Pramipeksol Orion
Producer: Orion Pharma (Orion of Pharm) Finland
Code of automatic telephone exchange: N04BC
Release form: Firm dosage forms. Tablets.
General characteristics. Structure:
Active ingredient: - 0,125 mg of a pramipeksol of dihydrochloride of monohydrate, equivalent of 0,088 mg of a pramipeksol;
- 0,25 mg of a pramipeksol of dihydrochloride of monohydrate, equivalent of 0,18 mg of a pramipeksol;
- 0,5 mg of a pramipeksol of dihydrochloride of monohydrate, equivalent of 0,35 mg of a pramipeksol;
- 1,0 mg of a pramipeksol of dihydrochloride of monohydrate, equivalent of 0,7 mg of a pramipeksol;
- 1,5 mg of a pramipeksol of dihydrochloride of monohydrate, equivalent of 1,1 mg of a pramipeksol.
Excipients: mannitol (E 421), starch corn, hydroxypropyl cellulose, silicon dioxide colloid anhydrous, magnesium stearate.
The drug used for treatment of an idiopathic disease of Parkinson (as monotherapy or in a combination with a levodopa). And, also, for a symptomatic treatment of an idiopathic syndrome of uneasy legs.
Pharmacological properties:
Pharmacodynamics. Pramipeksol is a dopamine agonist with high selectivity and specificity of rather dopamine receptors of the D2 subtype among which it has preferential affinity with D3, and has total internal activity.
Pramipeksol facilitates parkinsonichesky motive disturbances by stimulation of dopamine receptors of Stratium. Researches on animals showed that прамипексол synthesis, release and exchange of a dopamine oppresses.
The mechanism of action of a pramipeksol at treatment of a syndrome of uneasy legs is unknown. Neuropharmacological data confirm participation of primary dopaminergic system.
In the researches conducted on healthy volunteers dozozavisimy decrease in level of prolactin was observed.
Pharmacokinetics. Pramipeksol is quickly and completely absorbed after oral administration. Absolute bioavailability makes more than 90%, the maximum concentration in plasma are reached between the 1st and 3rd hour. Speed of absorption decreases against the background of meal, but extent of absorption does not decrease. Pramipeksol shows linear kinetics and insignificant fluctuations of plasma levels at different patients.
At people linkng of a pramipeksol with proteins is very low (<20%), and volume raspredeleniyao big (400 l). In researches on rats observed high concentration of drug in brain tissue (about 8 times higher in comparison with plasma).
Pramipeksol is metabolized at people in a small amount. Removal by kidneys of not changed pramipeksol is the main way of elimination. About 90% of the 14C-marked dose are removed by kidneys whereas less than 2% are defined in Calais. The general clearance of a pramipeksol makes about 500 ml/min., and pochechnyyo about 400 ml/min. An elimination half-life (t 1/2) - of 8 o'clock at persons of young age till 12 o'clock at elderly people.
Indications to use:
Idiopathic disease of Parkinson (as monotherapy or in a combination with a levodopa). Symptomatic treatment of an idiopathic syndrome of uneasy legs
Route of administration and doses:
Parkinson's disease. A pill should be taken orally, to swallow, washing down with water, irrespective of meal. The daily dose is appointed in 3 receptions equal parts.
Initiation of treatment: doses should be increased gradually as it is provided in table 1, since an initial dose of 0,264 mg of the basis (0,375 mg of salt) in days each 5-7 days. On condition of absence at patients of intolerable by-effects the dose should be titrated before achievement of the maximum therapeutic effect.
Tablitsa1. Scheme of increase in a dose of drug Pramipeksol Orion
Week Dose General dose Dose General dose
(basis mg) (basis mg) (salt mg) (salt mg)
1 3 h0,088 0,264 3 h0,125 0,375
2 3 h0,18 0,54 3 h0,25 0,75
3 3 h0,35 1,1 3 h0,5 1,50
In need of further increase in a dose the daily dose should be increased by 0,54 mg of the basis (0,75 mg of salt) through week intervals to the maximum dose of 3,3 mg of the basis (4,5 mg of salt) in days.
