Fluoxetine

Brand Name: Prozac, Serafem

Description

Fluoxetine (Prozac) is a selective serotonin reuptake inhibitor (SSRI) used to treat depression, obsessive-compulsive disorder (OCD), or bulimia. Fluoxetine is also used to treat premenstrual dysphoric disorder (PMDD), symptoms of which occur in the week or two before a woman's menstrual period and commonly include irritability, mood swings, and tension as well as the physical symptoms of bloating and breast tenderness. Prozac is also approved to treat panic disorder with or without agoraphobia.

Pharmacology

The antidepressant, antiobsessive-compulsive, and antibulimic actions of fluoxetine (Prozac) are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Studies at clinically relevant doses in man have demonstrated that fluoxetine blocks the uptake of serotonin into human platelets. Studies in animals also suggest that fluoxetine is a much more potent uptake inhibitor of serotonin than of norepinephrine.

In humans, following a single oral 40 mg dose, peak plasma concentrations of fluoxetine from 15 to 55 ng/ mL are observed after 6 to 8 hours.

Sometimes fluoxetine must be taken for up to 4 weeks or longer before you begin to feel better. Your doctor should check your progress at regular visits during this time.

Indications and Usage

Prozac is indicated for the treatment of depression.

Prozac is indicated for the treatment of obsessions and compulsions in patients with obsessive-compulsive disorder (OCD).

Bulimia Nervosa -- Prozac is indicated for the treatment of binge-eating and vomiting behaviors in patients with moderate to severe bulimia nervosa.

Contraindications

Prozac is contraindicated in patients known to be hypersensitive to it.

Monoamine Oxidase Inhibitors: 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) in patients receiving fluoxetine in combination with a monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued fluoxetine and are then started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Therefore, Prozac should not be used in combination with an MAOI, or within a minimum of 14 days of discontinuing therapy with an MAOI.

In addition, at least 5 weeks, perhaps longer, should be allowed after stopping Prozac before starting an MAOI.

Warnings

Rash and Possibly Allergic Events: In US fluoxetine clinical trials, 7% of 10,782 patients developed various types of rashes and/ or urticaria. Among the cases of rash and/ or urticaria reported in premarketing clinical trials, almost a third were withdrawn from treatment because of the rash and/ or systemic signs or symptoms associated with the rash. Clinical findings reported in association with rash include fever, leukocytosis, arthralgias, edema, carpal tunnel syndrome, respiratory distress, symphadenopathy, proteinuria, and mild transaminase elevation. Most patients improved promptly with discontinuation of fluoxetine and/ or adjunctive treatment with antihistamines or steroids, and all patients experiencing these events were reported to recover completely.

In premarketing clinical trials, 2 patients are known to have developed a serious cutaneous systemic illness. In neither patient was there an unequivocal diagnosis, but 1 was considered to have a leukocytoclastic vasculitis, and the other, a severe desquamating syndrome that was considered variously to be a vasculitis or erythema multiforme. Other patients have had systemic syndromes suggestive of serum sickness.

Since the introduction of Prozac, systemic events, possibly related to vasculitis, have developed in patients with rash. Although these events are rare, they may be serious, involving the lung, kidney, or liver. Death has been reported to occur in association with these systemic events.

Anaphylactoid events, including bronchospasm, angioedema, and urticaria alone and in combination, have been reported.

Pulmonary events, including inflammatory processes of varying histopathology and/ or fibrosis, have been reported rarely. These events have occurred with dyspnea as the only preceding symptom.

Whether these systemic events and rash have a common underlying cause or are due to different etiologies or pathogenic processes is not known. Furthermore, a specific underlying immunologic basis for these events has not been identified.

Upon the appearance of rash or of other possibly allergic phenomena for which an alternative etiology cannot be identified, Prozac should be discontinued.

Precautions

Anxiety and Insomnia: In clinical trials for depression, 12% to 16% of patients treated with Prozac reported anxiety, nervousness, or insomnia.

