283 IG PILL – IDENTIFICATION, MECHANISM OF ACTION, SIDE EFFECTS

The 283 IG pill (properly identified with imprint IG 283) is a delayed-release capsule containing Duloxetine Hydrochloride (60 mg), manufactured and distributed by InvaGen Pharmaceuticals (a subsidiary of Cipla). Duloxetine is a prescription Serotonin and Norepinephrine Reuptake Inhibitor (SNRI) primarily indicated for major depressive disorder, generalized anxiety, and various chronic neuropathic and musculoskeletal pain syndromes. It is not a federally controlled substance

Pill Identification & Physical Characteristics

Property – Description

• Active Ingredient – Duloxetine Hydrochloride (60 mg, base equivalent)
• Imprint – IG on the cap and 283 on the body (or IG 283 across capsule sections)
• Form & Color – Delayed-release hard gelatin capsule; Green / Blue (or Opaque Green/White depending on formulation series)
• Size – Approximately 19 mm
• Drug Class – Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) / Antidepressant
• Manufacturer / Distributor – InvaGen Pharmaceuticals Inc. / Cipla USA

Mechanism of Action

Duloxetine exerts its therapeutic effects by enhancing central monoaminergic neurotransmission:

• Dual Reuptake Inhibition: It potently inhibits the neuronal reuptake of both serotonin and norepinephrine via their respective transporters (SERT and NET), with weak inhibition of dopamine reuptake.
• Synaptic Neurotransmitter Elevation: By blocking reuptake, it increases available concentrations of serotonin and norepinephrine within the synaptic cleft in the brain and spinal cord.
• Pain Pathway Modulation: Beyond elevating mood and reducing anxiety via forebrain monoamines, elevated norepinephrine and serotonin in the descending inhibitory pain pathways of the spinal cord suppress ascending nociceptive inputs, providing relief for chronic neuropathic and musculoskeletal pain.

Indications & Dosage

Approved Clinical Indications

• Major Depressive Disorder (MDD) in adults
• Generalized Anxiety Disorder (GAD) in adults and pediatric patients 7 years of age
• Diabetic Peripheral Neuropathic Pain (DPNP)
• Fibromyalgia
• Chronic Musculoskeletal Pain (such as chronic low back pain and osteoarthritis of the knee)

General Adult Dosing

• MDD & GAD: Typically initiated at 30 mg to 60 mg orally once daily. May be titrated up to a maximum of 120 mg/day (though doses above 60 mg/day show little evidence of additional therapeutic benefit in clinical trials).
• Neuropathic / Musculoskeletal Pain & Fibromyalgia: Started at 30 mg once daily for 1 week, then increased to the standard target maintenance dose of 60 mg orally once daily.
• Administration Guidelines:
• Swallow whole with water; can be taken with or without food.
• Do not chew, crush, or open the capsule to sprinkle the pellets on food, as the enteric coating protects duloxetine from acid degradation in the stomach.

Side Effects

Common Adverse Reactions

• Nausea, dry mouth (xerostomia), and constipation
• Somnolence (drowsiness) or insomnia
• Fatigue, dizziness, and headache
• Decreased appetite and weight loss
• Diaphoresis (excessive sweating)
• Sexual dysfunction (delayed ejaculation, decreased libido, anorgasmia)

Severe & Emergent Adverse Reactions

• Hepatotoxicity: Elevation of liver transaminases, cholestatic jaundice, or acute hepatic failure (higher risk in patients with chronic alcohol use or pre-existing liver disease).
• Serotonin Syndrome: Autonomic instability, hyperthermia, clonus, tremors, and mental status changes.
• Severe Cutaneous Reactions: Erythema multiforme, Stevens-Johnson syndrome (SJS).
• Hypertension & Tachycardia: Dose-dependent increases in blood pressure and heart rate due to noradrenergic stimulation.
• Orthostatic Hypotension & Syncope: Especially during initiation or dose escalation.
• Angle-Closure Glaucoma: Pupillary dilation may trigger angle closure in individuals with anatomically narrow angles.

Precautions & Drug Interactions

• Monoamine Oxidase Inhibitors (MAOIs): Strictly contraindicated with or within 14 days of discontinuing MAOIs (e.g., phenelzine, linezolid, methylene blue) due to life-threatening serotonin syndrome risk.
• Potent CYP1A2 and CYP2D6 Inhibitors: Duloxetine is extensively metabolized by hepatic CYP1A2 and CYP2D6. Concurrent use with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) causes a marked surge in duloxetine exposure and should be avoided.
• Bleeding Risk (Anticoagulants / NSAIDs): Inhibition of serotonin reuptake in platelets impairs platelet aggregation. Combining duloxetine with NSAIDs, aspirin, or warfarin increases the risk of upper gastrointestinal bleeding.
• Hepatic Impairment & Heavy Alcohol Use: Duloxetine should ordinarily not be prescribed to patients with chronic liver disease or substantial alcohol consumption due to the compounding risk of severe liver injury.
• Renal Impairment: Avoid use in severe renal impairment (estimated GFR 30 min).
• Discontinuation Syndrome: Abrupt cessation can cause significant withdrawal symptoms (dizziness, electric shock sensations/”brain zaps”, nausea, paresthesia, headache, vivid dreams). Gradual tapering is required.

Black Box Warning

• FDA Boxed Warning — Suicidal Thoughts and Behaviors:
• Pediatric and Young Adult Risk: Antidepressants, including duloxetine, increase the risk of suicidal thoughts and behaviors in children, adolescents, and young adults ( 24 years of age) during initial treatment and dosage adjustments.
• Clinical Monitoring: Patients of all ages should be monitored closely for clinical worsening, emergent suicidality, agitation, irritability, or unusual changes in behavior. Duloxetine is not approved for pediatric depression. >