Paxil (Paroxetine HCl)

PAXIL®

SmithKline Beecham

Paroxetine HCl

Antidepressant – Antiobsessional – Antipanic Agent

Action And Clinical Pharmacology: Paroxetine is a potent and selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitor (SSRI). This activity of the drug on brain neurons is thought to be responsible for its antidepressant action as well as its efficacy in the treatment of obsessive-compulsive disorder (OCD) and panic disorder.

Paroxetine is a phenylpiperidine derivative which is chemically unrelated to the tricyclic or tetracyclic antidepressants. In receptor binding studies, paroxetine did not exhibit significant affinity for the adrenergic (a1, a2, b), dopaminergic, serotonergic (5HT1, 5HT2), or histaminergic receptors of rat brain membrane. A weak affinity for the muscarinic acetylcholine receptor was evident. The predominant metabolites of paroxetine are essentially inactive as 5-HT reuptake inhibitors.

Pharmacokinetics: Paroxetine is well absorbed after oral administration. In healthy volunteers, the absorption of a single 30 mg oral dose of paroxetine was not appreciably affected by the presence or absence of food. Owing to the extensive distribution of paroxetine into the tissues, less than 1% of the total drug in the body is believed to reside in the systemic circulation.

Paroxetine is subject to a biphasic process of metabolic elimination which involves presystemic (first-pass) and systemic pathways. First-pass metabolism is extensive, but may be partially saturable, accounting for the increased bioavailability observed with multiple dosing. As with other selective serotonin reuptake inhibitors, the metabolism of paroxetine is accomplished in part by cytochrome P450(IID6). 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 Precautions). The majority of the dose appears to be oxidized to a catechol intermediate which is converted to highly polar glucuronide and sulfate metabolites through methylation and conjugation reactions. The glucuronide and sulfate conjugates of paroxetine are about >10 000 and 3 000 times less potent, respectively, than the parent compound as inhibitors of 5-HT reuptake in rat brain synaptosomes. Approximately 64% of an administered dose of paroxetine is eliminated by the kidneys and 36% in the feces. Less than 2% of the dose is recovered in the form of the parent compound.

A wide range of interindividual variation is observed for the pharmacokinetic parameters. Following the single or multiple dose administration of paroxetine at doses of 20 to 50 mg, the mean elimination half-life value for healthy subjects appears to be about 24 hours, although a range of 3 to 65 hours has been reported. Both the rate of absorption and the terminal elimination half-life appear to be independent of dose. Steady-state plasma concentrations of paroxetine are generally achieved in 7 to 14 days. No correlation has been established between paroxetine plasma concentrations and therapeutic efficacy or the incidence of adverse reactions.

No clear dose relationship has been demonstrated for the antidepressant effects of paroxetine at doses above 20 mg/day. The results of fixed-dose studies comparing paroxetine and placebo in the treatment of depression and panic disorder revealed the dose dependency for some of the more common adverse events.

In healthy young volunteers receiving a 20 mg daily dose of paroxetine for 15 days, the mean maximal plasma concentration was 41 ng/mL at steady-state (see Table I). Peak plasma levels generally occurred within 3 to 7 hours.

In elderly subjects, increased steady-state plasma concentrations and prolongation of the elimination half-life were observed relative to younger adult controls (see Table I). Elderly patients should, therefore, be initiated and maintained at the lowest daily dosage of paroxetine which is associated with clinical efficacy.

The results from a multiple dose pharmacokinetic study in subjects with severe hepatic dysfunction suggest that the clearance of paroxetine is markedly reduced in this patient group (see Table I). As the elimination of paroxetine is dependent upon extensive hepatic metabolism, its use in patients with hepatic impairment should be undertaken with caution (see Dosage).

In a single dose pharmacokinetic study in patients with mild to severe renal impairment, plasma levels of paroxetine tended to increase with deteriorating renal function (see Table II). As multiple-dose pharmacokinetic studies have not been performed in patients with renal disease, paroxetine should be used with caution in such patients.

