Pramipexol - instructions for use, dose, side effects, contraindications

Active substance: pramipexole dihydrochloride monohydrate 0.25 mg
Excipients: magnesium stearate - 1 mg, ludipress® (lactose monohydrate - 184.83 mg, povidone K-30 - 6.96 mg, crospovidone - 6.96 mg) - 198.75 mg.

Tablets 1 mg:

Active substance: pramipexole dihydrochloride monohydrate - 1 mg
Excipients: magnesium stearate - 1 mg, ludipress® (lactose monohydrate - 184.14 mg, povidone K-30 - 6.93 mg, crospovidone - 6.93 mg) - 198 mg

Description:

Tablets 0.25 mg: round flat-cylindrical tablets white or almost white with a bevel. On one side of the risk and engraving "P1".

Tablets 1 mg: round flat-cylindrical tablets white or almost white with a bevel. On one side of the risk and engraving "P2".

Pharmacotherapeutic group:An antiparkinsonian remedy. Dopamine receptor agonist.

ATX: & nbsp

N.04.B.C.05 Pramipexole

Pharmacodynamics:

Pramipexole is a dopamine agonist, with high selectivity and specificity binds to the subfamily of dopamine receptors D₂; has a preferential affinity for the receptors D₃. Pramipexole softens the motor function disorders inherent in Parkinson's disease by stimulating dopamine receptors in the striatum. The exact mechanism of action is not known. Studies in animals have shown that pramipexole suppresses the synthesis, release and circulation of dopamine. Pramipexole reduces the severity of symptoms of idiopathic Parkinson's disease. Pramipexole in vitro protects dopamine neurons from degeneration arising in response to ischemia or methamphetamine neurotoxicity.

Pharmacokinetics:

Pramipexole is rapidly and completely absorbed after oral administration. Absolute bioavailability exceeds 90%. FROM_max in blood plasma is achieved in the interval of 1-3 hours. The rate of absorption decreases with food intake, however, the total amount of intake does not affect the intake of food. Pramipexole is characterized by linear kinetics and, regardless of the dosage form, relatively small fluctuations in plasma levels in different patients. The binding of pramipexole with plasma proteins is very low (<20 %), and the volume of distribution is large (400 liters). Pramipexole is metabolized in humans only in a small amount. Renal excretion of unchanged pramipexole is the most important way of elimination. About 90% ¹⁴The C-labeled dose is excreted by the kidneys, whereas less than 2% is detected in the stool. Total clearance of pramipexole is approximately 500 ml / min, the renal clearance is about 400 ml / min. T1 varies from 8 h in young people, up to 12 h in the elderly.

Indications:

Symptomatic treatment of idiopathic Parkinson's disease in adults as monotherapy (without levodopa) or in combination with levodopa at a late stage of the disease, when the effect of levodopa decreases or becomes unstable and there is a fluctuation in the therapeutic effect (on-off phenomenon).

Contraindications:

Hypersensitivity to pramipexole or to one of the components of the drug.
Children under 18 years of age (efficacy and safety not established).
Breastfeeding period.

Carefully:

Renal failure, hepatic insufficiency, cardiovascular diseases, arterial hypotension, simultaneous administration of dopamine receptor agonists, sedatives, cimetidine, amantadine, ethanol.
If you have one of the listed diseases (conditions), before taking the drug always consult a doctor.

Pregnancy and lactation:

The effect on pregnancy and lactation in humans has not been investigated.

In pregnancy, the drug Pramipexole should be prescribed only if the potential benefit to the mother exceeds the potential risk to the fetus.
Excretion of the drug with breast milk has not been studied. Because the pramipexole inhibits the secretion of prolactin, we can assume that it also suppresses lactation. Therefore, the drug should not be taken during breastfeeding.

In experimental animal studies, the possible effects of pramipexole on reproductive function have been studied. Pramipexole does not show teratogenicity in rats and rabbits, but at doses toxic to pregnant females, it was embryotoxic in rats.

