Adult: Initially, 20 mg bid or 60 mg daily as a single dose or in 2 divided doses. For some patients, lower starting dose of 30 mg once daily for 1 week may be suitable before increasing to the maintenance dose. Maintenance: 60 mg once daily. Max: 120 mg daily.
Oral Neuropathic pain associated with diabetic peripheral neuropathy
Adult: Initially, 60 mg once daily. Max: 120 mg daily in divided doses.
Oral Generalised anxiety disorder
Adult: Initially, 60 mg once daily. For some patients, lower starting dose of 30 mg once daily for 1 week may be suitable before increasing to 60 mg once daily. If a dosage increase beyond 60 mg once daily is necessary, increase the dosage in increments of 30 mg once daily. Max: 120 mg daily. Elderly: Initially, 30 mg once daily for 2 weeks, then increase to 60 mg once daily. If a dosage increase beyond 60 mg once daily is necessary, increase the dosage in increments of 30 mg once daily. Max: 120 mg daily. Child: 7-17 years Initially, 30 mg once daily for 2 weeks, then increase to 60 mg once daily. Recommended dosage range: 30-60 mg once daily. If a dosage increase beyond 60 mg once daily is necessary, increase the dosage in increments of 30 mg once daily. Max: 120 mg daily.
Oral Moderate to severe stress urinary incontinence in women
Adult: 40 mg bid. Alternatively, initiate at 20 mg bid for 2 weeks, then increase to 40 mg bid. Re-assess the patient after 2-4 weeks of treatment to evaluate the treatment benefit and patient tolerability.
Oral Chronic musculoskeletal pain, Fibromyalgia
Adult: Initially, 30 mg once daily for 1 week, then increase to 60 mg once daily.
Renal Impairment
CrCl (mL/min)
Dosage
<30
Contraindicated.
Hepatic Impairment
Contraindicated.
Administration
May be taken with or without food. Swallow whole, do not chew/crush.
Contraindications
Uncontrolled hypertension. Hepatic and severe renal (CrCl <30 mL/min) impairment. Concomitant use with or within 14 days of discontinuing nonselective, irreversible MAOIs. Concomitant use with linezolid, IV methylthioninium chloride (also known as methylene blue), thioridazine, and potent CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin, enoxacin).
Special Precautions
Patient with history of mania or bipolar disorder; history of seizure disorder or condition predisposing to seizures (e.g. brain damage); history of suicide-related events or exhibiting a significant degree of suicidal thoughts or behaviour; increased IOP or those at risk of acute angle-closure glaucoma; controlled hypertension and/or other cardiac diseases, condition that may be compromised by an increased heart rate or blood pressure; known bleeding tendencies, susceptibility to hyponatraemia (e.g. dehydration, concomitant use with diuretics), impaired gastric motility. Smokers and heavy alcohol drinkers. Avoid abrupt discontinuation. Mild to moderate renal impairment. Children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Suicidal thoughts and behaviour (particularly in children and young adults), activation of mania or hypomania, mydriasis, increase in blood pressure and clinically significant hypertension, bleeding abnormalities (e.g. ecchymoses, purpura, gastrointestinal haemorrhage), hyponatraemia, akathisia, increased liver enzymes, hepatitis, jaundice, withdrawal symptoms (particularly upon abrupt discontinuation), increased fasting blood glucose and HbA1c, orthostatic hypotension, syncope, falls, acute angle-closure glaucoma, urinary hesitation and retention; decreased libido, erectile dysfunction, ejaculatory delay or failure (male), delayed or absent orgasm (female); severe skin reactions (e.g. erythema multiforme, Stevens-Johnson syndrome). Rarely, hypertensive crisis. Cardiac disorders: Palpitations. Ear and labyrinth disorders: Tinnitus, vertigo. Eye disorders: Blurred vision. Gastrointestinal disorders: Dry mouth, nausea, vomiting, constipation, diarrhoea, abdominal pain, dyspepsia, flatulence. General disorders and administration site conditions: Fatigue, asthenia, chills. Investigations: Decreased weight. Metabolism and nutrition disorders: Decreased appetite. Musculoskeletal and connective tissue disorders: Musculoskeletal pain, muscle spasm. Nervous system disorders: Headache, somnolence, dizziness, tremor, paraesthesia, lethargy. Psychiatric disorders: Insomnia, agitation, anxiety, abnormal dreams, sleep disorder. Renal and urinary disorders: Dysuria, pollakiuria. Respiratory, thoracic and mediastinal disorders: Yawning. Skin and subcutaneous tissue disorders: Hyperhidrosis, rash. Vascular disorders: Flushing. Potentially Fatal: Serotonin syndrome, hepatic failure.
This drug may cause sedation or dizziness, if affected, do not drive or operate machinery.
