Drug Monograph
Duloxetine (Cymbalta)
duloxetine hydrochloride delayed-release capsules
Pharmacokinetic Profile
Half-Life
~12 h (range 8–17 h)
Metabolism
CYP1A2 and CYP2D6 (dual pathway)
Protein Binding
>90% (albumin & α1-acid glycoprotein)
Bioavailability
~50% (range 32–80%)
Volume of Distribution
~1,640 L
Clinical Information
Drug Class
SNRI
Available Doses
20, 30, 60 mg delayed-release capsules
Route
Oral, once daily, with or without food
Renal Adjustment
Avoid in severe impairment (GFR <30 mL/min)
Hepatic Adjustment
Avoid in chronic liver disease or cirrhosis
Pregnancy
3rd trimester: neonatal adaptation syndrome; may cause fetal harm (animal data)
Lactation
Excreted in breast milk (animal data)
Schedule
Prescription only (not scheduled)
Generic Available
Yes
Black Box Warning
Suicidal thoughts & behaviours in young adults
Hepatotoxicity
Fatal hepatic failure reported; avoid with alcohol or liver disease
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Major Depressive Disorder (MDD) | Adults | Monotherapy | FDA Approved |
| Generalized Anxiety Disorder (GAD) | Adults & paediatric ≥7 years | Monotherapy | FDA Approved |
| Diabetic Peripheral Neuropathic Pain (DPNP) | Adults | Monotherapy | FDA Approved |
| Fibromyalgia (FM) | Adults & paediatric ≥13 years | Monotherapy | FDA Approved |
| Chronic Musculoskeletal Pain | Adults (OA & CLBP) | Monotherapy | FDA Approved |
Duloxetine is the most broadly indicated SNRI, with five FDA-approved indications spanning psychiatry, neurology, and pain medicine. Initially approved in 2004 for MDD, its dual serotonin-norepinephrine reuptake inhibition makes it particularly suited to conditions involving comorbid pain and depression. The 60 mg once-daily dose is the therapeutic target across most indications, with no consistent evidence of added benefit above this dose. Duloxetine is one of only two SNRIs (with milnacipran) approved for fibromyalgia, and it is the only SNRI approved specifically for chronic musculoskeletal pain including osteoarthritis and chronic low back pain.
Off-Label Uses
Stress urinary incontinence: Approved outside the US (e.g., UK); failed US approval due to hepatotoxicity and suicidality concerns. Evidence quality: High (multiple RCTs).
Chemotherapy-induced peripheral neuropathy: Evidence quality: Moderate.
OCD (adjunctive or monotherapy): Evidence quality: Low–Moderate.
Dosing
Adult Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Major depression | 40–60 mg/day | 60 mg once daily | 120 mg/day | Can start at 20 mg BID or 30 mg BID or 60 mg QD. May start at 30 mg QD for 1 week for tolerability. No evidence >60 mg adds benefit 120 mg effective but no clear advantage over 60 mg |
| Generalised anxiety — adults <65 y | 60 mg once daily | 60 mg once daily | 120 mg/day | May start at 30 mg QD for 1 week. If dose increase needed, use 30 mg increments. No evidence >60 mg adds benefit |
| Generalised anxiety — geriatric | 30 mg once daily | 60 mg once daily | 120 mg/day | Start 30 mg QD for 2 weeks before increasing to 60 mg Longer lead-in than younger adults |
| Diabetic neuropathic pain | 60 mg once daily | 60 mg once daily | 60 mg/day | No evidence higher doses add benefit; higher doses less well tolerated. Consider lower start if tolerability concern Consider renal function in diabetic patients |
| Fibromyalgia — adults | 30 mg once daily | 60 mg once daily | 60 mg/day | Start 30 mg for 1 week then increase to 60 mg. No evidence >60 mg helps; higher doses more adverse effects |
| Chronic musculoskeletal pain (OA/CLBP) | 30 mg once daily | 60 mg once daily | 60 mg/day | Start 30 mg for 1 week then increase to 60 mg. No evidence higher doses add benefit |
Paediatric Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| GAD (ages 7–17) | 30 mg once daily | 30–60 mg once daily | 120 mg/day | Start 30 mg for 2 weeks before considering increase to 60 mg. Some may benefit above 60 mg; increase by 30 mg increments |
| Fibromyalgia (ages 13–17) | 30 mg once daily | 30–60 mg once daily | 60 mg/day | May increase to 60 mg based on response and tolerability |
Critical: Hepatic and Renal Restrictions
Unlike venlafaxine (which allows dose reduction), duloxetine should be avoided entirely in patients with chronic liver disease, cirrhosis, or severe renal impairment (GFR <30 mL/min). In end-stage renal disease, duloxetine Cmax and AUC were approximately 100% higher, and metabolite levels 7–9 fold higher than normal. Also avoid in patients with substantial alcohol use due to hepatotoxicity risk. MAOI washout: 14 days before starting duloxetine; only 5 days after stopping duloxetine (shorter than venlafaxine at 7 days).