For obsessive-compulsive disorder, insomnia was reported in 28% of patients treated with Prozac. Anxiety was reported in 14% of patients treated with Prozac.

For bulimia nervosa, insomnia was reported in 33% of patients treated with Prozac. Anxiety and nervousness were reported respectively in 15% and 11% of patients treated with Prozac.

Altered Appetite and Weight: Significant weight loss, especially in underweight depressed or bulimic patients may be an undesirable result of treatment with Prozac.

Fluoxetine should be given with caution to patients suffering from anorexia nervosa and only if the expected benefits (e.g., co-morbid depression) markedly outweigh the potential weight reducing effect of the drug.

Activation of Mania/ Hypomania: In US clinical trials for depression, mania/ hypomania was reported in 0.1% of patients treated with Prozac.

Seizures: Fluoxetine should be used with caution in patients with a history of convulsive disorders.

Suicide: The possibility of a suicide attempt is inherent in depression and may persist until significant remission occurs. Close supervision of high risk patients should accompany initial drug therapy. Prescriptions for Prozac should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose.

Because of well- established comorbidity between both OCD and depression and bulimia and depression, the same precautions observed when treating patients with depression should be observed when treating patients with OCD or bulimia.

Use in Patients With Concomitant Illness: Clinical experience with Prozac in patients with concomitant systemic illness is limited. Caution is advisable in using Prozac in patients with diseases or conditions that could affect metabolism or hemodynamic responses.

Cardiovascular: Fluoxetine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease.

Liver: A lower or less frequent dose should be used in patients with cirrhosis.

Diabetics: In patients with diabetes, Prozac may alter glycemic control. Hypoglycemia has occurred during therapy with Prozac, and hyperglycemia has developed following discontinuation of the drug. As is true with many other types of medication when taken concurrently by patients with diabetes, insulin and/ or oral hypoglycemic dosage may need to be adjusted when therapy with Prozac is instituted or discontinued.

Usage in Children: The efficacy of Prozac for the treatment of major depressive disorder was demonstrated in two 8- to 9-week placebo-controlled clinical trials with 315 pediatric outpatients ages 8 to=18.

The efficacy of Prozac for the treatment of OCD was demonstrated in one 13-week placebo-controlled clinical trial with 103 pediatric outpatients ages 7 to <18.

The safety and effectiveness in pediatric patients <8 years of age in major depressive disorder and <7 years of age in OCD have not been established.

Fluoxetine pharmacokinetics were evaluated in 21 pediatric patients (ages 6 to=18) with major depressive disorder or OCD.

The acute adverse event profiles observed in the 3 studies (N=418 randomized; 228 fluoxetine-treated, 190 placebo-treated) were generally similar to that observed in adult studies with fluoxetine. The longer-term adverse event profile observed in the 19-week major depressive disorder study (N=219 randomized; 109 fluoxetine-treated, 110 placebo-treated) was also similar to that observed in adult trials with fluoxetine.

Manic reaction, including mania and hypomania, was reported in 6 (1 mania, 5 hypomania) out of 228 (2.6%) fluoxetine-treated patients and in 0 out of 190 (0%) placebo-treated patients. Mania/hypomania led to the discontinuation of 4 (1.8%) fluoxetine-treated patients from the acute phases of the 3 studies combined. Consequently, regular monitoring for the occurrence of mania/hypomania is recommended.

As with other SSRIs, decreased weight gain has been observed in association with the use of fluoxetine in children and adolescent patients. After 19 weeks of treatment in a clinical trial, pediatric subjects treated with fluoxetine gained an average of 1.1 cm less in height (p=0.004) 15 and 1.1 kg less in weight (p=0.008) than subjects treated with placebo. In addition, fluoxetine treatment was associated with a decrease in alkaline phosphatase levels. The safety of fluoxetine treatment for pediatric patients has not been systematically assessed for chronic treatment longer than several months in duration. In particular, there are no studies that directly evaluate the longer-term effects of fluoxetine on the growth, development, and maturation of children and adolescent patients. Therefore, height and weight should be monitored periodically in pediatric patients receiving fluoxetine.

