Paxil CR

Paroxetine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• headache
• dizziness
• weakness
• difficulty concentrating
• nervousness
• forgetfulness
• confusion
• sleepiness or feeling ''drugged''
• nausea
• vomiting
• diarrhea
• constipation
• gas
• stomach pain
• heartburn
• changes in ability to taste food
• decreased appetite
• weight loss or gain
• changes in sex drive or ability
• dry mouth
• sweating
• yawning
• sensitivity to light
• lump or tightness in throat
• pain in the back, muscles, bones, or anywhere in the body
• tenderness or swelling of joints
• muscle weakness or tightness
• flushing
• sore teeth and gums
• unusual dreams
• painful or irregular menstruation

Some side effects can be serious. If you experience any of the following symptoms or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS sections, call your doctor immediately or get emergency medical treatment:

• seeing things or hearing voices that do not exist (hallucinating)
• fainting
• rapid, pounding, or irregular heartbeat
• chest pain
• difficulty breathing
• seizures
• fever, sweating, confusion, fast or irregular heartbeat, and severe muscle stiffness or twitching
• abnormal bleeding or bruising
• tiny red spots directly under the skin
• peeling or blistering of skin
• sore throat, fever, chills, cough, and other signs of infection
• uncontrollable shaking of a part of the body
• unsteady walking that may cause falling
• sudden muscle twitching or jerking that you cannot control
• numbness or tingling in your hands, feet, arms, or legs
• difficult, frequent, or painful urination
• swelling, itching, burning, or infection in the vagina
• painful erection that lasts for hours
• sudden nausea, vomiting, weakness, cramping, bloating, swelling, tightness in hands and feet, dizziness, headache and/or confusion
• hives
• skin rash
• itching
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness
• black and tarry stools
• red blood in stools
• bloody vomit
• vomit that looks like coffee grounds
• bone pain
• tenderness, swelling, or bruising of one part of your body

Paroxetine may decrease appetite and cause weight loss in children. Your child's doctor will watch his or her growth carefully. Talk to your child's doctor if you have concerns about your child's growth or weight while he or she is taking this medication. Talk to your child's doctor about the risks of giving paroxetine to your child.

Paroxetine may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Clinical Worsening And Suicide Risk

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4,400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1,000 patients treated) are provided in Table 1.

Table 1

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.

It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (see PRECAUTIONS and DOSAGE AND ADMINISTRATION: Discontinuation of Treatment With PAXIL CR, for a description of the risks of discontinuation of PAXIL CR).

Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers.

Prescriptions for PAXIL CR should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Screening Patients For Bipolar Disorder

A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that PAXIL CR is not approved for use in treating bipolar depression.

Serotonin Syndrome

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including PAXIL CR, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome.

The concomitant use of PAXIL CR with MAOIs intended to treat psychiatric disorders is contraindicated. PAXIL CR should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue. All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. There may be circumstances when it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking PAXIL CR. PAXIL CR should be discontinued before initiating treatment with the MAOI (see CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION).

If concomitant use of PAXIL CR with certain other serotonergic drugs, i.e., triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John's Wort is clinically warranted, be aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.

Treatment with PAXIL CR and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.

Angle-Closure Glaucoma

The pupillary dilation that occurs following use of many antidepressant drugs including Paxil may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

Potential Interaction With Thioridazine

Thioridazine administration alone produces prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as torsade de pointes–type arrhythmias, and sudden death. This effect appears to be dose related.

An in vivo study suggests that drugs which inhibit CYP2D6, such as paroxetine, will elevate plasma levels of thioridazine. Therefore, it is recommended that paroxetine not be used in combination with thioridazine (see CONTRAINDICATIONS and PRECAUTIONS).

