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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(doo LOX e teen)
Generic Available (U.S.)
No
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088579.pdf, must be dispensed with this medication.
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Acute and maintenance treatment of major depressive disorder (MDD); treatment of generalized anxiety disorder (GAD); management of diabetic peripheral neuropathic pain (DPNP); management of fibromyalgia (FM); chronic musculoskeletal pain
Use: Unlabeled/Investigational
Treatment of stress incontinence
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in animal reproduction studies; therefore, duloxetine is classified as pregnancy category C. Nonteratogenic effects in the newborn following SSRI/SNRI exposure late in the third trimester include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hyper- or hypotonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor. The long-term effects on neurobehavior have not been studied.Women treated for major depression and who are euthymic prior to pregnancy are more likely to experience a relapse when medication is discontinued as compared to pregnant women who continue taking antidepressant medications. The ACOG recommends that therapy with SSRIs or SNRIs during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary healthcare provider, and pediatrician. If treatment during pregnancy is required, consider tapering therapy during the third trimester in order to prevent withdrawal symptoms in the infant. If this is done and the woman is considered to be at risk of relapse from her major depressive disorder, the medication can be restarted following delivery, although the dose should be readjusted to that required before pregnancy. The risks of medication treatment should be weighed against other treatment options and untreated depression. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (Yonkers, 2009). Healthcare providers are encouraged to enroll women exposed to duloxetine during pregnancy in the Cymbalta® Pregnancy Registry (866-814-6975 or http://cymbaltapregnancyregistry.com).
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Duloxetine is excreted in human milk. Duloxetine is not stable at an acidic pH; therefore, any drug which reaches the stomach of the breast-feeding infant may degrade, thus decreasing the amount reaching the systemic circulation. Breast-feeding is not recommended by the manufacturer. The long term effects on neurobehavior have not been studied, thus one should prescribe duloxetine to a mother who is breast-feeding only when the benefits outweigh the potential risks.
Contraindications
Concomitant use or within 2 weeks of MAO inhibitors; uncontrolled narrow-angle glaucoma
Note: MAO inhibitor therapy must be stopped for 14 days before duloxetine is initiated. Treatment with MAO inhibitors should not be initiated until 5 days after the discontinuation of duloxetine.
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to duloxetine or any component of the formulation; hepatic impairment; severe renal impairment (eg, Clcr <30 mL/minute) or end-stage renal disease (ESRD); concomitant use with thioridazine or with CYP1A2 inhibitors
Warnings/Precautions
Boxed warnings:
• Suicidal thinking/behavior: See “Major psychiatric warnings” below.
Major psychiatric warnings:
• [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor for clinical worsening, suicidality, or unusual changes in behavior; the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants in children and teenagers should be dispensed with each prescription. Duloxetine is not FDA approved for use in children.
• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial (generally first 1-2 months) few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.
• May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Duloxetine is not FDA approved for the treatment of bipolar depression.
Concerns related to adverse effects:
• Bleeding risk: May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin or NSAIDs due to ulcerogenic potential. Data are inconclusive regarding extent of bleeding risk of SNRIs in combination with warfarin or other anticoagulants. Bleeding related to SNRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.
• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.
• Hepatotoxicity: Avoid use in patients with substantial ethanol intake, evidence of chronic liver disease or hepatic impairment (contraindicated in Canadian labeling). Rare cases of hepatic failure (including fatalities) have been reported with use. Hepatitis with abdominal pain, hepatomegaly, elevated transaminase levels >20 times the upper limit of normal (ULN) with and without jaundice have all been observed. Discontinue therapy with the presentation of jaundice or other signs of hepatic dysfunction and do not reinitiate therapy unless another source or cause is identified.
• Hyperglycemia: Modest increases in serum glucose and hemoglobin A1c (Hb A1c) levels have been observed in some diabetic patients receiving duloxetine therapy for diabetic peripheral neuropathic pain (DPNP).
• Orthostatic hypotension/syncope: May cause orthostatic hypotension/syncope, especially within the first week of therapy and after dose increases. Carefully monitor blood pressure with initiation of therapy, dose increases (especially in patients receiving >60 mg/day), or when using concomitant vasodilators or CYP1A2 inhibitors.
