Paroxetine Information
Paroxetine () Suicidality And Antidepressant Drugs
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Paroxetine () tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. 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 in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Paroxetine () tablets are not approved for use in pediatric patients. (See , , and .)
Paroxetine () Description
Paroxetine () hydrochloride is an orally administered psychotropic drug. It is the hydrochloride salt of a phenylpiperidine compound identified chemically as (3-)-3-[(1,3-Benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)-piperidine hydrochloride hemihydrate and has the molecular formula of CHFNO•HCl•1/2HO. The molecular weight is 374.8 (329.4 as free base). The structural formula of Paroxetine () hydrochloride is:
Paroxetine () hydrochloride (hemihydrate), USP is an odorless, white or almost white crystalline powder, having a melting point range of 129° to 131°C and a solubility of 5.4 mg/mL in water.
Each film-coated tablet contains Paroxetine () hydrochloride hemihydrate equivalent to 10 mg, 20 mg, 30 mg or 40 mg Paroxetine () . Inactive ingredients consist of dibasic calcium phosphate dihydrate, FD&C Blue No. 1 Aluminum Lake, hydroxypropyl cellulose, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, sodium lauryl sulfate, sodium starch glycolate, titanium dioxide and triacetin.
Paroxetine () hydrochloride complies with
Paroxetine () Clinical Pharmacology
The efficacy of Paroxetine () in the treatment of major depressive disorder, social anxiety disorder, obsessive compulsive disorder (OCD), panic disorder (PD), and generalized anxiety disorder (GAD) 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. 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. radioligand binding studies indicate that Paroxetine () has little affinity for muscarinic, alpha-, alpha-, beta-adrenergic-, dopamine (D)-, 5-HT-, 5-HT-, and histamine (H)-receptors; antagonism of muscarinic, histaminergic, and alpha-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.
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 C, T, C, and T were 61.7 ng/mL (CV 45%), 5.2 hr. (CV 10%), 30.7 ng/mL (CV 67%), and 21 hours (CV 32%), respectively. The steady-state Cand Cvalues were about 6 and 14 times what would be predicted from single-dose studies. Steady-state drug exposure based on AUCwas 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 one 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 C 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 protein binding of phenytoin or warfarin.
The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets daily for 30 days of Paroxetine () hydrochloride. 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 Cvalues 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 (see ).
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.
Paroxetine () Indications And Usage
Paroxetine () tablets are indicated for the treatment of major depressive disorder.
The efficacy of Paroxetine () tablets in the treatment of a major depressive episode was established in 6-week controlled trials of outpatients whose diagnoses corresponded most closely to the DSM-III category of major depressive disorder (see ). A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least four of the following eight symptoms: Change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation.
The effects of Paroxetine () tablets in hospitalized depressed patients have not been adequately studied.
The efficacy of Paroxetine () tablets in maintaining a response in major depressive disorder for up to one year was demonstrated in a placebo-controlled trial (see ). Nevertheless, the physician who elects to use Paroxetine () tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Paroxetine () tablets are indicated for the treatment of obsessions and compulsions in patients with obsessive compulsive disorder (OCD) as defined in the DSM-IV. The obsessions or compulsions cause marked distress, are time consuming, or significantly interfere with social or occupational functioning.
The efficacy of Paroxetine () tablets was established in two 12-week trials with obsessive compulsive outpatients whose diagnoses corresponded most closely to the DSM-IIIR category of obsessive compulsive disorder (see ).
Obsessive compulsive disorder is characterized by recurrent and persistent ideas, thoughts, impulses, or images (obsessions) that are ego-dystonic and/or repetitive, purposeful, and intentional behaviors (compulsions) that are recognized by the person as excessive or unreasonable.
Long-term maintenance of efficacy was demonstrated in a 6-month relapse prevention trial. In this trial, patients assigned to Paroxetine () showed a lower relapse rate compared to patients on placebo (see ). Nevertheless, the physician who elects to use Paroxetine () tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (see ).
