Cymbalta Duloxetine Hydrochloride Enteric-coated Capsules

1. Indications and Usage
Major Depressive Disorder (MDD):
Indicated for the treatment of Major Depressive Disorder in adults.
Generalized Anxiety Disorder (GAD):
Indicated for the treatment of Generalized Anxiety Disorder in adults.
Chronic Musculoskeletal Pain:
Indicated for the management of chronic musculoskeletal pain.
2. Dosage and Administration
Recommended Dosage:
MDD & GAD: The recommended starting dose is 40 mg/day (20 mg twice daily) to 60 mg/day (given once daily or 30 mg twice daily). Some patients may benefit from starting at 30 mg/day for 1 week before increasing to 60 mg/day.
Chronic Musculoskeletal Pain: The recommended dose is 60 mg once daily.
Maximum Dose: Doses above 60 mg/day have not been shown to provide additional benefit for MDD, and doses above 120 mg/day have not been adequately evaluated for safety.
Administration Instructions:
Swallow capsules whole. Do not chew or crush, or open the capsule and sprinkle the contents on food or mix with liquids, as this may affect the enteric coating.
Can be taken with or without food.
Discontinuation:
Taper the dose gradually when discontinuing to avoid withdrawal symptoms. Abrupt cessation is not recommended.
3. Mechanism of Action
SNRI:
Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor (SNRI).
Physiological Effect:
It potently inhibits the neuronal reuptake of serotonin (5-HT) and norepinephrine (NE), and less potently inhibits dopamine reuptake. It has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, or GABA receptors. Its antidepressant and analgesic effects are believed to be related to the potentiation of serotonergic and noradrenergic activity in the central nervous system.
4. Safety and Warnings
Hepatotoxicity:
Duloxetine may increase serum transaminase levels and cause liver injury. It is contraindicated in patients with chronic liver disease or cirrhosis. Use with caution in patients who consume substantial amounts of alcohol.
Suicidality:
Antidepressants may increase the risk of suicidal thoughts and behavior in children, adolescents, and young adults, especially during the initial months of treatment. Monitor patients closely for clinical worsening or unusual changes in behavior.
Serotonin Syndrome:
Life-threatening serotonin syndrome may occur, particularly with concomitant use of other serotonergic drugs (e.g., SSRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort) or drugs that impair metabolism of serotonin (e.g., MAOIs).
Blood Pressure:
Duloxetine may cause an increase in blood pressure. Blood pressure should be measured prior to initiating treatment and periodically throughout treatment.
Contraindications:
Hypersensitivity to duloxetine or any inactive ingredients.
Use of Monoamine Oxidase Inhibitors (MAOIs) within 14 days of starting duloxetine, or within 5 days of stopping duloxetine.
Uncontrolled narrow-angle glaucoma.
5. Adverse Reactions
Most Common:
Nausea, dry mouth, constipation, decreased appetite, fatigue, somnolence, increased sweating, dizziness, and headache.
6. Drug Interactions
MAOIs:
Concomitant use is contraindicated due to the risk of serotonin syndrome. Allow a washout period of at least 14 days after stopping an MAOI before starting duloxetine, and at least 5 days after stopping duloxetine before starting an MAOI.
CYP1A2 Inhibitors:
Concomitant use with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, enoxacin) significantly increases duloxetine exposure and should be avoided.
CNS Depressants and Alcohol:
Use with caution when co-administered with other centrally acting drugs, including those with a similar side effect profile (e.g., sedatives, anxiolytics) or alcohol, as it may exacerbate sedation or increase the risk of liver injury.
7. Pharmaceutical Information
Chemical Description:
The active ingredient is duloxetine hydrochloride, a selective serotonin and norepinephrine reuptake inhibitor (SNRI).
Storage:
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Protect from light and moisture.