presence of 40% and 20% alcohol, respectively Serotonergic drugs Development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including duloxetine, when administered concomitantly with other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) If concomitant use with other serotonergic drugs is clinically warranted, advise patients of potential risk for serotonin syndrome, particularly during treatment initiation and dose increases; treatment with concomitant serotonergic agents, should be discontinued immediately if above events occur and initiate supportive symptomatic treatment Pregnancy Data from a postmarketing retrospective cohort study indicate that use in the month before delivery may be associated with an increased risk of postpartum hemorrhage; data from published literature and from a postmarketing retrospective cohort study have not identified a clear drug-associated risk of major birth defects or other adverse developmental outcomes; there are risks associated with untreated depression in pregnancy and with exposure to SNRIs and SSRIs, during pregnancy Women who discontinued antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continued antidepressants; consider risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum Pregnant women with fibromyalgia are at increased risk for adverse maternal and infant outcomes including preterm premature rupture of membranes, preterm birth, small for gestational age, intrauterine growth restriction, placental disruption, and venous thrombosis; not known if adverse maternal and fetal outcomes are a direct result of fibromyalgia or other comorbid factors Animal data Cymbalta In animal studies with duloxetine, fetal weights were decreased but there was no evidence of teratogenicity in pregnant rats and rabbits at oral doses administered during organogenesis up to 4 and 7 times the maximum recommended human dose (MRHD) of 120 mg/day When duloxetine was administered orally to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the MRHD Drizalma Sprinkle In rats and rabbits treated with duloxetine during organogenesis, fetal weights decreased but there was no evidence of developmental effects at doses up to 3 and 6 times, respectively, the MRHD of 120 mg/day given to adolescents on a mg/m2 basis When oral duloxetine was administered to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the MRHD given to adolescents on a mg/m2 basis For both formulations, pup behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity were observed Postweaning growth was not adversely affected Use in pregnancy only if the potential benefit justifies the potential risk to the fetus Pregnancy registry Pregnancy registry monitors the pregnancy outcomes in women exposed during pregnancy Cymbalta: Contact pregnancy registry at 1-866-814-6975 or www.cymbaltapregnancyregistry.com Drizalma Sprinkle: Contact the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/ Clinical considerations Neonates exposed during pregnancy to serotonin - norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding which can arise immediately upon delivery Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying These features are consistent with either a direct toxic effect of the SNRIs or SSRIs, or possibly, a drug discontinuation syndrome In some cases, the clinical picture is consistent with serotonin syndrome Lactation Cymbalta Drug present in human milk in a published study, lactating women who were weaning their infants were given duloxetine At steady state, duloxetine concentration in breast milk was ~25% that of maternal plasma Estimated daily infant dose was ~0.14% of the maternal dose Exercise caution when administering to a nursing woman Drizalma Sprinkle Data from the published literature report the presence of duloxetine in human milk There are reports of sedation, poor feeding, and poor weight gain in infants exposed to duloxetine through breast milk There are no data on effect of duloxetine 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 therapy or from underlying maternal condition Women given 40 mg of duloxetine PO BID for 3.5 days; peak concentration measured in breast milk occurred at a median of 3 hrs post-dose Amount of duloxetine in breast milk was ~7 mcg/day while on that dose; estimated daily infant dose was ~2 mcg/kg/day, which is <1% of the maternal dose 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 Exact mechanism of action unknown; inhibits reuptake of serotonin and norepinephrine; weakly inhibits reuptake of dopamine; has no MAOI activity; has no significant activity for histaminergic H1 receptor or alpha2-adrenergic receptor Absorption Well absorbed Duloxetine steady-state plasma concentration was comparable in children (7-12 years), adolescents (13-17 years), and adults Peak plasma time Cymbalta: 6 hr (empty stomach); 10 hr (with food) Drizalma Sprinkle: 5 hr; there is a 3 hr delay in absorption and a one-third