Drug Name

Prozac (Fluoxetine)

Generic Name

Fluoxetine (floo-OX-e-teen)

Looks like

• Prozac 10 mg-opaque green cap and opaque green body, imprinted with DISTA 3104 on the cap and Prozac 10 mg on the body
• Prozac 20 mg-opaque green cap and opaque yellow body, imprinted with DISTA 3105 on the cap and Prozac 20 mg on the body
• Prozac 40 mg-opaque green cap and opaque orange body, imprinted with DISTA 3107 on the cap and Prozac 40 mg on the body

Dosage Form

Capsule

Route Of Administration

ORAL

Imprint Code

DISTA;3104;Prozac;10;mg / DISTA;3105;Prozac;20;mg / DISTA;3107;Prozac;40;mg

Size

16mm / 16mm / 18mm

Alternatives

Depression
Lexapro (Escitalopram), Zoloft (Sertraline), Cymbalta (Duloxetine), Celexa (Citalopram)
Panic Disorder
Zoloft (Sertraline), Paxil (Paroxetine)
Obsessive Compulsive Disorder
Zoloft (Sertraline), Paxil (Paroxetine), Celexa (Citalopram)

Drug Uses

Treating depression or obsessive-compulsive disorder (OCD) in adults and children. It is used to treat bulimia nervosa and panic disorder in adults. It may also be used for other conditions as determined by your doctor.

Drug class

Prozac is a selective serotonin reuptake inhibitor (SSRI). It works by restoring the balance of serotonin, a natural substance in the brain, which helps to improve certain mood problems.

Contains

Each Prozac Capsule contains fluoxetine hydrochloride equivalent to 10 mg (32.3 umol), 20 mg (64.7 umol), or 40 mg (129.3 umol) of fluoxetine. The Prozac Capsules also contain starch, gelatin, silicone, titanium dioxide, iron oxide, and other inactive ingredients. The 10- and 20-mg Prozac Capsules also contain FD&C Blue No. 1, and the 40-mg Prozac Capsule also contains FD&C Blue No. 1 and FD&C Yellow No. 6.

Chemical formula

Prozac (fluoxetine capsules) is a psychotropic drug for oral administration. It is also marketed for the treatment of premenstrual dysphoric disorder (Sarafem, fluoxetine hydrochloride). It is designated (±) - N - methyl - 3 - phenyl - 3 - [(a,a,a - trifluoro - p - tolyl) oxy] propylamine hydrochloride and has the empirical formula of C17H18F3NO * HCl. Its molecular weight is 345.79. The structural formula is:

Fluoxetine hydrochloride is a white to off-white crystalline solid with a solubility of 14 mg/mL in water.

How Taken

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results from the medication.

Do not break, chew, or open an extended-release capsule. Swallow the pill whole. It is specially made to release medicine slowly in the body. Breaking the pill would cause too much of the drug to be released at one time.
Measure the liquid form of Prozac with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one.

It may take 4 weeks or longer before you start feeling better. Do not stop using Prozac without first talking to your doctor. You may have unpleasant side effects if you stop taking this medication suddenly.
To treat premenstrual dysphoric disorder, the usual dose of Prozac is once daily while you are having your period, or 14 days before you expect your period to start. Follow your doctor's instructions.

Dosage and Administration

Major Depressive Disorder
Initial Treatment
Adult - In controlled trials used to support the efficacy of fluoxetine, patients were administered morning doses ranging from 20 to 80 mg/day. Studies comparing fluoxetine 20, 40, and 60 mg/day to placebo indicate that 20 mg/day is sufficient to obtain a satisfactory response in major depressive disorder in most cases. Consequently, a dose of 20 mg/day, administered in the morning, is recommended as the initial dose.

A dose increase may be considered after several weeks if insufficient clinical improvement is observed. Doses above 20 mg/day may be administered on a once-a-day (morning) or BID schedule (i.e., morning and noon) and should not exceed a maximum dose of 80 mg/day.

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.

All patients - As with other drugs effective in the treatment of major depressive disorder, the full effect may be delayed until 4 weeks of treatment or longer.

As with many other medications, a lower or less frequent dosage should be used in patients with hepatic impairment. A lower or less frequent dosage should also be considered for the elderly, and for patients with concurrent disease or on multiple concomitant medications. Dosage adjustments for renal impairment are not routinely necessary.

Maintenance/Continuation/Extended Treatment
It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacologic therapy. Whether the dose needed to induce remission is identical to the dose needed to maintain and/or sustain euthymia is unknown.

Daily Dosing
Systematic evaluation of Prozac in adult patients has shown that its efficacy in major depressive disorder is maintained for periods of up to 38 weeks following 12 weeks of open-label acute treatment (50 weeks total) at a dose of 20 mg/day.