• Serotonin syndrome (SS)/neuroleptic malignant syndrome (NMS)-like reactions: SS and NMS-like reactions have occurred with serotonin/norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) when used alone, and particularly when used in combination with serotonergic agents (eg, triptans) or antidopaminergic agents (eg, antipsychotics). The diagnosis of SS can be made using the Hunter Serotonin Toxicity Criteria (Dunkley, 2003). Identification and differentiation of SS (eg, tremor, myoclonus, agitation) and more severe NMS-like reactions (eg, hyperthermia, muscle rigidity, autonomic instability, mental status changes) can be complex; monitor patients closely for either syndrome. Discontinue treatment (and any concomitant serotonergic and/or antidopaminergic agents) immediately if signs/symptoms arise.
• Sexual dysfunction: May cause or exacerbate sexual dysfunction.
• SIADH and hyponatremia: SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported rarely (including severe cases with serum sodium <110 mmol/L), predominately in the elderly. Volume depletion and/or concurrent use of diuretics likely increases risk.
• Urinary hesitancy: May cause increased urinary resistance; advise patient to report symptoms of urinary hesitation/difficulty.
Disease-related concerns:
• Gastroparesis: Use caution in patients with impaired gastric motility (eg, some diabetics); may affect stability of the capsule's enteric coating.
• Hypertension: Use caution in patients with hypertension. Although no statistically significant differences in the frequency of sustained elevations of blood pressure were observed in clinical trials when compared with placebo, modest increases in blood pressure have been reported with use. Additionally, rare cases of hypertensive crisis have been reported in patients with pre-existing hypertension; blood pressure should be evaluated prior to initiating therapy and periodically thereafter; consider dose reduction or gradual discontinuation of therapy in individuals with sustained hypertension during therapy
• Narrow-angle glaucoma: Associated with an increased risk of mydriasis in patients with controlled narrow-angle glaucoma.
• Renal impairment: Use with caution; clearance is decreased and plasma concentrations are increased; not recommended for use when Clcr <30 mL/minute or ESRD (contraindicated in Canadian labeling).
• Seizure disorders: Use caution with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism.
Concurrent drug therapy issues:
• Agents which lower seizure threshold: Concurrent therapy with other drugs which lower the seizure threshold.
• Anticoagulants/antiplatelets: Use caution with concomitant use of NSAIDs, ASA, or other drugs that affect coagulation; the risk of bleeding may be potentiated.
• CNS depressants: Use caution with concomitant therapy.
• CYP1A2 inhibitors (eg, fluvoxamine, ciprofloxacin): Concomitant use with duloxetine may increase levels/adverse effects of duloxetine and is not recommended (contraindicated in Canadian labeling).
• CYP2D6 inhibitors/substrates: Concomitant use of CYP2D6 inhibitors with duloxetine may increase levels/adverse effects of duloxetine; concomitant use of duloxetine with CYP2D6 substrates (tricyclic antidepressants, type 1C antiarrhythmics) may lead to substrate-induced toxicity.
• MAO inhibitors: Potential for severe reaction when used with MAO inhibitors; autonomic instability, coma, death, delirium, diaphoresis, hyperthermia, mental status changes/agitation, muscular rigidity, myoclonus, neuroleptic malignant syndrome features, and seizures may occur. Concurrent use is contraindicated.
• Serotonin syndrome/NMS-like reactions: Symptoms of agitation, confusion, hallucinations, hyper-reflexia, myoclonus, shivering, and tachycardia may occur with concomitant proserotonergic drugs (ie, SSRIs/SNRIs or triptans), agents which reduce duloxetine's metabolism, or antidopaminergic agents (including antipsychotics). Use caution with concurrent use of triptans; concurrent use of serotonin precursors (eg, tryptophan) is not recommended.
• Thioridazine: Concomitant use is contraindicated in Canadian labeling.
Special populations:
• Sucrose intolerance: Formulation contains sucrose; patients with fructose intolerance, glucose-galactose malabsorption, or sucrose-isomaltase deficiency should avoid use
Other warnings/precautions:
• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.
