Paxil.

SSRI. Symptomatic relief of depressive illness: Initially, usually in the morning, a 25 mg single daily dose. Patients unresponsive to a 25 mg dose may benefit from dose increases, in 12.5 mg/day increments, at intervals of at least 1 week, to a maximum of 62.5 mg/day. Symptomatic relief of panic disorder: Initially, usually in the morning, a 12.5 mg single daily dose. Dose changes at intervals of at least 1 week should occur in 12.5 mg/day increments. Maximum dosage: 75 mg/day. Social phobia (social anxiety disorder): Initially, usually in the morning, a 12.5 mg single daily dose. Patients unresponsive to a 12.5 mg dose may benefit from dose increases, in 12.5 mg/day increments, at intervals of at least 1 week, to a maximum of 37.5 mg/day. Tablets should be swallowed whole and not chewed or crushed.

Contraindications Paxil

Not to be used with an MAOI or within 14 days of starting or discontinuing MAOI therapy. Concomitant administration of thioridazine. Contraindicated in patients < 18 years of age due to possible increased risk of suicide-related events in this patient populations.

Precautions "Paxil"

Not recommended for use during pregnancy, in nursing mothers. Epileptic patients, glaucoma, neuroleptic malignant syndrome, renal or hepatic impairment, activation of mania/hypomania, suicidal tendency, MI or unstable heart disease. Efficacy/safety of combined Paxil and electroconvulsive therapy has not been studied. Hyponatremia (reversible), abnormal bleeding. If a decision is made to stop Paxil therapy, the drug should be gradually withdrawn, as abrupt discontinuation may cause withdrawal symptoms.

Side effects "Paxil"

Nausea, somnolence, sweating, tremor, insomnia, asthenia, dry mouth, dizziness, male sexual dysfunction, constipation, diarrhea, decreased appetite.

Interactions "Paxil"

See Contraindications. MAOIs, Phenobarbital, theophylline, 5HT1 agonists (e.g., sumatriptan), phenytoin, lithium, anticoagulants (increased bleeding), procyclidine, cimetidine, St. John's Wort, drugs highly bound to plasma protein, drugs affecting liver enzymes. Avoid concurrent use of paxil and tryptophan.

Supplied "Paxil"

12.5 mg and 25 mg controlled-release tablets.

Pharmacology "Paxil"

Antidepressant

paxil 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 effects.

paxil is a phenylpiperidine derivative which is chemically unrelated to the tricyclic or tetracyclic antidepressants. In receptor binding studies, paxil did not exhibit significant affinity for the adrenergic (alpha(1), alpha(2), beta), dopaminergic, serotonergic (5HT(1), 5HT(2)), or histaminergic receptors of rat brain membrane. A weak affinity for the muscarinic acetylcholine receptor was evident. The predominant metabolites of paxil are essentially inactive as 5-HT reuptake inhibitors.

Pharmacokinetics Paxil

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

paxil 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. 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 paxil are about >10000 and 3000 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 paxil 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 paxil 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 paxil are generally achieved in 7 to 14 days. No correlation has been established between paxil plasma concentrations and therapeutic efficacy or the incidence of adverse reactions. No clear dose relationship has been demonstrated for the antidepressant effects of paxil at doses above 20 mg/day. The results of a fixed-dose study comparing paxil and placebo revealed the dose dependency for some of the more common adverse events.

In healthy young volunteers receiving a 20 mg daily dose of paxil for 15 days, the mean maximal plasma concentration was 41 ng/mL at steady state. 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. Elderly patients should, therefore, be initiated and maintained at the lowest daily dosage of paxil 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 paxil is markedly reduced in this patient group. As the elimination of paxil is dependent upon extensive hepatic metabolism, its use in patients with hepatic impairment should be undertaken with caution.

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

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

Indications "Paxil"

For symptomatic relief of depressive illness. Clinical trials have provided evidence that continuation treatment with paxil in patients with moderate to moderately severe depressive disorder is effective for at least 6 months.

Contraindications "Paxil"

Hypersensitivity Paxil: paxil is contraindicated in patients who are known to be hypersensitive to the drug.

Monoamine Oxidase Inhibitors Paxil: paxil should not be used in combination with MAO inhibitors or within 2 weeks of terminating treatment with MAO inhibitors. Treatment with paxil 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 paxil.

Precautions "Paxil"

Suicide Paxil: 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 and consideration should be given to the possible need for hospitalization. In order to minimize the opportunity for overdosage, prescriptions for paxil should be written for the smallest quantity of drug consistent with good patient management.