Weekly Dosing
Systematic evaluation of Prozac Weekly in adult patients has shown that its efficacy in major depressive disorder is maintained for periods of up to 25 weeks with once-weekly dosing following 13 weeks of open-label treatment with Prozac 20 mg once daily. However, therapeutic equivalence of Prozac Weekly given on a once-weekly basis with Prozac 20 mg given daily for delaying time to relapse has not been established.

Weekly dosing with Prozac Weekly capsules is recommended to be initiated 7 days after the last daily dose of Prozac 20 mg.

If satisfactory response is not maintained with Prozac Weekly, consider reestablishing a daily dosing regimen.
Switching Patients to a Tricyclic Antidepressant (TCA)
Dosage of a TCA may need to be reduced, and plasma TCA concentrations may need to be monitored temporarily when fluoxetine is coadministered or has been recently discontinued.

Switching Patients to or from a Monoamine Oxidase Inhibitor (MAOI)
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.

Obsessive Compulsive Disorder
Initial Treatment
Adult - In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of OCD, patients were administered fixed daily doses of 20, 40, or 60 mg of fluoxetine or placebo.In 1 of these studies, no dose-response relationship for effectiveness was demonstrated. Consequently, a dose of 20 mg/day, administered in the morning, is recommended as the initial dose. Since there was a suggestion of a possible dose-response relationship for effectiveness in the second study, a dose increase may be considered after several weeks if insufficient clinical improvement is observed. The full therapeutic effect may be delayed until 5 weeks of treatment or longer.

Doses above 20 mg/day may be administered on a once-a-day (i.e., morning) or BID schedule (i.e., morning and noon). A dose range of 20 to 60 mg/day is recommended; however, doses of up to 80 mg/day have been well tolerated in open studies of OCD. The maximum fluoxetine dose should not exceed 80 mg/day.

Pediatric (children and adolescents) - 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 a 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.

All patients - As with the use of Prozac in the treatment of major depressive disorder, a lower or less frequent dosage should be used in patients with hepatic impairment. A lower or less frequent dosage should also be considered for the elderly, and for patients with concurrent disease or on multiple concomitant medications. Dosage adjustments for renal impairment are not routinely necessary.

Maintenance/Continuation Treatment
While there are no systematic studies that answer the question of how long to continue Prozac, OCD is a chronic condition and it is reasonable to consider continuation for a responding patient. Although the efficacy of Prozac after 13 weeks has not been documented in controlled trials, adult patients have been continued in therapy under double-blind conditions for up to an additional 6 months without loss of benefit. However, dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for treatment.

Bulimia Nervosa
Initial Treatment
In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of bulimia nervosa, patients were administered fixed daily fluoxetine doses of 20 or 60 mg, or placebo. Only the 60-mg dose was statistically significantly superior to placebo in reducing the frequency of binge-eating and vomiting. Consequently, the recommended dose is 60 mg/day, administered in the morning. For some patients it may be advisable to titrate up to this target dose over several days. Fluoxetine doses above 60 mg/day have not been systematically studied in patients with bulimia.

As with the use of Prozac in the treatment of major depressive disorder and OCD, a lower or less frequent dosage should be used in patients with hepatic impairment. A lower or less frequent dosage should also be considered for the elderly, and for patients with concurrent disease or on multiple concomitant medications. Dosage adjustments for renal impairment are not routinely necessary.

Maintenance/Continuation Treatment
Systematic evaluation of continuing Prozac 60 mg/day for periods of up to 52 weeks in patients with bulimia who have responded while taking Prozac 60 mg/day during an 8-week acute treatment phase has demonstrated a benefit of such maintenance treatment. Nevertheless, patients should be periodically reassessed to determine the need for maintenance treatment.

Panic Disorder
Initial Treatment
In the controlled clinical trials of fluoxetine supporting its effectiveness in the treatment of panic disorder, patients were administered fluoxetine doses in the range of 10 to 60 mg/day. Treatment should be initiated with a dose of 10 mg/day. After 1 week, the dose should be increased to 20 mg/day. The most frequently administered dose in the 2 flexible-dose clinical trials was 20 mg/day.

A dose increase may be considered after several weeks if no clinical improvement is observed. Fluoxetine doses above 60 mg/day have not been systematically evaluated in patients with panic disorder.

As with the use of Prozac in other indications, a lower or less frequent dosage should be used in patients with hepatic impairment. A lower or less frequent dosage should also be considered for the elderly, and for patients with concurrent disease or on multiple concomitant medications. Dosage adjustments for renal impairment are not routinely necessary.

Maintenance/Continuation Treatment
While there are no systematic studies that answer the question of how long to continue Prozac, panic disorder is a chronic condition and it is reasonable to consider continuation for a responding patient. Nevertheless, patients should be periodically reassessed to determine the need for continued treatment.

