AGICETAM®800

Composition: Each film-coated tablet contains:<br/>
Piracetam. . . . . . . . . . . . . . . . . . . . . . 800 mg<br/>
Presentation:<br/>
Box of 10 blisters x 10 film-coated tablets.<br/>
Indications:<br/>

For the symptomatic treatment of vertigo.<br/>

Treatment of memory impairment, dizziness, poor concentration or lack of alertness, mood changes, behavioral disorders, personal negligence, dementia produced by multiple infarcts in elderly patients.<br/>

Treatment of acute ischaemic stroke. It is noted that age and initial severity of stroke are the most important factors to predict the potential survival after acute ischaemic stroke.<br/>

Treatment of alcoholism.<br/>

Treatment of sickle-cell anemia.<br/>

Piracetam is used as an adjunct in the treatment of myoclonus of cortical origin.

Category:

Additional information

Dosage and administration:

Follow the doctor’s instructions:
– Usual dose is 30 – 160 mg per kg of body weight daily in 2, 3 or 4 divided doses.
– Long term therapy for psycho-organic syndromes in the elderly: 1.2 to 2.4 g /daily, depending on the individuals. The doses can be as high as 4.8 g/day during the initial weeks of treatment.
– Treatment of alcoholism: 12g daily during the initial withdrawal period. Subsequent maintenance therapy is an oral daily dose of 2.4g.
– Cognitive impairment after traumatic brain injury (with or without vertigo): Initial dose is 9 – 12 g daily. Maintenance dose is 2.4 g for at least 3 weeks.
– Treatment of sickle-cell anemia: 160 mg per kg of body weight daily in 4 divided doses.
– Treatment of myoclonus: 7.2 g per day in two or three divided doses. Depending on response increase the dose by 4.8 g per day every 3-4 days, to a maximum at 20 g daily. After optimal dose of piracetam is obtained, the dosage of other such medicinal products should be reduced.
Dose adjustment is required in patients with renal impairment:
Creatinine clearance is 50 to 79 ml/min: 2/3 usually daily dose, divided in 2 or 3 doses.
Creatinine clearance is 30 to 49 ml/min: 1/3 usually daily dose, divided in 2 doses.
Creatinine clearance is 20 to 29 ml/min: 1/6 usually daily dose, divided in a single dose.
Administration:
Caplets should be swallowed whole with a glass of water, regardless of meals.

Contraindications:

Patients with hypersensitivity to piracetam or any of excipient of this drug.
– Patients with severe renal failure (Creatinine clearance is below 20 ml/minute).
– Patients with Huntington's disease.
– Patients with hepatic impairment.
– Patients with cerebral hemorrhage.
– Pregnant women and breastfeeding mothers.

Warnings and precautions for use:

Piracetam is excreted by the kidney, so the increase in half-life is directly related to the decrease in renal function and creatinine clearance. Special care must be taken when treating patients known to suffer from renal insufficiency. Monitoring of renal function is recommended in such cases and in elderly patients. (Dosage adjustment is based on creatinine clearance)
Avoid abrupt discontinuation in patients with myoclonus due to the risk of seizures.
Caution should be used in patients with gastric ulcers, a history of hemorrhagic stroke, using concomitantly anticoagulants due to risk of bleeding.
Caution should be taken in major surgery due to potential coagulation disorder.

Recommendation for pregnant women and breastfeeding mothers:

Piracetam should not be administered to pregnant women and breastfeeding mothers.

Effects on ability to drive and use machines:

Piracetam almost does not affect the ability to drive and operate machinery. However, the risk of dizziness has been also reported, therefore depending on specific case the doctor may recommend the patients whether to drive or use machinery or not.

Interactions, incompatibilities of medicine:

– Conventional treatment may still be applied to treat alcoholism (vitamins and sedatives) in case of patients suffering from vitamin deficiency or strong agitation.
– Concomitant use with thyroid extract: In a single case, confusion, irritability and sleep disorders were reported in concomitant use with thyroid extract.
– Prothrombin time increased in a patient whose condition had previously been stabilized with warfarin when piracetam was concurrently used.

