Oprymea^® (Tablets) Instructions for Use

ATC Code

N04BC05 (Pramipexole)

Active Substance

Pramipexole (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antiparkinsonian drug – stimulator of dopaminergic transmission in the CNS

Pharmacotherapeutic Group

Dopamine receptor agonist

Pharmacological Action

Pramipexole is a dopamine receptor agonist that binds with high selectivity and specificity to dopamine receptors of the D₂ subgroup, with the most pronounced affinity for D₃ receptors.

It reduces the motor activity deficit in Parkinson’s disease by stimulating dopamine receptors in the striatum. Pramipexole inhibits the synthesis, release, and metabolism of dopamine. Pramipexole in vitro protects dopaminergic neurons from the neurotoxicity of levodopa.

It reduces prolactin secretion (dose-dependently).

Pharmacokinetics

Pramipexole is rapidly and completely absorbed after oral administration.

The absolute bioavailability is more than 90%, and C_max in blood plasma is reached within 1-3 hours.

The rate of absorption decreases when taken with food, but food intake does not affect the total extent of absorption. Pramipexole is characterized by linear kinetics and relatively low variability in concentrations between individual patients.

Pramipexole binds to plasma proteins to a very small extent (less than 20%) and has a large V_d (400 L). It undergoes metabolism to a small extent. About 90% of the dose is excreted through the kidneys (80% unchanged) and less than 2% is excreted through the intestines.

The total clearance of pramipexole is about 500 ml/min, and renal clearance is 400 ml/min. The half-life (T_1/2) ranges from 8 hours in young people to 12 hours in the elderly.

Indications

• Symptomatic treatment of idiopathic Parkinson’s disease (monotherapy or in combination with levodopa) at a late stage of the disease, when the effects of levodopa weaken or become inconsistent.

ICD codes

Dosage Regimen

Tablets

Orally, regardless of meals, with a small amount of water.

The daily dose should be evenly divided into 3 doses.

Initial therapy

The dose of the drug should be increased gradually, every 5-7 days, starting from 0.375 mg per day.

To reduce the risk of side effects, the dose must be titrated gradually until the maximum therapeutic effect is achieved.

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

It should be taken into account that when taking doses above 1.5 mg/day, the frequency of drowsiness increases.

Maintenance therapy

The individual dose should be in the range from 0.375 mg to 4.5 mg per day. Both in the early and late stages of the disease, the drug is effective starting from a daily dose of 1.5 mg.

Further dose adjustment should depend on the patient’s response to treatment and the development of adverse effects. It is not excluded that in some patients a dose above 1.5 mg per day may 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

Sudden discontinuation of dopamine receptor agonist therapy can lead to the development of neuroleptic malignant syndrome.

Pramipexole must be discontinued gradually, by 0.75 mg per day until complete withdrawal of the drug (see the “Special Precautions” section).

Patients with renal impairment

The dose of pramipexole depends on creatinine clearance (CrCl).

Initial therapy

• Patients with CrCl greater than 50 ml/min: no reduction in the daily dose of the drug is required;
• Patients with CrCl 20 – 50 ml/min: 0.125 mg 2 times a day (0.25 mg per day);
• Patients with CrCl less than 20 ml/min: 0.125 mg once a day.

If renal function decreases during maintenance therapy, the daily dose of the drug should be reduced by the same percentage by which CrCl decreases, i.e., if CrCl decreases by 30%, the daily dose of the drug must be reduced by 30%.

The daily dose can be divided into two doses if CrCl is within 20 – 50 ml/min or taken once a day if CrCl is less than 20 ml/min.

Patients with hepatic impairment

In patients with hepatic impairment, there is no need to change the dose of the drug.

Patients receiving concurrent levodopa therapy

During concurrent therapy with levodopa, it is recommended to reduce the dose of levodopa as the dose is increased, as well as during maintenance therapy with pramipexole. This is necessary to avoid excessive dopaminergic stimulation.

Adverse Reactions

Classification of the frequency of side effects (WHO): very common > 1/10; common from > 1/100 to < 1/10; uncommon from > 1/1000 to 1/100; rare from > 1/10000 to < 1/1000; very rare < 1/10000; including individual reports.

From the central (CNS) and peripheral nervous systems: very common – dyskinesia, dizziness, drowsiness; common – insomnia, hallucinations, headache, abnormal dreams, anxiety; uncommon – paranoia, hyperkinesia, sudden onset of sleep, confusion, syncope; very rare – hypersexuality, pathological gambling.

From the digestive system: very common – nausea; common – constipation, vomiting.

From the cardiovascular system: very common – decrease in BP (at the beginning of therapy, if the drug dose is increased too quickly).

From the genitourinary system: uncommon – libido disorders (increase (0.1%) or decrease (0.4%)).

From the respiratory system: uncommon – dyspnea.