Pharmacology
Mechanism of Action
Duloxetine is a potent inhibitor of both serotonin (5-HT) and norepinephrine (NE) reuptake with weak inhibition of dopamine reuptake. Unlike venlafaxine, duloxetine exhibits relatively balanced 5-HT and NE inhibition even at lower doses, rather than becoming predominantly noradrenergic only at higher doses. This balanced dual activity from the outset contributes to its efficacy across both psychiatric and pain indications. Duloxetine does not inhibit monoamine oxidase and has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, or GABA receptors. Notably, duloxetine is a moderate inhibitor of CYP2D6, which distinguishes it from venlafaxine (weak CYP2D6 inhibitor) and creates clinically important interactions with CYP2D6 substrates.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Well absorbed; bioavailability ~50% (range 32–80%); Tmax ~6 h; delayed-release enteric coating prevents degradation in acid; food does not affect AUC but delays Tmax by ~6–10 h | Must swallow whole — do not crush or chew (acid degrades to naphthol); conditions slowing gastric emptying may affect coating integrity |
| Distribution | Vd ~1,640 L; >90% protein-bound (albumin and α1-acid glycoprotein) | Very large Vd indicates extensive tissue distribution; high protein binding — potential for displacement interactions with other highly bound drugs not fully studied |
| Metabolism | Extensive hepatic via CYP1A2 and CYP2D6 (dual pathway); metabolites not pharmacologically active; moderate CYP2D6 inhibitor; does not significantly inhibit CYP1A2, CYP2C9, CYP2C19, or CYP3A | Dual CYP dependence creates vulnerability: CYP1A2 inhibitors (fluvoxamine: 6-fold AUC increase) and CYP2D6 inhibitors (paroxetine: AUC +60%) both raise levels; smokers (CYP1A2 inducers) have ~1/3 lower exposure; avoid potent CYP1A2 inhibitors |
| Elimination | t½ ~12 h (range 8–17 h); primarily renal excretion (~70% as metabolites, <1% unchanged); ~20% faecal; elderly females: AUC ~25% higher, t½ ~4 h longer; ESRD: Cmax and AUC ~100% higher, metabolites 7–9× | Moderate t½ supports once-daily dosing; significant accumulation in ESRD — avoid use; hepatic impairment markedly increases exposure (5-fold in cirrhosis) — contraindicated |
Side Effects
≥10%Very Common (Pooled Adult Data)
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nausea | Up to 30% (dose-dependent; 14% at 20 mg, 22% at 60 mg QD) | Most common AE across all indications; usually improves in 1–2 weeks; main driver of early discontinuation |
| Headache | Up to 18% | Similar across indications; usually transient |
| Somnolence | Up to 21% (dose-dependent; 7% at 20 mg, 15% at 60 mg QD) | Includes hypersomnia and sedation; caution with driving |
| Dizziness | Up to 17% (dose-dependent; 6% at 20 mg, 14% at 60 mg QD) | Usually transient; related to orthostatic effects |
| Dry mouth | Up to 15% | More common in MDD/GAD vs pain populations; encourage oral hygiene |
| Constipation | Up to 15% | Noradrenergic effect; manage with fibre and fluids |
1–10%Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Decreased appetite | Up to 10% | May lead to weight loss; monitor especially in paediatric patients |
| Fatigue | Up to 10% | More common in fibromyalgia and pain trials |