Dosing and Administration:

The drug should be taken orally, regardless of food intake, with water. The daily dose should be evenly divided into 3 divided doses.
Calculation of doses is done by pramipexole dihydrochloride monohydrate.

Treatment of Parkinson's Disease
Initial therapy:
At initial therapy, the initial daily dose of 0.375 mg should be increased every 5-7 days. To reduce unwanted reactions, the dose should be selected gradually until the maximum therapeutic effect is achieved.

Table 1. Scheme of increasing the dose of Pramipexol

A week	Dose	Daily dose
1	by 0,125 mg 3 times / day	0.375 mg
2	0.25 mg 3 times / day	0.75 mg
3	0.5 mg 3 times daily	1.5 mg

If it is necessary to further increase the daily dose, add 0.75 mg per week to a maximum daily dose of 4.5 mg.

Supportive therapy:
With maintenance therapy, the individual maintenance daily dose ranges from 0.375 mg to 4.5 mg. Both at the early and late stages of the disease, the drug was effective starting at a daily dose of 1.5 mg. It is not excluded that in some patients doses above 1.5 mg / day can provide an additional therapeutic effect, especially at a late stage of the disease, when a reduction in the dose of levodopa is indicated.

Discontinuation of therapy:
Pramipexole should be withdrawn gradually over several days at 0.75 mg per day until complete withdrawal.

Patients receiving concurrent therapy with levodopa
With simultaneous therapy with levodopa is recommended as the dose increases, as well as during maintenance therapy with the drug Pramipexole reduce the dose of levodopa. This is necessary to avoid excessive dopaminergic stimulation.

Patients with renal insufficiency
In renal failure for initial therapy in patients with creatinine clearance (CK) of more than 50 ml / min, a daily dose or frequency of administration is not required. In patients with SC from 20 to 50 ml / min the initial daily dose of the drug should be divided into 2 doses and begin with a dose of 0.125 mg 2 times / day (daily dose - 0.25 mg); do not exceed the maximum daily dose of 2.25 mg. Patients with SC less than 20 ml / min show a single intake of the entire daily dose, starting at a dose of 0.125 mg / day; do not exceed the maximum daily dose of 1.5 mg.

If the function of the kidneys is reduced against the background of maintenance therapy, the daily dose of the drug is reduced by the same percentage, for which the QC decreases, i.е. If the QC was reduced by 30%, then the daily dose should also be reduced by 30%. The daily dose should be divided into 2 doses, if the CK value is 20-50 ml / min. The drug should be taken 1 time / day, if the QC is less than 20 ml / min.

Patients with hepatic insufficiency
In patients with hepatic insufficiency, there is no need to reduce the dose of the drug.

Side effects:

The following undesirable reactions are given in accordance with the following gradations of their frequency: very often (≥1/10), often (>1/100 - <1/10), infrequently (≥1/1000 - <1/100), rarely (≥1/10000 - <1/1000), very rarely (<1/10 000), including hotel messages.
In patients with Parkinson's disease with pramipexole compared with placebo, frequent adverse reactions (≥5%) were nausea, dyskinesia, arterial hypotension, dizziness, drowsiness, insomnia, constipation, hallucinations, headache and fatigue. The incidence of drowsiness increased with doses above 1.5 mg / day. The most common adverse reaction when taken in combination with levodopa was dyskinesia. Arterial hypotension can occur at the beginning of treatment, especially if pramipexole titrated too quickly.