Usage In Pregnancy

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. The findings from these studies are summarized below:

• A study based on Swedish national registry data demonstrated that infants exposed to paroxetine during pregnancy (n = 815) had an increased risk of cardiovascular malformations (2% risk in paroxetine-exposed infants) compared to the entire registry population (1% risk), for an odds ratio (OR) of 1.8 (95% confidence interval 1.1 to 2.8). No increase in the risk of overall congenital malformations was seen in the paroxetine-exposed infants. The cardiac malformations in the paroxetine-exposed infants were primarily ventricular septal defects (VSDs) and atrial septal defects (ASDs). Septal defects range in severity from those that resolve spontaneously to those which require surgery.
• A separate retrospective cohort study from the United States (United Healthcare data) evaluated 5,956 infants of mothers dispensed antidepressants during the first trimester (n = 815 for paroxetine). This study showed a trend towards an increased risk for cardiovascular malformations for paroxetine (risk of 1.5%) compared to other antidepressants (risk of 1%), for an OR of 1.5 (95% confidence interval 0.8 to 2.9). Of the 12 paroxetine-exposed infants with cardiovascular malformations, 9 had VSDs. This study also suggested an increased risk of overall major congenital malformations including cardiovascular defects for paroxetine (4% risk) compared to other (2% risk) antidepressants (OR 1.8; 95% confidence interval 1.2 to 2.8).
• Two large case-control studies using separate databases, each with > 9,000 birth defect cases and > 4,000 controls, found that maternal use of paroxetine during the first trimester of pregnancy was associated with a 2-to 3-fold increased risk of right ventricular outflow tract obstructions. In one study the OR was 2.5 (95% confidence interval, 1.0 to 6.0, 7 exposed infants) and in the other study the OR was 3.3 (95% confidence interval, 1.3 to 8.8, 6 exposed infants).

Other studies have found varying results as to whether there was an increased risk of overall, cardiovascular, or specific congenital malformations. A meta-analysis of epidemiological data over a 16-year period (1992 to 2008) on first trimester paroxetine use in pregnancy and congenital malformations included the above-noted studies in addition to others (n = 17 studies that included overall malformations and n = 14 studies that included cardiovascular malformations; n = 20 distinct studies). While subject to limitations, this meta-analysis suggested an increased occurrence of cardiovascular malformations (prevalence odds ratio [POR] 1.5; 95% confidence interval 1.2 to 1.9) and overall malformations (POR 1.2; 95% confidence interval 1.1 to 1.4) with paroxetine use during the first trimester. It was not possible in this meta-analysis to determine the extent to which the observed prevalence of cardiovascular malformations might have contributed to that of overall malformations, nor was it possible to determine whether any specific types of cardiovascular malformations might have contributed to the observed prevalence of all cardiovascular malformations.

If a patient becomes pregnant while taking paroxetine, she should be advised of the potential harm 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 (see PRECAUTIONS: Discontinuation of Treatment With PAXIL CR). For women who intend to become pregnant or are in their first trimester of pregnancy, paroxetine should only be initiated after consideration of the other available treatment options.

Reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. These doses are approximately 8 (rat) and 2 (rabbit) times the maximum recommended human dose (MRHD) on an mg/m² basis. These studies have revealed no evidence of teratogenic effects. However, in rats, there was an increase in pup deaths during the first 4 days of lactation when dosing occurred during the last trimester of gestation and continued throughout lactation. This effect occurred at a dose of 1 mg/kg/day or approximately one-sixth of the MRHD on an mg/m² basis. The no-effect dose for rat pup mortality was not determined. The cause of these deaths is not known.

Neonates exposed to PAXIL CR and other SSRIs or serotonin and norepinephrine reuptake inhibitors (SNRIs), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome (see WARNINGS: Serotonin Syndrome).

Infants exposed to SSRIs in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1 – 2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Several recent epidemiologic studies suggest a positive statistical association between SSRI use (including PAXIL CR) in pregnancy and PPHN. Other studies do not show a significant statistical association.

Physicians should also note the results of a prospective longitudinal study of 201 pregnant women with a history of major depression, who were either on antidepressants or had received antidepressants less than 12 weeks prior to their last menstrual period, and were in remission. Women who discontinued antidepressant medication during pregnancy showed a significant increase in relapse of their major depression compared to those women who remained on antidepressant medication throughout pregnancy.

When treating a pregnant woman with PAXIL CR, the physician should carefully consider both the potential risks of taking an SSRI, along with the established benefits of treating depression with an antidepressant. This decision can only be made on a case by case basis (see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS, Postmarketing Reports).