Pregnancy & Nursing: The effect of Prozac on labor and delivery in humans is unknown. However, because fluoxetine crosses the placenta and because of the possibility that fluoxetine may have adverse effects on the newborn, fluoxetine should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus.

Because Prozac is excreted in human milk, nursing while on Prozac is not recommended.

Interference with Cognitive or Motor Performance: Any psychoactive drug may impair judgment, thinking, or motor skills, and patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that the drug treatment does not affect them adversely.

Drug Interactions

As with all drugs, the potential for interaction by a variety of mechanisms (eg, pharmacodynamic, pharmacokinetic drug inhibition or enhancement, etc) is a possibility.

Do not use fluoxetine and MAO inhibitors at the same time.

BEFORE USING THIS MEDICINE: INFORM YOUR DOCTOR OR PHARMACIST of all prescription and over-the-counter medicine that you are taking. This includes cyproheptadine, lithium, dextromethorphan, selegiline, and medicines used to treat high blood pressure, seizures, and depression. Using these medicines in combination with Prozac can produce an adverse reaction.

Antipsychotics: Some clinical data suggests a possible pharmacodynamic and/ or pharmacokinetic interaction between serotonin specific reuptake inhibitors (SSRIs) and antipsychotics. Elevation of blood levels of haloperidol and clozapine has been observed in patients receiving concomitant fluoxetine. A single case report has suggested possible additive effects of pimozide and fluoxetine leading to bradycardia.

Anticonvulsants: Patients on stable doses of phenytoin and carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant fluoxetine treatment.

Five patients receiving fluoxetine in combination with tryptophan experienced adverse reactions, including agitation, restlessness and gastrointestinal distress.

Inform your doctor of any other medical conditions, including kidney or liver disease, allergies, pregnancy, or breast-feeding.

Adverse Reactions

Side Effects That Should Be Reported To Your Doctor: Characterized as less common- Chills or fever; joint or muscle pain; skin rash, hives, or itching; trouble in breathing.

Characterized as rare- Burning or tingling in fingers, hands, or arms; convulsions (seizures); signs of low blood sugar, including anxiety or nervousness, cold sweats, confusion, cool pale skin, difficulty in concentration, drowsiness, excessive hunger, fast heartbeat, headache, shakiness or unsteady walk, or unusual tiredness or weakness; swelling of feet or lower legs; swollen glands; talking, feeling, and acting with excitement and activity you cannot control.

Side Effects That Usually Do Not Require Immediate Medical Attention

In clinical trials, the most commonly observed adverse events associated with the use of fluoxetine include nervousness, trouble sleeping, headache, drowsiness, fatigue, nausea, vomiting, diarrhea, loss of appetite, dry mouth, sweating, dizziness, lightheadedness, muscle spasms, or changes in sexual function. If they continue or are bothersome, check with your doctor.

Other less common side effects- Abnormal dreams; change in taste; changes in vision; chest pain; constipation; cough; decrease in concentration; fast or irregular heartbeat; feeling of warmth or heat; flushing or redness of skin, especially on face and neck; frequent urination; increased appetite; menstrual pain; stomach cramps, gas, or pain; stuffy nose; tiredness or weakness; tremor.

If you notice other effects not listed above, contact your doctor, nurse, or pharmacist.

Drug Abuse and Dependence

Prozac is not a controlled substance. Since introduction, reports of death attributed to overdose of fluoxetine alone have been rare.

Overdose

Signs and Symptoms

Symptoms of overdose of Prozac may include nausea, vomiting, seizures, and restlessness.

Treatment

If you or someone you know may have used more than the recommended dose of this medicine, contact your local poison control center or emergency room immediately.

