duloxetine hydrochloride: clinical use

Prescribing considerations

• Confirm the indication and product-specific licence because duloxetine products have different authorised uses.
• Assess blood pressure, cardiovascular history, hepatic and renal function, bipolar or seizure history, glaucoma risk, bleeding risk and interacting medicines.
• Discuss suicidality, possible activation or akathisia, sexual dysfunction and withdrawal before treatment.
• Use caution where hyponatraemia is more likely, including older, dehydrated or cirrhotic patients and those taking diuretics.

Contraindications and cautions

• Hypersensitivity to duloxetine or product excipients.
• Concomitant non-selective irreversible monoamine oxidase inhibitor treatment.
• Liver disease resulting in hepatic impairment.
• Severe renal impairment.
• Concomitant fluvoxamine, ciprofloxacin or enoxacin.
• Starting treatment in uncontrolled hypertension where hypertensive crisis is a risk.

Monitoring

• Blood pressure, particularly early in treatment and in people with hypertension or cardiovascular disease.
• Clinical response, tolerability and continuing treatment need.
• Suicidal thinking, behavioural change, mania, seizures, akathisia and serotonin toxicity.
• Serum sodium when symptoms or risk factors suggest hyponatraemia.
• Liver tests when clinically indicated or if symptoms of hepatic injury develop.
• Bleeding where anticoagulants, antiplatelets, NSAIDs or bleeding disorders are relevant.

Clinical pharmacology

Duloxetine is a serotonin and noradrenaline reuptake inhibitor with weak dopamine-reuptake inhibition. It is well absorbed, highly protein bound and extensively metabolised through CYP1A2 and CYP2D6 to largely inactive metabolites that are mainly excreted in urine. It also moderately inhibits CYP2D6.

Formulation and product differences

• All selected products are hard gastro-resistant capsules containing duloxetine as the hydrochloride salt.
• Products licensed for depression, anxiety and neuropathic pain differ from those intended for stress urinary incontinence.
• The selected higher-strength Neuraxpharm product is licensed for major depressive disorder and generalised anxiety disorder rather than diabetic neuropathic pain.
• Capsule appearance, excipients, sucrose content, storage requirements and pack presentation vary by manufacturer; consult the exact product information.

Capsule

Route: Oral

Strengths: 20 mg, 30 mg, 40 mg, 60 mg

Gastro-resistant capsule

Route: Oral

Strengths: 20 mg, 30 mg, 40 mg, 60 mg, 90 mg, 120 mg