective serotonin reuptake inhibitors (SSRIs). Paxil affects chemicals in the brain that may become unbalanced.

Contains

Each film-coated tablet contains paroxetine hydrochloride equivalent to paroxetine as follows: 10 mg-yellow (scored); 20 mg-pink (scored); 30 mg-blue, 40 mg-green. 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, D&C Yellow No. 10, FD&C Blue No. 2, FD&C Yellow No. 6.

Chemical formula

Paxil (paroxetine hydrochloride) is an orally administered psychotropic drug. 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). The structural formula of paroxetine hydrochloride is:
Paroxetine hydrochloride is an odorless, off-white powder, having a melting point range of 120C to 138C and a solubility of 5.4 mg/mL in water.

Mechanism of Action

The efficacy of paroxetine in the treatment of major depressive disorder, social anxiety disorder, obsessive compulsive disorder (OCD), panic disorder (PD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD) 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). Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. In vitro radioligand binding studies indicate that paroxetine has little affinity for muscarinic, alpha1-, alpha2-, beta-adrenergic-, dopamine (D2)-, 5-HT1-, 5-HT2-, and histamine (H1)-receptors; antagonism of muscarinic, histaminergic, and alpha1-adrenergic receptors has been associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs.

Because the relative potencies of paroxetine's major metabolites are at most 1/50 of the parent compound, they are essentially inactive.

How Taken

Take Paxil exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Your doctor may occasionally change your dose to make sure you get the best results from the medication.

Try to take the medicine at the same time each day. Follow the directions on your prescription label.

Do not crush, chew, or break a controlled-release tablet. Swallow the pill whole. It is specially made to release medicine slowly in the body. Breaking the pill would cause too much of the drug to be released at one time. Shake the liquid form of Paxil well just before you measure a dose. To be sure you get the correct dose, measure the liquid with a marked measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one. It may take up to 4 weeks of using this medicine before your symptoms improve. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after 4 weeks of treatment.
You may have withdrawal symptoms (such as agitation, dizziness, numbness or tingling, ringing in your ears, confusion, or behavior changes) after you stop taking Paxil. Do not stop taking Paxil suddenly without first talking to your doctor.

Dosage and Administration

Major Depressive Disorder

Usual Initial Dosage
Paxil should be administered as a single daily dose with or without food, usually in the morning. The recommended initial dose is 20 mg/day. Patients were dosed in a range of 20 to 50 mg/day in the clinical trials demonstrating the effectiveness of Paxil in the treatment of major depressive disorder. As with all drugs effective in the treatment of major depressive disorder, the full effect may be delayed. Some patients not responding to a 20-mg dose may benefit from dose increases, in 10-mg/day increments, up to a maximum of 50 mg/day. Dose changes should occur at intervals of at least 1 week.

Maintenance Therapy
There is no body of evidence available to answer the question of how long the patient treated with Paxil should remain on it. It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy. Whether the dose needed to induce remission is identical to the dose needed to maintain and/or sustain euthymia is unknown.

Systematic evaluation of the efficacy of Paxil has shown that efficacy is maintained for periods of up to 1 year with doses that averaged about 30 mg.

Obsessive Compulsive Disorder

Usual Initial Dosage
Paxil should be administered as a single daily dose with or without food, usually in the morning. The recommended dose of Paxil in the treatment of OCD is 40 mg daily. Patients should be started on 20 mg/day and the dose can be increased in 10-mg/day increments. Dose changes should occur at intervals of at least 1 week. Patients were dosed in a range of 20 to 60 mg/day in the clinical trials demonstrating the effectiveness of Paxil in the treatment of OCD. The maximum dosage should not exceed 60 mg/day.

Maintenance Therapy
Long-term maintenance of efficacy was demonstrated in a 6-month relapse prevention trial. In this trial, patients with OCD assigned to paroxetine demonstrated a lower relapse rate compared to patients on placebo. OCD is a chronic condition, and it is reasonable to consider continuation for a responding patient. Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Panic Disorder

Usual Initial Dosage
Paxil should be administered as a single daily dose with or without food, usually in the morning. The target dose of Paxil in the treatment of panic disorder is 40 mg/day. Patients should be started on 10 mg/day. Dose changes should occur in 10-mg/day increments and at intervals of at least 1 week. Patients were dosed in a range of 10 to 60 mg/day in the clinical trials demonstrating the effectiveness of Paxil. The maximum dosage should not exceed 60 mg/day.