Drinking alcohol can increase some of the side effects of paroxetine.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

• Apotex Inc.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• MAO inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Emsam, Eldepryl, Zelapar) and tranylcypromine (Parnate)
• Mellaril (thioridazine)
• Orap (pimozide)
• triptans used to treat migraine headache
• other antidepressants (SSRIs, SNRIs, tricyclics, or lithium) or antipsychotics
• drugs that affect serotonin, such as lithium, tramadol, tryptophan, St. John’s wort
• certain drugs used to treat irregular heart beats
• certain drugs used to treat schizophrenia
• certain drugs used to treat HIV infection
• certain drugs that affect the blood, such as warfarin, aspirin, and ibuprofen
• certain drugs used to treat epilepsy
• atomoxetine
• cimetidine
• fentanyl
• metoprolol
• certain medicines used to treat seizures (like phenobarbital and phenytoin)
• procyclidine
• tamoxifen

Ask your healthcare provider if you are not sure if you are taking any of these medications.

• Paxil CR comes as an extended release tablet and is to be taken by mouth.
• It is usually taken once daily in the morning, with or without food.
• If you are being treated for Premenstrual Dysphoric Disorder, Paxil CR can be taken daily, either daily throughout the menstrual cycle or on certain days of the cycle.
• You may want to take Paxil CR with food to prevent stomach upset. Take Paxil CR at around the same time every day.
• Follow the directions on your prescription label carefully.
• Take Paxil CR exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
• Swallow Paxil CR tablets whole; do not chew or crush the tablets.
• If you miss a dose of Paxil CR, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Paxil CR at the same time.
• If you take too much Paxil CR call your healthcare provider or poison control center right away, or get emergency treatment.

Paxil CR controls your condition but does not cure it. It may take several weeks or longer before you feel the full benefit of Paxil CR. Continue to take Paxil CR even if you feel well. Do not stop taking Paxil CR without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking Paxil CR, you may experience withdrawal symptoms such as depression; mood changes; frenzied or abnormally excited mood; irritability; anxiety; confusion; dizziness; headache; tiredness; numbness or tingling in the arms, legs, hands, or feet; unusual dreams; difficulty falling asleep or staying asleep; nausea; or sweating. Tell your doctor if you experience any of these symptoms when your dose of Paxil CR is decreased.

Take Paxil CR exactly as prescribed. Follow the directions on your prescription label carefully. Your healthcare provider will determine the best dose for you based on the medical condition being treated, as well as your age, other medical conditions you have, and other medications you are taking.

Major Depressive Disorder

The recommended starting dose of Paxil CR for Major Depressive Disorder is 25 mg daily.

Panic Disorder

The recommended starting dose of Paxil CR for Panic Disorder is 12.5 mg daily. The maximum daily dose is 75 mg/day.

Social Anxiety Disorder

The recommended starting dose of Paxil CR for Social Anxiety Disorder is 12.5 mg daily. The maximum daily dose is 37.5 mg/day.

Premenstrual Dysphoric Disorder

The recommended starting dose for Paxil CR of Premenstrual Dysphoric Disorder is 12.5 mg/day. PAXIL CR can be taken daily, either daily throughout the menstrual cycle or on certain days of the cycle.

Paroxetine is used to treat depression, obsessive-compulsive disorder (OCD), panic disorder, generalized anxiety disorder (GAD), social anxiety disorder (also known as social phobia), premenstrual dysphoric disorder (PMDD), and posttraumatic stress disorder (PTSD). Brisdelle™ is used only to treat moderate to severe hot flashes caused by menopause.

Paroxetine belongs to a group of medicines known as selective serotonin reuptake inhibitors (SSRIs). These medicines are thought to work by increasing the activity of the chemical called serotonin in the brain.

This medicine is available only with your doctor's prescription.

This section provides information on the proper use of a number of products that contain paroxetine. It may not be specific to Paxil CR. Please read with care.

Take this medicine only as directed by your doctor to benefit your condition as much as possible. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine should come with a Medication Guide. Follow the instructions carefully. Ask your doctor if you have any questions.

Paroxetine may be taken with or without food.

You may have to take paroxetine for a month or longer before you begin to feel better.

If you are taking the oral suspension, shake the bottle well before measuring each dose. Use a small measuring cup or a measuring spoon to measure each dose. The teaspoons and tablespoons that are used for serving and eating food do not measure exact amounts.

