Duloxetine
(restricted to pain team or specialist diabetes team initiation only)
Mechanism of action: Duloxetine is a potent reuptake inhibitor of serotonin and norepinephrine, thus potentiating serotonergic and noradrenergic activity in the CNS. It has a weak effect on dopamine reuptake.
Presentation: capsule
Suggested initial dose: 30mg once a day for adults over 50kg with normal hepatic and renal function
It usually takes 3-7 days for the analgesic effect to become clinically beneficial.
Oral absorption: well-absorbed in the small intestine, bioavailability approx. 45-50%
Protein binding: greater than 90%, primarily to albumin and alpha1-acid glycoprotein
Metabolism: Hepatic metabolism by CYP450 enzymes, particularly CYP1A2 and CYP2D6.
Patients with clinically important hepatic impairment have a substantial decrease in the metabolism and elimination of duloxetine, so the use of duloxetine in liver disease should be avoided.
Elimination: Mainly excreted in urine as metabolites and conjugates, with around 5% excreted in the faeces.
Patients with end stage renal failure or eGFR less than 30ml/min exhibit high plasma concentrations of duloxetine, so it should be avoided.
Half-life: 10-12 hours
Common side effects include: nausea, dry mouth, sedation, insomnia, dizziness.
Important cautions include: glaucoma, and the risk of serotonin syndrome if co-prescribed with tramadol or other drugs that act on serotonin pathways.
Further prescribing information (side effects, contraindications, interactions):