DULOXETINE HYDROCHLORIDE
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Serotonin and norepinephrine reuptake inhibitor (SNRI); increases extracellular levels of serotonin and norepinephrine by inhibiting their reuptake into presynaptic neurons.
| Metabolism | Extensively metabolized in the liver via CYP1A2 and CYP2D6 to multiple inactive metabolites. |
| Excretion | Renal: 70% as metabolites, <1% unchanged; Fecal: 20% |
| Half-life | 12.1 hours (range 8-17 hours); steady-state achieved in 3 days |
| Protein binding | 90% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 3.4 L/kg (1640 L for 70 kg); extensive tissue distribution |
| Bioavailability | Oral: 50% (range 30-80%) due to first-pass metabolism |
| Onset of Action | Oral: 1-2 weeks for antidepressant effect; 1 week for pain relief |
| Duration of Action | 24 hours; once-daily dosing |
| Molecular Weight | 333.38 |
60 mg orally once daily, with or without food; may start at 30 mg once daily for 1 week to allow adjustment to the drug, then increase to 60 mg once daily; maximum 120 mg per day given in divided doses for major depressive disorder; for diabetic peripheral neuropathic pain, 60 mg once daily; for fibromyalgia, 60 mg once daily; for chronic musculoskeletal pain, 60 mg once daily.
| Dosage form | CAPSULE, DELAYED RELEASE |
| Renal impairment | For GFR 30-60 mL/min: reduce dose to 30 mg once daily; for GFR <30 mL/min: not recommended; consider discontinuation if CrCl <30 mL/min; avoid use in end-stage renal disease (ESRD) requiring dialysis. |
| Liver impairment | Child-Pugh Class A: no adjustment necessary; Child-Pugh Class B: reduce starting dose to 30 mg once daily, maximum 60 mg once daily; Child-Pugh Class C: not recommended. |
| Pediatric use | Not approved for use in pediatric patients aged <18 years; safety and efficacy not established; for pediatric generalized anxiety disorder (off-label), limited data suggest starting 30 mg once daily, titrated to 60 mg once daily; maximum 120 mg per day. |
| Geriatric use | In elderly patients, start at 30 mg once daily for 2 weeks, then increase to 60 mg once daily if tolerated; monitor for hyponatremia, falls, bleeding risk, and drug interactions; for patients >65 years, maximum 120 mg per day is not recommended; consider lower maintenance dose (e.g., 60 mg once daily). |
| 1st trimester | Use only if potential benefit justifies risk; associated with increased risk of congenital malformations (e.g., cardiac defects) in some studies. |
| 2nd trimester | Use only if clearly needed; monitor for maternal adverse effects and fetal growth. |
| 3rd trimester | Avoid near term; risk of neonatal serotonin discontinuation syndrome, pulmonary hypertension. |
Clinical note
MAOIs can cause serotonin syndrome Can cause hepatotoxicity and increase suicidal thoughts and behaviors.
| Placental transfer | Duloxetine crosses the placenta (fetal-to-maternal concentration ratio ~0.5-1.3). |
| Breastfeeding | Duloxetine is excreted into breast milk in low concentrations; infant exposure estimated at <2% of maternal weight-adjusted dose. Monitor infant for irritability, poor feeding, and sedation. |
■ FDA Black Box Warning
Suicidality and Antidepressant Drugs: Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with MDD and other psychiatric disorders.
| Common Effects | anxiety |
| Serious Effects |
Concomitant use with MAOIs (including linezolid and intravenous methylene blue)Uncontrolled narrow-angle glaucoma
| Precautions | Suicide risk: Monitor for worsening depression and suicidality, especially early in treatment., Hepatotoxicity: Use caution in patients with substantial alcohol use or pre-existing liver disease; can cause elevated liver enzymes and severe hepatic injury., Serotonin syndrome: Risk, especially with concomitant use of serotonergic drugs., Discontinuation syndrome: Abrupt discontinuation may cause dizziness, headache, nausea, irritability, and insomnia; taper gradually., Mydriasis: May worsen narrow-angle glaucoma., Blood pressure elevation: Monitor blood pressure, especially in patients with hypertension., Hypomania/mania: May precipitate in patients with bipolar disorder., Seizures: Use with caution in patients with seizure disorders., Hyponatremia: May occur, especially in elderly or volume-depleted patients., Sexual dysfunction: Can cause ejaculatory delay, decreased libido, or erectile dysfunction. |
Loading safety data…
| Lactation Rating |
| L2 (Safer) |
| Teratogenic Risk | First trimester: Epidemiologic studies suggest a small increased risk of cardiovascular malformations (primarily ventricular septal defects) with exposure (RR 1.1-1.7). Second/third trimester: Late exposure may increase risk of persistent pulmonary hypertension of the newborn (PPHN) (odds ratio ~1.5-2.0). Third trimester use associated with neonatal adaptation syndrome (irritability, feeding difficulties, respiratory distress) in 25-30% of neonates. |
| Fetal Monitoring | Monitor for maternal serotonin syndrome, hypertension, and bleeding risk. Fetal monitoring for growth parameters and amniotic fluid index recommended in third trimester. Neonatal assessment for adaptation syndrome (poor suck, tremors, jitteriness) postpartum. Consider serial ultrasounds to detect congenital heart defects if first trimester exposure. |
| Fertility Effects | In animal studies, duloxetine did not impair fertility at doses up to 2.7 times the maximum recommended human dose (MRHD). In humans, no dedicated fertility studies exist; however, SSRIs/SNRIs may cause reversible sexual dysfunction (delayed ejaculation, anorgasmia) affecting fertility indirectly. Hyperprolactinemia is rare but possible. |
| Food/Dietary | Avoid alcohol consumption as it may exacerbate CNS effects and hepatotoxicity. No specific food restrictions; however, grapefruit juice may increase duloxetine levels (based on theoretical CYP1A2 inhibition, though clinical significance uncertain). |
| Clinical Pearls | Avoid abrupt discontinuation; taper over 1-2 weeks to prevent withdrawal symptoms (e.g., dizziness, nausea, headache). Contraindicated with MAOIs; allow a 14-day washout. Monitor blood pressure at baseline and regularly due to potential increase. Use with caution in hepatic impairment; reduce dose in moderate impairment (Child-Pugh B) and avoid in severe impairment. May increase risk of bleeding, especially with NSAIDs or anticoagulants. Onset of therapeutic effect may take 2-4 weeks. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly without consulting your doctor. · May cause drowsiness or dizziness; avoid driving until you know how it affects you. · Report any signs of serotonin syndrome (e.g., agitation, hallucinations, rapid heart rate, fever). · Avoid alcohol while taking duloxetine. · Inform your doctor of all medications, including over-the-counter and herbal supplements. · May take with or without food; if gastrointestinal upset occurs, taking with food may help. |