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12 Articles in Volume 17, Issue #2
Chronic Pain and Bipolar Disorders: A Bridge Between Depression and Schizophrenia Spectrum
Differences in Pain Management of Peripheral Vascular Disease and Peripheral Artery Disease
Duloxetine and Liver Function Tests
How Well Do You Know Your Patient?
Insurers End Policies Requiring Prior Authorization for Opioid Use Disorder
Letters to the Editor: Initiating Hormones
Managing Opioid Use Disorders and Chronic Pain
Opportunities and Challenges of Pain Management: The Family Physician’s Perspective
Pathways to Recovery From Co-Occurring Chronic Pain and Addiction
Strategies for Weaning Opioids in Patients With an Opioid Use Disorder and Chronic Pain
Treating Multiple Pain Syndromes: A Case Series Using a Functional Medicine Model
Treatment of Chronic Exhaustion and Chronic Fatigue Syndrome

Duloxetine and Liver Function Tests

Ask the Expert March 2017

Question: When prescribing duloxetine, what are the recommendations for monitoring liver function tests?

Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that also exhibits weak inhibition of dopamine. It is approved by the Food and Drug Administration for the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain. Duloxetine dosing for pain is up to 60 mg daily and can be increased to 120 mg daily when depression is present.1

Recommendation concerning liver function tests for Duloxetine, for neuropathic pain

Transient elevations in alanine aminotransferase (ALT) levels have been reported in less than 1% of individuals taking duloxetine and do not require any dosing adjustments or discontinuation.2 During clinical trials, elevation of serum transaminase levels resulted in 0.3% of patients discontinuing duloxetine, but this is a well-known side effect of antidepressants.1

Antidepressant-related liver injury is rare and not always reversible, with onset usually seen within 1 to 6 months of starting therapy.1 Certain antidepressants, such as nefazodone, phenelzine, imipramine, amitriptyline, duloxetine, bupropion, and trazodone, have been associated with the greatest risk of hepatotoxicity, while other antidepressants, including citalopram, escitalopram, paroxetine, and fluvoxamine, have shown the least risk.3 Risk factors for duloxetine-induced liver injury are not­­­­ well understood; however, female gender and age over 50 years may present greater risks.4 Patients with these risk factors should have liver function levels monitored at baseline and again during the first 12 to 16 weeks after initiating duloxetine therapy.4 Another possible risk factor is taking multiple medications (polypharmacy). When a patient is taking more than 1 medication that targets the same metabolic pathways, such as cytochrome P 450 (CYP)1A2 and CYP2D6 for duloxetine, serum liver enzyme levels may be altered.1,3

Most drug information compendia do not recommend any specific monitoring parameters for liver function once a patient has started taking duloxetine. However, baseline liver function testing (LFT) is advisable for all patients, with repeat testing within 2 to 4 months for patients presenting with known risk factors. This is suggested despite the lack of any recommendations to check liver function levels prior to use and to avoid prescribing duloxetine in patients with evidence of liver disease, cirrhosis, substantial alcohol intake, or hepatic impairment.3

LFT generally is not performed again unless signs of organ dysfunction develop, such as dark urine, fatigue, itching, lack of appetite, nausea, vomiting, abdominal pain, light-colored stools, or jaundice. If evidence of liver dysfunction is present, then the prescribing information recommends discontinuing duloxetine and not reinitiating therapy unless another source or cause is identified.² It is important to note that discontinuation of the drug requires gradual tapering to avoid adverse effects.1 The median time to detect elevated liver enzymes is roughly 2 months. It is also relevant to know that drug-induced liver injury is dose-dependent, so escalating the dose of duloxetine may increase the risk of this occurring. It should be noted that there are 2 doses of duloxetine: 30 mg and 60 mg. Most patients are started on the 30 mg dose and, if needed, increased gradually to 60 mg. With other antidepressants, this usually is not the case.³  

To conclude, no specific recommendations were found with regard to the frequency necessary for performing LFT after initiating duloxetine, but if patients have known risk factors or if a pain practitioner determines a need to proceed with caution, then an order for LFT may be requested at any time. However, the best recommendation is to order a LFT at baseline for all patients prior to initiating duloxetine, and then again in 2 to 4 months for patients at higher risk of hepatic injury.3

For patients who are not determined to be at increased risk for hepatic dysfunction, it may not be necessary to request LFT after baseline unless they begin showing signs of liver injury.

Last updated on: March 17, 2017
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Pathways to Recovery From Co-Occurring Chronic Pain and Addiction

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