Therapeutic indications
For treatment of cortical myoclonus together with other myoclonal medicines.
Posology and method of administration
Doses are adjusted individually.
Areasonable protocol would be to introduce piracetam at a dose of 7.2g/day, increasing by 4.8 g/day every 3 to 4 days up to a maximum of 24g/day, given in either 2 or 3 divided doses while keeping otherantimyoclonic drugs unchanged at their optimal dosage. If possible,depending on clinical benefit, an attempt should be made tosubsequently reduce the dosage of other antimyoclonic drugs.
Therapywith piracetam should last until initial cerebral pathology disappears.It is advised to try to reduce dose or stop administration every 6months. In order to prevent recurrence of initial symptoms, dose shouldbe reduced by 1.2 g every second day.
Capsules should be administered with large amount of water (1/2 – 1 glass), advisably together with meal or after meal.
It should be taken into account that administration of piracetam should not be discontinued abruptly.
Dose adjustment for elderly patients
Dosesshould be adjusted for elderly patients with reduced renal functions.In long term therapy of elderly patients, creatinine clearance shouldbe checked regularly, to adjust doses if necessary.
Dose adjustment for patients with reduced renal functions
Doses should be adjusted individually according to creatinine clearance (see table below).
| Group | Creatinine clearance
(ml/min)
| Posology and frequency
|
Normal
Mild
Moderate
Severe
Terminal phase of renal disease
| > 80
50-79
30-49
< 30
| usual daily dose, 2 to 4 sub-doses
2/3 usual daily dose, 2 or 3 sub-doses
1/3 usual daily dose, 2 sub-doses
1/6 usual daily dose, 1 single intake
Contraindicated
|
Dose adjustment for patients with reduced liver functions
Ifpatient has only reduced liver function, doses may not be adjusted. Ifpatient has both liver and kidney impairments, doses should be adjusted(see Dose adjustment for patients with reduced renal functions).
Contraindications
Hypersensitivity to piracetam or other pyrolidone derivatives, or any excipients of this medicine.
Liverinsufficiency, severe renal insufficiency (creatinine clearance lowerthan 20 ml/min) or renal disease in terminal phase, cerebralhemorrhage, children under
16 years.
Special warnings and precautions for use
Dueto the effect of piracetam on platelet aggregation (see section 5.1Pharmacodynamic properties), caution is recommended in patients withunderlying disorders of haemostasis, major surgery or severehaemorrhage.
As piracetam is almost exclusively excreted via kidneyscaution should be exercised in treating patients with known renalimpairment. In renally impaired and elderly patients an increase interminal half-life is directly related to renal function as measured bycreatinine clearance. Dosage adjustment is therefore required in thosewith mild to moderate renal impairment and elderly patients withdiminished renal function.
Abrupt discontinuation of treatmentshould be avoided as this may induce myoclonic or generalised seizuresin some myoclonic patients.
In case of hepatic diseases liver functions should be monitored.
Insome patients with increased excitability of neurons, piracetam canlower threshold of spasms. Patients who take anticonvulsants shouldcontinue use of them during piracetam therapy.
Interaction with other medicines and other forms of interaction
Itis predicted that potential of interaction that causes changes inpiracetam pharmacokinetics will be low, because approximately 90% ofpiracetam is excreted with urine as an unchanged drug.
Piracetam interacts with medicines that stimulate CNS and with neuroleptics (increased hyperkinesia).
In a single case, confusion, irritability and sleep disorders were reported in concomitant use with thyroid extract (T3 + T4).
Concomitantuse with warfarin elongates prothrombin time. Concomitant use withacenocumarol resulted in reduced platelet aggregation and β-thromboglobine release, reduced levels of fibrinogen and vonWillebrand's factors (VIII : C; VIII : vW : Ag; VIII: vW : RCo) andwhole blood and plasma viscosity.
No interaction has been foundwith the following anti-eptileptic medications: clonazepam,carbamazepine, phenytoin, phenobarbitone, valproate.
Alcohol did notinfluence serum level of piracetam; alcohol level remained unchanged,if it was used together with piracetam (1.6 g perorally).
Pregnancy and lactation
Inanimal studies piracetam was not teratogenic and had no effect onfertility at the maximal tested dose of 2.7 /g/kg/day for the rabbitsand 4.8 g/kg/day for rats and mice.
Piracetam readily crosses theplacental barrier. Since the safety of use in human pregnancy is notestablished, piracetam is to be avoided during pregnancy; usage isadmissible only in case of absolute indication. If it is necessary,women of childbearing potential using the product should use adequatecontraceptive.
Piracetam is excreted in human breast milk.Therefore, piracetam should be avoided during breast-feeding orbreast-feeding should be discontinued, while receiving treatment withpiracetam.
Effects on ability to drive and use machines
Itshould be taken into consideration that side effects (hyperkinesia,somnolence, nervousness, depression) caused by piracetam can influenceability to drive and use machines.
Undesirable effects
Following side effects were observed in clinical trials.
| Organ class
| Common (>1/100, < 1/10)
| Uncommon (>1/1 000,
< 1/100)
|
Central and peripheral nervous system disorders
| Hyperkynesia
|
|
Metabolic disorders
| Weight increase
|
|
Psychiatric disorders
| Nervousness
| Somnolence, depression
|
Body as a whole – general disorders
|
| Asthenia
|
From the post-marketing experience, the following undesirable effects have been reported:
- Ear and labyrinth disorders:
vertigo
- Gastrointestinal disorders:
abdominal pain, abdominal pain upper, diarrhoea, nausea, vomiting
- Immune system disorders:
anaphylactoid reaction, hypersensitivity
- Nervous system disorders:
ataxia, balance impaired, epilepsy aggravated, headache, insomnia, somnolence
- Psychiatric disorders:
agitation, anxiety, confusion, hallucination.
- Skin and subcutaneous tissue disorders:
angioneurotic oedema, dermatitis, pruritus, urticaria, rash.
Veryrare in elderly patients heart failure may be aggravated. In such acase dose of medicine should be lowered or administration discontinued.
Overdose
The patient's generalcondition should be monitored. Close attention should be given tokeeping the patient well hydrated and monitoring the urine flow.
Doses up to 400 mg/kg/day are well tolerated.
