Overview
11 DESCRIPTION Duloxetine delayed-release capsules, USP are a selective serotonin and norepinephrine reuptake inhibitor (SNRI) for oral administration. Its chemical designation is (+)-( S )- N -methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine hydrochloride. The empirical formula is C 18 H 19 NOS∙HCl, which corresponds to a molecular weight of 333.88.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS. 12.2 Pharmacodynamics Preclinical studies have shown that 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 in vitro . Duloxetine does not inhibit monoamine oxidase (MAO).
Indications
- 1 INDICATIONS AND USAGE Duloxetine delayed-release capsules is indicated for the treatment of: Major depressive disorder in adults Generalized anxiety disorder in adults and pediatric patients 7 years of age and older Diabetic peripheral neuropathic pain in adults Fibromyalgia in adults and pediatric patients 13 years of age and older Chronic musculoskeletal pain in adults Duloxetine delayed-release capsules are a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of the following conditions: Major depressive disorder (MDD) in adults ( 1 ) Generalized anxiety...
Common Doses
- 40 mg
- 60 mg
- 20 mg
- 30 mg
Dosage
2 DOSAGE AND ADMINISTRATION Take Duloxetine delayed-release capsules once daily, with or without food. Swallow whole; do not crush, chew, or open capsule ( 2.1 ) Indication Starting Dose Target Dose Maximum Dose MDD ( 2.2 ) 40 mg/day to 60 mg/day Acute Treatment: 40 mg/day (20 mg twice daily) to 60 mg/day (once daily or as 30 mg twice daily); Maintenance Treatment: 60 mg/day 120 mg/day GAD ( 2.3 ) Adults 60 mg/day 60 mg/day (once daily) 120 mg/day Geriatric 30 mg/day 60 mg/day (once daily) 120 mg/day Pediatrics (7 to 17 years of age) 30 mg/day 30 to 60 mg/day (once daily) 120 mg/day DPNP ( 2.
Black Box Warning
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older [see Warnings and Precautions (5.1) ] . In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors.
Contraindications
- 4 CONTRAINDICATIONS The use of MAOIs intended to treat psychiatric disorders with Duloxetine delayed-release capsules or within 5 days of stopping treatment with Duloxetine delayed-release capsules is contraindicated because of an increased risk of serotonin syndrome. The use of Duloxetine delayed-release capsules within 14 days of stopping an MAOI intended to treat psychiatric disorders is contraindicated [see Dosage and Administration (2.8) and Warnings and Precautions (5.4) ].
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults [see Boxed Warning and Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Orthostatic Hypotension, Falls and Syncope [see Warnings and Precautions (5.3) ] Serotonin Syndrome [see Warnings and Precautions (5.4) ] Increased Risk of Bleeding [see Warnings and Precautions (5.5) ] Severe Skin Reactions [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Both CYP1A2 and CYP2D6 are responsible for duloxetine metabolism. Potent inhibitors of CYP1A2 should be avoided ( 7.1 ) Potent inhibitors of CYP2D6 may increase Duloxetine delayed-release capsules concentrations ( 7.2 ) Duloxetine delayed-release capsules is a moderate inhibitor of CYP2D6 ( 7.9 ) 7.1 Inhibitors of CYP1A2 When duloxetine 60 mg was co-administered with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to male subjects (n=14) duloxetine AUC was increased approximately 6-fold, the C max was increased about 2.