• Withdrawal syndrome: May cause dysphoric mood, irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. To discontinue therapy with duloxetine, gradually taper dose. If intolerable symptoms occur following a decrease in dosage or upon discontinuation of therapy, then resuming the previous dose with a more gradual taper should be considered.
Adverse Reactions
>10%:
Central nervous system: Headache (13% to 14%), somnolence (10% to 12%; dose related), fatigue (10 to 11%)
Gastrointestinal: Nausea (23% to 25%), xerostomia (11% to 15%; dose related)
1% to 10%:
Cardiovascular: Palpitation (1% to 2%)
Central nervous system: Dizziness (10%), insomnia (10%; dose related), agitation (3% to 5%), anxiety (3%), dreams abnormal (1% to 2%), yawning (1% to 2%), hypoesthesia (≥1%), lethargy (≥1%), vertigo (≥1%), chills (1%), sleep disorder (1%)
Dermatologic: Hyperhydrosis (6% to 7%)
Endocrine & metabolic: Libido decreased (2% to 4%), hot flushes (1% to 3%), orgasm abnormality (1% to 3%)
Gastrointestinal: Constipation (10%; dose related), diarrhea (9% to 10%), appetite decreased (7% to 9%; dose related), abdominal pain (4% to 6%), vomiting (3% to 5%), dyspepsia (2%), weight loss (2%), flatulence (≥1%), taste abnormal (≥1%), weight gain (≥1%)
Genitourinary: Erectile dysfunction (4% to 5%), ejaculation delayed (3%; dose related), ejaculatory dysfunction (2%)
Hepatic: ALT >3x ULN (1%)
Neuromuscular & skeletal: Muscle spasms (3%), tremor (2% to 3%; dose related), musculoskeletal pain (≥1%), paresthesia (≥1%), rigors (≥1%)
Ocular: Blurred vision (1% to 3%)
Respiratory: Nasopharyngitis (5%), cough (3%)
Miscellaneous: Influenza (3%)
<1%, postmarketing, and/or case reports: Aggression, alkaline phosphatase increased, anaphylactic reaction, anger, angioneurotic edema, apathy, attention disturbance, bruxism, contact dermatitis, dehydration, diastolic blood pressure increased, diplopia, disorientation, dysarthria, dyskinesia, dyslipidemia, dysuria, ecchymosis, eructation, erythema, erythema multiforme, EPS, flushing, gait instability, galactorrhea, gastric ulcer, gastritis, gastroenteritis, glaucoma, gynecological bleeding, halitosis, hallucinations, Hb A1c increased, hematochezia, hepatic failure, hepatitis, hepatomegaly, hyperbilirubinemia, hypercholesterolemia, hyperglycemia, hyperlipidemia, hyperprolactinemia, hypersensitivity, hypertensive crisis, hyponatremia, hypothyroidism, irritability, jaundice, laryngitis, malaise, mania, melena, MI, micturition urgency, mood swings, muscle spasm, muscle tightness, muscle twitching, myoclonus, night sweats, nocturia, orthostatic hypotension, peripheral coldness, photosensitivity, polyuria, rash, restless leg syndrome, seizure, serotonin syndrome, sexual dysfunction, SIADH, Stevens-Johnson syndrome, stomatitis, suicide, supraventricular arrhythmia, syncope, systolic blood pressure increased, tachycardia, thirst, throat tightness, tinnitus, trismus, urinary retention, urine odor, urticaria
Metabolism/Transport Effects
Substrate (major) of CYP1A2, 2D6; inhibits CYP2D6 (moderate)
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification
Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the adverse/toxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Specifically, risks of psychomotor impairment may be enhanced. Alcohol (Ethyl) may enhance the hepatotoxic effect of Serotonin/Norepinephrine Reuptake Inhibitors. Particularly duloxetine and milnacipran. Management: Patients receiving serotonin/norepinephrine reuptake inhibitors (SNRIs) should be advised to avoid alcohol. Monitor for increased psychomotor impairment and hepatotoxicity in patients who consume alcohol during treatment with SNRIs. Risk D: Consider therapy modification
Alpha-/Beta-Agonists: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Risk D: Consider therapy modification
Alpha2-Agonists: Serotonin/Norepinephrine Reuptake Inhibitors may diminish the antihypertensive effect of Alpha2-Agonists. Exceptions: Apraclonidine; Brimonidine. Risk C: Monitor therapy
