these types of drugs is clinically warranted, inform patients of potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases (see Contraindications and Drug Interactions) Risk of bleeding (GI and other) when used in combination with NSAIDs, aspirin, or drugs affecting coagulation; may impair platelet aggregation Activation of mania/hypomania (screen for bipolar disorder) Fluoxetine therapy has been associated with occurrence of rash and allergic reaction, including vasculitis; discontinue if they occur Bone fractures have been associated with antidepressant therapy; consider possibility of bone fracture when patient presents with bone pain May cause or exacerbate sexual dysfunction Use caution in patients with risk for QT prolongation, including congenital long QT syndrome, history of prolonged QT, or history of prolonged QT; QT prolongation and ventricular arrhythmia, including torsade de pointes Hyponatremia reported with use; consider discontinuation if symptomatic hyponatremia occurs Use caution in patients with history of seizure disorders May prolong QT interval and cause ventricular arrhythmia, including torsade de pointes May cause nervousness, anxiety, insomnia, or anorexia Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomical narrow angles without a patent iridectomy Hypoglycemia reported; may alter glycemic control in patients with diabetes Conflicting evidence reported regarding use of SSRIs during pregnancy and increased risk of persistent pulmonary hypertension of the newborn, or PPHN (see Pregnancy) Risk of complications in neonates exposed to SNRIs/SSRIs late in third trimester (eg, feeding difficulties, irritability, and respiratory problems) Wait 1 week after discontinuation of Prozac before starting Prozac Weekly Gradually decrease dose when discontinuing Has long half-life, decrease in dose will not be fully reflected in plasma for several weeks Conditions that predispose to QT prolongation and ventricular arrhythmia; such conditions include concomitant use of drugs that prolong the QT interval; hypokalemia or hypomagnesemia; recent myocardial infarction, uncompensated heart failure, bradyarrhythmias, and other significant arrhythmias Consider ECG assessment and periodic ECG monitoring if initiating treatment with fluoxetine in patients with risk factors for QT prolongation and ventricular arrhythmia; consider discontinuing fluoxetine and obtaining a cardiac evaluation if patients develop signs or symptoms consistent with ventricular arrhythmia Sexual dysfunction Use may cause symptoms of sexual dysfunction in both male and female patients; inform patients that they should discuss any changes in sexual function and potential management strategies with their healthcare provider Use of SSRIs, may cause symptoms of sexual dysfunction; in male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction In female patients, SSRI/SNRI use may result in decreased libido and delayed or absent orgasm Important for prescribers to inquire about sexual function prior to initiation of therapy and to inquire specifically about changes in sexual function during treatment because sexual function may not be spontaneously reported When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including underlying psychiatric disorder Discuss potential management strategies to support patients in making informed decisions about treatment Pregnancy A pregnancy exposure registry monitors pregnancy outcome in women exposed to antidepressants during pregnancy; healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research­programs/pregnancyregistry/antidepressants/ Available data from published epidemiologic studies and postmarketing reports over several decades have not established an increased risk of major birth defects or miscarriage; some studies have reported an increased incidence of cardiovascular malformations; however, these studies results do not establish a causal relationship There are risks associated with untreated depression in pregnancy and risks of persistent pulmonary hypertension of the newborn (PPHN) and poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), during pregnancy Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants; this finding is from a prospective, longitudinal study that followed 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at beginning of pregnancy Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Neonates exposed to drug and other SSRI or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; such complications can arise immediately upon delivery; reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability, and constant crying These findings are consistent with either a direct toxic effect of SSRIs and SNRIs or possibly a drug discontinuation syndrome; it should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome Animal data In rats and rabbits treated with fluoxetine during the period of organogenesis, there was no evidence of developmental effects at doses up to 1.6 and 3.9 times, respectively, the maximum recommended human dose (MRHD) of 60 mg/day given to adolescents on a mg/m2 basis However, in other reproductive studies in rats, an increase in stillborn pups, a decrease in pup weight, and an increase in pup deaths early after birth occurred at doses that are 1.5 times (during gestation) and 0.97 time (during gestation and lactation) the MRHD given to adolescents on a mg/m2 basis A study of nearly 28,000 women taking SSRIs confirmed 2 previously reported birth defects associated with fluoxetine - heart wall defects and craniosynostosis Persistent pulmonary hypertension of the newborn Potential risk of PPHN when used during pregnancy Initial public health advisory, in 2006, was based on a single published study; since then, there have been conflicting findings from new studies, making it unclear whether the use of SSRIs during pregnancy can cause PPHN The FDA has reviewed the new study results and has concluded