Paroxetine () tablets are 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 Paroxetine () tablets was established in three 10- to 12-week trials in panic disorder patients whose diagnoses corresponded to the DSM-IIIR category of panic disorder (see ).
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 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 (see ). Nevertheless, the physician who prescribes Paroxetine () tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Paroxetine () tablets are 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 one 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 Paroxetine () tablets was established in three 12-week trials in adult patients with social anxiety disorder (DSM-IV). Paroxetine () tablets have not been studied in children or adolescents with social phobia (see ).
The effectiveness of Paroxetine () tablets 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 Paroxetine () tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (see ).
Paroxetine () tablets are indicated for the treatment of Generalized Anxiety Disorder (GAD), as defined in DSM-IV. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.
The efficacy of Paroxetine () tablets in the treatment of GAD was established in two 8-week placebo-controlled trials in adults with GAD. Paroxetine () tablets have not been studied in children or adolescents with Generalized Anxiety Disorder (see ).
Generalized Anxiety Disorder (DSM-IV) is characterized by excessive anxiety and worry (apprehensive expectation) that is persistent for at least 6 months and which the person finds difficult to control. It must be associated with at least three of the following six symptoms: Restlessness or feeling keyed up or on edge, being easily fatigued, difficulty concentrating or mind going blank, irritability, muscle tension, sleep disturbance.
The efficacy of Paroxetine () tablets in maintaining a response in patients with Generalized Anxiety Disorder, who responded during an 8-week acute treatment phase while taking Paroxetine () tablets and were then observed for relapse during a period of up to 24 weeks, was demonstrated in a placebo-controlled trial (see ). Nevertheless, the physician who elects to use Paroxetine () tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (see ).
Paroxetine () Contraindications
Concomitant use in patients taking either monoamine oxidase inhibitors (MAOIs), including linezolid, an antibiotic which is a reversible non-selective MAOI, or thioridazine is contraindicated (see and ).
Concomitant use in patients taking pimozide is contraindicated (see ).
Paroxetine () tablets are contraindicated in patients with a hypersensitivity to Paroxetine () or any of the inactive ingredients in Paroxetine () tablets.
Paroxetine () Warnings
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 to 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 nine 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.
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 and , for a description of the risks of discontinuation of Paroxetine () tablets).
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.
In patients receiving another serotonin reuptake inhibitor drug in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued that drug and have been started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. While there are no human data showing such an interaction with Paroxetine () hydrochloride, limited animal data on the effects of combined use of Paroxetine () and MAOIs suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that Paroxetine () hydrochloride not be used in combination with an MAOI (including linezolid, an antibiotic which is a reversible non-selective MAOI), or within 14 days of discontinuing treatment with an MAOI (see ). At least 2 weeks should be allowed after stopping Paroxetine () hydrochloride before starting an MAOI.
The development of a potentially life threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SNRIs and SSRIs alone, including treatment with Paroxetine () hydrochloride, but particularly with concomitant use of serotonergic drugs (including triptans), with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome, in its most severe form can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms.
The concomitant use of Paroxetine () hydrochloride with MAOIs intended to treat depression is contraindicated. If concomitant treatment of Paroxetine () hydrochloride with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
The concomitant use of Paroxetine () hydrochloride with serotonin precursors (such as tryptophan) is not recommended. Treatment with Paroxetine () hydrochloride and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.
Thioridazine administration alone produces prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as Torsades de pointes-type arrhythmias, and sudden death. This effect appears to be dose related.
An 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 and ).
Paroxetine () Precautions
Paroxetine () tablets should not be chewed or crushed, and should be swallowed whole.
Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of Paroxetine () hydrochloride and triptans, tramadol, or other serotonergic agents.
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Paroxetine () hydrochloride and should counsel them in its appropriate use. A patient Medication Guide about ‘Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions’ is available for Paroxetine () hydrochloride. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.
Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking Paroxetine () hydrochloride.
Safety and effectiveness in the pediatric population have not been established (see and ). Three placebo-controlled trials in 752 pediatric patients with MDD have been conducted with Paroxetine () hydrochloride, and the data were not sufficient to support a claim for use in pediatric patients. Anyone considering the use of Paroxetine () hydrochloride in a child or adolescent must balance the potential risks with the clinical need.
In placebo-controlled clinical trials conducted with pediatric patients, the following adverse events were reported in at least 2% of pediatric patients treated with Paroxetine () hydrochloride and occurred at a rate at least twice that for pediatric patients receiving placebo: emotional lability (including self-harm, suicidal thoughts, attempted suicide, crying, and mood fluctuations), hostility, decreased appetite, tremor, sweating, hyperkinesia, and agitation.
Events reported upon discontinuation of treatment with Paroxetine () hydrochloride in the pediatric clinical trials that included a taper phase regimen, which occurred in at least 2% of patients who received Paroxetine () hydrochloride and which occurred at a rate at least twice that of placebo, were: emotional lability (including suicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness, dizziness, nausea, and abdominal pain (see ).
SSRIs and SNRIs, including Paroxetine () hydrochloride, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event (see ).
In worldwide premarketing clinical trials with Paroxetine () hydrochloride, 17% of patients treated with Paroxetine () hydrochloride (approximately 700) were 65 years of age or older. Pharmacokinetic studies revealed a decreased clearance in the elderly, and a lower starting dose is recommended; there were, however, no overall differences in the adverse event profile between elderly and younger patients, and effectiveness was similar in younger and older patients (see and ).
Paroxetine () Adverse Reactions
A comparison of adverse event rates in a fixed-dose study comparing 10 mg, 20 mg, 30 mg, and 40 mg/day of Paroxetine () hydrochloride with placebo in the treatment of major depressive disorder revealed a clear dose dependency for some of the more common adverse events associated with use of Paroxetine () hydrochloride, as shown in the following table:
In a fixed-dose study comparing placebo and 20 mg, 40 mg, and 60 mg of Paroxetine () hydrochloride in the treatment of OCD, there was no clear relationship between adverse events and the dose of Paroxetine () hydrochloride to which patients were assigned. No new adverse events were observed in the group treated with 60 mg of Paroxetine () hydrochloride compared to any of the other treatment groups.
In a fixed-dose study comparing placebo and 10 mg, 20 mg, and 40 mg of Paroxetine () hydrochloride in the treatment of panic disorder, there was no clear relationship between adverse events and the dose of Paroxetine () hydrochloride to which patients were assigned, except for asthenia, dry mouth, anxiety, libido decreased, tremor, and abnormal ejaculation. In flexible-dose studies, no new adverse events were observed in patients receiving 60 mg of Paroxetine () hydrochloride compared to any of the other treatment groups.
In a fixed-dose study comparing placebo and 20 mg, 40 mg, and 60 mg of Paroxetine () hydrochloride in the treatment of social anxiety disorder, for most of the adverse events, there was no clear relationship between adverse events and the dose of Paroxetine () hydrochloride to which patients were assigned.
In a fixed-dose study comparing placebo and 20 mg and 40 mg of Paroxetine () hydrochloride in the treatment of generalized anxiety disorder, for most of the adverse events, there was no clear relationship between adverse events and the dose of Paroxetine () hydrochloride to which patients were assigned, except for the following adverse events: Asthenia, constipation, and abnormal ejaculation.
During its premarketing assessment in major depressive disorder, multiple doses of Paroxetine () hydrochloride were administered to 6,145 patients in phase two and three studies. The conditions and duration of exposure to Paroxetine () hydrochloride varied greatly and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, and fixed-dose, and titration studies. During premarketing clinical trials in OCD, panic disorder, social anxiety disorder, and generalized anxiety disorder, 542, 469, 522, and 735 patients, respectively, received multiple doses of Paroxetine () hydrochloride. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories.