However it should be noted that at doses higher than 1,1 mg of the basis (1,5 mg of salt) the frequency of cases of drowsiness increases. Maintenance therapy: the individual dose has to be within 0,264 mg of the basis (0,375 mg of salt) to the maximum dose of 3,3 mg of the basis (4,5 mg of salt) in days. During increase in a dose in three main researches efficiency was observed, since a daily dose of 1,1 mg of the basis (1,5 mg of salt). Further correction of a dose should be carried out depending on the clinical answer and emergence of undesirable effects. In clinical trials about 5% of patients treated doses lower than 1,1 mg (1,5 salts).
At the progressing Parkinson's disease of a dose a day patients to whom therapy reduction is planned by a levodopa can have effective higher than 1,1 mg (1,5 mg of salt). It is recommended to reduce a levodopa dose in
time of increase in a dose and carrying out a maintenance therapy by Pramipeksol Orion, depending on reaction of each certain patient.
Treatment termination: the sudden termination of dopaminergic therapy can lead to development of a malignant antipsychotic syndrome. Therefore the dose of a pramipeksol should be lowered gradually, by 0,54 mg of the basis (0,75 mg of salt) a day, before decrease in a daily dose to 0,54 mg of the basis (0,75 mg of salt). After that the dose should be reduced by 0,264 mg of a basis (0,375 mg of salt) a day.
Renal failure: removal of a pramipeksol depends on function of kidneys. To start therapy the following scheme is offered:
- more than 50 ml/min. are not required to patients with clearance of creatinine decrease in a daily dose;
- patients with clearance kreatinina20-50 ml/min. Pramipeksola Orion should apply an initial daily dose two separate receptions, since 0,088 mg of the basis (0,125 mg of salt) two times a day (0,176 mg of the basis of 0,25 mg of salt a day);
- patients with clearance of creatinine less than 20 ml/min. Pramipeksola Orion should accept a daily dose in one step, since 0,088 mg of the basis (0,125 mg of salt) a day.
At depression of function of kidneys during a maintenance therapy the daily dose Pramipeksola Orion is lowered by the same percent by which the clearance of creatinine decreased, that is if the clearance of creatinine decreased by 30%, then and a daily dose Pramipeksola Orion it is necessary to lower by 30%. The daily dose can be accepted in two steps if the clearance of creatinine is in limits of 20-50 ml/min., and at one time if the clearance of creatinine is lower than 20 ml/min.
Abnormal liver function: dose adjustment is not required to patients with an abnormal liver function as about 90% of the absorbed active ingredient are allocated with kidneys though potential influence of a liver failure on pharmacokinetics of a pramipeksol was not studied.
Syndrome of uneasy legs. A pill should be taken orally, to swallow, washing down with water, irrespective of meal.
The recommended initial dose Pramipeksola Orion makes 0,088 mg of the basis (0,125 mg of salt) in 2-3 hours prior to a dream once a day. Patients who need additional symptomatic simplification can increase a dose each 4-7 days to the maximum dose of 0,54 mg of the basis (0,75 mg of salt) in days (as it is provided in table 2).
Scheme of dosing Pramipeksola Orion
Titration stage Single sutoch.vecherny dose Single sutoch.vecherny dose
(basis mg) (salt mg)
1 0,088 0,125
2 * 0,18 0,25
3 * 0,35 0,50
4 * 0,54 0,75
* If necessary
As long-term efficiency of a pramipeksol at treatment of a syndrome of uneasy legs is studied insufficiently, in 3 months of treatment it is necessary to carry out assessment of the answer of the patient and to reconsider expediency of continuation of therapy. If treatment is interrupted more than for several days, it should be begun repeatedly with titration of a dose as it is stated above.
Treatment termination: as the daily dose for treatment of a syndrome of uneasy legs does not exceed 0,54 mg of the basis (0,75 mg of salt), use Pramipeksola Orion can be stopped without gradual dose decline. It is impossible to exclude effect of return (deterioration in symptoms after the sharp termination of treatment).
Dysfunction a pochek:vyvedeniye of a pramipeksol depends on function of kidneys. More than 20 ml/min. are not required to patients with clearance of creatinine decrease in a daily dose.
Use of a pramipeksol for the patients staying on a hemodialysis or for patients with a heavy renal failure was not studied.
Abnormal liver function: dose adjustment is not required to patients with an abnormal liver function as about 90% of the absorbed active ingredient are allocated with kidneys.
Children: Pramipeksol Orion is not recommended for use to children.