Maintenance Therapy
Long-term maintenance of efficacy was demonstrated in a 3-month relapse prevention trial. In this trial, patients with panic disorder assigned to paroxetine demonstrated a lower relapse rate compared to patients on placebo. Panic disorder is a chronic condition, and it is reasonable to consider continuation for a responding patient. Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Social Anxiety Disorder

Usual Initial Dosage
Paxil should be administered as a single daily dose with or without food, usually in the morning. The recommended and initial dosage is 20 mg/day. In clinical trials the effectiveness of Paxil was demonstrated in patients dosed in a range of 20 to 60 mg/day. While the safety of Paxil has been evaluated in patients with social anxiety disorder at doses up to 60 mg/day, available information does not suggest any additional benefit for doses above 20 mg/day.

Maintenance Therapy
There is no body of evidence available to answer the question of how long the patient treated with Paxil should remain on it. Although the efficacy of Paxil beyond 12 weeks of dosing has not been demonstrated in controlled clinical trials, social anxiety disorder is recognized as a chronic condition, and it is reasonable to consider continuation of treatment for a responding patient. Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Generalized Anxiety Disorder

Usual Initial Dosage
Paxil should be administered as a single daily dose with or without food, usually in the morning. In clinical trials the effectiveness of Paxil was demonstrated in patients dosed in a range of 20 to 50 mg/day. The recommended starting dosage and the established effective dosage is 20 mg/day. There is not sufficient evidence to suggest a greater benefit to doses higher than 20 mg/day. Dose changes should occur in 10 mg/day increments and at intervals of at least 1 week.

Maintenance Therapy
Systematic evaluation of continuing Paxil for periods of up to 24 weeks in patients with Generalized Anxiety Disorder who had responded while taking Paxil during an 8-week acute treatment phase has demonstrated a benefit of such maintenance. Nevertheless, patients should be periodically reassessed to determine the need for maintenance treatment.

Posttraumatic Stress Disorder

Usual Initial Dosage
Paxil should be administered as a single daily dose with or without food, usually in the morning. The recommended starting dosage and the established effective dosage is 20 mg/day. In 1 clinical trial, the effectiveness of Paxil was demonstrated in patients dosed in a range of 20 to 50 mg/day. However, in a fixed dose study, there was not sufficient evidence to suggest a greater benefit for a dose of 40 mg/day compared to 20 mg/day. Dose changes, if indicated, should occur in 10 mg/day increments and at intervals of at least 1 week.

Maintenance Therapy
There is no body of evidence available to answer the question of how long the patient treated with Paxil should remain on it. Although the efficacy of Paxil beyond 12 weeks of dosing has not been demonstrated in controlled clinical trials, PTSD is recognized as a chronic condition, and it is reasonable to consider continuation of treatment for a responding patient. Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Special Populations

Treatment of Pregnant Women During the Third Trimester
Neonates exposed to Paxil and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see WARNINGS). When treating pregnant women with paroxetine during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering paroxetine in the third trimester.

Dosage for Elderly or Debilitated Patients, and Patients With Severe Renal or Hepatic Impairment
The recommended initial dose is 10 mg/day for elderly patients, debilitated patients, and/or patients with severe renal or hepatic impairment. Increases may be made if indicated. Dosage should not exceed 40 mg/day.

Switching Patients to or From a Monoamine Oxidase Inhibitor
At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with Paxil. Similarly, at least 14 days should be allowed after stopping Paxil before starting an MAOI.

Discontinuation of Treatment With Paxil
Symptoms associated with discontinuation of Paxil have been reported. Patients should be monitored for these symptoms when discontinuing treatment, regardless of the indication for which Paxil is being prescribed. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered.
Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

Missed Dose

Take the missed dose as soon as you remember. However, if it is almost time for the next regularly scheduled dose, skip the missed dose and take the next one as directed. Do not take extra medicine to make up the missed dose.

Overdose

Seek emergency medical attention if you think you have taken too much of Paxil. Symptoms of a Paxil overdose may include nausea, vomiting, tremor, sweating, decreased urination, blurred vision, rapid heartbeat, confusion, aggression, seizures, and coma.

Storage

Store Paxil at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Paxil out of the reach of children and away from pets.

