Trade Names:Cymbalta- Capsules, delayed-release 20 mg- Capsules, delayed-release 30 mg- Capsules, delayed-release 60 mg
Unknown; however, potentiation of serotonergic and noradrenergic activity in the CNS is suspected.
Well absorbed. C max occurs 6 h postdose. Steady state reached after 3 days.
Vd about 1,640 L. Protein binding is more than 90%.
Hepatic metabolism by CYP1A2 and CYP2D6 to numerous metabolites.
Elimination half-life is approximately 12 h. Less than 1% excreted unchanged in urine. Of the administered dose, 70% appears in urine as metabolites and 20% in feces.
Duloxetine bioavailability is reduced by about 33% in smokers; dosage adjustments are not recommended.
Diabetic peripheral neuropathic pain; fibromyalgia; generalized anxiety disorder; major depressive disorder.
Stress urinary incontinence.
Uncontrolled narrow-angle glaucoma; MAOI therapy; hypersensitivity to any component of product.
PO 60 mg once daily without regard to meals.FibromyalgiaAdults
PO Start with 30 mg once daily for 1 wk. The dosage may be increased to 60 mg once daily after 1 wk.Generalized Anxiety DisorderAdults
PO Start with 30 or 60 mg once daily without regard to meals. If the starting dosage is 30 mg once daily, the dosage may be increased to 60 mg once daily after 1 wk. Additional dosage increases should be in increments of 30 mg once daily (max, 120 mg once daily). There is no evidence that dosages of more than 60 mg once daily confer additional benefit.Major Depressive DisorderAdults
PO 40 mg daily (given as 20 mg twice daily) to 60 mg daily (given once daily or as 30 mg twice daily) without regard to meals.
Store at controlled room temperature (59° to 86°F).
Not recommended with substantial alcohol use.Aspirin, NSAIDs, warfarin
Risk of bleeding may be increased.Beta-blockers (eg, metoprolol, propranolol)
Increased risk of excessive beta-blockade (eg, bradycardia).CNS-active drugs
Use with caution because of possible additive effects.Drugs affecting gastric acidity
Because duloxetine is enteric-coated, drugs that raise GI pH may lead to earlier release of duloxetine; however, aluminum- and magnesium-containing antacids and famotidine have no significant effect on the rate or extent of duloxetine absorption.Drugs highly bound to plasma proteins
Plasma concentrations of these drugs may be increased, potentially resulting in adverse reactions.Drugs with a narrow therapeutic index and extensively metabolized by CYP2D6 (eg, amitriptyline, desipramine, flecainide, imipramine, nortriptyline, phenothiazines, propafenone)
Plasma concentrations of these agents may be elevated, increasing the risk of adverse reactions. Avoid thioridazine because of possible serious ventricular arrhythmias and sudden death resulting from elevated plasma levels.Food
Food delays the T max from 6 to 10 h and decreases the extent of absorption 10%. The C max is not affected. However, duloxetine may be taken without regard to meal.Inhibitors of CYP1A2 (eg, cimetidine, fluvoxamine, some quinolone antibiotics), inhibitors of CYP2D6 (eg, fluoxetine, paroxetine, quinidine)
Duloxetine plasma levels may be elevated, increasing the risk of adverse reactions.MAOIs (eg, isocarboxazid)
Concurrent use with duloxetine is contraindicated. It is recommended that duloxetine not be used with an MAOI or within 14 days of discontinuing treatment with an MAOI. Allow at least 5 days after stopping duloxetine before starting an MAOI.Methylene blue
Risk of neurologic adverse reactions, including serotonin syndrome, may be increased.Serotonergic drugs (eg, 5-HT 1 agonists [eg, sumatriptan], linezolid, lithium, St. John's wort, sympathomimetics [eg, amphetamine], tramadol, tryptophan)
Risk of serotonin syndrome may be increased.
None well documented.
