Paxil CR (Paroxetine Hydrochloride) - Indications and Dosage

INDICATIONS AND USAGE

Major Depressive Disorder

PAXIL CR is indicated for the treatment of major depressive disorder.

The efficacy of PAXIL CR in the treatment of a major depressive episode was established in two 12-week controlled trials of outpatients whose diagnoses corresponded to the DSM-IV category of major depressive disorder (see CLINICAL PHARMACOLOGY: Clinical Trials).

A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed mood or loss of interest or pleasure in nearly all activities, representing a change from previous functioning, and includes the presence of at least 5 of the following 9 symptoms during the same 2-week period: Depressed mood, markedly diminished interest or pleasure in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt, or suicidal ideation.

The antidepressant action of paroxetine in hospitalized depressed patients has not been adequately studied.

PAXIL CR has not been systematically evaluated beyond 12 weeks in controlled clinical trials; however, the effectiveness of immediate-release paroxetine hydrochloride in maintaining a response in major depressive disorder for up to 1 year has been demonstrated in a placebo-controlled trial (see CLINICAL PHARMACOLOGY: Clinical Trials). The physician who elects to use PAXIL CR for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION).

Panic Disorder

PAXIL CR is indicated for the treatment of panic disorder, with or without agoraphobia, as defined in DSM-IV. Panic disorder is characterized by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and/or a significant change in behavior related to the attacks.

The efficacy of PAXIL CR controlled-release tablets was established in two 10-week trials in panic disorder patients whose diagnoses corresponded to the DSM-IV category of panic disorder (see CLINICAL PHARMACOLOGY: Clinical Trials).

Panic disorder (DSM-IV) is characterized by recurrent unexpected panic attacks, i.e., a discrete period of intense fear or discomfort in which 4 (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: (1) palpitations, pounding heart, or accelerated heart rate; (2) sweating; (3) trembling or shaking; (4) sensations of shortness of breath or smothering; (5) feeling of choking; (6) chest pain or discomfort; (7) nausea or abdominal distress; (8) feeling dizzy, unsteady, lightheaded, or faint; (9) derealization (feelings of unreality) or depersonalization (being detached from oneself); (10) fear of losing control; (11) fear of dying; (12) paresthesias (numbness or tingling sensations); (13) chills or hot flushes.

Long-term maintenance of efficacy with the immediate-release formulation of paroxetine was demonstrated in a 3-month relapse prevention trial. In this trial, patients with panic disorder assigned to immediate-release paroxetine demonstrated a lower relapse rate compared to patients on placebo (see CLINICAL PHARMACOLOGY: Clinical Trials). Nevertheless, the physician who prescribes PAXIL CR for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION).

Social Anxiety Disorder

PAXIL CR is indicated for the treatment of social anxiety disorder, also known as social phobia, as defined in DSM-IV (300.23). Social anxiety disorder is characterized by a marked and persistent fear of 1 or more social or performance situations in which the person is exposed to unfamiliar people or to possible scrutiny by others. Exposure to the feared situation almost invariably provokes anxiety, which may approach the intensity of a panic attack. The feared situations are avoided or endured with intense anxiety or distress. The avoidance, anxious anticipation, or distress in the feared situation(s) interferes significantly with the person's normal routine, occupational or academic functioning, or social activities or relationships, or there is marked distress about having the phobias. Lesser degrees of performance anxiety or shyness generally do not require psychopharmacological treatment.

The efficacy of PAXIL CR as a treatment for social anxiety disorder has been established, in part, on the basis of extrapolation from the established effectiveness of the immediate-release formulation of paroxetine. In addition, the efficacy of PAXIL CR was established in a 12-week trial, in adult outpatients with social anxiety disorder (DSM-IV). PAXIL CR has not been studied in children or adolescents with social phobia (see CLINICAL PHARMACOLOGY: Clinical Trials).

The effectiveness of PAXIL CR in long-term treatment of social anxiety disorder, i.e., for more than 12 weeks, has not been systematically evaluated in adequate and well-controlled trials. Therefore, the physician who elects to prescribe PAXIL CR for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION).

Premenstrual Dysphoric Disorder

PAXIL CR is indicated for the treatment of PMDD.

The efficacy of PAXIL CR in the treatment of PMDD has been established in 3 placebo-controlled trials (see CLINICAL PHARMACOLOGY: Clinical Trials).

The essential features of PMDD, according to DSM-IV, include markedly depressed mood, anxiety or tension, affective lability, and persistent anger or irritability. Other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. Physical symptoms associated with PMDD include breast tenderness, headache, joint and muscle pain, bloating, and weight gain. These symptoms occur regularly during the luteal phase and remit within a few days following the onset of menses; the disturbance markedly interferes with work or school or with usual social activities and relationships with others. In making the diagnosis, care should be taken to rule out other cyclical mood disorders that may be exacerbated by treatment with an antidepressant.

The effectiveness of PAXIL CR in long-term use, that is, for more than 3 menstrual cycles, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use PAXIL CR for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION).

DOSAGE AND ADMINISTRATION

Major Depressive Disorder

Usual Initial Dosage

PAXIL CR should be administered as a single daily dose, usually in the morning, with or without food. The recommended initial dose is 25 mg/day. Patients were dosed in a range of 25 mg to 62.5 mg/day in the clinical trials demonstrating the effectiveness of PAXIL CR 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 25-mg dose may benefit from dose increases, in 12.5-mg/day increments, up to a maximum of 62.5 mg/day. Dose changes should occur at intervals of at least 1 week.

Patients should be cautioned that PAXIL CR should not be chewed or crushed, and should be swallowed whole.

