Duloxetine: Difference between revisions
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MDElliottMD (talk | contribs) Comprehensive categorization: +Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs), Antidepressants |
MDElliottMD (talk | contribs) Sweep: "indications" -> "problems" sitewide terminology update (preserves MedTemplate param name) |
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| pregnancy = Category C | | pregnancy = Category C | ||
| legal = Rx-only | | legal = Rx-only | ||
| intro = '''Duloxetine''' is a serotonin–norepinephrine reuptake inhibitor (SNRI) with a relatively balanced affinity for the serotonin (SERT) and norepinephrine (NET) transporters, distinguishing it from venlafaxine, which is primarily serotonergic at low doses. Beyond its psychiatric | | intro = '''Duloxetine''' is a serotonin–norepinephrine reuptake inhibitor (SNRI) with a relatively balanced affinity for the serotonin (SERT) and norepinephrine (NET) transporters, distinguishing it from venlafaxine, which is primarily serotonergic at low doses. Beyond its psychiatric problems, duloxetine is one of the most commonly prescribed agents for chronic pain syndromes — particularly diabetic peripheral neuropathy and fibromyalgia — where its norepinephrine activity in descending inhibitory pain pathways is thought to underlie analgesic efficacy. | ||
| pharmacokinetics = Well-absorbed orally with ~50% bioavailability, though substantial interindividual variability. Extensive first-pass metabolism, primarily via '''CYP1A2''' (major) and CYP2D6 (minor). Highly protein-bound (>90%). Half-life ~12 hours; steady state in ~3 days. No active metabolites of clinical significance. Capsules are enteric-coated — should not be crushed or chewed. | | pharmacokinetics = Well-absorbed orally with ~50% bioavailability, though substantial interindividual variability. Extensive first-pass metabolism, primarily via '''CYP1A2''' (major) and CYP2D6 (minor). Highly protein-bound (>90%). Half-life ~12 hours; steady state in ~3 days. No active metabolites of clinical significance. Capsules are enteric-coated — should not be crushed or chewed. | ||
| pharmacodynamics = Inhibits reuptake of both serotonin and norepinephrine at the synaptic cleft via SERT and NET. The serotonergic and noradrenergic effects are relatively balanced across the clinical dose range (60–120 mg/day), unlike venlafaxine. Modest indirect dopaminergic activity in the prefrontal cortex (via NET inhibition, since DA reuptake in PFC depends partly on NET). Minimal affinity for muscarinic, histaminic, or alpha-adrenergic receptors. | | pharmacodynamics = Inhibits reuptake of both serotonin and norepinephrine at the synaptic cleft via SERT and NET. The serotonergic and noradrenergic effects are relatively balanced across the clinical dose range (60–120 mg/day), unlike venlafaxine. Modest indirect dopaminergic activity in the prefrontal cortex (via NET inhibition, since DA reuptake in PFC depends partly on NET). Minimal affinity for muscarinic, histaminic, or alpha-adrenergic receptors. | ||
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* Chronic musculoskeletal pain (osteoarthritis, chronic low back pain) | * Chronic musculoskeletal pain (osteoarthritis, chronic low back pain) | ||
* Stress urinary incontinence (approved in Europe; not FDA-approved) | * Stress urinary incontinence (approved in Europe; not FDA-approved) | ||
| dosing = '''Start:''' 30 mg PO daily × 1 week, then increase to 60 mg daily (target dose for most | | dosing = '''Start:''' 30 mg PO daily × 1 week, then increase to 60 mg daily (target dose for most problems). | ||
'''Range:''' 60–120 mg/day. Higher doses (>60 mg) often add modest benefit at the cost of more side effects. | '''Range:''' 60–120 mg/day. Higher doses (>60 mg) often add modest benefit at the cost of more side effects. | ||
'''Renal/hepatic:''' avoid in CrCl <30 mL/min or significant hepatic impairment. | '''Renal/hepatic:''' avoid in CrCl <30 mL/min or significant hepatic impairment. | ||