Monitoring Parameters
Screen patients for personal or family history of bipolar disorder, mania, or hypomania before treatment. Monitor blood pressure (at baseline and periodically during treatment), hepatic and renal functions; blood glucose and HbA1c in diabetic patients (at baseline and as clinically indicated). Closely monitor for clinical worsening, suicidality, or unusual changes in behaviour (particularly during the initial 1-2 months of therapy or during periods of dosage adjustments). Monitor for signs and symptoms of serotonin syndrome (e.g. mental status changes, seizures, tachycardia, hyperthermia, diaphoresis, tremor, rigidity).
Overdosage
Symptoms: Somnolence, seizures, vomiting, tachycardia, syncope, hypotension or hypertension, coma, and serotonin syndrome. Management: Symptomatic and supportive treatment. Establish adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Gastric lavage may be considered if ingestion is recent or in symptomatic patients. Activated charcoal may be administered to reduce absorption. If serotonin syndrome occurs, specific treatment such as cyproheptadine and/or temperature control may be considered.
Drug Interactions
May increase the risk of serotonin syndrome with other serotonergic agents such as selective, reversible MAOIs (e.g. moclobemide), SSRIs, other SNRIs, TCAs, triptans, tramadol, pethidine, buspirone, and tryptophan. May increase the risk of bleeding with anticoagulants, antiplatelet agents, and other drugs known to affect platelet function (e.g. NSAIDs). May increase the CNS effects with other centrally acting drugs (e.g. benzodiazepines, morphinomimetics, antipsychotics, phenobarbital, sedative antihistamines). May increase the plasma concentrations of drugs predominantly metabolised by CYP2D6 (e.g. risperidone, amitriptyline, desipramine, flecainide, propafenone, metoprolol). Increased plasma concentration with potent CYP2D6 inhibitors (e.g. paroxetine, quinidine). Potentially Fatal: Increased risk of serotonin syndrome with nonselective, irreversible MAOIs, linezolid, and IV methylthioninium chloride. May increase the plasma levels of thioridazine resulting in serious ventricular arrhythmias. Increased serum level and risk of hypotension with potent CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin, enoxacin).
Food Interaction
Increased risk of serotonin syndrome with St. John's wort. Risk of severe liver injury with alcohol (particularly with heavy consumption).
Action
Description: Mechanism of Action: Duloxetine inhibits the neuronal reuptake of serotonin and norepinephrine, thereby potentiating serotonergic and noradrenergic activity in the CNS. It weakly inhibits dopamine reuptake with no significant affinity for histaminergic, dopaminergic, cholinergic, adrenergic, GABA, glutamate, and opiate receptors. Onset: Anxiety disorder: Within 2 weeks. Depression: Within 1-2 weeks. Pharmacokinetics: Absorption: Well absorbed from gastrointestinal tract. Bioavailability: 32-80% (mean: 50%). Time to peak plasma concentration: Approx 6 hours. Distribution: Enters breast milk. Volume of distribution: Approx 1,640 L. Plasma protein binding: Approx 96%, mainly to albumin and α1-acid glycoprotein. Metabolism: Extensively metabolised in the liver via oxidation by CYP1A2 and CYP2D6 isoenzymes into 2 major but inactive metabolites, 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate; followed by conjugation and further oxidation. Excretion: Mainly via urine (approx 70% as metabolites, <1% as unchanged drug); faeces (approx 20%). Elimination half-life: 8-17 hours (mean: 12 hours).
Chemical Structure
Duloxetine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 60835, Duloxetine. https://pubchem.ncbi.nlm.nih.gov/compound/Duloxetine. Accessed Feb. 23, 2023.
N06AX21 - duloxetine ; Belongs to the class of other antidepressants.
References
Anon. Duloxetine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 05/12/2022.Anon. Duloxetine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/12/2022.Buckingham R (ed). Duloxetine Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/12/2022.Cymbalta 30 mg Hard Gastro-resistant Capsules (Eli Lilly Nederland B.V.). MHRA. https://products.mhra.gov.uk. Accessed 05/12/2022.Cymbalta Capsule, Delayed Release (Eli Lilly and Company). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/12/2022.Drizalma Sprinkle Capsule, Delayed Release (Sun Pharmaceutical Industries, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 31/01/2023.Dulox Delayed Release Capsules 30 mg and 60 mg (Camber Laboratories Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 31/01/2023.Duloxetine 40 mg Gastro-resistant Capsules, Hard (Wockhardt UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 05/12/2022.Duloxetine Capsule, Delayed Release (Ascend Laboratories, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/12/2022.Joint Formulary Committee. Duloxetine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/12/2022.Onelar 30 mg and 60 mg Hard Gastro-resistant Capsules (Komedic Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 31/01/2023.
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