Aspirin: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk C: Monitor therapy
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Deferasirox: May increase the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
FluvoxaMINE: May decrease the metabolism of DULoxetine. Risk C: Monitor therapy
Iobenguane I 123: Serotonin/Norepinephrine Reuptake Inhibitors may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
MAO Inhibitors: May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Methylene Blue: Serotonin/Norepinephrine Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
NSAID (Nonselective): Serotonin/Norepinephrine Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy
PARoxetine: May decrease the metabolism of DULoxetine. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible. Risk D: Consider therapy modification
Thioridazine: CYP2D6 Inhibitors may decrease the metabolism of Thioridazine. Risk X: Avoid combination
Tricyclic Antidepressants: DULoxetine may decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Ethanol may increase hepatotoxic potential of duloxetine. Ethanol may also increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Herb/Nutraceutical: Avoid valerian, St John's wort, SAMe, kava kava, and gotu kola (may increase CNS depression).
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)
Mechanism of Action
Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a weak inhibitor of dopamine reuptake. Duloxetine has no significant activity for muscarinic cholinergic, H1-histaminergic, or alpha2-adrenergic receptors. Duloxetine does not possess MAO-inhibitory activity.
Pharmacodynamics/Kinetics
Absorption: Well absorbed, 2-hour delay in absorption after ingestion; food decreases extent of absorption ~10% (no effect on Cmax)
Distribution: 1640 L (range: 701-3800 L)
Protein binding: >90%; primarily to albumin and α1-acid glycoprotein
Metabolism: Hepatic, via CYP1A2 and CYP2D6; forms multiple metabolites (inactive)
Half-life elimination: 12 hours (range: 8-17 hours)
Time to peak: 6 hours; 10 hours when ingested with food
Excretion: Urine (~70%; <1% of total dose as unchanged drug); feces (~20%)
Dosage
Oral:
Adults:
Major depressive disorder: Initial: 40-60 mg/day; dose may be divided (ie, 20 or 30 mg twice daily) or given as a single daily dose of 60 mg; maintenance: 60 mg once daily; for doses >60 mg/day, titrate dose in increments of 30 mg/day over 1 week as tolerated to a maximum dose: 120 mg/day. Note: Doses >60 mg/day have not been demonstrated to be more effective.
Diabetic neuropathy: 60 mg once daily; lower initial doses may be considered in patients where tolerability is a concern and/or renal impairment is present. Note: Doses up to 120 mg/day administered in clinical trials offered no additional benefit and were less well tolerated than dose of 60 mg/day.
Fibromyalgia: 30 mg once daily for 1 week, then increase to 60 mg once daily as tolerated. Note: Doses up to 120 mg/day administered in clinical trials offered no additional benefit and were less well tolerated than dose of 60 mg/day.
Generalized anxiety disorder: Initial: 30-60 mg/day as a single daily dose; patients initiated at 30 mg/day should be titrated to 60 mg/day after 1 week; maximum dose: 120 mg/day. Note: Doses >60 mg/day have not been demonstrated to be more effective than 60 mg/day.
Chronic musculoskeletal pain: 30 mg once daily for 1 week, then increase to 60 mg once daily as tolerated
Stress incontinence (unlabeled use): 40 mg twice daily (Dmochowski, 2003)
Note: Upon discontinuation of duloxetine therapy, gradually taper dose. If intolerable symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate.
Elderly:
Major depressive disorder: Manufacturer does not recommend specific dosage adjustment. Conservatively, may initiate at a dose of 20 mg 1-2 times/day; increase to 40-60 mg/day as a single daily dose or in divided doses or initiate therapy at 30 mg/day for 1 week then increase to 60 mg/day as tolerated.
