Pronoran^® (Tablets) Instructions for Use

Marketing Authorization Holder

Les Laboratoires Servier (France)

Manufactured By

Les Laboratoires Servier Industrie (France)

Or

Servier Rus, LLC (Russia)

ATC Code

N04BC08 (Piribedil)

Active Substance

Piribedil (Rec.INN registered by WHO)

Dosage Form

Pronoran®

Prolonged-release coated tablets, 50 mg: 29 or 30 pcs.

Dosage Form, Packaging, and Composition

Prolonged-release coated tablets, red in color, round, biconvex; slight heterogeneity in coloring, gloss level, and the presence of minor inclusions are allowed.

Excipients: magnesium stearate, povidone K-30, talc.

Coating: sodium carboxymethylcellulose, polysorbate 80, Ponceau 4R dye [Ponzo 4R] (E124), povidone K-30, sodium bicarbonate, colloidal anhydrous silicon dioxide, sucrose, talc, titanium dioxide (E171), white beeswax.

29 pcs. – blisters (1) – cardboard packs with first-opening control (if necessary).
30 pcs. – blisters (1) – cardboard packs with first-opening control (if necessary).

Clinical-Pharmacological Group

Antiparkinsonian drug – dopaminergic receptor agonist

Pharmacotherapeutic Group

Antiparkinsonian drugs. Dopaminergic agents. Dopamine receptor agonists

Pharmacological Action

Antiparkinsonian agent. The mechanism of action is associated with the stimulation of dopamine receptors, primarily in the nuclei of the extrapyramidal system. It increases blood supply to tissues and stimulates nerve impulse transmission, which contributes to the improvement of cerebral metabolism.

It has a vasodilatory effect due to its influence on dopamine receptors located in the smooth muscle of peripheral vessels.

Pharmacokinetics

After oral administration, Piribedil is rapidly and almost completely absorbed from the gastrointestinal tract. Plasma protein binding is moderate. The plasma elimination of piribedil is biphasic and consists of an initial phase and a second, slower phase, leading to the maintenance of a stable plasma concentration of piribedil for more than 24 hours. Piribedil is intensively metabolized in the liver and excreted mainly by the kidneys: 75% of the absorbed piribedil is excreted by the kidneys in the form of metabolites.

Indications

Parkinson’s disease (both as monotherapy and in combination with levodopa), chronic disorders of cognitive function and neurosensory deficits (including attention and memory disorders) in senile dementia (as additional symptomatic therapy), intermittent claudication due to obliterating arterial diseases of the lower extremities (as additional therapy), ischemic circulatory disorders of the eye.

ICD codes

Dosage Regimen

Administer orally. Swallow the prolonged-release tablet whole with water; do not crush, split, or chew.

Initiate treatment at a low dose and titrate upward slowly based on individual therapeutic response and tolerability.

For Parkinson’s disease (monotherapy or adjunct to levodopa): Start with 50 mg once daily. Increase the dose gradually by 50 mg every 15 days. The standard maintenance dose is 150 mg to 250 mg per day, administered in a single daily dose or divided into two doses (morning and evening).

For cognitive disorders in senile dementia: The recommended dose is 50 mg once daily. The maximum daily dose is 150 mg, administered in divided doses if necessary.

For intermittent claudication: The recommended dose is 50 mg twice daily (morning and evening).

For ischemic eye disorders: The recommended dose is 50 mg twice daily.

Take the tablet during a meal to improve gastrointestinal tolerability and reduce the incidence of nausea.

In elderly patients, initiate therapy at the lowest possible dose and titrate with particular caution, monitoring for orthostatic hypotension and sedation.

In patients with severe hepatic or renal impairment, use is not recommended; if treatment is essential, exercise extreme caution and monitor closely.

Do not abruptly discontinue treatment. To terminate therapy, gradually reduce the dose over a period of several days to weeks to prevent the onset of neuroleptic malignant syndrome.

Regularly monitor patients for the emergence of dopamine dysregulation syndrome, impulse control disorders, daytime somnolence, and hypotension, particularly during dose escalation.