At therapeutic concentrations, the plasma protein binding of paroxetine is approximately 95%. After the administration of a single 50 mg oral dose to lactating women, the concentrations of paroxetine detected in breast milk were similar to those in plasma.

Indications And Clinical Uses: Depression: Paroxetine is indicated for symptomatic relief of depressive illness.

Clinical trials have provided evidence that continuation treatment with paroxetine in patients with moderate to moderately severe depressive disorder is effective for at least 6 months.

Obsessive-Compulsive Disorder: Paroxetine is indicated for the symptomatic treatment of obsessive-compulsive disorder (OCD). The obsessions or compulsions must be experienced as intrusive, markedly distressing, time-consuming, or interfering significantly with the person’s social or occupational functioning.

Panic Disorder: Paroxetine is indicated for the symptomatic treatment of panic disorder, with or without agoraphobia.

The effectiveness in long-term use (i.e., for more than 12 weeks) has not yet been established in controlled trials for OCD and panic disorder. Therefore, the physician who elects to use paroxetine for extended periods in these diseases should periodically re-evaluate the long-term usefulness of the drug for individual patients.

Contra-Indications: Hypersensitivity: Paroxetine is contraindicated in patients who are known to be hypersensitive to the drug.

MAO Inhibitors: In patients receiving another serotonin reuptake inhibitor drug in combination with a MAO inhibitor, 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 begun treatment on a MAO inhibitor. Some cases presented with features resembling neuroleptic malignant syndrome. Therefore, paroxetine should not be used in combination with MAO inhibitors or within 2 weeks of terminating treatment with MAO inhibitors. Treatment with paroxetine should then be initiated cautiously and dosage increased gradually until optimal response is reached. MAO inhibitors should not be introduced within 2 weeks of cessation of therapy with paroxetine.

Precautions: Suicide: The possibility of a suicide attempt is inherent in depression and may persist until remission occurs. Therefore, high risk patients should be closely supervised throughout therapy with appropriate consideration to the possible need for hospitalization. In order to minimize the opportunity for overdosage, prescriptions for paroxetine should be written for the smallest quantity of drug consistent with good patient management.

Seizures: During clinical trials, the overall incidence of seizures was 0.15% in patients treated with paroxetine. However, patients with a history of convulsive disorders were excluded from these studies. Caution is recommended when the drug is administered to patients with a history of seizures. The drug should be discontinued in any patient who develops seizures.

Activation of Mania/Hypomania: During clinical testing in depressed patients, approximately 1% of paroxetine-treated patients experienced manic reactions. When bipolar patients were considered as a subgroup the incidence of mania was 2%. As with other Selective Serotonin Reuptake Inhibitors (SSRIs), paroxetine should be used with caution in patients with a history of mania.

Occupational Hazards: Although paroxetine did not cause sedation or interfere with psychomotor performance in placebo-controlled studies in normal subjects, patients should be advised to avoid driving a car or operating hazardous machinery until they are reasonably certain that paroxetine does not affect them adversely.

Cardiac Conditions: Paroxetine does not generally produce clinically significant changes in blood pressure, heart rate or ECG. Paroxetine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Hence, the usual precautions should be observed in such patients.

Electroconvulsive Therapy (ECT): The efficacy and safety of the concurrent use of paroxetine and ECT have not been studied.

Geriatrics: Administration of paroxetine to the elderly is associated with increased plasma levels and prolongation of the elimination half-life relative to younger adults (see Pharmacology, Pharmacokinetics). Elderly patients should be initiated and maintained at the lowest daily dose of paroxetine which is associated with clinical efficacy.

Approximately 800 elderly patients (³65 years) have been treated with paroxetine in worldwide premarketing clinical trials. The pattern of adverse experiences in the elderly was comparable to that in younger patients.

Children: The safety and effectiveness of paroxetine in children under 18 years of age have not been established.

