Duloxetine Hydrochloride
Pronouncation: (doo-LOX-e-teen HYE-droe-KLOR-ide)Class: Serotonin and norepinephrine reuptake inhibitor
Trade Names:
Cymbalta
- Capsules 20 mg
- Capsules 30 mg
- Capsules 60 mg
Pharmacology
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Feedback for Duloxetine Hydrochloride
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Unknown; however, potentiation of serotonergic and noradrenergic activity in the CNS is suspected.
Pharmacokinetics
Absorption
Well absorbed. C max occurs 6 h postdose. Steady state reached after 3 days.
Distribution
Vd about 1,640 L. Protein binding is greater than 90%.
Metabolism
Hepatic metabolism by CYP1A2 and CYP2D6 to numerous metabolites.
Elimination
Elimination t ½ 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.
Indications and Usage
Diabetic peripheral neuropathic pain; generalized anxiety disorder; major depressive disorder.
Contraindications
Uncontrolled narrow-angle glaucoma; MAOI therapy; hypersensitivity to any component of product.
Dosage and Administration
Diabetic Peripheral Neuropathic PainAdults
PO 60 mg once daily without regard to meals.
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 doses greater 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.
General Advice
- Advise patient to swallow capsule whole and not to crush, chew, or open capsule.
Storage/Stability
Store at controlled room temperature (59° to 86°F).
Drug Interactions
AlcoholDo not use with substantial alcohol use.
CNS-active drugsUse with caution because of possible additive effects.
Drugs affecting gastric acidityBecause 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 rate or extent of duloxetine absorption.
Drugs highly bound to plasma proteinase (warfarin)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.
Inhibitors of CYP1A2 (eg, 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.
Serotonergic drugs (eg, 5-HT 1 agonists [eg, sumatriptan], linezolid, lithium, St. John's wort, tramadol)Risk of serotonin syndrome may be increased.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Cardiovascular
Hot flushes (3%); palpitations (at least 1%); hypertensive crisis, orthostatic hypotension, supraventricular arrhythmia, syncope (postmarketing).
CNS
Somnolence (21%); dizziness (17%); headache (15%); fatigue, insomnia (13%); asthenia (8%); decreased libido (7%); tremor (5%); abnormal orgasm, agitation (4%); anxiety, pyrexia (3%); paresthesia (2%); anorgasmia, dysgeusia, hypersomnia, hypesthesia, initial insomnia, irritability, lethargy, middle insomnia, nervousness, nightmare, restlessness, sleep disorder, vertigo (at least 1%); extrapyramidal disorder, hallucinations, mania, seizures (postmarketing).
Dermatologic
Hyperhidrosis (8%); increased sweating (6%); night sweats, pruritus, rash, skin ulcer (at least 1%); erythema multiforme, Stevens-Johnson syndrome, urticaria (postmarketing).
EENT
Nasopharyngitis (9%); blurred vision (4%); glaucoma (postmarketing).
GI
Nausea (38%); constipation, dry mouth (15%); diarrhea (8%); vomiting (5%); abdominal pain, dyspepsia (4%); gastritis (at least 1%); flatulence (postmarketing).
Genitourinary
Delayed ejaculation, erectile dysfunction, frequent micturition (5%); ejaculation dysfunction (3%); dysuria, urinary hesitation (at least 1%); abnormal orgasm, urinary retention (postmarketing).
Hepatic
Hepatitis, jaundice (postmarketing).
Hypersensitivity
Anaphylactic reaction, angioneurotic edema, hypersensitivity (postmarketing).
Lab Tests
Increased alkaline, ALT, AST, and bilirubin (postmarketing).
Metabolic-Nutritional
Decreased appetite, hyponatremia (11%); anorexia (5%); decreased weight (2%); hypoglycemia, increased appetite (at least 1%); SIADH (postmarketing).
Musculoskeletal
Muscle cramp, myalgia (4%); rigors (at least 1%); trismus (postmarketing).
Respiratory
Pharyngolaryngeal pain (6%); cough (5%); yawning (3%).
Miscellaneous
Chills, serotonin syndrome (postmarketing).
Precautions
WarningsAntidepressants increased the risk of suicidal thinking and behavior in short-term studies in children and adolescents 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. |
MonitorMonitor BP before starting therapy and periodically during prolonged treatment. |
Pregnancy
Category C . Neonates exposed to duloxetine late in the third trimester may develop complications requiring prolonged hospitalization, respiratory support, and tube feeding.
Lactation
Excreted in breast milk.
Children
Safety and efficacy not established.
Renal Function
Not recommend for patients with end-stage renal disease or severe renal function impairment (CrCl less than 30 mL/min).
Hepatic Function
Because greatly increased exposure to duloxetine occurs in patients with hepatic function impairment, do not administer duloxetine to these patients.
Special Risk Patients
Use with caution in patients with controlled narrow-angle glaucoma or conditions that may slow gastric emptying.
Blood pressure
Elevations in BP may occur.
Discontinuation of therapy
A gradual reduction in dose rather than abrupt discontinuation of therapy is recommended in order to minimize discontinuation symptoms (eg, dizziness, headache, nightmares, paresthesia).
Glycemic control
May worsen glycemic control in some patients with diabetes.
Hepatotoxicity
The risk of elevated transaminase levels may be increased.
Hyponatremia
Hyponatremia and SIADH have been reported and appear to be reversible when duloxetine is discontinued.
Mania/Hypomania
May be activated.
Orthostatic hypotension and syncope
May occur with therapeutic doses.
Seizures
Because seizures have been reported in a small number of patients, use with caution in patients with history of seizures.
Serotonin syndrome
Life-threatening serotonin syndrome may occur, particularly with coadministration of serotonergic drugs.
Suicide
Monitor depressed patients at risk during initial therapy. Prescribe smallest quantity consistent with good patient management in order to reduce risk of overdose.
Overdosage
Symptoms
Seizures, serotonin syndrome, somnolence, vomiting.
Patient Information
- Advise patient to read patient information leaflet before starting therapy and with each refill.
- Advise patient to take prescribed dose without regard to meals but to take with food if stomach upset occurs.
- Advise patient to swallow capsule whole; capsule should not be crushed or chewed. Caution patient not to open capsule and sprinkle contents on food or mix with liquids.
- Advise patient not to change dose or stop taking unless advised by health care provider.
- Inform patient that it may take 1 to 4 wk to note improvement in symptoms and to continue with prescribed therapy once improvement has been noted.
- Instruct patient to notify health care provider if symptoms do not appear to be getting better or are getting worse, or if bothersome adverse reactions (eg, changes in sexual function, diarrhea, drowsiness, headache, insomnia, nausea, nervousness, unusual sweating) occur.
- Advise patient being treated for depression, and family or caregiver of patient, to be alert for abnormal changes in mood or thinking and to immediately report any of the following to health care provider: agitation, anxiety, hostility or aggressiveness, impulsivity, irritability, panic attacks, or suicidal thoughts or behavior.
- Instruct patient in BP and pulse measurement skills.
- Advise patient to periodically monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also, advise patient to take record of BP and pulse to each follow-up visit.
- Advise patient that if medication needs to be discontinued, it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
- Advise patient to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
- Advise patient to avoid alcoholic beverages and other depressants while taking duloxetine.
- Advise patient that drug may impair judgment, thinking, or motor skills, or cause drowsiness or dizziness, and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
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Fibromyalgia, Bipolar Disorder, Anxiety, Depression, Pain, Diabetic Nerve Damage