| Insomnia | Up to 10% | Consider morning dosing |
| Hyperhidrosis | Up to 7% | Noradrenergic effect; includes night sweats; may persist |
| Diarrhoea | Up to 7% | Usually mild; serotonergic GI effect |
| Abdominal pain | Up to 6% | Includes upper and lower; monitor for hepatotoxicity |
| Vomiting | Up to 5% | Usually early and transient |
| Tremor | Up to 5% | Fine postural tremor |
| Erectile dysfunction (males) | Up to 5% | Enquire proactively; dose-related |
| Ejaculatory dysfunction (males) | Up to 5% | Includes delayed ejaculation and ejaculation failure |
| Decreased libido | Up to 4% | Both sexes; likely underreported |
SeriousSerious Adverse Effects
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Hepatotoxicity (including fatal hepatic failure) | ALT >3× ULN: 1.25% vs 0.45% placebo; fatal cases reported | Median ~2 months; can occur any time | Discontinue for jaundice or significant liver dysfunction; do not resume unless alternative cause identified. Avoid in liver disease/substantial alcohol use |
| Orthostatic hypotension, falls, syncope | Falls higher rate than placebo; fractures and hospitalisations reported | Often first week; can occur after dose increases | Dose reduction or discontinuation; particular concern in elderly; risk increases >60 mg and with concomitant antihypertensives or CYP1A2 inhibitors |
| Suicidal thoughts/behaviours | 14 per 1,000 (<18 y); 5 per 1,000 (18–24 y) | First weeks to months | Close monitoring at initiation and dose changes |
| SJS / erythema multiforme | Reporting rate exceeds background incidence (1–2 per million person-years) | Days to weeks | Discontinue at first sign of blisters, peeling rash, or mucosal erosions |
| Serotonin syndrome | Rare | Hours to days | Discontinue all serotonergic agents; supportive care |
| Mania/hypomania | MDD: 0.1% (4/3,779); none in GAD, DPNP, FM, pain trials | Days to weeks | Discontinue; psychiatric reassessment |
| Seizures | 0.02% (3/12,722) vs 0.01% placebo | Any time; also reported on discontinuation | Use cautiously in seizure disorders |
| Hyponatraemia (SIADH) | Uncommon; Na <110 mmol/L reported | Days to weeks; elderly at higher risk | Check sodium; discontinue; medical management |
DiscontinuationDiscontinuation Rates by Indication
MDD
8.4% vs 4.6% placebo
Nausea only AE meeting drug-related criteria (1.1% vs 0.4%)
Pain Indications (DPNP / FM / OA / CLBP)
12.9–17.5% vs 5.1–10.1% placebo
Nausea (2–3.5%), dizziness (1.2%), somnolence (1–1.1%), fatigue (1.1%) across pain trials
Discontinuation Syndrome
Following abrupt or tapered discontinuation, the following symptoms occurred at ≥1% and significantly higher than placebo: dizziness, headache, nausea, diarrhoea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue. Gradual dose reduction is recommended. Seizures upon treatment discontinuation have been reported in postmarketing.
Glycaemic Effects in Diabetic Patients
In DPNP trials (mean baseline HbA1c 7.8%), duloxetine was associated with a mean fasting glucose increase of 12 mg/dL and HbA1c increase of 0.5% during extension phases (up to 52 weeks), compared with decreases in routine care groups. Monitor glycaemic control in diabetic patients on duloxetine.