Pregnancy and Lactation: Although animal studies have not shown any teratogenic or selective embryotoxic effects, the safety of paroxetine in human pregnancy has not been established. Paroxetine should not be used during pregnancy unless the potential benefit to the patient outweighs the possible risk to the fetus.

The concentrations of paroxetine detected in the breast milk of lactating women are similar to those in plasma. Lactating women should not nurse their infants while receiving paroxetine.

Renal Impairment: Since paroxetine is extensively metabolized by the liver, excretion of unchanged drug in urine is a minor route of elimination. However, single dose pharmacokinetic studies in subjects with clinically significant renal impairment suggest that plasma levels of paroxetine are elevated in such subjects. Paroxetine should therefore be used with caution and the dosage restricted to the lower end of the range in patients with clinically significant renal impairment.

Hepatic Impairment: Pharmacokinetic studies of paroxetine in subjects with clinically significant hepatic impairment suggest that prolongation of the elimination half-life and increased plasma levels can be expected in this patient group. Paroxetine should be used with caution and dosages restricted to the lower end of the range in patients with clinically significant hepatic impairment.

Drug Interactions: MAO Inhibitors: See Contraindications.

Drugs Metabolized by Cytochrome P450(IID6): Like other selective serotonin reuptake inhibitors, paroxetine inhibits the specific hepatic cytochrome P450 isozyme (IID6) which is responsible for the metabolism of debrisoquine and sparteine. Poor metabolizers of debrisoquine/sparteine represent approximately 5 to 10% of Caucasians. The median Cmin(ss) for paroxetine (20 mg daily) at steady-state in poor metabolizers (n=8) was almost triple that reported for extensive metabolizers (n=9).

Although the full clinical significance of this effect has not been established, inhibition of IID6 can lead to elevated plasma levels of coadministered drugs which are metabolized by this isozyme.

In 2 studies, daily dosing of paroxetine (20 mg daily) under steady-state conditions increased the following mean pharmacokinetic parameters for a single (100 mg) dose of desipramine in extensive metabolizers: Cmax (2 fold), AUC (6 fold), and t 1/2 (3 to 5 fold). Concomitant steady-state paroxetine treatment did not result in any further impairment of desipramine elimination in poor metabolizers. Insufficient information is available to provide recommendations on the necessary dosage adjustments for tricyclic antidepressants or paroxetine, if these drugs are to be used in combination.

Concomitant use of paroxetine with other drugs metabolized by IID6 has not been formally studied but may require lower doses that usually prescribed for either paroxetine or the other drug. Drugs metabolized by cytochrome P450 (IID6) include certain tricyclic antidepressants (e.g., nortriptyline, amitriptyline, imipramine and desipramine), selective serotonin reuptake inhibitors (e.g., fluoxetine), phenothiazine neuroleptics (e.g., perphenazine and thioridazine) and Type IC antiarrhythmics (e.g., propafenone and flecainide).

CNS Drugs: Experience in a limited number of healthy subjects has shown that paroxetine does not increase the sedation and drowsiness associated with haloperidol, amylbarbitone or oxazepam, when given in combination. Since the effects of concomitant administration of paroxetine with neuroleptics have not been studied, the use of paroxetine with these drugs should be approached with caution.

Foods/Antacids: The absorption and pharmacokinetics of paroxetine are not affected by food or antacids.

Cardiovascular Drugs: Multiple dose treatment with paroxetine 30 mg/day has little or no effect on the steady-state pharmacokinetics of digoxin (0.25 mg daily) or propanolol (80 mg b.i.d.).

Anticoagulants: Paroxetine should be administered with great caution to patients receiving oral anticoagulants. Preliminary data suggest that a pharmacodynamic interaction between paroxetine and warfarin may result in increased bleeding in the presence of unaltered prothrombin times.

Microsomal Enzyme Inhibition/Induction: The metabolism and pharmacokinetics of paroxetine may be affected by the induction or inhibition of drug metabolizing enzymes.