Hot flush (3%); palpitations (2%); MI (0.1% to 1%); hypertensive crisis, supraventricular arrhythmia (postmarketing).
Somnolence (21%); headache (20%); dizziness (17%); insomnia (16%); fatigue (15%); decreased appetite (11%); asthenia (8%); agitation (6%); tremor (5%); decreased libido (4%); abnormal dreams, anxiety, dysgeusia, migraine, pyrexia, sleep disorder (3%); yawning (2%); hypoesthesia, lethargy, vertigo (at least 1%); aggression, anger, extrapyramidal disorder, hallucinations, trismus (postmarketing).
Hyperhidrosis (8%); rash (4%); pruritus (3%); erythema multiforme, Stevens-Johnson syndrome, urticaria (postmarketing).
Nasopharyngitis (9%); pharyngolaryngeal pain (6%); blurred vision (3%); glaucoma, tinnitus (postmarketing).
Nausea (30%); dry mouth (18%); constipation (15%); diarrhea (13%); vomiting (6%); dyspepsia (5%); loose stools (3%); flatulence (at least 1%).
Erectile dysfunction, pollakiuria (5%); ejaculation disorder (4%); abnormal orgasm, delayed ejaculation (3%); penis disorder (2%); anorgasmia (at least 1%).
Anaphylactic reaction, angioneurotic edema, hypersensitivity (postmarketing).
Anorexia (5%); decreased weight, increased weight (2%); hyperglycemia (postmarketing).
Muscle cramps, musculoskeletal pain (5%); muscle spasm, myalgia (4%); trismus (postmarketing).
Upper respiratory tract infection (7%); cough (6%).
Seasonal allergy (3%); chill/fever (at least 1%).
Antidepressants increased the risk of suicidal thinking and behavior in short-term studies in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Closely observe patients who are started on therapy for clinical worsening, suicidality, or unusual changes in behavior.
Monitor BP before starting therapy and periodically during prolonged treatment. Monitor for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of therapy and when increasing or decreasing the dose. Monitor for possible sexual adverse reactions.
Category C . Neonates exposed to duloxetine late in the third trimester may develop complications requiring prolonged hospitalization, respiratory support, and tube feeding.
Excreted in breast milk.
Safety and efficacy not established.
No dosage adjustment is recommended for elderly patients; use with caution.
Not recommend for patients with end-stage renal disease or severe renal function impairment (CrCl less than 30 mL/min).
Significantly increased exposure to duloxetine occurs in patients with hepatic function impairment; do not administer duloxetine to these patients.
Use with caution in patients with controlled narrow-angle glaucoma or conditions that may slow gastric emptying.
Bleeding events, ranging from ecchymosis, hematoma, epistaxis, petechiae, and life-threatening hemorrhage, have been reported. Aspirin, NSAIDs, and warfarin may add to this risk.
Elevations in BP may occur.
A gradual reduction in dose, rather than abrupt discontinuation of therapy, is recommended in order to minimize discontinuation symptoms (eg, dizziness, headache, nightmares, paresthesia).
May worsen glycemic control in some patients with diabetes.
Hepatic failure, sometimes fatal, presenting as hepatitis with abdominal pain, hepatomegaly, and elevated transaminase levels with or without jaundice have been reported.
Hyponatremia and SIADH have been reported and appear to be reversible when duloxetine is discontinued. Cholestatic jaundice and elevated transaminases, bilirubin, and alkaline phosphatase have occurred in patients with chronic liver disease or cirrhosis.
May be activated.
May occur with therapeutic doses.
Seizures have been reported in a small number of patients; use with caution in patients with history of seizures.
Life-threatening serotonin syndrome may occur, particularly with coadministration of serotonergic drugs.
Monitor depressed patients at risk during initial therapy. Prescribe smallest quantity consistent with good patient management in order to reduce risk of overdose.
Coma, death, hypertension, hypotension, seizures, serotonin syndrome, somnolence, syncope, tachycardia, vomiting.
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