increase in apparent duloxetine clearance after an evening dose as compared to a morning dose; ~1.7 hr delay when administered with a high-fat meal Distribution Vd: 1640 L Protein bound: >90% Metabolism Metabolized in liver by CYP2D6 and CYP1A2 Metabolites: 4-hydroxy duloxetine glucuronide; 5-hydroxy, 6-methoxy duloxetine sulfate Enzymes inhibited: CYP2D6 Elimination Half-life: 12 hr Excretion: Urine (70% as metabolites; <1% unchanged), feces (20%) Oral Administration Swallow capsule whole; do not chew or crush May be administer without regard to meals Cymbalta Do not open capsule and sprinkle its contents on food or mix with liquids All of these might affect the enteric coating Drizalma Sprinkle Patients with swallowing difficulty Open capsule and sprinkle contents over applesauce; swallow contents of the capsules along with a small amount (tablespoonful) of applesauce Swallow drug/food mixture immediately and do not store for future use Nasogastric tube administration Open and add contents of capsule to an all plastic catheter tip syringe and add 50 mL of water Gently shake syringe for ~10 seconds Promptly deliver through a 12 French or larger nasogastric tube; ensure no pellets are left in the syringe Rinse with additional water (~15 mL) if needed Missed dose If a dose is missed, take missed dose as soon as it is remembered If it is almost time for the next dose, skip missed dose and take the next dose at the regular time; do not take 2 doses at the same time Storage Cymbalta: Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF) Drizalma Sprinkle: Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF) BRAND FORM. UNIT PRICE PILL IMAGE Cymbalta oral- 30 mg capsuleCymbalta oral- 60 mg capsuleCymbalta oral- 60 mg capsuleCymbalta oral- 20 mg capsuleduloxetine oral- 40 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 20 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 20 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 20 mg capsuleduloxetine oral- 20 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 20 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 20 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 20 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 20 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 20 mg capsuleduloxetine oral- 20 mg capsuleduloxetine oral- 20 mg capsuleduloxetine oral- 40 mg capsuleduloxetine oral- 60 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 30 mg capsuleduloxetine oral- 40 mg capsuleCopyright © 2010 First DataBank, Inc.Print Patient Educationduloxetine oral DULOXETINE - ORAL (doo-LOX-e-teen) COMMON BRAND NAME(S): Cymbalta 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, 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: Duloxetine is used to treat depression and anxiety. In addition, duloxetine is used to help relieve nerve pain (peripheral neuropathy) in people with diabetes or ongoing pain due to medical conditions such as arthritis, chronic back pain, or fibromyalgia (a condition that causes widespread pain).Duloxetine may improve your mood, sleep, appetite, and energy level, and decrease nervousness. It can also decrease pain due to certain medical conditions. Duloxetine is known as a serotonin-norepinephrine reuptake inhibitor (SNRI). This medication works by helping to restore the balance of certain natural substances (serotonin and norepinephrine) in the brain. HOW TO USE: Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start using duloxetine 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 1 or 2 times a day with or without food. If you have nausea, it may help to take this drug with food. Swallow the capsule whole. Do not crush or chew the capsule or mix the contents with food or liquid. Doing so can release all of the drug at once, increasing the risk of side effects.The dosage is based on your age, medical condition and response to treatment. To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully. Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.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 dizziness, confusion, mood swings, headache, tiredness, diarrhea, sleep changes, and brief feelings similar to electric shock. Your dose may need to be gradually decreased to reduce side effects. Report any new or worsening symptoms right away.Tell your doctor if your condition lasts or gets worse. SIDE EFFECTS: See also Warning section.Nausea, dry mouth, constipation, loss of appetite, tiredness, drowsiness, or increased sweating may occur. If any of these effects last or get worse, tell your doctor promptly.Dizziness or lightheadedness may occur, especially when you first start or increase your dose of this drug. To reduce the risk of dizziness, lightheadedness, or falling, get up slowly when rising from a sitting or lying position.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.This medication may raise your blood pressure. Check your blood pressure