Citifar

Citicoline sodium.

Tablet: Each film-coated tablet contains: Citicoline Sodium e.q. to Citicoline 500 mg.
Injection: Each mL contains: Citicoline Sodium eq. to Citicoline 250 mg.
As preservative: Methyl Paraben BP 0.18 % w/v, Propyl Paraben BP 0.02 % w/v, Water for Injection BP q.s.

Pharmacology: Pharmacodynamics: Tablet: Citicoline is a complex organic molecule that functions as an intermediate in the biosynthesis of cell membrane phospholipids. Citicoline is also known as CDP-choline or cytidine diphosphate choline (cytidine 5' - liphosphocholine). CDP-choline belongs to the group of biomolecules in living systems known as nucleotides that play important roles in cellular metabolism.
The pharmacologic action of Citicoline appears to involve mechanisms that extend beyond phospholipid metabolism. Citicoline metabolites - choline, methionine, betaine, and cytidine derived nucleotides - enter a number of metabolic pathways.
Biochemical markers of cholinergic nerve transmission are known to be deficient in conditions characterized by degeneration of cholinergic neurons, such as Alzheimer's disease (AD). Citicoline modestly improves cognitive function in AD by serving as an acetylcholine precursor. The brain uses choline preferentially for acetylcholine synthesis, which can limit the amount of choline available for phosphatidylcholine production.
Citicoline has also been investigated as a therapy for stroke patients. Three mechanisms are postulated: (1) repair of the neuronal membrane via increased synthesis of phosphatidylcholine; (2) repair of damaged cholinergic neurons via potentiation of acetylcholine production; and (3) reduction of free fatty acid build-up at the site of stroke-induced nerve damage. Citicoline protects cholinergic neurons from autocannibalism, a process in which membrane phospholipids are catabolized to provide choline for synthesis of acetylcholine. This occurs when choline supplies are depleted, necessitating sacrifice of membrane phospholipids to maintain neurotransmission. As an exogenous source of choline for acetylcholine production, Citicoline thus spares membrane phospholipids (in particular, phosphatidylcholine) and prevents neuronal cell death.
Injection: Citicoline activates the biosynthesis of structural phospholipids in the neuronal membranes, increases cerebral metabolism and acts on the levels of various neurotransmitters. Thus, citicoline increases noradrenaline and dopamine levels in the CNS. In terms of its benefits in cerebral ischemia, citicoline primarily acts by increasing the synthesis of phosphatidylcholine, the primary neuronal membrane phospholipid, and enhancing the production of acetylcholine. It is normally reduced in brain cell membranes as a result of aging. Citicoline is also beneficial in patients experiencing ischemia where it is known to decrease the accumulation of free fatty acids at the site of lesion, which occurs as a result of neuronal cell damage and death. Citicoline also shows neural restorative effects by acting on the dopaminergic system of the central nervous system.
Pharmacokinetics: Tablet: Citicoline is a water-soluble compound with greater than 90% bioavailability. Pharmacokinetic studies in healthy adults have shown oral doses of Citicoline to be rapidly absorbed, with less than one percent excreted in the feces. Plasma levels peak in a biphasic manner, at one hour after ingestion followed by a second larger peak at 24 hours post-dosing.
Citicoline is metabolized in the gut wall and liver. The byproducts of exogenous Citicoline formed by hydrolysis in the intestinal wall are choline and cytidine. Following absorption, choline and cytidine are dispersed throughout the body, enter systemic circulation for utilization in various biosynthetic pathways and cross the blood-brain barrier for re-synthesis into Citicoline in the brain.
Pharmacokinetic studies using 14C citicoline show Citicoline elimination occurs mainly via respiratory CO2 and urinary excretion, in two phases, mirroring the biphasic plasma peaks. The initial peak in plasma concentration is followed by a sharp decline, which then slows over the next 4 - 10 hours. In the second phase, an initially rapid decline after the 24-hour plasma peak is similarly followed by a slower elimination rate. The elimination half-life is 56 hours for CO2 and 71 hours for urinary excretion.
Injection: The important pharmacokinetic properties of citicoline are: Oral and intravenous routes are bioequivalent.
Metabolized in intestine and liver with the formation of choline and cytidine.
Quickly reaches cerebral tissues and actively integrates into cell membrane, cytoplasm and mitochondria while choline is utilized in acetylcholine synthesis thereby enhancing the activity of phospholipids.
Chiefly excreted via respiratory tract whereas a minor part of the administered dose is excreted through urine and faeces (less than 3%).

