Xinolax DR Capsule (Delayed Release)

Xinolax DR is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for-

• Major Depressive Disorder (MDD)
• Generalized Anxiety Disorder (GAD)
• Diabetic Peripheral Neuropathic Pain (DPNP)
• Fibromyalgia and
• Chronic Musculoskeletal Pain.

Duloxetine Hydrochloride is a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) for oral administration. Duloxetine is 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). Orally administered Duloxetine hydrochloride is well absorbed. Elimination of Duloxetine is mainly through hepatic metabolism.

Major Depressive Disorder (MDD)-

• Starting Dose: 40 mg/day to 60 mg/day
• Target Dose: Acute: 40 mg/day (20 mg twice daily) to 60 mg/day (once daily or as 30 mg twice daily); Maintenance: 60 mg/day
• Maximum Dose: 120 mg/day

Generalized Anxiety Disorder (GAD)-

• Starting Dose: 60 mg/day
• Target Dose: 60 mg/day (once daily)
• Maximum Dose: 120 mg/day

Diabetic Peripheral Neuropathic Pain (DPNP)-

• Starting Dose: 60 mg/day
• Target Dose: 60 mg/day (once daily)
• Maximum Dose: 60 mg/day

Fibromyalgia-

• Starting Dose: 30 mg/day
• Target Dose: 60 mg/day (once daily)
• Maximum Dose: 60 mg/day

Chronic Musculoskeletal Pain-

• Starting Dose: 30 mg/day
• Target Dose: 60 mg/day (once daily)
• Maximum Dose: 60 mg/day

Some patients may benefit from starting at 30 mg once daily. There is no evidence that doses greater than 60 mg/day confers an additional benefit, while some adverse reactions were observed to be dose-dependent. A gradual dose reduction is recommended to avoid discontinuation symptoms.

Both CYP1A2 and CYP2D6 isozymes are responsible for Xinolax DR metabolism. When Xinolax DR was co-administered with fluvoxamine, a potent CYP1A2 inhibitor, the AUC, Cmax and t of Xinolax DR was increased. Other drugs that inhibit CYP1A2 metabolism include cimetidine and quinolone antimicrobials such as ciprofloxacin and enoxacin would be expected to have similar effects and these combinations should be avoided. Because CYP2D6 is involved in Xinolax DR metabolism, concomitant use of Xinolax DR with potent inhibitors of CYP2D6 may result in higher concentrations of Xinolax DR.

Duloxetine is contraindicated in patients with a known hypersensitivity to this drug or any of the inactive ingredients. Duloxetine is not approved for use in treating bipolar depression. Duloxetine should not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease. In clinical trials, Duloxetine was associated with an increased risk of mydriasis; therefore, it should be used cautiously in patients with controlled narrow-angle glaucoma.

The most commonly observed adverse events in Xinolax DR treated patients were nausea, dizziness, dry mouth, constipation, decreased appetite, fatigue, somnolence, increased sweating, hyperhidrosis and asthenia. It may slightly increase blood pressure. No clinically significant differences were observed for QT, PR, and QRS intervals between Xinolax DR-treated and placebo-treated patients.

Pregnancy: Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women; therefore, Duloxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery: The effect of Duloxetine on labor and delivery in humans is unknown. Duloxetine should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus.

Lactation: It is unknown whether or not Duloxetine and/or it's metabolites are excreted into human milk, but nursing while on Duloxetine is not recommended

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes. Blood pressure should be measured prior to initiating treatment and periodically measured throughout treatment. Patients should be cautioned about the risk of bleeding associated with the concomitant use of Xinolax DR and NSAIDs, aspirin, or other drugs that affect coagulation. Xinolax DR should be used cautiously in patients with a history of mania. Xinolax DR should be prescribed with care in patients with a history of a seizure disorder.

Use in the pediatric population: Safety and efficacy in pediatric patients have not been established

There is limited clinical experience with Xinolax DR overdose in humans. There is no specific antidote to Xinolax DR. In case of acute overdose, treatment should consist of those general measures employed in the management of overdose with any drug. An adequate airway, oxygenation, and ventilation should be assured, and cardiac rhythm and vital signs should be monitored. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients. Activated charcoal may be useful in limiting the absorption of Xinolax DR from the gastrointestinal tract.

Serotonin-norepinephrine reuptake inhibitor (SNRI)

Do not store above 30°C. Keep away from light and out of the reach of children.