System of organs	Frequency	Unwanted reaction
From the nervous system	Often	dizziness, dyskinesia, drowsiness
	often	headache
	infrequently	amnesia, hyperkinesia, sudden drowsiness, fainting.
From the heart	often	arterial hypotension
From the heart	infrequently	heart failure¹
From the gastrointestinal tract	Often	nausea
From the gastrointestinal tract	often	constipation, vomiting
From the side of the psyche	often	sleep disorders, symptoms of control disorder over motivation and compulsive behavior, confusion, hallucinations, insomnia
From the side of the psyche	infrequently	binge eating¹, a pathological attraction to shopping, mania, hyperphagia¹, hypersexuality, libido disorders (increase or decrease), paranoia, pathological attraction to gambling, anxiety
On the part of the respiratory system, the organs of the thorax and the mediastinum	infrequently	shortness of breath, hiccough
From the side of the organ of vision	often	visual impairment, including diplopia, blurred vision and visual acuity
From the skin and subcutaneous tissues	infrequently	hypersensitivity, itching, rash
Infectious and parasitic diseases	infrequently	pneumonia
General disorders and disorders at the site of administration	often	fatigability, peripheral edema
Violations revealed in special studies	often	weight loss, including decreased appetite
Violations revealed in special studies	infrequently	weight gain

¹An undesirable reaction was observed in the postmarketing period. In 95% of cases, the frequency is not higher than ≥1 / 1000- <1/100, but may be lower.The exact frequency can not be established, since no adverse reaction was detected during clinical trials among 2,762 patients with Parkinson's disease who were taking pramipexole.

Drowsiness. The use of pramipexole is often associated with drowsiness and infrequent - with excessive drowsiness during the day and cases of sudden onset of sleep (see Special instructions).

Motivation control disorders and compulsive behavior
During a cross-sectional retrospective screening and a case-control study in which 3090 patients with Parkinson's disease participated, 13.6% of patients who received dopaminergic or nedophaminergic therapy had symptoms of a control disorder over the last 6 months. Manifestations that were observed included a pathological attraction to gambling, an irresistible attraction to shopping, an excessive need for food, and compulsive sexual behavior (hypersexuality). Possible independent risk factors for disorders of control over motivation included dopaminergic therapy and higher doses for dopaminergic therapy, a younger age (≤65 years of age), non-continuation in marriage and the presence in the family of cases of pathological attraction to gambling, reported by the patient.

Heart failure. During clinical trials and the postmarketing period, heart failure was noted in patients who received pramipexole. During the pharmacoepidemiological study, the use of pramipexole was associated with an increased risk of heart failure compared to its lack of use (risk ratio 1.86, 95 % C1, 1.21-2.85).

If any of the unwanted reactions listed in the manual is aggravated, or if you notice any other undesirable reactions not listed in the instructions, inform the doctor about it.

Overdose:

Cases of severe overdose are not described. Presumptive symptoms inherent in the pharmacodynamic profile of dopamine receptor agonists: nausea, vomiting, hyperkinesia, hallucinations, excitation and lowering of blood pressure.

Treatment: gastric lavage, symptomatic therapy, ECG monitoring, dynamic observation. There is no specific antidote. In the presence of signs of CNS excitation, the appointment of neuroleptics is possible.The effectiveness of hemodialysis is not established.

Interaction:

Binding to blood plasma proteins. The ability of pramipexole to bind to plasma proteins is very low (<20%) and pramipexole has low biotransformation. Therefore, interaction with other drugs that affect the binding of the drug to blood proteins, or its removal by biotransformation, is unlikely. Since anticholinergic drugs are excreted from the body mainly by biotransformation in the liver, potential interaction is unlikely. Interaction with anticholinergic drugs was not investigated. There is no pharmacokinetic interaction with selegiline or levodopa.

Inhibitors / competitors of an active way of allocation of a preparation by kidneys. Cimetidine reduces the renal clearance of pramipexole by approximately 34%, probably by inhibiting the cationic secretory transport system of the renal tubules. Therefore, drugs that are inhibitors of this metabolic pathway of active release of the drug by the kidneys, or derived in this way, such as cimetidine, amantadine, mexiletine, zidovudine, cisplatin, quinine and procainamide, can interact with pramipexole, which can lead to a decrease in clearance of pramipexole. The possibility of reducing the dose of pramipexole should be considered when these drugs are taken simultaneously with the drug Pramipexole.