Swallow the tablet or extended-release tablet whole. Do not crush, break, or chew it.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For moderate to severe hot flashes caused by menopause:
    • Adults—7.5 milligrams (mg) once a day, at bedtime.
    • Children—Use is not recommended.
• For oral dosage form (suspension):
  • For depression:
    • Adults—At first, 20 milligrams (mg) (10 milliliters [mL]) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 50 mg (25 mL) per day.
    • Older adults—At first, 10 mg (5 mL) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 40 mg (20 mL) per day.
    • Children—Use and dose must be determined by your doctor.
  • For generalized anxiety disorder:
    • Adults—At first, 20 milligrams (mg) (10 milliliters [mL]) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 50 mg (25 mL) per day.
    • Older adults—At first, 10 mg (5 mL) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 40 mg (20 mL) per day.
    • Children—Use and dose must be determined by your doctor.
  • For obsessive-compulsive disorder:
    • Adults—At first, 20 milligrams (mg) (10 milliliters [mL]) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg (30 mL) per day.
    • Older adults—At first, 10 mg (5 mL) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 40 mg (20 mL) per day.
    • Children—Use and dose must be determined by your doctor.
  • For panic disorder:
    • Adults—At first, 10 milligrams (mg) (5 milliliters [mL]) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg (30 mL) per day.
    • Older adults—At first, 10 mg (5 mL) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 40 mg (20 mL) per day.
    • Children—Use and dose must be determined by your doctor.
  • For posttraumatic stress disorder:
    • Adults—At first, 20 milligrams (mg) (10 milliliters [mL]) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 50 mg (25 mL) per day.
    • Older adults—At first, 10 mg (5 mL) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose usually is not more than 40 mg (20 mL) per day.
    • Children—Use and dose must be determined by your doctor.
  • For social anxiety disorder:
    • Adults—At first, 20 milligrams (mg) (10 milliliters [mL]) once a day, usually taken in the morning.
    • Older adults—At first, 10 mg (5 mL) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose usually is not more than 20 mg (10 mL) per day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (tablets):
  • For depression:
    • Adults—At first, 20 milligrams (mg) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 50 mg per day.
    • Older adults—At first, 10 mg once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 40 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • For generalized anxiety disorder:
    • Adults—At first, 20 milligrams (mg) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 50 mg per day.
    • Older adults—At first, 10 mg once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose usually is not more than 40 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • For obsessive-compulsive disorder:
    • Adults—At first, 20 milligrams (mg) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose usually is not more than 60 mg per day.
    • Older adults—At first, 10 mg once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 40 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • For panic disorder:
    • Adults—At first, 10 milligrams (mg) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 60 mg per day.
    • Older adults—At first, 10 mg once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 40 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • For posttraumatic stress disorder:
    • Adults—At first, 20 milligrams (mg) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose usually is not more than 50 mg per day.
    • Older adults—At first, 10 mg once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 40 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • For social anxiety disorder:
    • Adults—At first, 20 milligrams (mg) once a day, usually taken in the morning.
    • Older adults—At first, 10 mg once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 20 mg per day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (extended-release tablets):
  • For depression:
    • Adults—At first, 25 milligrams (mg) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose usually is not more than 62.5 mg per day.
    • Older adults—At first, 12.5 mg once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 50 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • For panic disorder:
    • Adults—At first, 12.5 milligrams (mg) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose usually is not more than 75 mg per day.
    • Older adults—At first, 12.5 mg once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 50 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • For premenstrual dysphoric disorder:
    • Adults—At first, 12.5 milligrams (mg) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 25 mg per day.
    • Older adults and children—Use and dose must be determined by your doctor.
  • For social anxiety disorder:
    • Adults—At first, 12.5 milligrams (mg) once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 37.5 mg per day.
    • Older adults—At first, 12.5 mg once a day, usually taken in the morning. Your doctor may adjust your dose as needed. However, the dose is usually not more than 37.5 mg per day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Protect from light.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

The use of MAOIs intended to treat psychiatric disorders with Paxil CR or within 14 days of stopping treatment with Paxil CR is contraindicated because of an increased risk of serotonin syndrome. The use of Paxil CR within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated (see WARNINGS and DOSAGE AND ADMINISTRATION).