Features of use:
Influence on pregnancy and lactation at people was not investigated. Pramipeksol did not render teratogenic effect on animals, however rendered embriotoksichesky effect at rats at doses which were toxic for females. Pramipeksol Orion it is possible to apply during pregnancy only in that case when the expected advantage for mother exceeds potential risk for a fruit.
As treatment pramipeksoly inhibits secretion of prolactin at people, it is possible to expect decrease in a lactation. Excretion of a pramipeksol in maternal milk at people was not studied. At rats concentration of active ingredient was higher in milk, than in plasma.
In a type of lack of data on people Pramipeksol Orion it is not necessary to apply during feeding by a breast. However if its use cannot be avoided, feeding by a breast should be stopped.
Patients with Parkinson's disease who have a renal failure should appoint a reduced dose of drug Pramipeksol Orion. Hallucinations are the known side effect of treatment by dopamine agonists and a levodopa. Patients should be informed on possibility of hallucinations (preferential visual).
At treatment of the progressing Parkinson's disease a combination with a levodopa during initial titration Pramipeksola Orion can arise dyskinesia. When developing dyskinesia it is necessary to lower a levodopa dose.
Pramipeksol was associated with drowsiness and episodes of sudden backfilling, especially at patients with Parkinson's disease. There are infrequent messages on sudden backfilling during daily activity which in certain cases arose without understanding of it or without the warning signs. It is necessary to inform on it patients and to advise to be careful at control of motor transport and work with mechanisms during treatment by Pramipeksol Orion. Patients who felt drowsiness and/or had an episode of sudden backfilling should refrain from control of motor transport and work with mechanisms. Besides, it is necessary to consider expediency of a dose decline or the termination of treatment. Because of possible additive effects it is necessary to be careful at use by patients of other sedative medicines or alcohol in a combination with pramipeksoly.
It was reported about cases of a morbid attraction to gamblings, increases in a libido and hyper sexuality at patients, Parkinson's disease at whom treated dopamine agonists, including прамипексол. Besides, the patients and persons who are looking after patients should be informed on possibility of symptoms of disturbance of control of impulsive behavior and a morbid attraction, such as
overeating and morbid attraction to shopping. It is necessary to consider expediency of decrease in a dose / gradual drug withdrawal.
Patients with mental disorders should be treated dopamine agonists only in cases when the potential advantage justifies possible risk.
It is necessary to avoid simultaneous use of antipsychotic medicines with pramipeksoly.
Ophthalmologic observation is recommended to be made through regular periods or at emergence of vision disorders.
It is necessary to be careful in case of heavy cardiovascular pathology.
It is recommended to control arterial pressure, especially in an initiation of treatment, because of the general risk of postural hypotension which is associated with dopaminergic therapy.
The symptoms reminding a malignant antipsychotic syndrome were observed at sharp cancellation of dopaminergic therapy.
Messages in literature indicate that treatment of a syndrome of uneasy legs dopaminergic drugs can lead to augmentation. Augmentation is shown as more earlier emergence of symptoms in the evening (or even in the afternoon), strengthening of symptoms and distribution of symptoms on upper extremities. The controlled researches of use of a pramipeksol for patients with a syndrome of uneasy legs were insufficiently long to give an adequate assessment to the augmentation phenomenon. During the controlled clinical trials augmentation frequencies after more long use of a pramipeksol and the corresponding treatment of these phenomena did not carry out assessment.
Ability to influence speed of response at control of motor transport or work with other mechanisms. Pramipeksol Orion exerts considerable impact on ability to manage motor transport and to work with mechanisms.
Emergence of hallucinations or drowsiness is possible. Patients who are treated Pramipeksol Orion and at whom drowsiness and/or episodes of sudden backfilling is observed should be informed in need
to refrain from control of motor transport or types of activity at which disturbance of attention can lead to traumatizing itself either other people, or death (for example, work with mechanisms) until such recurrent episodes or drowsiness do not pass.
Side effects:
The undesirable phenomena which were most often observed at Parkinson's disease.
Infections and invasions. Pneumonia.
Mental disorders. Often: abnormal dreams, behavioural symptoms of disturbance of control of impulsive behavior and morbid attraction; confusion of consciousness, hallucination, sleeplessness, concern. Infrequently: a morbid attraction to shopping, a mania, hyper sexuality, disturbance a libido, paranoia, a morbid attraction to gamblings. Frequency neizvestna:pereedaniye, hyperphagia.