Drug Interactions
Duloxetine is metabolised by both CYP1A2 and CYP2D6, creating dual vulnerability to inhibitors of either pathway. It is itself a moderate CYP2D6 inhibitor, which creates important interactions with narrow-therapeutic-index CYP2D6 substrates. When both CYP1A2 and CYP2D6 are simultaneously inhibited (or a CYP1A2 inhibitor is given to a CYP2D6 poor metaboliser), duloxetine levels can increase 6-fold. Potent CYP1A2 inhibitors should be avoided. Smoking (CYP1A2 induction) reduces duloxetine exposure by approximately one-third.
MajorFluvoxamine (potent CYP1A2 inhibitor)
MechanismPotent CYP1A2 inhibition; duloxetine AUC increased ~6-fold, Cmax ~2.5-fold, t½ ~3-fold
EffectMarkedly elevated duloxetine exposure with high risk of toxicity
ManagementAvoid co-administration. Ciprofloxacin and enoxacin expected to have similar effects
FDA PIMajorMAOIs (linezolid, IV methylene blue)
MechanismDual serotonergic and noradrenergic enhancement
EffectSerotonin syndrome (potentially fatal)
ManagementContraindicated. 14 days before starting duloxetine; 5 days after stopping before starting MAOI
FDA PIMajorThioridazine
MechanismDuloxetine’s moderate CYP2D6 inhibition increases thioridazine levels
EffectQT prolongation, ventricular arrhythmias, sudden death risk
ManagementShould not be co-administered
FDA PIMajorAlcohol (heavy use)
MechanismAdditive hepatotoxicity
EffectSevere liver injury, including fatal hepatic failure
ManagementAvoid prescribing to patients with substantial alcohol use
FDA PIModerateCYP2D6 inhibitors (paroxetine, fluoxetine, quinidine)
MechanismCYP2D6 inhibition; paroxetine increased duloxetine AUC ~60%
EffectHigher duloxetine concentrations; greater in CYP2D6 PM patients
ManagementUse with caution; monitor for adverse effects
FDA PIModerateCYP2D6 substrates with narrow TI (TCAs, flecainide, propafenone)
MechanismDuloxetine is a moderate CYP2D6 inhibitor; increases levels of these substrates
EffectTCA toxicity (QT prolongation, seizures); antiarrhythmic toxicity
ManagementMonitor TCA levels; reduce TCA dose; approach with caution
FDA PIModerateNSAIDs / Aspirin / Warfarin / Anticoagulants
MechanismSNRI-mediated platelet serotonin depletion; additive bleeding risk
EffectIncreased bleeding risk; postpartum haemorrhage reported
ManagementMonitor; warfarin INR not significantly changed in study (n=15) but clinical caution recommended
FDA PIMinorSmoking / Tobacco
MechanismCYP1A2 induction by polycyclic aromatic hydrocarbons; duloxetine bioavailability reduced by ~1/3
EffectLower duloxetine levels in smokers
ManagementMay need higher doses in smokers; dose reduction if patient stops smoking
FDA PIMonitoring
- Liver FunctionBaseline; repeat if symptoms develop
RoutineHepatic failure (sometimes fatal) reported. ALT >3× ULN in 1.25% vs 0.45% placebo. Median onset ~2 months. Discontinue for jaundice or significant liver dysfunction - Blood PressureBaseline, then periodically
RoutineMean increase 0.5 mmHg systolic, 0.8 mmHg diastolic (small but clinically relevant in at-risk patients); larger increases at supratherapeutic doses - Mood & SuicidalityWeekly for 4 weeks, biweekly for 8 weeks, then per judgement
RoutineEspecially in patients <25 years; monitor at dose changes - Glycaemic ControlBaseline, then every 3–6 months in diabetic patients
RoutineDPNP trials: FBG +12 mg/dL, HbA1c +0.5% over 52 weeks vs routine care. Monitor fasting glucose and HbA1c - Falls / OrthostasisAt initiation, dose changes, and in elderly
Trigger-basedHigher fall rate than placebo. Falls with fractures and hospitalisations reported. Risk higher with antihypertensives, CYP1A2 inhibitors, doses >60 mg, and elderly - Sodium (Na+)Baseline in at-risk; recheck 2–4 weeks
Trigger-basedNa <110 mmol/L reported. Elderly, diuretic users at higher risk - Sexual FunctionBaseline, then each visit
RoutineEnquire proactively per FDA PI; rates likely underestimated - Urinary SymptomsIf symptoms develop
