Head trauma of varying severity; Cerebrovascular diseases such as stroke; Cognitive disorders of diverse etiology; Parkinson's disease.

Tablet: Usual Dose: 500 mg once or twice daily.
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.

May be taken with or without food.

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.

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.

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.

Citicoline seems to be safe when taken short-term (up to 90 days). The safety of long-term use is not known. Most people who take citicoline don't experience problematic side effects. But some people can have side effects such as trouble sleeping (insomnia), headache, diarrhea, low or high blood pressure, nausea, blurred vision, chest pains, and others.
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.

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. Protect from light.

Pharmacology: Pharmacodynamics: Mechanisms of Action: 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.
Phospholipid Precursor: Evidence of citicoline's role as a phosphatidylcholine precursor has been found in animal studies.
The brain uses choline preferentially for acetylcholine synthesis, which can limit the amount of choline available for phosphatidylcholine production.
When the demand for acetylcholine increases or choline stores in the brain are low, phospholipids in the neuronal membrane can be catabolized to supply the needed choline.
Exogenous citicoline thus helps preserve the structural and functional integrity of the neuronal membrane.
In an in vitro study, citicoline at high concentrations stimulated brain acetylcholinesterase (AChE) along with Na+K+-ATPase.
The postulated mechanism involves bioconversion of citicoline to phosphatidylcholine.
Neuronal Membrane Repair: Citicoline has been investigated as a therapy for stroke patients. Three mechanisms are postulated: repair of neuronal membranes via increased synthesis of phosphatidylcholine; repair of damaged cholinergic neurons via potentiation of acetylcholine production; and reduction of free fatty acid buildup at the site of stroke-induced nerve damage.
In addition to phosphatidylcholine, citicoline serves as an intermediate in the synthesis of sphingomyelin, another neuronal membrane phospholipid component. Citicoline has shown the potential to restore post-ischemic sphingomyelin levels.
Citicoline also restores levels of cardiolipin, a phospholipid component of the inner mitochondrial membrane. The mechanism for this is unknown, but data suggest citicoline inhibits enzymatic hydrolysis of cardiolipin by phospholipase A2.
In an animal study, citicoline decreased the formation of hydroxl radicals following ischemia and perfusion, again suggesting citicoline acts to decrease phospholipase stimulation.
Effect on beta-Amyloid: Evidence has surfaced that citicoline counteracts the deposition of beta-amyloid, a neurotoxic protein believed to play a central role in the pathophysiology of Alzheimer's disease (AD). The characteristic lesion in AD is the formation of plaques and neurofibrillary tangles in the hippocampus. The degree of cognitive dysfunction and neurodegeneration in AD is proportional to the build-up of beta-amyloid.
Citicoline counteracted neuronal degeneration in the rat hippocampus induced by intrahippocampal injection of beta-amyloid protein. The number of apoptotic cells was also reduced. Memory retention as measured by a passive-avoidance learning task improved in the rats.
Effect on Neurotransmitters: Evidence of citicoline's ability to enhance norepinephrine release in humans was found in a study showing citicoline raised urinary levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), a norepinephrine metabolite.
Citicoline increased brain levels of neurotransmitters in rats at a dose of 100 mg/kg, administered daily for seven days. Norepinephrine increased in the cerebral cortex and hypothalamus, dopamine increased in the corpus striatum, and serotonin increased in the cerebral cortex, striatum, and hypothalamus. Rat studies have found evidence that citicoline potentiates dopamine release in the brain, presumably by stimulating release of acetylcholine.
Pharmacokinetics: Film-coated tablet: Citicoline is a water-soluble compound with greater than 90-percent bioavailability. Pharmacokinetic studies on healthy adults show oral doses of citicoline are rapidly absorbed, with less than one percent excreted in 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 resynthesis into citicoline in the brain.
Pharmacokinetic studies using citicoline show citicoline elimination occurs in two phases mirroring the biphasic plasma peaks, mainly via respiratory and urinary excretion. 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 5-6 hours for respiratory CO₂ and 71 hours for urinary excretion.
Solution for 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%).

Nootropics & Neurotonics/Neurotrophics