Piribedil

Pharmacological properties

the active substance Piribedil is a dopaminergic agonist. it crosses the GEB and binds to dopamine receptors in the brain, has a strong and specific affinity for the d2 and d3 subtypes of dopamine receptors. this feature allows us to attribute Piribedil to agents for the treatment of early and late stages of Parkinsons disease with leading symptoms of impaired motor function. unlike other dopamine agonists, Piribedil is also an antagonist of the two main α2-adrenergic receptors in the central nervous system (α2a and α2c). The synergistic effect of Piribedil, as an antagonist of α2-adrenergic receptors and a dopamine agonist, has been proven on different models of Parkinson’s disease in animals: prolonged use of Piribedil caused less pronounced dyskinesia compared to levodopa with the same effectiveness in regressing the manifestations of the akinetic form of parkinsonism.

In clinical studies of the pharmacodynamics of the drug in humans, it was found that the drug stimulates the cortical electrogenesis of the “dopaminergic” type both during awakening and during sleep, and also activates various functions controlled by dopamine. This activity was confirmed using psychometric assessment and behavior scales.

It is also proven that in healthy volunteers, piribedil increases the attentiveness and diligence associated with the performance of cognitive tasks.

The effectiveness of Pronoran in the treatment of Parkinsons disease in monotherapy or in combination with levodopa was studied in three double-blind, randomized trials (in two trials, compared to placebo, and in one, compared to bromocriptine). In total, 1103 patients with I – III stage of Parkinsons disease according to the Hen and Yar scale took part in these studies, of which 543 patients took Pronoran.

The effectiveness of Pronoran in a dose of 150-300 mg / day was shown to reduce the severity of all symptoms of motor dysfunction by 30% on a unified rating scale for assessing Parkinsons disease (UPDRS), part III, when administered for at least 7 months in monotherapy and 12 month - in combination with levodopa. A similar degree of improvement was noted on the UPDRS scale, Part II (Activity in Everyday Life).

When using Piribedil in monotherapy, additional treatment with levodopa was necessary for a significantly smaller number of patients (16.6%) compared with patients who took placebo (40.2%).

Piribedil also improves blood circulation in the femoral vessels (the presence of dopaminergic receptors in the femoral vessels determines the effect of Piribedil on the peripheral blood circulation).

Pharmacokinetics In humans, Piribedil is rapidly and almost completely absorbed in the digestive tract and is extensively distributed. C_max in blood plasma is achieved 3-6 hours after taking piribedil in the form of prolonged-release tablets. In humans, piribedil binds moderately to plasma proteins (the unbound fraction is 0.2–0.3); therefore, the risk of drug interaction due to binding to blood plasma proteins is low. Excretion from blood plasma is two-phase and consists of an initial and second, slower phase, which leads to a stable concentration of Piribedil in blood plasma for 24 hours upon reaching equilibrium concentration. A pooled analysis of data from several studies showed that the average T_½ averages 12 hours regardless of the dose administered.

Piribedil is extensively metabolized in the liver, excreted mainly in the urine: 75% of the absorbed active substance is excreted by renal clearance mainly in the form of metabolites.

Indications

Parkinsons disease treatment:

• in the form of monotherapy;
• or in combination with levodopa, at the beginning of treatment or later.

Application

For oral use.

Take tablets after meals - swallow without chewing, drinking ¹/₂ glasses of water.

Dosage. Parkinsons disease treatment:

• the recommended doses for use as monotherapy are 150–250 mg (3-5 tablets per day), divided into 3 doses;
• the recommended dose for use in combination with levodopa is 150 mg (3 tablets per day), divided into 3 doses.

The dose should be increased gradually: by 1 tablet every 3 days.

Discontinuation of treatment. The sudden cessation of therapy with dopaminergic drugs leads to the risk of malignant antipsychotic syndrome. To prevent this risk, the dose of piribedil should be reduced gradually until the drug is completely discontinued.