Steady-state levels of paroxetine (30 mg daily) were elevated by about 50% when cimetidine (300 mg t.i.d.), a known drug metabolizing enzyme inhibitor, was coadministered to steady-state. Consideration should be given to using doses of paroxetine towards the lower end of the range when coadministered with known drug metabolizing enzyme inhibitors.

Coadministration of a single 30 mg dose of paroxetine to subjects receiving chronic daily dosing with 300 mg phenytoin, a known metabolizing enzyme inducer, is associated with decreased plama levels of paroxetine (AUC reduced approximately 30%) and an increased incidence of adverse experiences. When a single 300 mg dose of phenytoin was administered to subjects receiving chronic daily dosing with 30 mg paroxetine the mean AUC of phenytoin was reduced by 12%. No initial dosage adjustment of paroxetine is considered necessary when the drug is to be coadministered with known drug metabolizing enzyme inducers. Any subsequent dosage adjustment should be guided by clinical effect.

Alcohol: The concomitant use of paroxetine and alcohol has not been studied and is not recommended. Patients should be advised to avoid alcohol while taking paroxetine.

Tryptophan can be metabolized to serotonin. As with other serotonin reuptake inhibitors, the use of paroxetine together with tryptophan may result in adverse reactions consisting primarily of headache, nausea, sweating and dizziness. Consequently, concomitant use of paroxetine with tryptophan is not recommended.

Coadministration of paroxetine with anticonvulsants may be associated with an increased incidence of adverse experiences.

Chronic daily dosing with phenobarbital (100 mg q.i.d. for 14 days) decreased the systemic availability of a single 30 mg dose of paroxetine in some subjects. The AUC and t1/2 of paroxetine were reduced by an average of 25% and 38% respectively compared to paroxetine administered alone. The effect of paroxetine on phenobarbital pharmacokinetics was not studied. No initial paroxetine dosage adjustment is considered necessary when coadministered with phenobarbital; any subsequent adjustment should be guided by clinical effect. Paroxetine has been reported to increase the systemic bioavailability of procyclidine. Steady-state plasma levels of procyclidine (5 mg daily) were elevated by about 40% when 30 mg paroxetine was coadministered to steady-state.

Drugs Highly Bound to Plasma Protein: Paroxetine is highly bound to plasma protein, therefore administration of paroxetine to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, potentially resulting in adverse events. Conversely, adverse effects could result from displacement of paroxetine by other highly bound drugs.

In a study of depressed patients stabilized on lithium, no pharmacokinetic interaction between paroxetine and lithium was observed. However, since there is limited experience in patients, the concurrent administration of paroxetine and lithium should be undertaken with caution.

A multiple dose study of the interaction between paroxetine and diazepam showed no alteration in the pharmacokinetics of paroxetine that would warrant changes in the dose of paroxetine for patients receiving both drugs. The effects of paroxetine on the pharmacokinetics of diazepam were not evaluated.

Adverse Reactions: Commonly Observed: The most commonly observed adverse experiences associated with the use of paroxetine in clinical trials and not seen at an equivalent incidence among placebo-treated patients were: nausea, somnolence, sweating, tremor, asthenia, dizziness, dry mouth, insomnia, constipation, diarrhea, decreased appetite and male sexual dysfunction.

Adverse Events Leading to Discontinuation of Treatment: 21% of approximately 4 000 patients who received paroxetine in worldwide clinical trials in depression discontinued treatment due to an adverse experience. In obsessive-compulsive and panic disorder studies, 11.8% (64/542) and 9.4% (44/469) respectively of patients treated with paroxetine discontinued treatment because of adverse events. The most common events leading to discontinuation (reported by 1% or more of subjects) included: asthenia, headache, nausea, somnolence, insomnia, agitation, tremor, dizziness, constipation, impotence and abnormal ejaculation.

Adverse Effects Following Discontinuation of Treatment: Some patients may experience physical symptoms such as dizziness/lightheadedness, gastrointestinal complaints, headache, agitation/restlessness and sleep disturbance during the period following the discontinuation of paroxetine treatment. These events are generally mild and transient.