From a nervous system. Very much chasto:golovokruzheniye, dyskinesia, drowsiness. Chasto:amneziya, headache. Infrequently: hyperkinesia, episodes of sudden backfilling, syncope.
From an organ of sight. Often: vision disorders, including a zatumanennost of sight and decrease in visual acuity.
From cardiovascular system. Very chasto:arterialny hypotension.
From digestive tract. Very much chasto:toshnota. Chasto:zapor, vomiting.
From skin and hypodermic cellulose. Nechasto:povyshenny sensitivity, itch, rash. The general disturbances and reactions in an injection site. Chasto:utomlyaemost, peripheral hypostasis.
Results of researches. Often: decrease in body weight. Infrequently: increase in body weight.
The undesirable phenomena which were most often observed at a syndrome of uneasy legs.
Mental disorders. Chasto:anomalny dreams, sleeplessness. Infrequently: confusion of consciousness, hallucination, disturbance libido, concern. Frequency is unknown: behavioural symptoms of disturbance of control of impulsive behavior and a morbid attraction, such as overeating, morbid attraction to shopping, hyper sexuality and a morbid attraction to gamblings; mania, hyperphagia, paranoia.
From a nervous system. Often: dizziness, headache, drowsiness. Infrequently: episodes of sudden backfilling, syncope. Frequency neizvestna:amneziya, dyskinesia, hyperkinesia.
From an organ of sight. Often: vision disorders, including a zatumanennost of sight and decrease in visual acuity.
From cardiovascular system. Very chasto:arterialny hypotension.
From digestive tract. Very often: nausea. Chasto:zapor, vomiting.
From skin and hypodermic cellulose. Nechasto:povyshenny sensitivity, itch, rash. The general disturbances and reactions in an injection site. Chasto:utomlyaemost. Infrequently: peripheral hypostasis.
Results of researches. Infrequently: decrease in body weight, increase in body weight.
Interaction with other medicines:
Pramipeksol at people contacts proteins of plasma in very insignificant degree (<20%) and possesses low biotransformation. Therefore interactions with other medicines influencing linkng with proteins of plasma or elimination by biotransformation are improbable. As anticholinergics are removed preferential by biotransformation, an opportunity for interaction with them is limited though interaction with anticholinergics was not investigated. Pharmacokinetic interaction with selegiliny and a levodopa was not observed.
Cimetidinum reduced renal clearance of a pramipeksol approximately by 34%, it is probable at the expense of inhibition of cationic secretory transport system of renal tubules.
Medicines which are inhibitors of this active renal way of removal or which are removed this way such as Cimetidinum and амантадин, can interact with pramipeksoly that leads to decrease in clearance of one or both drugs. At combined use of these medicines with Pramipeksol Orion it is necessary to consider a tselosoobraznost of a dose decline of a pramipeksol.
At use Pramipeksola Orion with a levodopa is recommended to reduce a levodopa dose, and doses of other protivoparkinsonichesky means to leave not changed against the background of increase in a dose of drug Pramipeksol Orion.
Because of possible additive effects it is necessary to be careful at use of other sedatives or alcohol in a combination with pramipeksoly.
It is necessary to avoid combined use of antipsychotic medicines with pramipeksoly, for example, when antagonistic effects are possible.
Contraindications:
Hypersensitivity to active ingredient or to any of drug excipients.
Overdose:
Symptoms. Ċ Clinical experience of considerable overdose is absent. The expected side effects are connected with a pharmakodinamichesky profile of a dopamine agonist and include nausea, vomiting, a hyperkinesia, hallucinations, excitement and arterial hypotension.
Treatment. The antidote at overdose by a dopamine agonist is not established. In case of signs of excitement of the central nervous system neuroleptics can be appointed. Treatment of overdose can demand the general supporting measures, including a gastric lavage, intravenous injections of liquid, use of absorbent carbon and control of the electrocardiogram.
Storage conditions:
To store at a temperature not above 25 °C in the place, unavailable to children.
Issue conditions:
According to the recipe
Packaging:
On 10 tablets in the blister, on 3 blisters in a cardboard box.