Starting Paxil CR in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome (see WARNINGS and DOSAGE AND ADMINISTRATION).

Concomitant use with thioridazine is contraindicated (see WARNINGS and PRECAUTIONS).

Concomitant use in patients taking pimozide is contraindicated (see PRECAUTIONS).

Paxil CR is contraindicated in patients with a hypersensitivity to paroxetine or to any of the inactive ingredients in Paxil CR.

Applies to paroxetine: oral capsule, oral suspension, oral tablet, oral tablet extended release

General

Side effects are generally reported as mild. The most common side effects associated with treatment discontinuation in clinical trials included somnolence, insomnia, agitation, tremor, anxiety, dizziness, headache, constipation, nausea, diarrhea, dry mouth, vomiting, flatulence, asthenia, abnormal ejaculation, sweating, impotence, and decreased libido.

The most common dose-dependent side effects associated with treatment discontinuation in clinical trials for the treatment of premenstrual dysphoric disorder with controlled-release paroxetine (the active ingredient contained in Paxil CR) 25 mg compared with 12.5 mg included nausea, somnolence, impaired concentration, dry mouth, dizziness, decreased appetite, sweating, tremor, and yawn.

The most common side effects associated with treatment discontinuation in the treatment of vasomotor symptoms in clinical trials included abdominal pain, attention disturbances, headache, and suicidal ideation.

In a placebo-controlled study in elderly patients with major depressive disorder, the most common side effects associated with treatment discontinuation of controlled-release paroxetine included nausea, headache, depression, and abnormal LFTs.

There may be adaptation to some side effects (such as nausea and dizziness) but not to others (such as dry mouth, somnolence, and asthenia) with continued therapy. Paroxetine is less likely than tricyclic antidepressants to be associated with dry mouth, constipation, and somnolence.[Ref]

Psychiatric

Very common (10% or more): Insomnia
Common (1% to 10%): Abnormal dreams, agitation, anxiety, depersonalization, depression, drugged feeling, emotional lability, lack of emotion, nervousness
Uncommon (0.1% to 1%): Abnormal thinking, alcohol abuse, bruxism, euphoria, hallucinations, hostility, lack of emotion, manic reaction, neurosis, paranoid reaction
Rare (less than 0.1%): Abnormal electroencephalogram, antisocial reaction, bulimia, delirium, delusions, drug dependence, hysteria, irritability, manic-depressive reaction, panic attacks, psychosis, psychotic depression, stupor, withdrawal syndrome
Frequency not reported: Suicidal ideation and behavior
Postmarketing reports: Confusional state, disorientation, homicidal ideation, restlessness[Ref]

Antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. An increased risk of suicidal thinking and behavior in children, adolescents, and young adults (aged 18 to 24 years) with major depressive disorder (MDD) and other psychiatric disorders has been reported with short-term use of antidepressant drugs.

Adult and pediatric patients receiving antidepressants for MDD, as well as for psychiatric and nonpsychiatric indications, have reported symptoms that may be precursors to emerging suicidality, including anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania. Causality has not been established.

Pooled results from clinical trials report hallucinations in 22 of 9089 patients who received paroxetine and 4 of 3187 patients who received placebo.[Ref]

Nervous system

Extrapyramidal symptoms such as akathisia, bradykinesia, cogwheel rigidity, dystonia, hypertonia, and oculogyric crisis have been associated with concomitant pimozide therapy.

Potentially life-threatening serotonin syndrome has been reported with SSRIs and SNRIs as monotherapy, but particularly with concomitant use of other serotonergic drugs and drugs that impair the metabolism of serotonin. Signs and symptoms associated with serotonin syndrome or neuroleptic malignant syndrome included agitation, confusion, diaphoresis, diarrhea, fever, hypertension, rigidity, and tachycardia, and were in some cases associated with concomitant use of serotonergic drugs.[Ref]