Adverse Experience Reports: Multiple doses of paroxetine were administered to 4 126 subjects in clinical trials for depression, 542 subjects in clinical trials for OCD and 469 subjects in clinical trials for panic disorder. Untoward experiences associated with this exposure were recorded by clinical investigators using descriptive terminology of their own choosing.

Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse experiences without first grouping similar types of untoward experiences into a limited (i.e., reduced) number of standardized experience categories.

The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly the cited incidences cannot be compared with figures obtained from other clinical investigations involving different treatments, uses and investigators. The cited frequencies do however provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied. Reported adverse experiences were classified using a COSTART-based Dictionary terminology for the depression trials and an ADECS (a modified COSTART dictionary) for OCD and panic disorder trials.

fIncludes anorgasmia, erectile difficulties, delayed ejaculation/orgasm, sexual dysfunction and impotence. gIncludes difficulty with micturition and urinary hesitancy. hIncludes anorgasmia and difficulty reaching climax/orgasm.

In the tabulations which follow, a COSTART or modified COSTART-based Dictionary terminology has been used to classify reported adverse experiences. The frequencies presented therefore represent the portion of the 4 126, 542 and 469 paroxetine-exposed individuals in depression, OCD and panic trials, respectively, who experienced an event of the type cited on at least one occasion while receiving paroxetine. Experiences are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent experiences are defined as one of those occurring on one or more occasion in at least 1/100 patients; infrequent adverse experiences are those occurring in less than 1/100 but at least 1/1 000 patients; rare experiences are those occurring in less than 1/1 000 patients.

Body as a Whole: Frequent: malaise, pain. Infrequent: allergic reaction, chills, face edema, infection, moniliasis, neck pain, overdose. Rare: abnormal laboratory value, abscess, adrenergic syndrome, cellulitis, chills and fever, cyst, hernia, intentional overdose, neck rigidity, pelvic pain, peritonitis, substernal chest pain, ulcer.

Cardiovascular: Frequent: hypertension, syncope, tachycardia. Infrequent: bradycardia, conduction abnormalities, ECG abnormal, hypotension, migraine, ventricular extrasystoles. Rare: angina pectoris, arrhythmia, atrial arrhythmia, atrial fibrillation, bundle branch block, cerebral ischemia, cerebrovascular accident, congestive heart failure, extrasystoles, low cardiac output, myocardial infarct, myocardial ischemia, pallor, phlebitis, pulmonary embolus, supraventricular extrasystoles, thrombosis, varicose vein, vascular headache.

Dermatological: Frequent: pruritus. Infrequent: acne, alopecia, dry skin, ecchymosis, eczema, furunculosis, herpes simplex, urticaria. Rare: angioedema, contact dermatitis, erythema nodosum, herpes zoster, maculopapular rash, photosensitivity, skin discoloration, skin ulcer, skin hypertrophy.

Endocrine: Rare: diabetes mellitus, hyperthyroidism, hypothyroidism, thyroiditis.

Gastrointestinal: Frequent: nausea and vomiting. Infrequent: bruxism, buccal cavity disorders, dysphagia, eructation, gastroenteritis, gastrointestinal flu, glossitis, increased salivation, liver function tests abnormal, mouth ulceration, vomiting and diarrhea, rectal hemorrhage. Rare: aphthous stomatitis, bloody diarrhea, bulimia, colitis, duodenitis, esophagitis, fecal impaction, fecal incontinence, gastritis, gingivitis, hematemesis, hepatitis, ileus, jaundice, melena, peptic ulcer, salivary gland enlargement, stomach ulcer, stomatitis, tongue edema, tooth caries.

Hematologic and Lymphatic: Infrequent: anemia, leukopenia, lymphadenopathy, purpura, WBC abnormality. Rare: eosinophilia, iron deficiency anemia, leukocytosis, lymphedema, lymphocytosis, microcytic anemia, monocytosis, normocytic anemia.