Trigger-basedUrinary hesitation and retention reported postmarketing; some cases required catheterisation/hospitalisation
Contraindications & Cautions
Absolute Contraindications
- Concurrent MAOI use or within 14 days of stopping MAOI / within 5 days of stopping duloxetine (linezolid, IV methylene blue included)
- Chronic liver disease or cirrhosis — markedly increased exposure; fatal hepatic failure reported
- Severe renal impairment (GFR <30 mL/min) or end-stage renal disease — Cmax/AUC doubled, metabolites 7–9× higher
- Substantial alcohol use — additive hepatotoxicity risk
Relative Contraindications (Specialist Input Recommended)
- Concurrent potent CYP1A2 inhibitors (fluvoxamine, ciprofloxacin, enoxacin) — should be avoided; 6-fold AUC increase
- Concurrent thioridazine — should not be co-administered; QT prolongation risk via CYP2D6 inhibition
- Undiagnosed bipolar disorder — mania risk 0.1% in MDD trials
Use with Caution
- Elderly patients — higher fall risk, orthostatic hypotension risk, hyponatraemia risk; AUC 25% higher in elderly females
- Conditions slowing gastric emptying (e.g., diabetic gastroparesis) — may affect enteric coating integrity
- Seizure disorders — seizures in 0.02% (3/12,722); not systematically evaluated in epilepsy
- Anatomically narrow angles — angle-closure glaucoma risk
- Late pregnancy — neonatal adaptation syndrome; postpartum haemorrhage risk
- Smokers — ~1/3 lower duloxetine exposure; may need higher doses; stopping smoking requires dose reduction
- Concurrent CYP2D6 substrates with narrow TI — duloxetine is a moderate CYP2D6 inhibitor
FDA Boxed Warning
Suicidal Thoughts and Behaviours
Antidepressants increased the risk of suicidal thinking and behaviour in children, adolescents, and young adults (ages 18–24) in short-term studies. No suicides occurred in paediatric duloxetine trials. All patients started on antidepressant therapy should be closely monitored for clinical worsening and emergence of suicidal thoughts, especially during initial months and at dose changes. Families and caregivers should be advised of the need for daily observation.
Patient Counselling
Purpose of Therapy
Duloxetine works by increasing both serotonin and norepinephrine in the brain. It is used to treat depression, anxiety, nerve pain from diabetes, fibromyalgia, and chronic musculoskeletal pain. Full benefit for mood symptoms may take 2–4 weeks; pain benefits may appear within 1–2 weeks.
How to Take
Swallow capsules whole with water. Do not crush, chew, or open the capsule — the special coating protects the medicine from stomach acid. Take at approximately the same time each day. If you miss a dose, take it as soon as you remember unless it is almost time for the next dose.
Liver Safety
Tell patientDuloxetine can rarely cause liver problems. Avoid heavy alcohol use while taking this medication. Report any yellowing of skin or eyes, dark urine, unexplained nausea, or right-sided abdominal pain.
Call prescriberImmediately if jaundice, persistent abdominal pain, or dark urine develops.
Nausea
Tell patientNausea is the most common side effect and usually improves within 1–2 weeks. Taking the medication with food may help. Your prescriber may start with a lower dose to reduce nausea.
Call prescriberIf nausea is severe, lasts beyond 2 weeks, or prevents adequate fluid intake.
Dizziness & Falls
Tell patientDuloxetine can cause dizziness and drops in blood pressure when standing, especially in the first week. Rise slowly from sitting or lying positions. This risk is higher in elderly patients and those taking blood pressure medications.
Call prescriberIf you experience fainting, repeated dizziness, or a fall.
Do Not Stop Suddenly
Tell patientStopping duloxetine abruptly can cause withdrawal symptoms including dizziness, nausea, headache, tingling, and irritability. Always taper gradually under medical supervision.