Seizures Paxil: During clinical trials, the overall incidence of seizures was 0.15% in patients treated with paxil. 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 Paxil: During clinical testing in depressed patients, approximately 1% of paxil treated patients experienced manic reactions. When bipolar patients were considered as a sub-group the incidence of mania was 2%. As with other Selective Serotonin Reuptake Inhibitors (SSRIs), paxil should be used with caution in patients with a history of mania.

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

Occupational Hazards Paxil: Although paxil 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 paxil does not affect them adversely.

Cardiac Conditions Paxil: paxil does not generally produce clinically significant changes in blood pressure, heart rate or ECG. paxil 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) Paxil: The efficacy and safety of the concurrent use of paxil and ECT have not been studied.

Geriatrics Paxil: Administration of paxil 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 paxil which is associated with clinical efficacy.

A total of 459 elderly patients (>=65 years) have participated in therapeutic studies with paxil. The pattern of adverse experiences in the elderly was comparable to that in younger patients.

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

Pregnancy and Lactation Paxil: Although animal studies have not shown any teratogenic or selective embryotoxic effects, the safety of paxil in human pregnancy has not been established. paxil should not be used during pregnancy unless the potential benefit to the patient outweighs the possible risk to the fetus. The concentrations of paxil detected in the breast milk of lactating women are similar to those in plasma. Lactating women should not nurse their infants while receiving paxil.

Renal Impairment Paxil: Since paxil 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 paxil are elevated in such subjects. paxil 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 Paxil: Pharmacokinetic studies of paxil 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. paxil should be used with caution and dosages restricted to the lower end of the range in patients with clinically significant hepatic impairment.

Food/Antacids Paxil: The absorption and pharmacokinetics of paxil are not affected by food or antacids.

Cardiovascular Drugs Paxil: Multiple dose treatment with paxil 30 mg/day has little or no effect on the steady-state pharmacokinetics of digoxin or propranolol.

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

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

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

Co-administration of a single 30 mg dose of paxil to subjects receiving chronic daily dosing with 300 mg phenytoin, a known metabolizing enzyme inducer, is associated with decreased plasma levels of paxil (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 paxil the mean AUC of phenytoin was reduced by 12%. No initial dosage adjustment of paxil is considered necessary when the drug is to be co-administered with known drug metabolizing enzyme inducers. Any subsequent dosage adjustment should be guided by clinical effect.

Like other selective serotonin re-uptake inhibitors, paxil inhibits the specific hepatic cytochrome P450 isozyme (IID6) which is responsible for the metabolism of debrisoquine and sparteine. Although the clinical significance of this effect has not been established, inhibition of IID6 may lead to elevated plasma levels of co-administered drugs which are metabolized by this isozyme. Drugs metabolized by cytochrome P450IID6 include certain tricyclic antidepressants (e.g. nortriptyline, amitriptyline, imipramine and desipramine), phenothiazine neuroleptics (e.g. perphenazine and thioridazine) and Type Ic antiarrhythmics (e.g. propafenone and flecainide).

Alcohol Paxil: The concomitant use of paxil and alcohol in depressed patients has not been studied and is not recommended.

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

Tryptophan can be metabolized to serotonin. Therefore, the use of paxil together with tryptophan may result in adverse reactions including agitation, restlessness and gastrointestinal distress.

Co-administration of paxil with anticonvulsants may be associated with an increased incidence of adverse experiences.

Chronic daily dosing with 100 mg phenobarbitone decreased the systemic availability of a single 30 mg dose of paxil in some subjects. paxil 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 paxil was co-administered to steady-state.

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

A multiple dose study of the interaction between paxil and diazepam showed no alteration in the pharmacokinetics of paxil that would warrant changes in the dose of paxil for patients receiving both drugs.

Adverse "Paxil"

Commonly Observed Paxil: The most commonly observed adverse experiences associated with the use of paxil and not seen at an equivalent incidence among placebo treated patients were: Nausea, somnolence, sweating, tremor, asthenia, dizziness, dry mouth, insomnia and male sexual dysfunction (primarily ejaculatory delay).

Adverse Events Leading to Discontinuation of Treatment Paxil: 16% (656/4126) of patients who received paxil in worldwide clinical trials discontinued treatment due to an adverse experience. The most common events (reported by at least 1% of subjects) associated with discontinuation included: asthenia, headache, nausea, somnolence, insomnia and abnormal ejaculation. All other events associated with discontinuation occurred at rates of 1% or less.

