is directly attributable to SSRI treatment Bone fractures reported to be associated with antidepresant use Consider risk of serotonin syndrome if administered concomitantly with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort 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 Pregnancy category: D Teratogenic effects: Epidemiologic studies have shown that infants exposed to paroxetine in the first trimester of pregnancy have an increased risk of congenital malformations, particularly cardiovascular malformations Use late in the third trimester associated with complications in newborns and may require prolonged hospitalization, respiratory support, and tube feeding A study of nearly 28,000 women taking SSRIs confirmed 5 previously reported birth defercts associated with paroxetine, including heart defects, anencephaly, and abdominal wall defects (BMJ 2015; 351:h3190) Persistent pulmonary hypertension of the newborn Potential risk of persistent pulmonary hypertension of the newborn (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 use of SSRIs during pregnancy can cause PPHN FDA has reviewed the additional 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: 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 Excreted in breast milk; use caution (AAP states effect on nursing infants is unknown but may be of concern)Pregnancy 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 SSRI; little or no affinity for alpha-adrenergic histamine or cholinergic receptor Absorption Peak plasma time: 5.2-8.1 hr (immediate-release); 6-10 hr (controlled-release) Peak plasma concentration: 61.7 ng/mL Distribution Protein bound: 93-95% Vd: 8.7 L/kg Metabolism Metabolism: Hepatic P450 enzyme CYP2D6 Enzymes inhibited: CYP2D6 Metabolites: Inactive Elimination Half-life: 21 hr Dialyzable: No Excretion: Urine (64%); feces (36%) 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 it 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 in 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 Paxil oral- 10 mg/5 mL suspensionPaxil oral- 40 mg tabletPaxil oral- 20 mg tabletPaxil oral- 10 mg tabletPaxil oral- 30 mg tabletPaxil oral- 10 mg tabletparoxetine oral- 25 mg tabletparoxetine oral- 40 mg tabletparoxetine oral- 40 mg tabletparoxetine oral- 25 mg tabletparoxetine oral- 30 mg tabletparoxetine oral- 20 mg tabletparoxetine oral- 37.5 mg tabletparoxetine oral- 12.5 mg tabletparoxetine oral- 30 mg tabletparoxetine oral- 20 mg tabletparoxetine oral- 10 mg tabletparoxetine oral- 10 mg tabletparoxetine oral- 25 mg tabletparoxetine oral- 12.5 mg tabletparoxetine oral- 40 mg tabletparoxetine oral- 30 mg tabletparoxetine oral- 10 mg tabletparoxetine oral- 20 mg tabletparoxetine oral- 40 mg tabletparoxetine oral- 30 mg tabletparoxetine oral- 20 mg tabletparoxetine oral- 10 mg tabletparoxetine oral- 25 mg tabletparoxetine oral- 12.5 mg tabletparoxetine oral- 20 mg tabletparoxetine oral- 12.5 mg tabletparoxetine oral- 20 mg tabletparoxetine oral- 37.5 mg tabletparoxetine oral- 30 mg tabletparoxetine oral- 10 mg tabletparoxetine oral- 40 mg tabletparoxetine oral- 40 mg tabletparoxetine oral- 20 mg tabletparoxetine oral- 40 mg tabletparoxetine oral- 37.5 mg tabletparoxetine oral- 37.5 mg tabletparoxetine oral- 10 mg tabletparoxetine oral- 25 mg tabletparoxetine oral- 12.5 mg tabletparoxetine oral- 37.5 mg tabletparoxetine oral- 30 mg tabletparoxetine oral- 30 mg tabletparoxetine oral- 10 mg tabletparoxetine oral- 25 mg tabletparoxetine oral- 37.5 mg tabletparoxetine oral- 12.5 mg tabletparoxetine oral- 20 mg tabletPaxil CR oral- 37.5 mg tabletPaxil CR oral- 25 mg tabletPaxil CR oral- 37.5 mg tabletPaxil CR oral- 25 mg tabletPaxil CR oral- 12.5 mg tabletPaxil CR oral- 25 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationparoxetine oral PAROXETINE - ORAL (pa-ROX-e-teen) COMMON BRAND NAME(S): Paxil 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: Paroxetine is used to treat depression, panic attacks, obsessive-compulsive disorder (OCD), anxiety disorders, and post-traumatic stress disorder. It works by helping to restore the balance of a certain natural substance (serotonin) in the brain.Paroxetine is known as a selective serotonin reuptake inhibitor (SSRI). This medication may improve your mood, sleep, appetite, and energy level and may help restore your interest in daily living. It may decrease fear, anxiety, unwanted thoughts, and the number of panic attacks. It may also reduce the urge to perform repeated tasks (compulsions such as hand-washing, counting, and checking) that interfere with daily living. HOW TO USE: Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start taking paroxetine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually once daily in the morning. Taking this medication with food may decrease nausea. If this medication makes you sleepy during the day, then talk to your doctor about taking it in the evening.The dosage is based on your medical condition, response to treatment, age, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). To reduce your risk of side effects, your doctor may start you at a low dose and gradually increase your dose. Follow your doctor's instructions carefully. Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase. Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.If you are taking paroxetine for premenstrual problems, your doctor may direct you to take it every day of the month or just for the 2 weeks before your period through the first full day of your period.Keep taking this medication even if you feel well. Do not stop taking this medication without consulting your doctor. Some conditions may become worse when this drug is suddenly stopped. Also, you may experience symptoms such as mood swings, headache, tiredness, sleep changes, and brief feelings similar to electric shock. To prevent these symptoms while you are stopping treatment with this drug, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details. Report any new or worsening symptoms right away.It may take up to several weeks before you get the full benefit of this drug.Tell your doctor if your condition does not improve or if it worsens. SIDE EFFECTS: See also Warning section.Nausea, drowsiness, dizziness, trouble sleeping, loss of appetite, weakness, dry mouth, sweating, blurred vision, and yawning may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: shaking (tremor), restlessness, inability to keep still, decreased interest in sex, changes in sexual ability, numbness/tingling, easy bleeding/bruising, fast/irregular heartbeat, muscle weakness/spasm, seizures.Get medical help right away if you have any very serious side effects, including: black stools, vomit that looks like coffee grounds, eye pain/swelling/redness, widened pupils, vision changes (such as seeing rainbows around lights at night).This medication may increase serotonin and rarely cause a very serious condition called serotonin syndrome/toxicity. The risk increases if you are also taking other drugs that increase serotonin, so tell your doctor or pharmacist of all the drugs you take (see Drug Interactions section). Get medical help right away if you develop some of the following symptoms fast heartbeat, hallucinations, loss of coordination, severe dizziness, severe nausea/vomiting/diarrhea, twitching muscles, unexplained fever, unusual agitation/restlessness.Rarely, males may have a painful or prolonged erection lasting 4 or more hours. If this occurs, stop using this drug and get medical help right away, or permanent problems could occur.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. PRECAUTIONS: Before taking paroxetine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: personal or family history of