paroxetine hydrochloride
Paxil, Paxil CR

Available forms
Available by prescription only
Suspension: 10 mg/5ml
Tablets: 10 mg, 20 mg, 30 mg, 40 mg
Tablets (controlled-release): 12.5 mg, 25 mg, 37.5 mg

Indications and dosages
 Major depressive disorder. Adults: Initially, 20 mg P.O. daily, preferably in the morning. Increase dosage by 10 mg/day at 1-week intervals, to maximum of 50 mg daily, if needed. Alternatively, initially, 25 mg P.O. (Paxil CR) as a single daily dose, usually in the morning, with or without food. May increase dose at intervals of at least 1 week by 12.5-mg/day increments, up to a maximum of 62.5 mg/day.
 Obsessive-compulsive disorder (OCD). Adults: Initially, 20 mg P.O. daily, preferably in the morning. Increase dosage by 10 mg/day at 1-week intervals to target dose of 40 mg/day. Maximum dose is 60 mg/day.
 Panic disorder. Adults: Initially, 10 mg P.O. daily, preferably in the morning. Increase dosage by 10 mg/day at 1-week intervals, to target dose of 40 mg/day. Maximum dose is 60 mg/day. Alternatively, initially, 12.5 mg P.O. (Paxil CR) as a single daily dose, usually in the morning, with or without food. May increase dosage at intervals of at least 1 week by 12.5-mg/day increments, up to a maximum of 75 mg/day.
 Social anxiety disorder. Adults: 20 mg P.O. daily.
 Generalized anxiety disorder. Adults: Initially, 20 mg P.O. daily. Increase dosage by 10 mg/day at increments of at least 1 week. Maximum dose is 50 mg P.O. daily.
 Posttraumatic stress disorder. Adults: Initially, 20 mg P.O. daily. Increase dosage by 10 mg/day at increments of at least 1 week. Maximum dose is 50 mg P.O. daily.
 Diabetic neuropathy ◇. Adults: 10 to 60 mg P.O. daily.
 Headaches ◇. Adults: 10 to 50 mg P.O. daily.
 Premature ejaculation ◇. Adults: 10 to 40 mg P.O. daily.
 Premenstrual dysphoric disorder (PMDD) ◇. Adults: 5 to 30 mg P.O. daily.
≡ Dosage adjustment. For elderly or debilitated patients or patients with severe hepatic or renal disease, 10 mg P.O. daily, preferably in the morning. Increase dosage by 10 mg/day at 1-week intervals, p.r.n., to maximum of 40 mg daily.
≡ Dosage adjustment. For elderly or debilitated patients and patients with severe renal or hepatic impairment, the recommended initial dose of Paxil CR is 12.5 mg/day. May increase if indicated. Dosage shouldn’t exceed 50 mg/day.

Pharmacodynamics
Antidepressant action: Exact mechanism unknown. Presumed to be linked to potentiation of serotonergic activity in the CNS, from inhibition of neuronal reuptake of serotonin.

Pharmacokinetics
Absorption: Completely absorbed.
Distribution: Distributed throughout body, including CNS, with only 1% remaining in plasma. About 93% to 95% bound to plasma protein.
Metabolism: About 36% metabolized in liver. Principal metabolites are polar and conjugated products of oxidation and methylation; readily cleared.
Excretion: About 64% excreted in urine (2% as parent compound, 62% as metabolite).

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those taking MAO inhibitors or within 14 days of discontinuing an MAO inhibitor. Use cautiously in those with a history of seizures or mania; those with severe, concurrent systemic illness; and those at risk for volume depletion.

Interactions
Drug-drug. Cimetidine: Decreases hepatic metabolism of paroxetine, causing risk of toxicity. Dosage adjustments may be needed.
Digoxin: Decreases digoxin levels. Monitor patient closely.
MAO inhibitors: Increases risk of serious, sometimes fatal, adverse reactions. Avoid use together and don’t use paroxetine within 14 days of discontinuing MAO inhibitors.
Phenobarbital: Induces paroxetine metabolism and reduces plasma levels. Adjust dosage as needed.
Phenytoin: Alters pharmacokinetics of phenytoin. Adjust dosage as needed.
Procyclidine: Increases procyclidine levels. Monitor patient for excessive anticholinergic effects.
Sumatriptan: Causes weakness, hyperreflexia and incoordination. Monitor patient closely.
Theophylline: Increases theophylline levels. Monitor patient closely.
Tricyclic antidepressants: Inhibits metabolism of these drugs, resulting in increased serum levels. Monitor patient for toxicity.
Tryptophan: Increases adverse reactions, such as diaphoresis, headache, nausea, and dizziness. Avoid use together.
Warfarin: Increases risk of bleeding. Monitor INR.
Drug-herb. St. John’s wort: Serotonin levels may rise too high, causing serotonin syndrome.Discourage use together.
Drug-lifestyle. Alcohol use: Increases risk of adverse CNS effects. Discourage alcohol use.

Adverse reactions
CNS: somnolence, dizziness, insomnia, tremor, nervousness, anxiety, paresthesia, confusion, headache, agitation, asthenia, abnormal dreams.
CV: palpitations, vasodilation, orthostatic hypotension, chest pain.
EENT: lump or tightness in throat, dysgeusia, visual disturbances, double vision.
GI: dry mouth, nausea, constipation, diarrhea, flatulence, vomiting, dyspepsia, increased or decreased appetite, abdominal pain.
GU: ejaculatory disturbances, decreased libido, male genital disorders (including anorgasmia, erectile difficulties, delayed ejaculation or orgasm, impotence, and sexual dysfunction), urinary frequency, other urinary disorders, female genital disorders (including anorgasmia, difficulty with orgasm).
Musculoskeletal: myopathy, myalgia, myasthenia.
Skin: diaphoresis, rash, pruritus.
Other: yawning.

Effects on lab test results
None reported.

Overdose and treatment
Toxicity may cause nausea, vomiting, dizziness, sweating, facial flushing, drowsiness, sinus tachycardia, and dilated pupils.
 Perform gastric evacuation by emesis, lavage, or both. In most cases, 20 to 30 g of activated charcoal may then be used every 4 to 6 hours during the first 24 to 48 hours after ingestion.
 Special caution must be taken with a patient who receives or recently received paroxetine if the patient ingests an excessive quantity of a tricyclic antidepressant; 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.

Special considerations
 ALERT Don’t confuse Paxil (paroxetine) with Plavix (clopidogrel bisulfate).
• At least 14 days should elapse between stopping an MAO inhibitor and starting drug therapy. Similarly, at least 14 days should elapse between stopping paroxetine and starting MAO inhibitor.
• Hyponatremia may occur with paroxetine use, especially in elderly patients, those taking diuretics, and those who are otherwise volume depleted. Monitor serum sodium levels.
• If signs of psychosis occur or increase, reduce dosage. Monitor patients for suicidal tendencies and allow them only a minimum supply of drug.
Breast-feeding patients
• Drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and effectiveness in children haven’t been established.
Geriatric patients
• Use cautiously and in lower dosages in elderly patients.

Patient education
• Caution patient not to operate hazardous machinery, including automobiles, until reasonably certain that drug doesn’t affect ability to engage in such activity.
• Tell patient that he may notice improvement in 1 to 4 weeks but that he must continue with prescribed regimen to obtain continued benefits.
• Instruct patient to call before taking other drugs, including OTC preparations and herbal remedies, while taking paroxetine.
• Tell patient to abstain from alcohol while taking drug.
• Warn patient not to chew or crush Paxil CR tablet, and to swallow it whole.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use