Adverse Experience Reports Paxil: During clinical testing, multiple doses of paxil were administered to 4126 subjects. 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.

Table III lists adverse experiences that occurred in short-term flexible dose placebo-controlled trials at a frequency of 1% or more. (An additional 460 patients participated in a fixed-dose placebo-controlled study.)

The prescriber should be aware that these figures cannot be used to predict the incidences 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 non-drug factors to the side effect incidence rate in the population studied. Reported adverse experiences were classified using a COSTART-based Dictionary terminology.

Body as a Whole Paxil: 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 Paxil: 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 Paxil: 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.

Endocrine Paxil: Rare: Diabetes mellitus, hyperthyroidism, hypothyroidism, thyroiditis.

Gastrointestinal Paxil: 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 Paxil: Infrequent: Anemia, leukopenia, lymphadenopathy, purpura, WBC abnormality. Rare: Eosinophilia, iron deficiency anemia, leukocytosis, lymphedema, lymphocytosis, microcytic anemia, monocytosis, normocytic anemia.

Metabolic and Nutritional Paxil: 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 (SGOT) increased, ALT (SGPT) increased.

Musculoskeletal Paxil: Infrequent: Arthralgia, arthritis, traumatic fracture. Rare: Arthrosis, bursitis, cartilage disorder, myositis, osteoporosis, tetany.

Nervous System Paxil: 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. 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 Paxil: Frequent: Cough increased, rhinitis. Infrequent: Asthma, bronchitis, dyspnea, epistaxis, hyperventilation, pneumonia, respiratory flu, sinusitis. Rare: Hiccup, lung fibrosis, sputum increased, voice alteration.

Special Senses Paxil: 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.

Urogenital Paxil: 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 moniliasis*.

*Incidence corrected for gender.

Discontinuation Effects Paxil: Some patients may experience discontinuation effects such as dizziness/lightheadedness, gastrointestinal complaints, headache, agitation/restlessness and sleep disturbance in the period immediately following the discontinuation of paxil treatment. These events are generally mild and transient.

Dosage "Paxil"

Usual Adult Dose Paxil: The administration of paxil should be initiated at 20 mg daily. For most patients, 20 mg daily will also be the optimum dose. The therapeutic response may be delayed until the third or fourth week of treatment.

Dose Adjustments Paxil: Based on pharmacokinetic parameters, steady-state paxil 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.

Dose Range Paxil: For those patients who do not respond adequately to the 20 mg daily dose, a gradual increase in dosage up to 40 mg daily may be considered. The maximum recommended daily dose is 50 mg. paxil should be administered once daily in the morning and may be taken with or without food. The tablet should be swallowed rather than chewed.

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

Geriatrics Paxil: A lower dosage may be considered for elderly and/or debilitated patients. Increases in dose may be made if indicated up to a maximum of 40 mg daily.

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

Renal/Hepatic Impairment Paxil: paxil 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).

Supplied "Paxil"

20 mg Paxil: Each pink, bisected, film-coated, oval, biconvex tablet, with the product name engraved on one side and strength engraved on the other side, contains: paxil HCl equivalent to paxil free base 20 mg. Nonmedicinal ingredients: Dibasic calcium phosphate dihydrate USP, hydroxypropyl methylcellulose USP [2910], magnesium stearate NF, Opadry pink YS-1-1262, Opadry clear YS-1-7006 and sodium starch glycolate NF. HDPE bottles of 100 with polypropylene cap.

30 mg Paxil: Each blue, film-coated, oval, biconvex tablet, with the product name engraved on one side and strength engraved on the other side, contains: paxil HCl equivalent to paxil free base 30 mg. Nonmedicinal ingredients: Dibasic calcium phosphate dihydrate USP, hydroxypropyl methylcellulose USP [2910], magnesium stearate NF, Opadry blue YS-1-4256, Opadry clear YS-1-7006 and sodium starch glycolate NF. HDPE bottles of 30 with propylene cap.

Store at 15 to 30°C.

Paxil

Drug monograph "Paxil"

How To Use "Paxil"

Contraindications Paxil

Precautions "Paxil"

Side effects "Paxil"

Interactions "Paxil"

Supplied "Paxil"

Pharmacology "Paxil"

Pharmacokinetics Paxil

Indications "Paxil"

Contraindications "Paxil"

Precautions "Paxil"

Adverse "Paxil"

Dosage "Paxil"

Supplied "Paxil"