Citinex

Approved Indications:
• Ischemic Stroke (acute and recovery phases): Enhances neurological recovery and supports rehabilitation.
• Traumatic Brain Injury (TBI): Used in both acute and post-traumatic cognitive impairment stages.
• Vascular Cognitive Impairment: For mild to moderate stages; improves memory, attention, and executive functions.
• Parkinson’s Disease (as adjunct therapy): Helps support dopaminergic transmission.

Clinically Accepted Off-label Uses:
• Alzheimer’s Disease and other dementias: As adjunct in mild to moderate stages.
• Amblyopia and Glaucoma: Neuroprotective effect on retinal ganglion cells and optic nerve.
• Substance Abuse (alcohol, cocaine): Studied for improving cognitive deficits related to substance use.
• Post-surgical Cognitive Decline: Supports brain recovery and memory function.
• Mild Cognitive Impairment in elderly: Enhances memory and concentration.

Adults:
• Acute Ischemic Stroke: 500–2000 mg/day IV or orally, divided into 1–2 doses for up to 6 weeks.
• Post-stroke Recovery: 500–1000 mg/day orally for 6–12 weeks.
• TBI / Cognitive Dysfunction: 500–2000 mg/day orally or IV in 2 divided doses for 4–12 weeks.
• Parkinson’s Disease (adjunct): 500–1000 mg/day orally with standard therapy.

Elderly Patients:
• No specific dose adjustments required. Start at the lowest effective dose and monitor for tolerability.

Pediatric Use:
• Safety and efficacy not established. Use not routinely recommended.

Renal or Hepatic Impairment:
• Use with caution; no official dose adjustment, but monitoring is advised. Reduce dose if significant organ dysfunction is present.

Routes of Administration:
• Oral (tablet, capsule, or solution)
• Intravenous (IV slow injection or infusion)
• Intramuscular (less commonly used in modern practice)

Duration of Therapy:
• Typically ranges from 4 to 12 weeks. Chronic use possible in neurodegenerative conditions under clinical supervision.

Citicoline Sodium is a neuroprotective compound that serves as a precursor for the synthesis of phosphatidylcholine, a vital component of neuronal membranes. It is metabolized into cytidine and choline, which are reabsorbed by the brain and used to regenerate damaged cell membranes and promote membrane repair. Citicoline increases the availability of neurotransmitters such as dopamine and acetylcholine, which are essential for cognition and motor control. It also reduces the accumulation of free fatty acids during ischemic episodes, limits oxidative stress, and inhibits neuronal apoptosis—resulting in enhanced brain metabolism, improved cognitive function, and better neurological recovery.

• Absorption: Rapid and almost complete after oral or parenteral administration.
• Bioavailability: >90% (oral); similar efficacy between oral and IV routes.
• Distribution: Widely distributed in systemic circulation and central nervous system.
• Metabolism: Rapidly hydrolyzed to cytidine and choline.
• Half-life:

• Choline: ~2–6 hours
• Cytidine: ~30–60 minutes
  • Elimination:
• Excreted primarily as CO₂ via lungs (~60%)
• Renal excretion accounts for ~15% of dose
  • Onset of Action: Within 24–48 hours in acute settings
  • Duration of Action: Builds over weeks with regular dosing

• Pregnancy:

• Not formally classified by the FDA.
• Animal studies show no teratogenic effects.
• Human data are insufficient. Use only if benefits outweigh risks.

• Lactation:

• Unknown if excreted into breast milk.
• Caution advised; use only under medical supervision.
• Monitor infants for gastrointestinal or neurological effects.

Primary Class: Neuroprotective agent
Sub-Class: Nootropic / Brain Metabolism Enhancer
Pharmacologic Type: Choline precursor

• Hypersensitivity to citicoline or any excipients
• Hypertonic solution contraindicated in patients with intracranial hemorrhage (during acute phase)
• Severe vagotonia (parasympathetic hyperactivity)
• Children and adolescents (unless specifically prescribed under supervision)

• Severe Hepatic or Renal Impairment: Use with caution and monitor organ function.
• Intracranial Hemorrhage: Avoid IV use in the acute bleeding phase.
• Seizure History: May lower seizure threshold in predisposed individuals.
• Parkinson’s Disease: Monitor for worsening of dyskinesia due to increased dopaminergic activity.
• Injection Monitoring: Administer IV slowly to prevent hypotension or local irritation.
• Long-term Use: Requires periodic assessment of cognitive and neurological function.

Common (≥1%):
• Nervous System: Headache, insomnia, dizziness, tremor
• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal discomfort
• Cardiovascular: Mild hypotension, bradycardia or tachycardia
• General: Fatigue, restlessness, anxiety

Uncommon/Rare:
• Dermatologic: Rash, pruritus
• Psychiatric: Hallucinations, confusion
• Neurologic: Agitation, muscle cramps

Serious Adverse Effects (rare):
• Hypersensitivity reactions
• Seizures in predisposed individuals
• Worsened dyskinesia in patients on levodopa

Timing:
• Adverse effects usually occur within the first few days of treatment initiation and are dose-related.

• Levodopa: May enhance dopaminergic transmission; monitor for dyskinesia.
• Anticholinergic Drugs: Opposing action; may reduce therapeutic effects of citicoline.
• Cholinergic Drugs: Potential for additive cholinergic side effects.
• Alcohol: Chronic use may reduce efficacy.
• Enzymatic Pathways: Does not significantly interact with CYP450 enzymes.

• Increasing support for its use in post-stroke cognitive rehabilitation from recent clinical guidelines.
• Citicoline is being incorporated into neurorehabilitation protocols in Europe and Asia.
• New trials continue to explore benefits in glaucoma and Alzheimer’s disease.
• No new FDA or EMA safety alerts reported within the last 12 months.

• Oral Formulations:

• Store below 25°C.
• Protect from light and moisture.
• Do not use after expiration.

• Injectable Solutions:

• Store between 2°C and 8°C (refrigerated).
• Do not freeze.
• Use immediately after opening or follow dilution stability if applicable.

• Handling Precautions:

• Shake oral suspensions before use.
• Protect all formulations from direct sunlight.
• Discard any unused portion of injectable solutions properly.