Very common (10% or more): Dizziness, headache, somnolence, tremor
Common (1% to 10%): Amnesia, anxiety, CNS stimulation, confusion, hypertonia, impaired concentration, migraine, myoclonus, paresthesia, taste perversion
Uncommon (0.1% to 1%): Ataxia, convulsion, dyskinesia, dystonia, hyperesthesia, hyperkinesia, hypokinesia, incoordination, neuralgia, neuropathy, nystagmus, paralysis, syncope
Rare (less than 0.1%): Abnormal gait, adrenergic syndrome, akathisia, akinesia, anticholinergic syndrome, aphasia, cerebral ischemia, cerebrovascular accident, choreoathetosis, circumoral paresthesia, dysarthria, extrapyramidal syndrome, fasciculations, grand mal convulsions, hyperalgesia, meningitis, myelitis, peripheral neuritis, reflexes decreased, reflexes increased, taste loss, torticollis, trismus, vascular headache
Postmarketing reports: Eclampsia, Guillain-Barre syndrome, neuroleptic malignant syndrome, restless legs syndrome, serotonin syndrome, status epilepticus[Ref]

Metabolic

The results of one study appear to indicate that treatment with selective serotonin reuptake inhibitors (i.e., paroxetine (the active ingredient contained in Paxil CR) sertraline, citalopram) may cause an increase in serum total cholesterol, HDL cholesterol, and/or LDL cholesterol. However, additional studies are necessary to confirm these findings.

Numerous cases of hyponatremia have been reported following treatment with a selective serotonin reuptake inhibitor (SSRI). Risk factors for the development of SSRI- associated hyponatremia including advanced age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium levels have been identified. Hyponatremia tends to develop within the first few weeks of treatment (range 3 to 120 days) and typically resolves within 2 weeks (range 48 hours to 6 weeks) after therapy has been discontinued with some patients requiring treatment. The proposed mechanism for the development of hyponatremia involves the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) via release of antidiuretic hormone.[Ref]

Common (1% to 10%): Decreased appetite, increased appetite, increases in cholesterol levels, weight gain, weight loss
Uncommon (0.1% to 1%): Hypoglycemia, hypokalemia, thirst
Rare (less than 0.1%): Alkaline phosphatase increased, creatinine phosphokinase increased, dehydration, diabetes mellitus, gamma globulins increased, gout, hypercalcemia, hypercholesteremia, hyperglycemia, hyperkalemia, hyperphosphatemia, hypocalcemia, hyponatremia, ketosis, lactic dehydrogenase increased, non-protein nitrogen increased, obesity
Postmarketing reports: Porphyria[Ref]

Cardiovascular

Common (1% to 10%): Chest pain, edema, palpitation, peripheral edema, tachycardia, vasodilation (usually flushing)
Uncommon (0.1% to 1%): Abnormal electrocardiogram, angina pectoris, bradycardia, conduction abnormalities, hematoma, hypertension, hypotension, palpitation, postural hypotension, sinus tachycardia, supraventricular tachycardia
Rare (less than 0.1%): Arrhythmia, arrhythmia nodal, atrial arrhythmia, atrial fibrillation, bundle branch block, cellulitis, congestive heart failure, extrasystoles, heart block, low cardiac output, myocardial infarct, myocardial ischemia, pallor, phlebitis, substernal chest pain, supraventricular extrasystoles, thrombophlebitis, thrombosis, varicose vein, ventricular extrasystoles
Postmarketing reports: Atrial fibrillation, pulmonary edema, ventricular fibrillation, ventricular tachycardia (including torsades de pointes)[Ref]

Other

Fatigue, malaise, and lethargy were very commonly reported in Phase 2 and 3 clinical trials with paroxetine (the active ingredient contained in Paxil CR) for treatment of vasomotor symptoms in postmenopausal women.[Ref]

Very common (10% or more): Asthenia
Common (1% to 10%): Chills, pain, tinnitus, trauma, vertigo
Uncommon (0.1% to 1%): Ear pain, fever, malaise, otitis media, overdose
Rare (less than 0.1%): Abscess, deafness, hypothermia, otitis externa, sepsis, ulcer, abnormal laboratory value, cyst, hernia, intentional overdose
Postmarketing reports: Death[Ref]