Call prescriberIf you miss doses or experience withdrawal symptoms during a planned taper.
Blood Sugar (Diabetic Patients)
Tell patientDuloxetine may slightly worsen blood sugar control. Continue monitoring your blood sugar as directed and keep all diabetes appointments.
Call prescriberIf blood sugar readings are consistently higher than usual.
Mood Changes & Suicidality
Tell patientRarely, antidepressants may worsen mood or cause new thoughts of self-harm, especially in the first weeks. Have a trusted person watch for mood changes.
Call prescriberImmediately if new suicidal thoughts, agitation, or unusual behaviour. Go to the emergency department if in immediate danger.
Sources
Regulatory (PI / SmPC)
- CYMBALTA (duloxetine delayed-release capsules). Full Prescribing Information. Eli Lilly and Company. Revised July 2021. FDA LabelPrimary regulatory source for all dosing, adverse reaction data, contraindications, hepatotoxicity warnings, and pharmacokinetics.
- CYMBALTA (duloxetine) Summary of Product Characteristics. Electronic Medicines Compendium (eMC). eMCEuropean regulatory source cross-referenced for stress urinary incontinence indication and additional PK data.
Key Clinical Trials
- Detke MJ, Lu Y, Goldstein DJ, et al. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry. 2002;63(4):308–315. DOIPivotal MDD trial establishing efficacy of 60 mg once-daily dosing.
- Goldstein DJ, Lu Y, Detke MJ, et al. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain. 2005;116(1–2):109–118. DOIKey DPNP trial demonstrating significant pain reduction at 60 mg/day.
- Arnold LM, Lu Y, Crofford LJ, et al. A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. Arthritis Rheum. 2004;50(9):2974–2984. DOIPivotal fibromyalgia trial demonstrating efficacy independent of comorbid depression.
- Rynn M, Russell J, Erickson J, et al. Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trial. Depress Anxiety. 2008;25(3):182–189. DOIFlexible-dose GAD trial supporting the 60–120 mg dosing range.
Guidelines
- Lam RW, Kennedy SH, Adams C, et al. CANMAT 2023 update on clinical guidelines for management of MDD in adults. Can J Psychiatry. 2024;69(9):641–687. DOICurrent guideline recommending duloxetine as first-line for MDD, especially with comorbid pain.
- Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy. Neurology. 2011;76(20):1758–1765. DOIAAN guideline with Level B recommendation for duloxetine 60–120 mg/day in DPNP.
- Macfarlane GJ, Kronisch C, Dean LE, et al. EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis. 2017;76(2):318–328. DOIEULAR guideline recommending duloxetine for fibromyalgia pain management.
Mechanistic / Basic Science
- Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, et al. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001;25(6):871–880. DOIKey pharmacology comparison demonstrating duloxetine’s more balanced 5-HT/NE reuptake inhibition vs venlafaxine.
- Gahimer J, Wernicke J, Yalcin I, et al. A retrospective pooled analysis of duloxetine safety in 23,983 subjects. Curr Med Res Opin. 2007;23(1):175–184. DOILarge pooled safety analysis providing hepatotoxicity incidence and overall tolerability data.
Pharmacokinetics / Special Populations
- Lobo ED, Bergstrom RF, Reddy S, et al. In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. Clin Pharmacokinet. 2008;47(3):191–202. DOICharacterises the fluvoxamine–duloxetine interaction (6-fold AUC increase) and CYP1A2 pathway contribution.
- Skinner MH, Kuan H-Y, Pan A, et al. Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers. Clin Pharmacol Ther. 2003;73(3):170–177. DOIEstablishes duloxetine as a moderate CYP2D6 inhibitor and characterises paroxetine interaction.
- Lantz RJ, Gillespie TA, Rash TJ, et al. Metabolism, excretion, and pharmacokinetics of duloxetine in healthy human subjects. Drug Metab Dispos. 2003;31(9):1142–1150. DOIPrimary PK characterisation in humans defining t½, Vd, protein binding, and metabolic pathways.