Metabolic and Nutritional: Frequent: weight gain, weight loss.

Infrequent: edema, hyperglycemia, peripheral edema, thirst.

Rare: alkaline phosphatase increased, bilirubinemia, dehydration, gout, hypercholesteremia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, obesity, AST increased, ALT increased.

Musculoskeletal: Infrequent: arthralgia, arthritis, traumatic fracture. Rare: arthrosis, bursitis, cartilage disorder, myositis, osteoporosis, tetany.

Nervous System: Frequent: CNS stimulation, concentration impaired, depression, emotional lability, vertigo. Infrequent: akinesia, alcohol abuse, amnesia, ataxia, convulsion, depersonalization, hallucinations, hyperkinesia, hypertonia, incoordination, lack of emotion, manic reaction, paranoid reaction, thinking abnormal, hypesthesia. Rare: abnormal EEG, abnormal gait, antisocial reaction, choreoathetosis, circumoral paresthesia, delirium, delusions, diplopia, drug dependence, dysarthria, dyskinesia, dystonia, euphoria, fasciculations, grand mal convulsion, hostility, hyperalgesia, hypokinesia, hysteria, libido increased, manic depressive reaction, meningitis, myelitis, neuralgia, neuropathy, nystagmus, psychosis, psychotic depression, reflexes increased, stupor, withdrawal syndrome.

Respiratory: Frequent: cough increased, rhinitis. Infrequent: asthma, bronchitis, dyspnea, epistaxis, hyperventilation, pneumonia, respiratory flu, sinusitis. Rare: hiccup, lung fibrosis, sputum increased, voice alteration.

Special Senses: Infrequent: abnormality of accommodation, conjunctivitis, ear pain, eye pain, mydriasis, otitis media, tinnitus. Rare: amblyopia, cataract specified, conjunctival edema, corneal lesion, corneal ulcer, exophthalmos, eye hemorrhage, glaucoma, hyperacusis, otitis externa, photophobia, retinal hemorrhage, taste loss, anisocoria, deafness, keratoconjunctivitis.

Urogenital: Infrequent: abortion, amenorrhea, breast pain, cystitis, dysmenorrhea, dysuria, menorrhagia, nocturia, polyuria, urinary incontinence, urinary retention, urinary tract infection, urinary urgency, vaginitis. Rare: breast atrophy, female lactation, hematuria, kidney calculus, kidney function abnormal, kidney pain, mastitis, nephritis, oliguria, urethritis, urine abnormality, vaginal moniliasi.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Overdose attempts have been reported with paroxetine; up to 2 000 mg alone and in combination with other agents during premarketing clinical trials. In cases where paroxetine was used alone, no deaths have occurred and recovery was medically uneventful.

Symptoms of overdosage with paroxetine include nausea, vomiting, drowsiness, sinus tachycardia, tremor, dilated pupils, dry mouth and irritability. There are no reports of ECG abnormalities, coma or convulsions following overdosage with paroxetine alone.

No specific antidote is known. Treatment should consist of those general measures employed in the management of overdose with any antidepressant. Establish and maintain an airway; ensure adequate oxygenation and ventilation. The stomach should be emptied either by the induction of emesis, lavage or both. Following evacuation, 20 to 30 g of activated charcoal may be administered every 4 to 6 hours during the first 24 hours after ingestion. An ECG should be taken and monitoring of cardiac function instituted if there is any evidence of abnormality. Supportive care with frequent monitoring of vital signs and careful observation is indicated. Due to the large volume of distribution of paroxetine, forced diuresis, dialysis, hemoperfusion and exchange transfusions are unlikely to be of benefit.

A specific caution involves patients taking or recently having taken paroxetine who might ingest by accident or intent excessive quantities of a tricyclic antidepressant. In such a case, accumulation of the parent tricyclic and its active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation.

In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a Poison Control Centre for additional information on the treatment of any overdose.

