Deloxi

• Major Depressive Disorder (MDD):
  Treatment of major depressive episodes in adults.
• Generalized Anxiety Disorder (GAD):
  Management of symptoms associated with GAD in adults.
• Diabetic Peripheral Neuropathic Pain (DPNP):
  Relief of neuropathic pain associated with diabetic peripheral neuropathy.
• Fibromyalgia:
  Management of fibromyalgia symptoms.
• Chronic Musculoskeletal Pain:
  Treatment of chronic pain conditions including chronic low back pain and osteoarthritis pain.
• Off-label Uses (Clinically Accepted):
• Stress urinary incontinence
• Neuropathic pain from other etiologies
• Migraine prophylaxis (limited evidence)

Adults:

• Major Depressive Disorder and Generalized Anxiety Disorder:
• Initial dose: 40 mg orally once daily (divided as 20 mg twice daily)
• Usual therapeutic dose: 60 mg once daily
• Maximum dose: 120 mg per day
• Diabetic Peripheral Neuropathic Pain and Fibromyalgia:
• Initial dose: 60 mg once daily
• Dose may be increased up to 120 mg daily based on response and tolerability.
• Chronic Musculoskeletal Pain:
• 60 mg once daily.
• Administration:
  Oral capsules, can be taken with or without food. Swallow whole; do not crush or chew.

Elderly:

• No specific dose adjustment; use caution due to increased risk of adverse reactions.

Pediatrics:

• Safety and efficacy not established in patients under 18 years.

Renal Impairment:

• Moderate impairment (creatinine clearance 30–60 mL/min): Use lower doses with caution.
• Severe impairment (<30 mL/min): Use not recommended.

Hepatic Impairment:

• Contraindicated in patients with hepatic insufficiency or cirrhosis.

Duloxetine hydrochloride is a potent and selective inhibitor of serotonin (5-HT) and norepinephrine (NE) reuptake in the central nervous system. By blocking the reuptake transporters of these neurotransmitters, duloxetine increases their synaptic concentrations, enhancing neurotransmission and modulating pain pathways and mood regulation. This dual reuptake inhibition improves depressive symptoms, anxiety, and neuropathic pain by altering the balance of neurotransmitters implicated in mood and pain signaling.

• Absorption:
  Well absorbed orally with peak plasma concentrations reached within 6 hours.
• Bioavailability:
  Approximately 50% due to first-pass metabolism.
• Distribution:
  Widely distributed; volume of distribution approximately 1640 L.
  Plasma protein binding ~90%.
• Metabolism:
  Extensively metabolized in the liver primarily by CYP1A2 and CYP2D6 enzymes to inactive metabolites.
• Half-life:
  Approximately 12 hours (range 8–17 hours).
• Elimination:
  Primarily renal as metabolites; less than 1% excreted unchanged in urine.

• Pregnancy:
  Classified as FDA Category C. Use only if potential benefits justify potential risks; animal studies have shown adverse effects but human data are limited.
• Lactation:
  Duloxetine is excreted in human milk in small amounts. Caution advised when administered to breastfeeding mothers; weigh benefits against potential risks.

• Primary Class: Antidepressant
• Subclass: Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)

• Known hypersensitivity to duloxetine or any excipients.
• Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation.
• Uncontrolled narrow-angle glaucoma.
• Severe hepatic impairment or cirrhosis.
• Use with thioridazine or other CYP1A2 inhibitors causing QT prolongation.

• Suicidality Risk:
  Increased risk of suicidal thoughts and behaviors in young adults, adolescents, and children; close monitoring required.
• Serotonin Syndrome:
  Risk with concomitant serotonergic drugs; symptoms include agitation, hallucinations, tachycardia, hyperthermia.
• Hyponatremia:
  May occur due to SIADH, especially in elderly patients.
• Liver Toxicity:
  Rare but serious hepatic injury reported; monitor liver function.
• Blood Pressure Changes:
  May cause mild increases in blood pressure and heart rate; monitor regularly.
• Discontinuation Syndrome:
  Abrupt stopping may cause withdrawal symptoms; taper dose gradually.
• Bleeding Risk:
  Increased risk of bleeding events when combined with NSAIDs, aspirin, or anticoagulants.

Common:

• Nausea
• Dry mouth
• Dizziness
• Fatigue
• Insomnia
• Constipation
• Sweating
• Decreased appetite
• Sexual dysfunction

Serious/Rare:

• Hepatotoxicity
• Suicidal ideation
• Serotonin syndrome
• Hyponatremia
• Elevated blood pressure
• Allergic reactions (rash, angioedema)

• MAO Inhibitors:
  Risk of serotonin syndrome; contraindicated.
• CYP1A2 and CYP2D6 Inhibitors:
  May increase duloxetine levels (e.g., fluvoxamine, quinidine).
• Anticoagulants and NSAIDs:
  Increased bleeding risk.
• Other Serotonergic Drugs:
  Increased risk of serotonin syndrome (e.g., triptans, SSRIs, SNRIs, tramadol).
• Alcohol:
  Increases risk of hepatotoxicity and CNS depression.

• Updated warnings emphasize suicide risk and serotonin syndrome.
• Recent guidelines recommend duloxetine as first-line therapy for diabetic neuropathic pain and fibromyalgia.
• FDA alerts stress caution in hepatic impairment and use with CYP inhibitors.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep capsules in original container tightly closed.
• Keep out of reach of children.
• No refrigeration required.