Prozac, Prozac Weekly, Sarafem

Pharmacologic classification: selective serotonin reuptake inhibitor
Therapeutic classification: antidepressant
Pregnancy risk category C

Available forms
Available by prescription only
Capsules: 10 mg, 20 mg (Prozac and Sarafem), 40 mg (Prozac)
Capsules (delayed-release): 90 mg
Oral solution: 20 mg/5 ml
Tablets: 10 mg

Indications and dosages
 Depression, bipolar disorder ◇, alcohol dependence ◇, cataplexy ◇, myoclonus. Prozac. Adults: 20 mg P.O. daily in the morning. Increase dosage, p.r.n., after several weeks to 40 mg daily with a dose morning and midday. Don’t exceed 80 mg daily.
 Maintenance therapy for depression in stabilized patients (not for newly diagnosed depression). Prozac Weekly. Adults: 90 mg P.O. once weekly. Initiate once weekly dosing 7 days after the last daily dose of Prozac 20 mg.
 Obsessive-compulsive disorder. Prozac. Adults: Initially, 20 mg P.O. daily. Gradually increase dosage after several weeks as needed and tolerated to 60 to 80 mg daily.
 Bulimia nervosa. Prozac. Adults: 60 P.O. daily in the morning.
 Premenstrual dysphoric disorder (PMDD). Sarafem. Adults: 20 mg P.O. daily. Maximum dose is 80 mg P.O. daily. Drug may be given in a continuous or cyclic regimen.
 Short-term treatment of panic disorders with or without agoraphobia. Adults: 10 mg P.O. once daily for 7 days; then increase as needed to 20 mg daily. Maximum daily dose is 60 mg.

Antidepressant action: The antidepressant action of fluoxetine is purportedly related to its inhibition of CNS neuronal uptake of serotonin. Fluoxetine blocks uptake of serotonin, but not of norepinephrine, into human platelets. Animal studies suggest that it’s a much more potent uptake inhibitor of serotonin than of norepinephrine.

Absorption: Well absorbed after oral administration. Absorption isn’t altered by food.
Distribution: About 95% protein-bound.
Metabolism: Metabolized primarily in the liver to active metabolites.
Excretion: Excreted by the kidneys. Elimination half-life is 2 to 3 days. Norfluoxetine (the primary active metabolite) has an elimination half-life of 7 to 9 days.

Route Onset Peak Duration
P.O. Unknown 6-8 hr Unknown

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in patients who took an MAO inhibitor within 14 days of starting therapy. MAO inhibitors and thioridazine shouldn’t be given with fluoxetine or within 5 weeks after fluoxetine has been discontinued. Use cautiously in patients at high risk of suicide or in those with a history of seizures, diabetes mellitus, or renal, hepatic, or CV disease.

Drug-drug. Benzodiazepines (such as alprazolam), lithium, tricyclic antidepressants: Increases adverse CNS effects; increases tricyclic antidepressant and lithium levels. Monitor patient closely for adverse effects and toxicity. Dosage adjustments may be needed.
Carbamazepine, flecainide, vinblastine: Increases serum levels of these drugs. Monitor serum levels and patient for adverse effects.
Cyproheptadine: May reverse or decrease fluoxetine effects. Monitor patient closely.
Insulin, oral antidiabetics: Alters blood glucose levels. May alter requirements for antidiabetic.
Phenytoin: Increases phenytoin levels and risk of toxicity. Monitor phenytoin levels; dosage adjustment may be needed.
Tryptophan: Increases adverse CNS effects (agitation, restlessness) and GI distress. Use cautiously.
Warfarin: Increases risk of bleeding. Monitor PT and INR.
Warfarin and other highly protein-bound drugs: Increases levels of fluoxetine or other highly protein-bound drugs. Monitor patient closely.
Drug-herb. St. John’s wort: Increases risk of serotonin syndrome. Discourage use together.
Drug-lifestyle. Alcohol use: May increase CNS depression. Discourage alcohol use.

Adverse reactions
CNS: nervousness, anxiety, insomnia, headache, drowsiness, tremor, dizziness, asthenia, fatigue.
CV: palpitations, hot flashes.
EENT: nasal congestion, pharyngitis, sinusitis, fever.
GI: nausea, diarrhea, dry mouth, anorexia, dyspepsia, constipation, abdominal pain, vomiting, flatulence, increased appetite.
GU: sexual dysfunction.
Metabolic: weight loss, hyponatremia.
Musculoskeletal: muscle pain.
Respiratory: cough, upper respiratory infection, respiratory distress.
Skin: rash, pruritus, diaphoresis.
Other: flu syndrome.

Effects on lab test results
• May decrease sodium levels.

Overdose and treatment
Signs and symptoms of overdose include agitation, restlessness, hypomania, other signs of CNS excitation and, in patients who took higher doses of fluoxetine, nausea and vomiting.
 To treat fluoxetine overdose, establish and maintain an airway; ensure adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as effective as emesis or lavage. Monitor cardiac and vital signs, and provide usual supportive measures. Fluoxetine-induced seizures that don’t subside spontaneously may respond to diazepam. Forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit.

Special considerations
 ALERT Make sure patient isn’t doubling the dose of fluoxetine. Sarafem and Prozac are the same drug, but are used for different indications.
• Consider patient to have a risk of suicide until depressive state improves considerably. Supervise high-risk patients closely during early therapy. To reduce risk of intentional overdose, give the smallest quantity of pulvules consistent with good management.
• Full antidepressant effect may take 4 weeks or longer.
• Treatment of acute depression usually requires at least several months of continuous drug therapy; optimal duration of therapy hasn’t been established.
• Because of its long elimination half-life, changes in fluoxetine dosage won’t be reflected in plasma for several weeks, affecting titration to final dose and withdrawal from treatment.
• Fluoxetine therapy may activate mania or hypomania.
• Sarafem may be taken continuously or intermittently. Patient starts 2 weeks before menstruation and continues through the first full day of menses. Patient repeats regimen with each new cycle.
• If patient takes Sarafem for PMDD, reevaluate patient for long-term effectiveness of therapy. Clinical effectiveness hasn’t been studied beyond 6 months.
Pregnant patients
• Avoid use in pregnant women. Because of its long half-life, use drug only when risk to fetus has passed.
Breast-feeding patients
• Drug appears in breast milk and shouldn’t be used by breast-feeding women.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• No overall differences in safety and efficacy were observed in elderly patients; however, elderly patients may have increased sensitivity to drug.

Patient education
• Inform patient that drug may cause dizziness or drowsiness. Advise patient to avoid hazardous tasks that require alertness until CNS response to drug is established.
• Caution patient to avoid ingestion of alcohol and to seek medical approval before taking other drugs.
• Tell patient to promptly report rash or hives, anxiety, nervousness, anorexia (especially if underweight), suspicion of pregnancy, or intent to become pregnant.

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