Adverse Reactions

Psychiatric disorders Common – confusion, agitation, hallucinations (visual, auditory, mixed), which disappear upon discontinuation of piribedil; frequency unknown – aggression, delusions, delirium.

Nervous system disorders Common – dizziness, which disappears upon discontinuation of piribedil; rare – drowsiness, in some cases – pronounced daytime sleepiness, up to sudden falling asleep; frequency unknown – dyskinesia.

Cardiovascular system disorders Uncommon – hypotension, orthostatic hypotension with loss of consciousness or malaise or lability of blood pressure.

Gastrointestinal system disorders Common – nausea, vomiting, flatulence (may disappear, especially when selecting an appropriate individual dose).

Impulse control disorders and compulsions: In patients with Parkinson’s disease receiving therapy with dopamine agonists, including Piribedil, pathological gambling, increased libido and hypersexuality, compulsive shopping and binge eating/compulsive overeating may occur.

Other frequency unknown – peripheral edema.

Contraindications

Hypersensitivity to piribedil; collapse, acute phase of myocardial infarction, concomitant use with antipsychotics (except clozapine); children and adolescents under 18 years of age.

Use in Pregnancy and Lactation

Use during pregnancy and breastfeeding is not recommended.

Not recommended for use in women of childbearing potential who are not using reliable contraceptive measures.

Use in Hepatic Impairment

Use with caution in severe hepatic insufficiency.

Use in Renal Impairment

Use with caution in severe renal insufficiency.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age (efficacy and safety have not been established).

Geriatric Use

Should be prescribed with caution to elderly patients to avoid worsening of concomitant diseases.

Special Precautions

It is known that dopamine agonists impair the systemic regulation of blood pressure, which can lead to the development of orthostatic hypotension. Blood pressure monitoring is recommended, especially at the beginning of treatment. Given the age of the population receiving piribedil therapy, the risk of falls, which may be caused by sudden falling asleep, arterial hypotension, or confusion, should be considered.

Abrupt discontinuation of dopaminergic receptor agonist therapy is associated with the risk of developing neuroleptic malignant syndrome (NMS). To avoid this, the dose of piribedil should be gradually reduced until complete withdrawal.

Patients receiving Piribedil should be monitored for the development of impulse control disorders. Patients and their caregivers should be informed about the potential symptoms of impulse control disorders and compulsions (pathological gambling, increased libido and hypersexuality, compulsive shopping and binge eating/compulsive overeating). If such symptoms occur, consideration should be given to reducing the dose or gradually discontinuing piribedil therapy.

If symptoms such as confusion, agitation, or aggression occur, consideration should be given to reducing the dose or gradually discontinuing therapy.

If symptoms such as delusions, delirium, and hallucinations occur, consideration should be given to reducing the dose or gradually discontinuing therapy.

In patients with progressive Parkinson’s disease taking levodopa preparations, dyskinesia may develop at the beginning of piribedil dose titration. In this case, the dose of piribedil should be reduced.

Caution should be exercised when prescribing piribedil concomitantly with other medicinal products that have a sedative effect.

Alcohol should not be consumed during treatment with piribedil.

Effect on ability to drive vehicles and operate machinery

During the use of piribedil, patients should exercise caution when driving vehicles and operating machinery, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Due to mutual antagonism between dopaminergic antiparkinsonian drugs and antipsychotics, concomitant use with antipsychotics (except clozapine) is contraindicated.

Patients with extrapyramidal syndrome caused by antipsychotic use should be treated with anticholinergic drugs and should not be prescribed dopaminergic antiparkinsonian drugs (due to the blocking of dopaminergic receptors by antipsychotics).

Dopaminergic receptor agonists may cause or exacerbate psychotic disorders. If it is necessary to use antipsychotics in patients with Parkinson’s disease receiving treatment with dopaminergic antiparkinsonian drugs, the dose of the latter should be gradually reduced until final discontinuation (due to the risk of developing NMS).

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.