Tablet: Acute and recovery phase of cerebral infarction (e.g., ischemia due to stroke).
Cognitive dysfunction due to degenerative (i.e. Alzheimer's disease) and cerebrovascular disease.
Cerebral insufficiency (e.g., dizziness, memory loss, poor concentration, disorientation) due to head trauma or brain injury.
Parkinson's disease.
Injection: Head trauma of varying severity.
Cerebrovascular diseases such as stroke.
Cognitive disorders of diverse etiology.
Parkinson's disease.

Tablet: Dosage should be individualized.
The usually recommended dose of Citicoline Tablet is 500-1,000 mg daily.
Take this medicine in the dose and duration as advised by the doctor.
Injection: CITIFAR should be administered in the following dosages.
Adult: 1 g IM/IV daily.
Children: 100 - 500 mg IM/IV daily.
It can also be given in dosages as prescribed by the physician.

Tablet: Citicoline exhibits very low toxicity profile in humans. In a short term, placebo-controlled, cross-over study, 12 healthy adults took citicoline at daily doses of 600 and 1000 mg or placebo for consecutive five-day periods.
Transient headaches occurred in four subjects on 600-mg dose, five on the 1000-mg dose, and one in placebo.
No changes or abnormalities were observed in hematology, clinical biochemistry or neurological test.
The LD50 of a single intravenous dose of citicoline was 4,600 mg/kg and 4,150 mg/kg in mice and rats, respectively.
In an unpublished acute toxicity study, free-base citicoline was administered to male and female rats at a dose of 2000 mg/kg body weight for 14 days. No changes in body weight, deaths, clinical symptoms or gross pathological changes were observed.
Injection: CITIFAR exhibits very low toxicity profile in humans. Transient headache is reported most of the time after its overdosage. Therefore, it is not advisable to exceed the prescribed dosage of CITIFAR unless recommended by a healthcare provider. In case of accidental overdose, a symptomatic therapy should be carried out.

Tablet: Citicoline is contraindicated in: Patients with hypersensitivity to either citicoline or piracetam or any other component of the formulation.
Patients with severe renal impairment (renal creatinine clearance of less than 20 ml per minute) and/or hepatic impairment.
Patients with cerebral haemorrhage.
Injection: CITIFAR is contraindicated in patients with any allergy or hypersensitivity to the drug or to any of its components. It is also contraindicated in persons with hypertonia of the parasympathetic nervous system.

Tablet: Large doses of Citicoline could aggravate increase in cerebral blood flow in episodes of persistent intracranial hemorrhage.
Use in Children: No data on use in children.
Injection: CITIFAR is generally safe. However, it is recommended that, it should be taken under the supervision of a health care provider. CITIFAR should be administered cautiously in patients with persistent intracranial hemorrhage or stroke as administration of larger doses could provoke an increase of the cerebral blood flow.
Do not exceed the recommended doses. Use cautiously in patients with renal and hepatic damage.
CITIFAR should be administered with caution in patients suffering from trimethylaminuria, Parkinson's disease and patients with depression in anamnesis.
Use only once and discard any remaining portion.
Not to administer the solution undiluted.

Tablet: There is not enough evidence on Citicoline's safety in pregnant and breastfeeding women. Citicoline should be used in pregnancy and lactation only when benefits justify the potential risks.
Injection: There is inadequate evidence of safe use of CITIFAR in human pregnancy. It should be used in pregnancy and lactation only if the potential benefits justify the potential risks.

Tablet: Gastrointestinal disorders (i.e., stomach pain, diarrhea).
Vascular side effects (i.e., hypotension, tachycardia, bradycardia).
Injection: CITIFAR may cause fleeting and discrete hypotensive effect, increased parasympathetic effects and low blood pressure. Other effects which may occur with citicoline therapy includes itching or hives, swelling in face or hands, chest tightness, tingling in mouth and throat.

Tablet: Levodopa: Citicoline may enhance the effects of levodopa. The exact mechanism is unknown, but animal models suggest that citicoline may increase dopamine levels in the brain and/or improve dopaminergic cell survival. In patients with Parkinson's disease, a few studies have demonstrated levodopa-saving effects, whereby the addition of citicoline (500 to 1200 mg/day) allowed for lower dosages of levodopa to be used with stable or improved therapeutic efficacy and reduced side effects in some patients. However, data are limited.
Coadministration with meclofenoxate: Citicoline must not be administered in conjunction with medication containing meclofenoxate (also known as Clophenoxate).
Injection: CITIFAR potentiates the effects of L-dopa and L-dihydroxy phenylalanine. It exhibits incompatibility and hence must not be administered in conjunction with medicaments containing meclofenoxate (also known as centrophenoxine).

Store at temperatures not exceeding 30°C.
Tablet: Shelf Life: 36 months.
Special Precautions for Storage: This medicinal product does not require any special storage conditions.

Nootropics & Neurotonics/Neurotrophics

N06BX06 - citicoline ; Belongs to the class of other psychostimulants and nootropics.

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