From the sense organs: vision disorder (decreased visual acuity).

Allergic reactions: uncommon – skin itching, skin rash.

Other: common – general weakness, peripheral edema, weight loss; uncommon – weight gain; very rare – increased appetite.

Contraindications

• Hypersensitivity to pramipexole or to one of the components of the drug;
• Age under 18 years (efficacy and safety have not been studied);
• Concomitant use with neuroleptics.

With caution: renal failure, arterial hypotension, psychotic disorders, visual impairment, severe cardiovascular diseases.

Use in Pregnancy and Lactation

The effect of the drug on pregnancy and lactation in humans has not been studied.

Use of the drug during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus.

The drug should not be used during breastfeeding. If therapy is necessary, breastfeeding should be discontinued.

Use in Hepatic Impairment

In patients with hepatic impairment, there is no need to change the dose of the drug.

Use in Renal Impairment

Use this drug with caution in renal failure. In case of impaired renal function, it is recommended to reduce the dose in accordance with the recommendations (see the “Dosage Regimen” section).

Pediatric Use

Contraindicated under the age of 18 years (efficacy and safety have not been studied).

Special Precautions

When prescribing Oprymea^® to patients with Parkinson’s disease and impaired renal function, it is recommended to reduce the dose in accordance with the recommendations (see the “Dosage Regimen” section).

Patients should be warned about the possibility of developing hallucinations.

When using Oprymea^® in combination with levodopa, in the late stages of Parkinson’s disease, dyskinesias may develop during the initial dose titration phase.

If dyskinesias appear, the dose of levodopa should be reduced.

Cases of sudden onset of sleep have been observed during treatment with pramipexole, particularly in patients with Parkinson’s disease. Cases of falling asleep during daily activities, sometimes without any preceding signs, have been observed uncommonly.

Due to the possibility of an additive effect, other sedative substances or alcohol should be used with caution concomitantly with pramipexole.

During therapy for Parkinson’s disease with dopamine receptor agonists, including Pramipexole, cases of pathological gambling, increased libido, and development of hypersexuality have been observed.

Patients and their caregivers should be informed about possible behavioral changes. In such cases, the issue of reducing the dose of the drug or discontinuing it should be considered.

Patients with psychotic disorders may receive therapy with dopamine receptor agonists after a preliminary benefit/risk assessment.

Concomitant use of neuroleptics and pramipexole should be avoided (see the “Drug Interactions” section).

If visual disturbances develop, it is recommended to regularly conduct an ophthalmological examination.

Due to the risk of orthostatic hypotension, it is recommended to monitor BP, especially at the beginning of treatment.

Effect on ability to drive vehicles and operate machinery

Oprymea^® may significantly affect the ability to drive a car or operate machinery. Due to the possibility of drowsiness and hallucinations, to avoid episodes of falling asleep, patients taking the drug should refrain from driving vehicles and working with machinery that requires concentration and speed of psychomotor reactions during the treatment period.

Overdose

Presumed symptoms characteristic of the pharmacodynamic profile of dopamine receptor agonists: nausea, vomiting, hyperkinesia, hallucinations, agitation, decreased BP.

Treatment: there is no specific antidote; symptomatic therapy is recommended: gastric lavage, intake of activated charcoal, and ECG monitoring.

Intravenous administration of 0.9% sodium chloride solution is also necessary. If signs of CNS stimulation appear, neuroleptics may be recommended.

The effectiveness of hemodialysis has not been established.

Drug Interactions

Pramipexole binds to plasma proteins to a small extent (less than 20%) and undergoes biotransformation.

Therefore, interaction with other drugs affecting plasma protein binding or elimination via biotransformation is unlikely.

Selegiline and levodopa do not affect the pharmacokinetics of pramipexole.

Cimetidine reduces the renal clearance of pramipexole by approximately 34%, mainly due to inhibition of the cationic secretory transport system of the renal tubules.

Drugs that inhibit this mechanism of excretion via the renal tubules (e.g., cimetidine and amantadine) or that are themselves excreted by this route may interact with pramipexole, resulting in reduced clearance of one or both drugs.

In case of concomitant use of such drugs, the dose of pramipexole should be reduced.

When Oprymea^® is combined with levodopa, it is recommended to reduce the dose of levodopa, and the dose of other antiparkinsonian drugs should be maintained at a constant level when increasing the dose of pramipexole.

Other sedative drugs or alcohol should be used with caution in combination with pramipexole, as an additive effect is possible.

Concomitant use of neuroleptics and pramipexole should be avoided (antagonistic action is possible).

Dopamine receptor blockers (phenothiazine derivatives, butyrophenones, thioxanthenes, metoclopramide) reduce the effectiveness of treatment.

Storage Conditions

The drug should be stored at a temperature not exceeding 30°C (86°F).

Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

Do not use the drug after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.