Special Populations
Treatment of Pregnant Women During the Third Trimester
Neonates exposed to Prozac and other SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. When treating pregnant women with Prozac during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering Prozac in the third trimester.

Discontinuation of Treatment with Prozac
Symptoms associated with discontinuation of Prozac and other SSRIs and SNRIs, have been reported. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate. Plasma fluoxetine and norfluoxetine concentration decrease gradually at the conclusion of therapy which may minimize the risk of discontinuation symptoms with this drug.

Missed Dose

Take the missed dose as soon as you remember. However, if it is almost time for the next regularly scheduled dose, skip the missed dose and take the next one as directed. Do not take extra medicine to make up the missed dose.

If you miss a dose of Prozac Weekly, take the missed dose as soon as you remember and take the next dose 7 days later. However, if it is almost time for the next regularly scheduled weekly dose, skip the missed dose and take the next one as directed.Do not take extra medicine to make up the missed dose.

Overdose

Seek emergency medical attention if you think you have taken too much of this medication. Symptoms of a Prozac overdose may include nausea, vomiting, fever, sleepiness, rapid or uneven heartbeat, confusion, fainting, seizures, or coma.

Storage

Store Prozac at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Prozac out of the reach of children and away from pets.

How Supplied

Prozac are available in:

The 10-mg, Pulvule is opaque green cap and opaque green body, imprinted with DISTA 3104 on the cap and Prozac 10 mg on the body:
NDC 0777-3104-02 (PU3104) - Bottles of 100

The 20-mg Pulvule is an opaque green cap and opaque yellow body, imprinted with DISTA 3105 on the cap and Prozac 20 mg on the body:
NDC 0777-3105-30 (PU3105) - Bottles of 30
NDC 0777-3105-02 (PU3105) - Bottles of 100
NDC 0777-3105-07 (PU3105) - Bottles of 2000

The 40-mg Pulvule is an opaque green cap and opaque orange body, imprinted with DISTA 3107 on the cap and Prozac 40 mg on the body:
NDC 0777-3107-30 (PU3107) - Bottles of 30

What is the most important information I should know about Prozac (Fluoxetine)?

Do not take Prozac together with pimozide (Orap), thioridazine (Mellaril), or a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate).
You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Prozac is the only antidepressant that is FDA-approved for use in children with depression. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself. SSRI antidepressants may cause serious or life-threatening lung problems in newborn babies whose mothers take the medication during pregnancy. However, you may have a relapse of depression if you stop taking your antidepressant during pregnancy. If you are planning a pregnancy, or if you become pregnant while taking Prozac, do not stop taking the medication without first talking to your doctor.

What should I discuss with my doctor before taking Prozac (Fluoxetine)?

Do not use Prozac if you are using any of the following drugs:

• pimozide (Orap);
• thioridazine (Mellaril); or
• an MAO inhibitor such as isocarboxazid (Marplan), tranylcypromine (Parnate), phenelzine (Nardil), rasagiline (Azilect), or selegiline (Eldepryl, Emsam).

Serious and sometimes fatal reactions can occur when these medicines are taken with Prozac. You must wait at least 14 days after stopping an MAO inhibitor before you can take Prozac. You must wait 5 weeks after stopping Prozac before you can take thioridazine (Mellaril) or an MAOI.

Before taking Prozac, tell your doctor if you are allergic to any drugs, or if you have:

• cirrhosis of the liver;
• kidney disease;
• diabetes;
• seizures or epilepsy;
• bipolar disorder (manic depression); or
• a history of drug abuse or suicidal thoughts.

If you have any of these conditions, you may not be able to use Prozac, or you may need a dosage adjustment or special tests.

You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

FDA pregnancy category C. SSRI antidepressants may cause serious or life-threatening lung problems in newborn babies whose mothers take the medication during pregnancy. However, you may have a relapse of depression if you stop taking your antidepressant during pregnancy. If you are planning a pregnancy, or if you become pregnant while taking Prozac, do not stop taking the medication without first talking to your doctor. Prozac can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Do not give Prozac to anyone younger than 18 years old without a doctor's advice. Prozac is the only antidepressant that is FDA-approved for use in children with depression.

Absorption, Distribution, Metabolism, and Excretion

Systemic bioavailability - In man, 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.

The Pulvule, oral solution, and Prozac Weekly capsule dosage forms of fluoxetine are bioequivalent. Food does not appear to affect the systemic bioavailability of fluoxetine, although it may delay its absorption by 1 to 2 hours, which is probably not clinically significant. Thus, fluoxetine may be administered with or without food. Prozac Weekly capsules, a delayed-release formulation, contain enteric-coated pellets that resist dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. The enteric coating delays the onset of absorption of fluoxetine 1 to 2 hours relative to the immediate-release formulations.