How Supplied

Film-coated, modified-oval as follows:

10-mg yellow, scored tablets engraved on the front with Paxil and on the back with 10.
NDC 0029-3210-13 Bottles of 30

20-mg pink, scored tablets engraved on the front with Paxil and on the back with 20.
NDC 0029-3211-13 Bottles of 30
NDC 0029-3211-59 Bottles of 90
NDC 0029-3211-21 SUP 100s (intended for institutional use only)

30-mg blue tablets engraved on the front with Paxil and on the back with 30.
NDC 0029-3212-13 Bottles of 30

40-mg green tablets engraved on the front with Paxil and on the back with 40.
NDC 0029-3213-13 Bottles of 30

What is the most important information I should know about Paxil (Paroxetine)?

You may have an increased risk of suicidal thoughts or behavior at the start of treatment with an antidepressant medication, especially if you are a child or young adult. Talk with your doctor about this risk. While you are taking Paxil you will need to be monitored for worsening symptoms of depression and/or suicidal thoughts during the first weeks of treatment, or whenever your dose is changed. In addition to you watching for changes in your own symptoms, your family or other caregivers should be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

Contact your doctor promptly if you have any of the following side effects, especially if they are new symptoms or if they get worse: mood changes, anxiety, panic attacks, trouble sleeping, irritability, agitation, aggressiveness, severe restlessness, mania (mental and/or physical hyperactivity), thoughts of suicide or hurting yourself. Paxil may cause heart defects or serious, life-threatening lung problems in newborn babies whose mothers take the medication during pregnancy. However, you may have a relapse of depression if you stop taking your antidepressant during pregnancy. If you are planning a pregnancy, or if you become pregnant while taking Paxil, do not stop taking the medication without first talking to your doctor. Do not take Paxil together with pimozide (Orap), thioridazine (Mellaril), or a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate).

What should I discuss with my doctor before taking Paxil (Paroxetine)?

You may have an increased risk of suicidal thoughts or behavior at the start of treatment with an antidepressant medication, especially if you are a child or young adult. Talk with your doctor about this risk. While you are taking Paxil you will need to be monitored for worsening symptoms of depression and/or suicidal thoughts during the first weeks of treatment, or whenever your dose is changed. In addition to you watching for changes in your own symptoms, your family or other caregivers should be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits for at least the first 12 weeks.

Do not use Paxil if you are using pimozide (Orap), thioridazine (Mellaril), or an MAO inhibitor such as isocarboxazid (Marplan), tranylcypromine (Parnate), phenelzine (Nardil), rasagiline (Azilect), or selegiline (Eldepryl, Emsam). Serious and sometimes fatal reactions can occur when these medicines are taken with Paxil. You must wait at least 14 days after stopping an MAO inhibitor before you can take Paxil. After you stop taking Paxil, you must wait at least 14 days before you start taking an MAOI.
Before taking Paxil, tell your doctor if you are allergic to any drugs, or if you have:

• liver or kidney disease;
• seizures or epilepsy;
• bipolar disorder (manic depression), or a history of drug abuse or suicidal thoughts.

If you have any of these conditions, you may not be able to use Paxil, or you may need a dosage adjustment or special tests.

FDA pregnancy category D. Paxil may cause heart defects or serious, life-threatening lung problems in newborn babies whose mothers take the medication during pregnancy. However, you may have a relapse of depression if you stop taking your antidepressant during pregnancy. If you are planning a pregnancy, or if you become pregnant while taking Paxil, do not stop taking the medication without first talking to your doctor. Paxil can pass into breast milk and may harm a nursing baby. Do not use Paxil without telling your doctor if you are breast-feeding a baby.

Absorption and Distribution

Paroxetine is equally bioavailable from the oral suspension and tablet.

Paroxetine hydrochloride is completely absorbed after oral dosing of a solution of the hydrochloride salt. In a study in which normal male subjects (n = 15) received 30 mg tablets daily for 30 days, steady-state paroxetine concentrations were achieved by approximately 10 days for most subjects, although it may take substantially longer in an occasional patient. At steady state, mean values of Cmax, Tmax, Cmin, and T1/2 were 61.7 ng/mL (CV 45%), 5.2 hr. (CV 10%), 30.7 ng/mL (CV 67%), and 21.0 hours (CV 32%), respectively. The steady-state Cmax and Cmin values were about 6 and 14 times what would be predicted from single-dose studies. Steady-state drug exposure based on AUC0-24 was about 8 times greater than would have been predicted from single-dose data in these subjects. The excess accumulation is a consequence of the fact that 1 of the enzymes that metabolizes paroxetine is readily saturable.