Genitourinary

Very common (10% or more): Decreased libido, ejaculation disturbance, other male genital disorders (primarily ejaculatory delay)
Common (1% to 10%): Female genital disorders (primarily anorgasmia and difficulty reaching climax/orgasm), dysmenorrhea, impotence, menorrhagia, menstrual disorder, urinary disorder (primarily difficulty with micturition and urinary hesitancy), urinary frequency, urination impaired, urinary tract infection, vaginal moniliasis, vaginitis
Uncommon (0.1% to 1%): Albuminuria, amenorrhea, breast pain, cystitis, dysuria, hematuria, increased libido, nocturia, ovarian cyst, polyuria, pyuria, pregnancy and puerperal disorders, testes pain, urinary incontinence, urinary retention, urinary urgency,
Rare (0.01% to 0.1%): Abortion, breast atrophy, breast enlargement, endometrial disorder, epididymitis, female lactation, fibrocystic breast, kidney calculus, kidney pain, leukorrhea, mastitis, metrorrhagia, nephritis, oliguria, pelvic pain, salpingitis, urethritis, urinary abnormality, urinary casts, uterine spasm, urolith, vaginal hemorrhage
Very rare (less than 0.01%): Priapism
Postmarketing reports: Premature births in pregnant women, symptoms suggestive of galactorrhea[Ref]

There are several reports of priapism associated with paroxetine use. In cases in which outcome was reported, all patients fully recovered.

In placebo-controlled clinical trials, ejaculatory disturbance in men was reported in 13% to 28% of men taking paroxetine, compared to 0% to 2% in the placebo group. Decreased libido was reported in 6% to 15% in men treated with paroxetine, compared to 0% to 5% in the placebo group, and in 0% to 9% in women treated with paroxetine, compared with 0% to 2% in placebo patients. The estimates of the incidence of untoward sexual experience and performance may underestimate their actual incidence, partly because patients and physicians may be reluctant to discuss this issue.[Ref]

Dermatologic

Seven cases of alopecia have been reported. In all cases, hair loss was eventually reversible.

A case of cutaneous leukocytoclastic vasculitis has been reported following treatment with paroxetine (the active ingredient contained in Paxil CR) The patient originally developed the lesions after treatment with escitalopram. The lesions disappeared one week following discontinuation of escitalopram and reappeared upon rechallenge. When the patient was switched to paroxetine a similar reaction occurred.[Ref]

Very common (10% or more): Sweating
Common (1% to 10%): Eczema, hypertension, photosensitivity, pruritus, rash, sweat gland disorder
Uncommon (0.1% to 1%): Acne, alopecia, contact dermatitis, dry skin, ecchymosis, furunculosis, purpura, urticaria
Rare (0.01% to 0.1%): Angioedema, erythema multiforme, erythema nodosum, exfoliative dermatitis, fungal dermatitis, hirsutism, maculopapular rash, pustular rash, seborrhea, skin discoloration, skin hypertrophy, skin ulcer, sweating decreased, vesiculobullous rash
Very rare (less than 0.01%): Severe cutaneous reactions such as Stevens Johnson syndrome and toxic epidermal necrolysis)
Postmarketing reports: Vasculitic syndromes (such as Henoch-Schonlein purpura)[Ref]

Endocrine

Rare (less than 0.1%): Goiter, hyperthyroidism, hypothyroidism, thyroiditis
Postmarketing reports: Syndrome of inappropriate antidiuretic hormone secretion, symptoms suggestive of prolactinemia[Ref]

Gastrointestinal

A study of 26,005 antidepressant users has reported 3.6 times more upper GI bleeding episodes with the use of SSRIs relative to the population who did not receive antidepressant medications. Upper gastrointestinal tract bleeding was observed up to 3.2 times more frequently in patients receiving paroxetine (the active ingredient contained in Paxil CR) [Ref]

Very common (10% or more): Constipation, diarrhea, dry mouth, nausea
Common (1% to 10%): Abdominal pain, dyspepsia, flatulence, gastrointestinal disorder, gingivitis, stomatitis, tooth disorder, vomiting
Uncommon (0.1% to 1%): Buccal cavity disorders, colitis, dysphagia, eructation, gastritis, gastroenteritis, gastroesophageal reflux, gastrointestinal flu, gingivitis, glossitis, increased salivation, melena, pancreatitis, rectal hemorrhage, toothache, ulcerative stomatitis
Rare (less than 0.1%): Aphthous stomatitis, bloody diarrhea, cardiospasm, cholelithiasis, duodenitis, enteritis, esophagitis, fecal impaction, fecal incontinence, gum hemorrhage, gum hyperplasia, hematemesis, ileitis, ileus, intestinal obstruction, mouth ulceration, peptic ulcer, peritonitis, salivary gland enlargement, sialadenitis, stomach ulcer, tooth caries, tongue discoloration, tongue edema, tooth malformation
Postmarketing reports: Acute pancreatitis, pancreatitis hemorrhagic[Ref]