Undesirable effects (ADR):

Common, ADR > 1/100
Body as a whole: Fatigue.
Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain, abdominal distention.
Nervous system: Nervousness, agitation, headache, insomnia, somnolence.
Uncommon, 1/1000 <ADR <1/100
Body as a whole: Vertigo, weight gain, asthenia.
Nervous system: Trembling, sexual stimulation, stress, increased advocacy, depression.
Hematologic: Coagulation disorders or severe bleeding.
Skin: Dermatitis, pruritis, urticaria.
Guidelines for ADR management
Adverse reactions can be mitigated by reducing the dosage.

Overdose and treatment:

Piracetam is non-toxic even in high doses. Special measures are not required in case of accidental overdose.

Pharmacodynamics:

Piracetam (a cyclic derivative of gamma-aminobutyric acid (GABA) acts directly on the brain to improve the efficacy of the telencephalon (this area of the brain is involved in cognition and also has a role to play in learning and memory, in alertness and in consciousness). Piracetam acts on a number of neurotransmitters such as acetylcholine, noradrenaline, dopamine etc. This may explain the positive effects of piracetam on learning and improving the ability to perform memory test. It can alter neurotransmission within the brain, and can help to improve the metabolic environment essential for good neuronal function.
In experimental studies, piracetam has a protective effect against metabolic disorders induced by ischemia due to the increase of cerebral resistance to hypoxic conditions. Piracetam increases the mobilization and utilization of glucose whereas it does not depend on the oxygen supply. This facilitates the pentose pathway and sustains brain energy synthesis. Piracetam enhances recovery rate after hypoxic brain injury by increasing the turnover of inorganic phosphate and decreasing glucose and lactic acid accumulation. In normal conditions as well as hypoxia, it is found that Piracetam increases the amount of ATP in the brain by increasing the conversion of ADP to ATP, this could be a mechanism to explain some of the beneficial effects of the drug. The impact on the acetylcholine transmission may also contribute to the mechanism of piracetam activity. Piracetam also has the effect on the dopamine release and this may have a positive effect on the memory formation. Piracetam has no hypnotic, sedative, analgesic effect, recovery or tranquilizing action as well as no effect of GABA.
Piracetam reduces platelet aggregation and in the conditions where there is abnormal rigidity of the red blood cell it can restore the potential of red blood cell membranes flexibility and passing through capillaries. Piracetam has effect on cortical myoclonus.

Pharmacokinetics:

Piracetam is rapidly and almost completely absorbed from the gastrointestinal tract. Bioavailability is approximately 100%. Peak plasma levels (40 – 60 micrograms/ml) are reached within 30 minutes after oral dose of 2 g. Peak cerebrospinal fluid concentrations are achieved 2-8 hours after oral administration. Long term use of piracetam does not change the absorption. The volume of distribution is approximately 0.6 L/kg.
Piracetam permeates all tissues, crosses the blood-brain and placental barrier and diffuses across membranes used in renal dialysis. Piracetam accumulates highly in the cerebral cortex, predominantly in the frontal, parietal and occipital lobes, the cerebellum and basal ganglia. Plasma half-life is 4-5 hours, half-life in the CSF is about 6-8 hours.
Piracetam does not bind to plasma proteins and is eliminated unchanged principally via the kidney. Renal clearance rate of piracetam in normal people is 86 ml/min. 30 hours after oral administration, over 95% of the drug is excreted in the urine. In case of renal failure, elimination half-life is increased: In patients with completely impaired and unrecovered kidney function, this time is 48-50 hours.

Storage conditions, shelf-life, quality specification of the medicine:

Storage conditions: Store the medicine below 30 degree C. Protect from humidity and light.
Shelf-life: 36 months from the manufacture date.
Quality specification: In house.