Other indications: Refer to adult dosing
Dosage adjustment in renal impairment: Not recommended for use in Clcr <30 mL/minute or ESRD (contraindicated in Canadian labeling); in mild-moderate impairment, lower initial doses may be considered with titration guided by response and tolerability
Dosage adjustment in hepatic impairment: Not recommended for use in hepatic impairment (contraindicated in Canadian labeling)
Administration: Oral
Capsule should be swallowed whole; do not crush or chew. Although the manufacturer does not recommend opening the capsule to facilitate administration; the contents of capsule may be sprinkled on applesauce or in apple juice and swallowed (without chewing) immediately. Do not sprinkle contents on chocolate pudding (Wells, 2008). Administer without regard to meals.
Monitoring Parameters
Blood pressure should be checked prior to initiating therapy and then regularly monitored, especially in patients with a high baseline blood pressure; mental status for depression, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; glucose levels and Hb A1c levels in diabetic patients, creatinine, BUN, transaminases
For musculoskeletal pain: Pain relief
Dietary Considerations
May be taken without regard to meals.
Patient Education
Swallow capsule whole; do not open or crush. It may take 2-3 weeks to achieve desired results. Maintain adequate hydration, unless instructed to restrict fluid intake. Avoid alcohol use. If you have diabetes, monitor blood glucose levels closely. May cause increase in glycemic levels. Can cause drowsiness, dizziness, fatigue, or insomnia. You may experience headache, nausea, diarrhea, constipation, appetite decrease, or xerostomia. Report persistent insomnia, dizziness, headache, suicide ideation, worsening of anxiety, panic attacks, agitation, irritability, akathisia, hostility, hypomania, and mania.
Geriatric Considerations
In an 8-week study of elderly patients with a history of recurrent major depressive disorder, improvements in verbal learning and memory, and depression response and remission rates were significantly greater in subjects randomized to duloxetine 60 mg per day compared to placebo. Duloxetine was well tolerated. No dose adjustment is necessary for age alone; adjust dose for renal function in the elderly. Higher doses are generally required for treatment of general anxiety disorder, neuropathic pain and stress urinary incontinence (unlabeled use). The elderly are more prone to SSRI/SNRI-induced hyponatremia.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation). See Effects on Bleeding.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Although duloxetine is not a tricyclic antidepressant, it does block norepinephrine reuptake within the CNS synapses as part of its mechanism. It has been suggested that vasoconstrictors be administered with caution and to monitor vital signs in dental patients taking antidepressants that affect norepinephrine in this way.
Nursing: Physical Assessment/Monitoring
Monitor blood pressure (can cause elevation or orthostatic hypotension) at the beginning of treatment and periodically throughout. Monitor for worsening of depression and suicide ideation. Taper dosage slowly when discontinuing. Do not discontinue abruptly.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, delayed release, enteric coated pellets, oral:
Cymbalta®: 20 mg, 30 mg, 60 mg
Pricing: U.S. (www.drugstore.com)
Capsule, enteric pellets (Cymbalta)
20 mg (30): $145.99
30 mg (30): $155.99
60 mg (30): $159.99
References
American College of Obstetricians and Gynecologists, ACOG Practice Bulletin: Clinical Management Guidelines for Obstetricians-Gynecologists No. 92 April 2008 (Replaces Practice Bulletin Number 87, November 2007), “Use of Psychiatric Medications During Pregnancy and Lactation,” Obstet Gynecol, 2008, 111(4):1001-20.
Arnold LM, Lu Y, Crofford LJ, et al, “A Double-Blind, Multicenter Trial Comparing Duloxetine With Placebo in the Treatment of Fibromyalgia Patients With or Without Major Depressive Disorder,” Arthritis Rheum, 2004, 50(9):2974-84.
Boyer EW and Shannon M, “The Serotonin Syndrome,” N Engl J Med, 2005, 352:1112-20.
Bril V, England J, Franklin GM, et al, "Evidence-Based Guideline: Treatment of Painful Diabetic Neuropathy: Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation," Neurology, 2011 [epub ahead of print]
Chambers CD, Hernandez-Diaz S, Van Marter LJ, et al, “Selective Serotonin-Reuptake Inhibitors and Risk of Persistent Pulmonary Hypertension of the Newborn,” N Engl J Med, 2006, 354(6):579-87.
