Duloxetine

Cymbalta is labeled for MDD in adults; GAD in adults and children age 7 and older; diabetic peripheral neuropathic pain in adults; fibromyalgia in adults and adolescents age 13 and older; and chronic musculoskeletal pain in adults. Pediatric MDD, diabetic neuropathic pain, and chronic musculoskeletal pain safety/effectiveness are not established.

MDD: start 40 mg/day as 20 mg twice daily, or 60 mg/day once daily or as 30 mg twice daily. A 30-mg daily first week may improve tolerability before 60 mg. Adult GAD under age 65: usually start 60 mg daily, with optional 30 mg daily for one week. Although 120 mg/day was effective in trials, doses above 60 mg do not show added benefit for most adults; reassess before escalating. If GAD is increased above 60 mg, use 30-mg steps.

Age 7–17 and geriatric GAD: start 30 mg once daily for 2 weeks before considering 60 mg daily. The pediatric recommended range is 30–60 mg daily. Selected patients may benefit above 60 mg; increases are 30-mg steps and the maximum studied is 120 mg/day. These are GAD instructions, not a universal geriatric regimen.

Review renal function in diabetic neuropathy and consider a lower start/slow titration when impaired; avoid severe impairment as below.

Take Cymbalta with or without food and swallow capsules whole. Do not crush, chew, open, sprinkle, or mix the contents; the enteric coating must be preserved. Take a missed dose when remembered unless the next dose is near; then skip it and do not double. Taper rather than stop abruptly when feasible. No fixed taper fits every patient; if symptoms are intolerable, the clinician may restore the previous dose and reduce more slowly. Other sprinkle-capable duloxetine brands need their own label.

Psychiatric MAOIs are contraindicated with duloxetine, within 5 days after stopping duloxetine, or when duloxetine is started within 14 days of stopping an MAOI. Starting duloxetine during linezolid or IV methylene-blue therapy is also contraindicated. Liver disease, substantial alcohol use, severe renal impairment, and CYP1A2 inhibitors are avoid-use warnings, rather than entries in Cymbalta’s formal section 4 list.

Short-term antidepressant trials found increased suicidal thoughts/behavior in children, adolescents, and young adults through age 24. Monitor all ages for worsening or emerging suicidality, especially early treatment and dose changes. Involve caregivers in observation and prompt communication. A treatment-related warning does not establish approval for pediatric depression.

Common adult reactions include nausea, dry mouth, somnolence, constipation, decreased appetite, and sweating; dizziness, sleep disturbance, and sexual effects also occur. Children may lose appetite or weight and need growth monitoring. Withdrawal can cause dizziness, nausea, headache, sensory symptoms, irritability, anxiety, insomnia, sweating, and fatigue. Overdose may cause serotonin syndrome, seizures, coma, cardiovascular instability, and death. Obtain emergency/poison-center support; no specific antidote exists, and dialysis is unlikely to help.

Do not combine with MAOIs. If linezolid/IV methylene blue is urgently necessary without an acceptable alternative, follow the label’s supervised interruption and monitoring protocol; do not improvise a washout. Other serotonergic drugs—such as tramadol, triptans, TCAs, lithium, buspirone, amphetamines, or St. John’s wort—raise serotonin-syndrome risk; review need, counsel, and monitor.

Avoid potent CYP1A2 inhibitors such as fluvoxamine; ciprofloxacin and other inhibitors also require review. Potent CYP2D6 inhibitors can increase duloxetine exposure. Duloxetine itself moderately inhibits CYP2D6: use caution with narrow-index substrates, including TCAs and flecainide/propafenone; TCA levels or dose reductions may be needed. Do not coadminister thioridazine because raised levels can cause dangerous arrhythmias.

NSAIDs, aspirin, and anticoagulants can add bleeding risk; carefully monitor warfarin-treated patients when duloxetine begins or ends, even though a healthy-volunteer trial showed no meaningful INR change. Substantial alcohol use adds liver-injury risk. Review other CNS drugs and agents causing orthostasis. Antacids/famotidine did not materially alter absorption in the cited study; proton-pump inhibitor effects are unknown, not proven absent.

Available observational data have not identified a clear major-birth-defect signal, but do not prove zero risk. Late pregnancy exposure can lead to neonatal adaptation/toxicity complications, and use in the month before delivery may increase postpartum hemorrhage risk. Balance this against untreated illness and relapse from stopping. Duloxetine enters milk; labeling reports infant sedation, poor feeding, and poor growth. LactMed permits cautious use when needed on limited data and prefers a better-studied alternative for a newborn/preterm infant. Monitor feeding, alertness, weight, and development.

Pediatric approvals and doses are restricted to the ages/conditions above. Monitor growth, weight, clinical worsening, and suicidality. Older adults may be more sensitive to hyponatremia and falls, especially with diuretics, dehydration, or interacting medicines. The slower GAD start is specific to that indication; age alone does not require an across-the-board dose adjustment.

Avoid GFR below 30 mL/min and chronic liver disease/cirrhosis. Mild/moderate renal impairment (estimated CrCl 30–80) did not significantly alter apparent clearance in population analyses; for diabetic neuropathy, the label still supports a cautious lower start and gradual increase when renal function is impaired. Cirrhosis substantially increases exposure; no validated rescue dose is supplied.

Duloxetine inhibits serotonin and norepinephrine reuptake. Its antidepressant, anxiety, and central pain effects are thought to reflect enhanced CNS monoamine signaling, although their precise mechanisms in humans are not established.

The elimination half-life is about 12 hours, with steady state generally after 3 days. CYP1A2 and CYP2D6 produce metabolites, largely cleared in urine; less than 1% is excreted unchanged. The delayed-release coating preserves delivery past acidic gastric conditions. These kinetics support interaction and organ-function review rather than an assumed universal dose.

Assess indication-specific response and periodically reassess maintenance need. Measure blood pressure before treatment and periodically; review orthostasis/falls, mood/mania, suicidality, liver symptoms/alcohol, bleeding, urinary function, and sexual effects. Monitor growth/weight in children and glycemic control in diabetes. Assess sodium when symptoms or risk factors suggest hyponatremia; the label does not prescribe a universal routine laboratory schedule.

Avoid sudden unsupervised stopping and preserve the whole capsule. Seek urgent help for suicidal intent, marked agitation with fever/tremor, jaundice, severe rash/blistering, eye pain/vision changes, serious bleeding, seizures, or inability to urinate. Discuss pregnancy plans and breastfeeding, medicines/supplements, alcohol, and driving impairment. Missing or changing doses should prompt individualized advice rather than doubling.

Cymbalta 30 mg has an opaque white body and blue cap, marked Lilly 3240 and 30mg; a 30-count bottle is NDC 0002-3240-30. The 20-mg capsule is green (Lilly 3235 / 20mg), and 60 mg green/blue (Lilly 3270 / 60mg). These are Lilly examples; generic appearance varies.

Selected Cymbalta delayed-release capsules contain 20, 30, or 60 mg duloxetine equivalent. Do not extrapolate these whole-capsule instructions to sprinkle-labeled brands without their own product labeling. Duloxetine is not a U.S. controlled substance.

Store at 25°C (77°F), with excursions of 15–30°C (59–86°F) permitted. Keep medicines away from children and maintain capsule integrity until swallowed.