The effects of food on the bioavailability of paroxetine were studied in subjects administered a single dose with and without food. AUC was only slightly increased (6%) when drug was administered with food but the Cmax was 29% greater, while the time to reach peak plasma concentration decreased from 6.4 hours post-dosing to 4.9 hours.

Paroxetine distributes throughout the body, including the CNS, with only 1% remaining in the plasma.

Approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/mL and 400 ng/mL, respectively. Under clinical conditions, paroxetine concentrations would normally be less than 400 ng/mL. Paroxetine does not alter the in vitro protein binding of phenytoin or warfarin.

Metabolism and Excretion

The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets daily for 30 days of Paxil. In steady-state dose proportionality studies involving elderly and nonelderly patients, at doses of 20 mg to 40 mg daily for the elderly and 20 mg to 50 mg daily for the nonelderly, some nonlinearity was observed in both populations, again reflecting a saturable metabolic pathway. In comparison to Cmin values after 20 mg daily, values after 40 mg daily were only about 2 to 3 times greater than doubled.

Paroxetine is extensively metabolized after oral administration. The principal metabolites are polar and conjugated products of oxidation and methylation, which are readily cleared. Conjugates with glucuronic acid and sulfate predominate, and major metabolites have been isolated and identified. Data indicate that the metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolism of paroxetine is accomplished in part by CYP2D6. Saturation of this enzyme at clinical doses appears to account for the nonlinearity of paroxetine kinetics with increasing dose and increasing duration of treatment. The role of this enzyme in paroxetine metabolism also suggests potential drug-drug interactions.

Approximately 64% of a 30-mg oral solution dose of paroxetine was excreted in the urine with 2% as the parent compound and 62% as metabolites over a 10-day post-dosing period. About 36% was excreted in the feces (probably via the bile), mostly as metabolites and less than 1% as the parent compound over the 10-day post-dosing period.

Special Populations

Renal and Liver Disease

Increased plasma concentrations of paroxetine occur in subjects with renal and hepatic impairment. The mean plasma concentrations in patients with creatinine clearance below 30 mL/min. were approximately 4 times greater than seen in normal volunteers. Patients with creatinine clearance of 30 to 60 mL/min. and patients with hepatic functional impairment had about a 2-fold increase in plasma concentrations (AUC, Cmax).

Hepatic Impairment

The initial dosage should therefore be reduced in patients with severe renal or hepatic impairment, and upward titration, if necessary, should be at increased intervals.

Elderly Patients

In a multiple-dose study in the elderly at daily paroxetine doses of 20, 30, and 40 mg, Cmin concentrations were about 70% to 80% greater than the respective Cmin concentrations in nonelderly subjects. Therefore the initial dosage in the elderly should be reduced.

Possible side effects

Get emergency medical help if you have any of these signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Contact your doctor promptly if you have any of the following side effects, especially if they are new symptoms or if they get worse: mood changes, anxiety, panic attacks, trouble sleeping, irritability, agitation, aggressiveness, severe restlessness, mania (mental and/or physical hyperactivity), thoughts of suicide or hurting yourself.
Call your doctor at once if you have any of these serious side effects:

• seizure (convulsions);
• tremors, shivering, muscle stiffness or twitching;
• problems with balance or coordination; or
• agitation, confusion, sweating, fast heartbeat.

Other less serious side effects are more likely to occur, such as:

• feeling nervous, restless, or unable to sit still;
• drowsiness, dizziness, weakness;
• sleep problems (insomnia);
• nausea, constipation, loss of appetite;
• weight changes;
• decreased sex drive, impotence, or difficulty having an orgasm; or
• dry mouth, yawning, or ringing in your ears.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect Paxil (Paroxetine)?

Talk to your doctor before taking any medicine for pain, arthritis, fever, or swelling. This includes aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), diclofenac (Voltaren), indomethacin, piroxicam (Feldene), nabumetone (Relafen), etodolac (Lodine), and others. Taking an