Maintenance Therapy

There is no body of evidence available to answer the question of how long the patient treated with PAXIL CR 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 of an antidepressant needed to induce remission is identical to the dose needed to maintain and/or sustain euthymia is unknown.

Systematic evaluation of the efficacy of immediate-release paroxetine hydrochloride has shown that efficacy is maintained for periods of up to 1 year with doses that averaged about 30 mg, which corresponds to a 37.5-mg dose of PAXIL CR, based on relative bioavailability considerations (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

Panic Disorder

Usual Initial Dosage

PAXIL CR should be administered as a single daily dose, usually in the morning. Patients should be started on 12.5 mg/day. Dose changes should occur in 12.5-mg/day increments and at intervals of at least 1 week. Patients were dosed in a range of 12.5 to 75 mg/day in the clinical trials demonstrating the effectiveness of PAXIL CR. The maximum dosage should not exceed 75 mg/day.

Patients should be cautioned that PAXIL CR should not be chewed or crushed, and should be swallowed whole.

Maintenance Therapy

Long-term maintenance of efficacy with the immediate-release formulation of paroxetine was demonstrated in a 3-month relapse prevention trial. In this trial, patients with panic disorder assigned to immediate-release 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 CR should be administered as a single daily dose, usually in the morning, with or without food. The recommended initial dose is 12.5 mg/day. Patients were dosed in a range of 12.5 mg to 37.5 mg/day in the clinical trial demonstrating the effectiveness of PAXIL CR in the treatment of social anxiety disorder. If the dose is increased, this should occur at intervals of at least 1 week, in increments of 12.5 mg/day, up to a maximum of 37.5 mg/day.

Patients should be cautioned that PAXIL CR should not be chewed or crushed, and should be swallowed whole.

Maintenance Therapy

There is no body of evidence available to answer the question of how long the patient treated with PAXIL CR should remain on it. Although the efficacy of PAXIL CR 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.

Premenstrual Dysphoric Disorder

Usual Initial Dosage

PAXIL CR should be administered as a single daily dose, usually in the morning, with or without food. PAXIL CR may be administered either daily throughout the menstrual cycle or limited to the luteal phase of the menstrual cycle, depending on physician assessment. The recommended initial dose is 12.5 mg/day. In clinical trials, both 12.5 mg/day and 25 mg/day were shown to be effective. Dose changes should occur at intervals of at least 1 week.

Patients should be cautioned that PAXIL CR should not be chewed or crushed, and should be swallowed whole.

Maintenance/Continuation Therapy

The effectiveness of PAXIL CR for a period exceeding 3 menstrual cycles has not been systematically evaluated in controlled trials. However, women commonly report that symptoms worsen with age until relieved by the onset of menopause. Therefore, it is reasonable to consider continuation of a responding patient. 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 CR and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see WARNINGS: Usage in Pregnancy). 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 of PAXIL CR is 12.5 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 50 mg/day.

Switching Patients to or From a Monoamine Oxidase Inhibitor Antidepressant

At least 14 days should elapse between discontinuation of an MAOI intended to treat depression and initiation of therapy with PAXIL CR. Conversely, at least 14 days should be allowed after stopping PAXIL CR before starting an MAOI antidepressant (see CONTRAINDICATIONS).

Use of PAXIL CR With Reversible MAOIs Such as Linezolid or Methylene Blue

  Do not start PAXIL CR in a patient who is being treated with linezolid or methylene blue because there is increased risk of serotonin syndrome or NMS-like reactions. In a patient who requires more urgent treatment of a psychiatric condition, non-pharmacological interventions, including hospitalization, should be considered (see CONTRAINDICATIONS). In some cases, a patient receiving therapy with PAXIL CR may require urgent treatment with linezolid or methylene blue. If acceptable alternatives to linezolid or methylene blue treatment are not available and the potential benefits of linezolid or methylene blue treatment are judged to outweigh the risks of serotonin syndrome or NMS-like reactions in a particular patient, PAXIL CR should be stopped promptly, and linezolid or methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome or NMS-like reactions for 2 weeks or until 24 hours after the last dose of linezolid or methylene blue, whichever comes first. Therapy with PAXIL CR may be resumed 24 hours after the last dose of linezolid or methylene blue (see WARNINGS).

Discontinuation of Treatment With PAXIL CR

Symptoms associated with discontinuation of immediate-release paroxetine hydrochloride or PAXIL CR have been reported (see PRECAUTIONS: Discontinuation of Treatment with PAXIL CR). Patients should be monitored for these symptoms when discontinuing treatment, regardless of the indication for which PAXIL CR 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.

HOW SUPPLIED

PAXIL CR is supplied as an enteric film-coated, controlled-release, round tablet, as follows:

12.5-mg yellow tablets

NDC 54868-5347-0     Bottles of 30 (engraved with PAXIL CR and 12.5)

25-mg pink tablets

NDC 54868-4791-0     Bottles of 30 (engraved with PAXIL CR and 25)

37.5 mg blue tablets

NDC 54868-5365-0     Bottles of 30 (engraved with PAXIL CR and 37.5)

Store at or below 25°C (77°F) [see USP].

PAXIL CR is a registered trademark of GlaxoSmithKline.

GEOMATRIX is a trademark of Jago Pharma, Muttenz, Switzerland.

GlaxoSmithKline

Research Triangle Park, NC 27709

©2011, GlaxoSmithKline. All rights reserved.

July 2011 PCR:40PI

Additional barcode labeling by:
Physicians Total Care, Inc.
Tulsa, OK       74146