Combination with levodopa. If the drug Pramipexole is taken simultaneously with levodopa, it is recommended to reduce the dose of levodopa, and the doses of other drugs used in Parkinson's disease should be kept constant with an increase in the dose of the drug Pramipexole.

Because of the possible additive effects, patients should be advised to use caution when taking other sedative medications or alcohol in combination with the drug Pramipexole.

Antipsychotic medicines. Simultaneous administration of antipsychotic drugs and pramipexole should be avoided (see Special instructions), possibly antagonistic action.

In the event that you take other medicines, before taking the drug always consult a doctor.

Special instructions:

When the drug is prescribed Pramipexole patients with Parkinson's disease and renal failure are recommended a reduced dose.

Hallucinations and confusion are known unwanted reactions when treated with dopamine receptor agonists and levodopa. When using the drug Pramipexole in combination with levodopa in later stages of the disease hallucinations were observed more often than with monotherapy with pramipexole in patients at an early stage of the disease. Patients should be informed of the possibility of hallucinations (mainly visual), which can affect the ability to drive a car.

With progressive Parkinson's disease, dyskinesia may occur during the initial titration of the drug Pramipexole in combination with levodopa treatment. If this happens, the dose of levodopa should be reduced.

Patients and people who care about them should be aware that, in connection with the treatment of patients with dopaminergic drugs, there may be signs of manic behavior (symptoms impulsive and compulsive actions), such as a tendency to overeating (hyperphagia), obsessive desire to shop (pathological shopping), hypersexuality and pathological craving for gambling.In such cases, a decision should be made to reduce the dose / gradually stop treatment.

Patients and those who care about them should be aware that patients who take pramipexole there can be a mania and must constantly monitor its development. In such cases, the question of reducing the dose of the drug or its withdrawal should be decided.

In patients with mental disorders, the administration of dopamine receptor agonists in combination with pramipexole is only possible after a preliminary assessment of the relationship between the possible risk and the expected benefit of therapy. It is necessary to avoid simultaneous administration of pramipexole with antipsychotic drugs.

It is recommended to monitor the eyesight at regular intervals or immediately after the administration of the drug in the presence of such disorders.

Care should be taken when a patient has a serious cardiovascular disease. In connection with the risk of orthostatic hypotension during therapy with dopaminergic drugs, it is recommended to monitor blood pressure, especially at the beginning of treatment. Patients should be warned about a possible sedative effect of the drug.It was reported that cases of drowsiness and sudden falling asleep during daily activities (including when driving a car or managing complex mechanisms) may occur at any time during the treatment period, and patients should be informed about it.

When using pramipexole in a single case, rhabdomyolysis was observed, the symptoms of which disappeared after the drug was withdrawn.

In the treatment of Parkinson's disease, with a sharp cessation of therapy, there was a symptom complex resembling a malignant neuroleptic syndrome.

Effect on the ability to drive transp. cf. and fur:

Pramipexole may have a significant effect on the ability to drive vehicles or work with machinery. There may be hallucinations or drowsiness.

Patients with drowsiness and / or sudden onset of sleep should refrain from driving or engaging in activities in which, due to weakened vigilance, they may expose themselves or others to serious injury or death during the use of the drug.

Form release / dosage:Tablets, 0.25 mg and 1 mg.

Packaging:

10 tablets per contour cell pack.
3 contour packs with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.

Shelf life:

3 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003529

Date of registration:25.03.2016

Expiration Date:25.03.2021

The owner of the registration certificate:FARMZASCHITA NPC, FSUE FARMZASCHITA NPC, FSUE Russia

Manufacturer: & nbsp

FARMZASCHITA NPC, FSUE Russia

Information update date: & nbsp25.08.16

Illustrated instructions

Instructions

Pramipexole (Pramipexole)