In the tabulations that follow, reported adverse events were classified using a standard COSTART-based Dictionary terminology. The frequencies presented, therefore, represent the proportion of the 9,089 patients exposed to multiple doses of Paroxetine () hydrochloride who experienced an event of the type cited on at least one occasion while receiving Paroxetine () hydrochloride. All reported events are included except those already listed in Tables 2 to 4, those reported in terms so general as to be uninformative and those events where a drug cause was remote. It is important to emphasize that although the events reported occurred during treatment with Paroxetine () , they were not necessarily caused by it.
Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: Frequent adverse events are those occurring on one or more occasions in at least 1/100 patients (only those not already listed in the tabulated results from placebo-controlled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1,000 patients; rare events are those occurring in fewer than 1/1,000 patients. Events of major clinical importance are also described in the section.
Paroxetine () Overdosage
Since the introduction of Paroxetine () hydrochloride in the United States, 342 spontaneous cases of deliberate or accidental overdosage during Paroxetine () treatment have been reported worldwide (circa 1999). These include overdoses with Paroxetine () alone and in combination with other substances. Of these, 48 cases were fatal and of the fatalities, 17 appeared to involve Paroxetine () alone. Eight fatal cases that documented the amount of Paroxetine () ingested were generally confounded by the ingestion of other drugs or alcohol or the presence of significant comorbid conditions. Of 145 nonfatal cases with known outcome, most recovered without sequelae. The largest known ingestion involved 2000 mg of Paroxetine () (33 times the maximum recommended daily dose) in a patient who recovered.
Commonly reported adverse events associated with Paroxetine () overdosage include somnolence, coma, nausea, tremor, tachycardia, confusion, vomiting, and dizziness. Other notable signs and symptoms observed with overdoses involving Paroxetine () (alone or with other substances) include mydriasis, convulsions (including status epilepticus), ventricular dysrhythmias (including Torsades de pointes), hypertension, aggressive reactions, syncope, hypotension, stupor, bradycardia, dystonia, rhabdomyolysis, symptoms of hepatic dysfunction (including hepatic failure, hepatic necrosis, jaundice, hepatitis, and hepatic steatosis), serotonin syndrome, manic reactions, myoclonus, acute renal failure, and urinary retention.
Treatment should consist of those general measures employed in the management of overdosage with any drugs effective in the treatment of major depressive disorder.
Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients.
Activated charcoal should be administered. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. No specific antidotes for Paroxetine () are known.
A specific caution involves patients who are taking or have recently taken Paroxetine () who might ingest excessive quantities of a tricyclic antidepressant. In such a case, accumulation of the parent tricyclic and/or an active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation (see ).
In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the (PDR).
Paroxetine () How Supplied:
Paroxetine () Tablets, USP are available as 20 mg tablets.
The 20 mg tablet is a blue film-coated, modified capsule-shaped, scored tablet debossed with on one side of the tablet andto the left of the score andto the right of the score on the other side. They are available as follows:
NDC 51079-774-20 - Unit dose blister packages of 100 (10 cards of 10 tablets each).
Store at 20° to 25 °C (68° to 77°F). [See USP for Controlled Room Temperature.]
Manufactured by:Mylan Pharmaceuticals Inc. Morgantown, WV 26505
Distributed by:UDL Laboratories, Inc.Rockford, IL 61103
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Paroxetine () Medication Guide Antidepressant Medicines, Depression And Other Serious Mental Illnesses, And Suicidal Thoughts Or Actions
Read the Medication Guide that comes with your or your family member’s antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines.
Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.
Revised 1/2008
Manufactured by:Mylan Pharmaceuticals Inc. Morgantown, WV 26505
Distributed by:UDL Laboratories, Inc.Rockford, IL 61103
S-9998 R3 12/09
Paroxetine () Principal Display Panel
Paroxetine () Tablets, USP
20 mg
10 Tablets