Dosage And Administration: General: Paroxetine should be administered once daily in the morning and may be taken with or without food. The tablet should be swallowed rather than chewed.

Dose Adjustments: Based on pharmacokinetic parameters, steady-state paroxetine plasma levels are achieved over a 7 to 14 days interval. Hence, dosage adjustments in 10 mg increments should be made at 1- to 2-week intervals or according to clinician’s judgment.

Maintenance: During long-term therapy for any indication, the dosage should be maintained at the lowest effective level.

Discontinuation: Some patients may experience physical symptoms following discontinuation of treatment. Although it is unknown if gradual discontinuation will reduce or prevent these symptoms, a gradual tapering of dosage should be considered when treatment is to be discontinued (see Adverse Effects, Adverse Effects Following Discontinuation of Treatment).

Depression: Usual Adult Dose: Administration should be initiated at 20 mg daily. For most patients, 20 mg daily will also be the optimum dose. Therapeutic response may be delayed until the third or fourth week of treatment.

Dose Range: For patients who do not respond adequately to the 20 mg daily dose, a gradual increase of dosage up to 40 mg daily may be considered. Maximum recommended dose is 50 mg.

Obsessive-Compulsive Disorder: Usual Adult Dose: Administration should be initiated at 20 mg/day. The recommended dose of paroxetine in the treatment of OCD is 40 mg daily.

Dose Range: For patients who do not respond adequately to the 40 mg daily dose, a gradual increase in dosage may be considered. Maximum recommended daily dose is 60 mg.

Panic Disorder: Usual Adult Dose: Recommended starting dose is 10 mg/day. The recommended dose of paroxetine in the treatment of panic disorder is 40 mg daily.

Dose Range: For patients who do not respond adequately to the 40 mg daily dose, a gradual increase in dosage may be considered. Maximum recommended daily dose is 60 mg. Special Patient Populations: For any Indication: Geriatrics: A lower initial dose may be considered for elderly and/or debilitated patients. The dose may be increased if indicated up to a maximum of 40 mg daily.

Children: The use of paroxetine in children under 18 years of age is not recommended as safety and efficacy have not been established in this population.

Renal/Hepatic Impairment: Paroxetine should be used with caution in patients with renal or hepatic impairment. Dosage should be restricted to the lower end of the range in patients with clinically significant renal or hepatic impairment (see Precautions). A maximum dose of 40 mg should not be exceeded.

Availability And Storage: 10 mg: Each yellow, film-coated, oval, biconvex tablet, with the product name engraved on one side and strength engraved on the other side, contains: paroxetine HCl equivalent to paroxetine free base 10 mg. Nonmedicinal ingredients: dibasic calcium phosphate dihydrate, hydroxypropyl methylcellulose, magnesium stearate, Opadry yellow, Opadry clear and sodium starch glycolate. HDPE bottles of 30 with polypropylene cap.

20 mg: Each pink, bisected, film-coated, oval, biconvex tablet, with the product name engraved on one side and strength engraved on the other side, contains: paroxetine HCl equivalent to paroxetine free base 20 mg. Nonmedicinal ingredients: dibasic calcium phosphate dihydrate, hydroxypropyl methylcellulose, magnesium stearate, Opadry pink, Opadry clear and sodium starch glycolate. HDPE bottles of 100 with polypropylene cap. “Patient Compliance Pack” blister cards of 30, cartons of 6.

30 mg: Each blue, film-coated, oval, biconvex tablet, with the product name engraved on one side and strength engraved on the other side, contains: paroxetine HCl equivalent to paroxetine free base 30 mg. Nonmedicinal ingredients: dibasic calcium phosphate dihydrate, hydroxypropyl methylcellulose, magnesium stearate, Opadry blue, Opadry clear and sodium starch glycolate. HDPE bottles of 30 with polypropylene cap.

Store at 15 to 30°C.

PAXIL® SmithKline Beecham Paroxetine HCl Antidepressant – Antiobsessional – Antipanic Agent

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