Protein binding - Over the concentration range from 200 to 1000 ng/mL, approximately 94.5% of fluoxetine is bound in vitro to human serum proteins, including albumin and a1-glycoprotein. The interaction between fluoxetine and other highly protein-bound drugs has not been fully evaluated, but may be important.

Enantiomers - Fluoxetine is a racemic mixture (50/50) of R-fluoxetine and S-fluoxetine enantiomers. In animal models, both enantiomers are specific and potent serotonin uptake inhibitors with essentially equivalent pharmacologic activity. The S-fluoxetine enantiomer is eliminated more slowly and is the predominant enantiomer present in plasma at steady state.

Metabolism - Fluoxetine is extensively metabolized in the liver to norfluoxetine and a number of other unidentified metabolites. The only identified active metabolite, norfluoxetine, is formed by demethylation of fluoxetine. In animal models, S-norfluoxetine is a potent and selective inhibitor of serotonin uptake and has activity essentially equivalent to R- or S-fluoxetine. R-norfluoxetine is significantly less potent than the parent drug in the inhibition of serotonin uptake. The primary route of elimination appears to be hepatic metabolism to inactive metabolites excreted by the kidney.

Clinical issues related to metabolism/elimination - The complexity of the metabolism of fluoxetine has several consequences that may potentially affect fluoxetine's clinical use.

Variability in metabolism - A subset (about 7%) of the population has reduced activity of the drug metabolizing enzyme cytochrome P450 2D6 (CYP2D6). Such individuals are referred to as "poor metabolizers" of drugs such as debrisoquin, dextromethorphan, and the TCAs. In a study involving labeled and unlabeled enantiomers administered as a racemate, these individuals metabolized S-fluoxetine at a slower rate and thus achieved higher concentrations of S-fluoxetine. Consequently, concentrations of S-norfluoxetine at steady state were lower. The metabolism of R-fluoxetine in these poor metabolizers appears normal. When compared with normal metabolizers, the total sum at steady state of the plasma concentrations of the 4 active enantiomers was not significantly greater among poor metabolizers. Thus, the net pharmacodynamic activities were essentially the same. Alternative, nonsaturable pathways (non-2D6) also contribute to the metabolism of fluoxetine. This explains how fluoxetine achieves a steady-state concentration rather than increasing without limit.

Because fluoxetine's metabolism, like that of a number of other compounds including TCAs and other selective serotonin reuptake inhibitors (SSRIs), involves the CYP2D6 system, concomitant therapy with drugs also metabolized by this enzyme system (such as the TCAs) may lead to drug interactions.

Accumulation and slow elimination - The relatively slow elimination of fluoxetine (elimination half-life of 1 to 3 days after acute administration and 4 to 6 days after chronic administration) and its active metabolite, norfluoxetine (elimination half-life of 4 to 16 days after acute and chronic administration), leads to significant accumulation of these active species in chronic use and delayed attainment of steady state, even when a fixed dose is used. After 30 days of dosing at 40 mg/day, plasma concentrations of fluoxetine in the range of 91 to 302 ng/mL and norfluoxetine in the range of 72 to 258 ng/mL have been observed. Plasma concentrations of fluoxetine were higher than those predicted by single-dose studies, because fluoxetine's metabolism is not proportional to dose. Norfluoxetine, however, appears to have linear pharmacokinetics. Its mean terminal half-life after a single dose was 8.6 days and after multiple dosing was 9.3 days. Steady-state levels after prolonged dosing are similar to levels seen at 4 to 5 weeks.

The long elimination half-lives of fluoxetine and norfluoxetine assure that, even when dosing is stopped, active drug substance will persist in the body for weeks (primarily depending on individual patient characteristics, previous dosing regimen, and length of previous therapy at discontinuation). This is of potential consequence when drug discontinuation is required or when drugs are prescribed that might interact with fluoxetine and norfluoxetine following the discontinuation of Prozac.

Weekly dosing - Administration of Prozac Weekly once weekly results in increased fluctuation between peak and trough concentrations of fluoxetine and norfluoxetine compared with once-daily dosing [for fluoxetine: 24% (daily) to 164% (weekly) and for norfluoxetine: 17% (daily) to 43% (weekly)]. Plasma concentrations may not necessarily be predictive of clinical response. Peak concentrations from once-weekly doses of Prozac Weekly capsules of fluoxetine are in the range of the average concentration for 20-mg once-daily dosing. Average trough concentrations are 76% lower for fluoxetine and 47% lower for norfluoxetine than the concentrations maintained by 20-mg once-daily dosing. Average steady-state concentrations of either once-daily or once-weekly dosing are in relative proportion to the total dose administered. Average steady-st