Buy Paroxetine HCI

Use:
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:
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:
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 If a decision is made to stop paxil therapy, the drug should be gradually withdrawn, as abrupt discontinuation may cause withdrawal symptoms.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:
Nausea, somnolence, sweating, tremor, insomnia, asthenia, dry mouth, dizziness, male sexual dysfunction, constipation, diarrhea, decreased appetite.

Interactions:
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 paroxetine and tryptophan.

Supplied:
12.5 mg and 25 mg controlled-release tablets.

Pharmacology

Antidepressant

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 effects.

Paroxetine online 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 (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 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 buy paroxetine 30 mg online 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.

Buy paroxetine online 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 paroxetine 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 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 a fixed-dose study comparing paroxetine 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 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.

Buy Online Indications

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.

Contraindications

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

Monoamine Oxidase Inhibitors:
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 and consideration should be given to the possible need for hospitalization. In order to minimize the opportunity for overdosage, prescriptions for buy paroxetine online 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 sub-group 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 overnight 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.

A total of 459 elderly patients (>=65 years) have participated in therapeutic studies with paroxetine. 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 fedex 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:
Food/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 or propranolol.

Anticoagulants:
Paroxetine should be administered with great caution to patients receiving oral anticoagulants. Preliminary data suggest fedex 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 co-administered to steady-state. Consideration should be given to using doses of paroxetine towards the lower end of the range when co-administered with known drug metabolizing enzyme inhibitors.

Co-administration of a single 30 mg overnight dose of paroxetine to subjects receiving chronic daily dosing with 300 mg phenytoin, a known metabolizing enzyme inducer, is associated with decreased plasma 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 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, paroxetine 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:
The concomitant use of paroxetine and alcohol in depressed patients has not been studied and is not recommended.

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

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

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

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

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.

Overdose

Symptoms and Treatment:
Overdose attempts have been reported with paroxetine; up to 850 mg alone and in combination with other agents. In cases where paroxetine was used alone, no deaths have occurred and recovery was medically uneventful.

Symptoms of overdosage with paroxetine include nausea, vomiting, 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.

The stomach should be emptied either by the induction of emesis, lavage or both. Following evacuation, 20 to 30 g of activated fedex charcoal may be administered every 4 to 6 hours during the first 24 hours after ingestion. Supportive care with frequent monitoring of vital signs and careful observation is indicated.

Paroxetine Dosage

Usual Adult Dose:
The administration of paroxetine 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:
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.

Dose Range:
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.

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.

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

Geriatrics:
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.

Paroxetine and 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).

Supplied

Paroxetine 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 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.

Paroxetine 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 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 buy paroxetine online overnight fedex delivery.

Store at 15 to 30°C.

Note: This information is from a Canadian monograph. There can be differences in indications, dosage forms and warnings for this drug in other countries.