that, given the conflicting results from different studies, it is premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN FDA recommendation: The FDA advises health-care professionals not to alter their current clinical practice of treating depression during pregnancy and to report any adverse events to the FDA MedWatch program A meta-analysis of 7 observational studies, found exposure to SSRIs in late pregnancy (ie, >20 weeks' gestation) more than doubled the risk of PPHN that could not be explained by other etiologies (eg, congenital malformations, meconium aspiration) (BMJ 2014;348:f6932) Lactation Data from published literature report the presence of fluoxetine and norfluoxetine in human milk; there are reports of agitation, irritability, poor feeding, and poor weight gain in infants exposed to fluoxetine through breast milk There are no data on effect of fluoxetine or its metabolites on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or underlying maternal condition Infants exposed to drug should be monitored for agitation, irritability, poor feeding, and poor weightPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Selective serotonin reuptake inhibitor; little or no affinity for alpha-adrenergic histamine or cholinergic receptor Absorption Peak plasma time: 6-8 hr Peak plasma concentration: 15-55 ng/mL Steady-state plasma concentration: 91-302 ng/mL (parent drug), 72-258 ng/mL (metabolite) Time to peak: 6-8 hr (serum) Distribution Protein bound: 95% Vd: 12-43 L/kg Metabolism Hepatic P450 enzyme CYP2D6 substrate Enzymes induced: CYP2C9 Enzymes inhibited: CYP2C19, CYP2D6, CYP3A4 Metabolites: Norfluoxetine Elimination Half-life: 4-6 days (chronic administration); 1-3 days (acute); 7-6 days (cirrhosis) Dialyzable: No Excretion: Urine (15%) Pharmacogenomics Several SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline) are metabolized by CYP2D6 CYP2D6 is involved in the metabolism of approximately 20% of drugs in clinical use and displays large individual-to-individual variability in activity due to genetic polymorphisms More than 80 CYP2D6 variant alleles have been identified; however, 4 of the most prevalent alleles, CYP2D6*3, *4, *5, and *6, account for 93-97% of CYP2D6 poor metabolizers (PMs) CYP2D6*4, the most common variant (~25% frequency in whites), causes a splicing defect, CYP2D6*3 (2.7% frequency) causes a frameshift mutation, and CYP3D6*5 (2.6%) is an entire deletion of the CYP2D6 gene; individuals homozygous for these alleles have no CYP2D6 activity The impact of CYP2D6 activity is further complicated by some SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline) that, in addition to being substrates for CYP2D6, are also known to moderately inhibit CYP2D6 activity Genetic testing laboratories Genotyping tests for CYP2D6 variants are commercially available through the following companies Applied Biosystems (http://www.appliedbiosystems.com/) GenPath Diagnostics (http://www.genpathdiagnostics.com/) BRAND FORM. UNIT PRICE PILL IMAGE fluoxetine oral- 40 mg capsulefluoxetine oral- 20 mg capsulefluoxetine oral- 10 mg capsulefluoxetine oral- 20 mg capsulefluoxetine oral- 60 mg tabletfluoxetine oral- 20 mg tabletfluoxetine oral- 10 mg tabletfluoxetine oral- 20 mg capsulefluoxetine oral- 20 mg capsulefluoxetine oral- 20 mg/5 mL (4 mg/mL) solutionfluoxetine oral- 60 mg tabletfluoxetine oral- 10 mg capsulefluoxetine oral- 60 mg tabletfluoxetine oral- 20 mg tabletfluoxetine oral- 10 mg tabletfluoxetine oral- 10 mg tabletfluoxetine oral- 20 mg/5 mL (4 mg/mL) solutionfluoxetine oral- 20 mg tabletfluoxetine oral- 40 mg capsulefluoxetine oral- 40 mg capsulefluoxetine oral- 40 mg capsulefluoxetine oral- 20 mg capsulefluoxetine oral- 10 mg capsulefluoxetine oral- 90 mg capsulefluoxetine oral- 10 mg tabletfluoxetine oral- 10 mg capsulefluoxetine oral- 20 mg capsulefluoxetine oral- 10 mg capsulefluoxetine oral- 10 mg capsulefluoxetine oral- 10 mg capsulefluoxetine oral- 20 mg tabletfluoxetine oral- 10 mg tabletfluoxetine oral- 60 mg tabletfluoxetine oral- 20 mg tabletfluoxetine oral- 10 mg tabletfluoxetine oral- 20 mg capsulefluoxetine oral- 60 mg tabletfluoxetine oral- 20 mg tabletfluoxetine oral- 40 mg capsulefluoxetine oral- 40 mg capsulefluoxetine oral- 40 mg capsulefluoxetine oral- 40 mg capsulefluoxetine oral- 20 mg tabletfluoxetine oral- 10 mg tabletfluoxetine oral- 20 mg tabletfluoxetine oral- 60 mg tabletfluoxetine oral- 20 mg capsulefluoxetine oral- 40 mg capsulefluoxetine oral- 60 mg tabletfluoxetine oral- 10 mg capsulefluoxetine oral- 60 mg tabletfluoxetine oral- 40 mg capsulefluoxetine oral- 20 mg/5 mL (4 mg/mL) solutionProzac oral- 20 mg capsuleProzac oral- 10 mg capsuleProzac oral- 40 mg capsuleCopyright © 2010 First DataBank, Inc.Print Patient Educationfluoxetine oral FLUOXETINE ENTERIC-COATED - ORAL (flew-OX-eh-teen) COMMON BRAND NAME(S): Prozac Weekly WARNING: Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, studies have shown that a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. It is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition.Tell the doctor right away if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed. USES: This long-acting form of fluoxetine is used to treat depression in people who have been successfully treated with the form of fluoxetine that is taken daily. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI).SSRIs work by helping to restore the balance of certain natural substances in the brain (neurotransmitters such as serotonin). Fluoxetine may decrease anxiety, improve your mood, sleep, appetite, and energy level and may help restore your interest in daily living. HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using fluoxetine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth as directed by your doctor, usually once a week with or without food. Swallow the capsule whole. Do not crush or chew the contents of the capsule. Start taking this medication 7 days after your last dose of the form