Establish and maintain an airway; ensure adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdose. Cardiac and vital signs monitoring is recommended, along with general symptomatic and supportive measures. There are no specific antidotes for Prozac.

In managing overdosage, consider the possibility of multiple drug involvement.

Dosage

As with other antidepressants, the full antidepressant effect of Prozac may be delayed until 4 weeks of treatment or longer.

At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with Prozac. In addition, at least 5 weeks, perhaps longer, should be allowed after stopping Prozac before starting an MAOI.

Follow the directions for using this medicine provided by your doctor.
Store this medicine at room temperature, away from heat and light.
Continue to take this medicine even if you feel better. Do not stop without checking with your doctor.
If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.
This medicine may be taken with food if it upsets your stomach.

Additional Information: Do not share this medicine with others for whom it was not prescribed. Do not use this medicine for other health conditions. Keep this medicine out of the reach of children.

Depression:
Adults: The recommended initial dosage is 20 mg administered once daily in the morning. A gradual dose increase should be considered only after a trial period of several weeks if the expected clinical improvement does not occur.

Bulimia Nervosa:
Adults: The recommended dosage is 60 mg/day, although studies show that lower doses may also be efficacious. Electrolyte levels should be assessed prior to initiation of treatment.

Obsessive-Compulsive Disorder:
Adults: A dose range of 20 mg/day to 60 mg/day is recommended.

For all indications, the total Prozac dosage should not exceed a maximum of 80 mg/day.

Maintenance/ Continuation/ Extended Treatment: It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacologic therapy.

While there are no systematic studies that answer the question of how long to continue Prozac, bulimia and ocd are chronic conditions and it is reasonable to consider continuation for a responding patient.

Elderly & Debilitated Patients: Lower doses are recommended in these patients since they may be more sensitive to the drug.

Pediatric (children and adolescents): In the short-term (8 to 9 week) controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of major depressive disorder, patients were administered fluoxetine doses of 10 to 20 mg/day. Treatment should be initiated with a dose of 10 or 20 mg/day. After 1 week at 10 mg/day, the dose should be increased to 20 mg/day.

However, due to higher plasma levels in lower weight children, the starting and target dose in this group may be 10 mg/day. A dose increase to 20 mg/day may be considered after several weeks if insufficient clinical improvement is observed.

In the controlled clinical trial of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fluoxetine doses in the range of 10 to 60 mg/day.

In adolescents and higher weight children, treatment should be initiated with a dose of 10 mg/day. After 2 weeks, the dose should be increased to 20 mg/day. Additional dose increases may be considered after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 60 mg/day is recommended.

In lower weight children, treatment should be initiated with dose of 10 mg/day. Additional dose increases may be considered after several more weeks if insufficient clinical improvement is observed. A dose range of 20 to 30 mg/day is recommended. Experience with daily doses greater than 20 mg is very minimal, and there is no experience with doses greater than 60 mg.

IF USING THIS MEDICINE FOR AN EXTENDED PERIOD OF TIME, obtain refills before your supply runs out.

How Supplied

Liquid: Oral Solution is available in: 20 mg per 5 mL with mint flavor. It contains Fluoxetine HCl equivalent to fluoxetine 20 mg.

Capsules: 10 mg: The 10 mg Pulvule is opaque green and green, imprinted with DISTA 3104 on the cap and Prozac 10 mg on the body, contains: Fluoxetine HCl equivalent to fluoxetine 10 mg.

20 mg: The 20 mg Pulvule is an opaque green cap and off- white body, imprinted with DISTA 3105 on the cap and Prozac 20 mg on the body, contains: Fluoxetine HCl equivalent to fluoxetine 20 mg.

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The information in this monograph is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects. This information is generalized and is not intended as specific medical advice. If you have questions about the medicines you are taking or would like more information, check with your doctor, pharmacist, or nurse.