Hematologic

Uncommon (0.1% to 1%): Anemia, eosinophilia, hypochromic anemia, leukocytosis, leukopenia, lymphadenopathy, WBC abnormality
Rare (less than 0.1%): Abnormal erythrocytes, abnormal lymphocytes, anisocytosis, basophilia, bleeding time increased, iron deficiency anemia, lymphedema, lymphocytosis, lymphopenia, microcytic anemia, monocytosis, normocytic anemia, thrombocytopenia, thrombocythemia,
Postmarketing reports: Events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, agranulocytosis), hemolytic anemia, idiopathic thrombocytopenic purpura[Ref]

Hepatic

Uncommon (0.1% to 1%): Abnormal liver function tests, SGOT increased, SGPT increased
Rare (less than 0.1%): Bilirubinemia, hepatitis, hepatosplenomegaly, jaundice
Postmarketing reports: Drug-induced liver injury, elevated liver function tests, hepatic failure[Ref]

In placebo-controlled clinical trials patients receiving paroxetine experienced abnormal values on liver function tests at a rate equal to or less than that reported in patients receiving placebo. However, there have been postmarketing reports of patients developing elevated serum transaminases resulting in severe liver dysfunction, as well as, a few cases of elevated liver function tests resulting in death secondary to liver necrosis.[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Allergic reaction, face edema
Rare (less than 0.1%): Anaphylactoid reaction
Postmarketing reports: Anaphylaxis[Ref]

Immunologic

Common (1% to 10%): Infection
Uncommon (0.1% to 1%): Flu syndrome, herpes simplex
Rare (less than 0.1%): Herpes zoster, moniliasis[Ref]

Musculoskeletal

Epidemiological studies, primarily in patients aged 50 years or older, have shown an increased risk of bone fractures in patients receiving SSRIs or TCAs.[Ref]

Common (1% to 10%): Arthralgia, back pain, migraine, myalgia, myasthenia, myopathy
Uncommon (0.1% to 1%): Arthritis, arthrosis, bursitis, myositis, neck pain, tendonitis, traumatic fracture
Rare (less than 0.1%): Cartilage disorder, generalized spasm, myositis, neck rigidity, osteoporosis, tenosynovitis, tetany[Ref]

Ocular

Common (1% to 10%): Abnormality of accommodation, abnormal vision, blurred vision
Uncommon (0.1% to 1%): Conjunctivitis, eye pain, keratoconjunctivitis, mydriasis, photophobia, retinal hemorrhage
Rare (less than 0.1%): Anisocoria, blepharitis, cataract, conjunctival edema, corneal lesion, corneal ulcer, diplopia, exophthalmos, eye hemorrhage, glaucoma, hyperacusis, night blindness, ptosis, visual field defect
Frequency not reported: Angle-closure glaucoma, eye pain
Postmarketing reports: Acute glaucoma, optic neuritis[Ref]

Renal

Rare (less than 0.1%): Abnormal kidney function, BUN increased
Postmarketing reports: Acute renal failure[Ref]

Respiratory

Common (1% to 10%): Bronchitis, cough increased, oropharynx disorder, pharyngitis, respiratory disorder, rhinitis, sinusitis, yawn
Uncommon (0.1% to 1%): Asthma, dyspnea, epistaxis, hyperventilation, laryngitis, pneumonia, respiratory flu
Rare (less than 0.1%): Dysphonia, emphysema, hemoptysis, hiccups, lung fibrosis, parosmia, pulmonary edema, pulmonary embolus, sputum increased, stridor, throat tightness, voice alteration
Postmarketing reports: Allergic alveolitis, laryngismus, pulmonary hypertension[Ref]

Some side effects of Paxil CR may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of Paxil CR can be fatal.