Disorders of habits and addictions. A low dose is recommended to prevent the risk of habits and addictions. In case of symptoms of habits and addictions, you should reduce the dose or gradually stop taking the drug (see SPECIAL INSTRUCTIONS).

Patients with impaired liver and / or kidney function. The use of Piribedil has not been studied in this group of patients. Caution is advised to prescribe the drug to patients with impaired liver and / or kidney function.

Contraindications

Hypersensitivity to Piribedil or any other excipients of the drug, cardiogenic shock, acute phase of myocardial infarction; concomitant use with antipsychotics (with the exception of clozapine) (see interactions).

Side effects

During treatment with Piribedil, the following adverse reactions according to the classification can be noted: very often (≥1 / 10); often (from ≥1 / 100 to 1/10); infrequently (from ≥1 / 1000 to 1/100); rarely (from ≥1 / 10,000 to 1/1000); very rarely (1/10 000); frequency is unknown (cannot be determined according to available data).

From the digestive tract: often - mild gastrointestinal disorders (nausea, vomiting, flatulence), which can disappear, in particular, with individual dose adjustment. You can significantly reduce the severity of symptoms during phased titration of the dose (increase of 50 mg every 2 weeks).

From the psyche: often - mental disorders, such as confusion, agitation, hallucinations (visual, auditory, mixed), which disappeared after the treatment was canceled; the frequency is unknown - aggressiveness, psychotic disorders (delirium, delirium).

From the nervous system: often - dizziness, which disappeared after discontinuation of treatment.

The use of Piribedil can be accompanied by drowsiness and very rarely excessive drowsiness in the daytime, as well as episodes of sudden falling asleep (see SPECIAL INSTRUCTIONS).

The frequency is unknown - dyskinesia.

From the cardiovascular system: infrequently - arterial hypotension, orthostatic hypotension with syncope or malaise, or unstable blood pressure.

Disorders of habits and addictions. When using dopamine agonists, a pathological tendency to gambling, an increase in libido, hypersexuality, an irresistible attraction to spending or making purchases, overeating and an uncontrolled attraction to food can occur (see SPECIAL INSTRUCTIONS).

General disorders and disorders at the injection site: the frequency is unknown - with the use of dopamine agonists, the occurrence of peripheral edema was observed.

On the part of the immune system: the frequency is unknown - hypersensitivity reactions (including urticaria). The preparation contains dye Cochineal Red A (E124), which can cause allergic reactions.

Report on suspected adverse reactions. Reporting suspected adverse reactions during the post-registration period of the drug is important.This report allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals are required to report any suspected adverse reactions through the national reporting system.

special instructions

Episodes of sudden falling asleep. there is evidence of drowsiness and episodes of sudden falling asleep when using piribedil, especially in patients with Parkinsons disease. cases of sudden falling asleep during the daytime, sometimes without awareness or warning signs, were extremely rare. patients should be warned about this and informed of the need to be careful when driving vehicles or working with machinery during the period of treatment with piribedil. patients who have reported cases of drowsiness and / or sudden falling asleep should refrain from driving vehicles or working with machinery. in addition, consideration should be given to reducing the dose or discontinuing therapy.

Orthostatic hypotension. It is known that dopamine agonists affect the systemic regulation of blood pressure, which, in turn, can lead to postural orthostatic hypotension.

It is recommended to control blood pressure, especially at the beginning of treatment, because of the risk of orthostatic hypotension associated with dopaminergic therapy.

Given the age of patients taking Piribedil, the possibility of falls due to sudden falling asleep, hypotension, or confusion should be taken into account.

Disorders of habits and addictions. Patients should be monitored regularly to detect the development of habits and addictions. Patients and caregivers should be informed that when using dopamine agonists, including piribedil, there may be behavioral symptoms of disorders of habits and addictions, including a pathological addiction to gambling, increased libido and hypersexuality, an irresistible attraction to expenses and commitments purchases, overeating and an uncontrolled craving for food consumption. In case of the occurrence of these symptoms, consider reducing the dose or phasing out the drug.

