Duloxetine
Cymbalta | Irenka
Overview
Serotonin-norepinephrine reuptake inhibitor (SNRI) used for depression, anxiety, diabetic neuropathy, fibromyalgia, and chronic musculoskeletal pain.
Indications
- Major depressive disorder
- Generalized anxiety disorder
- Diabetic peripheral neuropathy
- Fibromyalgia
- Chronic musculoskeletal pain
- Stress urinary incontinence (EU)
Contraindications
- Use of MAOIs within 14 days
- Uncontrolled narrow-angle glaucoma
- Severe hepatic impairment
- Severe renal impairment (CrCl <30)
Classification
Mechanism of Action
Potent inhibitor of both serotonin and norepinephrine reuptake in the CNS. The dual mechanism contributes to both antidepressant and pain-relieving properties.
Pharmacodynamics
SNRI with balanced serotonin and norepinephrine reuptake inhibition. Also weakly inhibits dopamine reuptake. Analgesic effects mediated through descending pain inhibitory pathways.
Pharmacokinetics
- Absorption
- Well absorbed. Delayed-release capsule. Food delays Tmax but does not affect extent.
- Distribution
- Apparent volume of distribution ~1640 L. Crosses blood-brain barrier.
- Metabolism
- Extensive hepatic via CYP1A2 and CYP2D6.
- Excretion
- Renal (70% as metabolites), fecal (20%).
- Half-life
- 12 hours (range 8-17)
- Bioavailability
- ~50% (range 32-80%)
- Protein Binding
- >90%
Dosage
Typical dosage: 60mg once daily (depression/anxiety). 60mg once or twice daily (pain).
Available Forms
- Delayed-release capsule
Side Effects
Common
- Nausea
- Dry mouth
- Somnolence
- Constipation
- Decreased appetite
- Increased sweating
Serious
- Serotonin syndrome
- Hepatotoxicity
- Suicidal ideation (<25 years)
- Severe skin reactions
Rare
- Seizures
- Hyponatremia
- Angle-closure glaucoma
Drug Interactions
Risk of serotonin syndrome. Contraindicated within 14 days of MAOI use.
Fluvoxamine can increase duloxetine levels 5-6 fold. Avoid combination.
Increased risk of hepatotoxicity. Avoid heavy alcohol use.
Warnings
Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults. Monitor for clinical worsening and suicidality.
Pregnancy
Category C
Toxicity
LD50 not established in humans.
Overdose
Symptoms: somnolence, coma, serotonin syndrome, seizures, vomiting, tachycardia. Treatment: activated charcoal (if early), supportive care, serotonin antagonists if needed.
References
Looking for patient-friendly information? Visit RemedyDoor for easy-to-read guides about this medication.