Duloxetine
Mechanism :
Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors. The antidepressant and pain inhibitory actions of duloxetine are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS. The mechanism of action of duloxetine in SUI has not been determined but is thought to be associated with the potentiation of serotonin and norepinephrine activity in the spinal cord, which increases urethral closure forces and thereby reduces involuntary urine loss.
Indication :
- Generalized anxiety disorder
Contraindications :
Contraindicated in patients with a known hypersensitivity to duloxetine or any of the inactive ingredients, in patients taking monoamine oxidase inhibitors (MAOIs) and in patients with uncontrolled narrow-angle glaucoma. It is not recommended in children less than 18 years.
Dosing :
Under 7 years:
Safety and efficacy not established.
7 to 17 years:
30 mg orally daily. After 2 weeks, dose can be increased to 60 mg/day. Max dose: 120 mg/day.
Adverse Effect :
Nausea, vomiting, dry mouth, fatigue, dizziness, anaphylactic reaction, edema, angioneurotic hypersensitivity, seizures upon treatment discontinuance, restless legs syndrome, extrapyramidal disorders, somnolence, galactorrhea, hyperglycemia, gynecologic bleeding, hyperprolactinemia, hypertensive crisis, supraventricular arrhythmia, glaucoma, aggression, anger, hallucinations, tinnitus, trismus, muscle spasm, erythema multiforme, Stevens-Johnson syndrome, urticaria, rash.
Interaction :
CNS Acting Drugs: It should be used with caution when it is taken in combination with or substituted for other centrally acting drugs, including those with a similar mechanism of action.
Serotonergic Drugs: Caution is advised when duloxetine is coadministered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, linezolid
Triptan: There have been rare post marketing reports of serotonin syndrome with use of an SSRI and a triptan.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 30-50 | Dose as in normal renal function; start with a low dose |
| 10-30 | Start at low dose and increase according to response |
| <10 | Start at very low dose and increase according to response |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in GFR <10 mL/min |
| HD | Not dialysed. Dose as in GFR <10 mL/min |
| HDF/High flux | Unlikely to be dialysed. Dose as in GFR <10 mL/min |
| CAV/VVHD | Not dialysed. Dose as in GFR =10–30 mL/min |
Hepatic Dose :
Do not use in chronic hepatic disease or cirrhosis.