Abnormal behavior. It was reported the occurrence of abnormal behavior, which can manifest itself in the form of confusion, agitation, aggressiveness.

In case of the occurrence of these symptoms, consider reducing the dose or phasing out the drug.

Psychotic disorders. Dopaminergic agonists can cause or exacerbate psychotic disorders such as delusions, delirium and hallucinations (see INTERACTIONS).

If these symptoms occur, consider the need to reduce the dose or gradually stop taking the drug.

Dyskinesia. When using Pronoran in patients with advanced Parkinsons disease in combination with levodopa, dyskinesia may occur at the beginning of Piribedil titration. If it occurs, the dose of Piribedil should be reduced.

Malignant antipsychotic syndrome. Symptoms of malignant antipsychotic syndrome have been reported with sudden cessation of therapy with dopaminergic drugs (see APPLICATION).

Peripheral edema. With the use of dopamine agonists, the appearance of peripheral edema was observed. This should also be taken into account when prescribing Piribedil.

Due to the sucrose content, patients with rare hereditary fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase deficiency should not take this drug.

Use during pregnancy and lactation. Pregnancy.Animal studies have shown that Piribedil crosses the placental barrier and is distributed in the organs of the fetus.

Due to the lack of relevant data, the use of Piribedil during pregnancy and in women of reproductive age who do not use contraceptives is not recommended.

Lactation. Due to the lack of relevant data, the use of this drug during lactation is not recommended.

Fertility. Animal studies have not revealed a direct or indirect harmful effect on embryonic / fetal development, the course of labor or postnatal development.

Children. The use of Pronoran in children is not recommended, since the safety and effectiveness of this drug have not been established in this group of patients. No data available.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Patients who take piribedil and who have experienced drowsiness and / or sudden falling asleep episodes should be informed of the need to refrain from driving vehicles or other activities in which a violation of attention and reaction could put the patient or others at risk of serious injury or death outcome (for example, when working with mechanisms) until these symptoms disappear (see SPECIAL INSTRUCTIONS).

Interactions

The simultaneous use of antipsychotics (with the exception of clozapine) is contraindicated, since there is a mutual antagonism of dopaminergic antiparkinsonian drugs with antipsychotics.

1. Patients with extrapyramidal syndrome caused by antipsychotics must be treated with anticholinergics, but not with dopaminergic antiparkinsonian drugs (dopaminergic receptors are blocked by antipsychotics).

2. Dopaminergic receptor agonists can cause or exacerbate psychotic disorders (see SPECIAL INSTRUCTIONS). If it is necessary to use antipsychotic therapy in patients with Parkinsons disease who are taking dopamine agonists, the dose of the latter should be gradually reduced until it is completely canceled (abrupt cancellation of dopaminergic drugs leads to the risk of developing malignant antipsychotic syndrome).

3. Regarding antipsychotic antiemetics: anti-emetics deprived of extrapyramidal effects should be used.

Concomitant use with tetrabenazine is not recommended, since there is mutual antagonism between dopaminergic antiparkinsonian drugs and tetrabenazine.

Drinking alcohol during treatment with Piribedil is not recommended.

Piribedil should be prescribed with caution in combination with other sedative drugs.

Overdose

Symptoms: Given that piribedil in a very high dose causes vomiting, its overdose when taking pills is unlikely. treatment: however, in case of accidentally exceeding the recommended doses, the following signs and symptoms of an overdose may occur: unstable hell (arterial hyper- or hypotension); symptoms of the gastrointestinal tract (nausea, vomiting).

These symptoms disappear with discontinuation of the drug and symptomatic therapy.

Storage conditions

It does not require special storage conditions. Keep out of the reach of children.