Chappell AS, Ossanna MJ, Liu-Siefert H, et al, “Duloxetine, A Centrally Acting Analgesic, in the Treatment of Patients With Osteoarthritis Knee Pain: A 13-Week, Randomized, Placebo-Controlled Trial,” Pain, 2009, 146(3):253-60.
Dmochowski RR, Miklos JR, Norton PA, et al, “Duloxetine Versus Placebo for the Treatment of North American Women With Stress Urinary Incontinence,” J Urol, 2003, 170(4 Pt 1):1259-63.
Dunkley EJ, Isbister GK, Sibbritt D, et al, “The Hunter Serotonin Toxicity Criteria: Simple and Accurate Diagnostic Decision Rules for Serotonin Toxicity,” QJM, 2003, 96(9):635-42.
Fava M, Mallinckrodt CH, Detke MJ, et al, “The Effect of Duloxetine on Painful Physical Symptoms in Depressed Patients: Do Improvements in These Symptoms Result in Higher Remission Rates?”, J Clin Psychiatry, 2004, 65(4):521-30.
Goldstein DJ, Lu Y, Detke MJ, et al, “Duloxetine in the Treatment of Depression: A Double-Blind Placebo-Controlled Comparison With Paroxetine,” J Clin Psychopharmacol, 2004, 24(4):389-99.
Hardy T, Sachson R, Shen S, et al, “Does Treatment With Duloxetine for Neuropathic Pain Impact Glycemic Control?,” Diabetes Care, 2007, 30(1):21-6.
Millard RJ, Moore K, Rencken R, et al, “Duloxetine vs Placebo in the Treatment of Stress Urinary Incontinence: A Four-Continent Randomized Clinical Trial,” BJU Int, 2004, 93(3):311-8.
Pass SE and Simpson RW, “Discontinuation and Reinstitution of Medications During the Perioperative Period,” Am J Health Syst Pharm, 2004, 61(9):899-912.
Raskin J, Wiltse CG, Siegal A, et al, “Efficacy of Duloxetine on Cognition, Depression, and Pain in Elderly Patients With Major Depressive Disorder: An 8-Week, Double-Blind, Placebo-Controlled Trial,” Am J Psychiatry, 2007, 164(6):900-9.
Skljarevski V, Desaiah D, Liu-Siefert H, et al, “Efficacy and Safety of Duloxetine in Patients With Chronic Low Back Pain,” Spine, 2010, 35(13):E578-85.
Skljarevski V, Zhang S, Chappell AS, et al, “Maintenance of Effect of Duloxetine in Patients With Chronic Low Back Pain: A 41-Week Uncontrolled, Dose-Blinded Study,” Pain Med, 2010, 11(5):648-57.
Skljarevski V, Zhang S, Desaiah D, et al, “Duloxetine Versus Placebo in Patients With Chronic Low Back Pain: A 12-Week, Fixed-Dose, Randomized, Double-Blind Trial,” J Pain, 2010, 11(12):1282-90.
Stevens DL, “Association Between Selective Serotonin-Reuptake Inhibitors, Second-Generation Antipsychotics, and Neuroleptic Malignant Syndrome,” Ann Pharmacother, 2008, 42(9):1290-7.
van Kerrebroeck P, Abrams P, Lange R, et al, “Duloxetine Versus Placebo in the Treatment of European and Canadian Women With Stress Urinary Incontinence,” BJOG, 2004, 111(3):249-57.
Wells KA and Losin WG, “In vitro Stability, Potency, and Dissolution of Duloxetine Enteric-Coated Pellets After Exposure to Applesauce, Apple Juice, and Chocolate Pudding,” Clin Ther, 2008, 30(7):1300-8.
Yonkers KA, Wisner KL, Stewart DE, et al, “The Management of Depression During Pregnancy: A Report From the American Psychiatric Association and the American College of Obstetricians and Gynecologists,” Obstet Gynecol, 2009, 114(3):703-13.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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