Trivastal Retard 50

Trivastal Retard 50

piribedil

Manufacturer:

Servier

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Piribedil.
Description
Piribedil 50.00 mg.
For one sustained release coated tablet.
Excipients/Inactive Ingredients: Povidone, magnesium stearate, talc, sodium hydrogen carbonate, carmellose sodium, white beeswax, titanium dioxide (E171), cochineal red A aluminium lake (E124), polysorbate 80, sucrose, anhydrous colloidal silica.
Action
Pharmacotherapeutic group: DOPAMINERGIC AGONISTS. ATC Code: N04BC08.
Pharmacology: Pharmacodynamics: Mechanism of action: Piribedil: dopaminergic agonist (stimulates dopamine receptors and the cerebral dopaminergic pathways).
In humans, the mechanism of action is demonstrated by the clinical pharmacology studies: stimulation of "dopaminergic" type cortical electrogenesis both while awake and during sleep; clinical activity on the different functions controlled by dopamine, with this activity being demonstrated via the use of behavioural or psychometric scales.
In addition, piribedil results in an increase in femoral blood flow (the existence of dopaminergic receptors in the femoral vascular bed explains the action of piribedil on peripheral circulation).
Pharmacokinetics: Absorption: Piribedil is absorbed rapidly.
Distribution: The maximum concentration is reached one hour after oral administration of piribedil. Plasma elimination is biphasic and is composed of a first phase characterised by a half-life of 1.7 hours and a second, slower phase characterised by a half-life of 6.9 hours.
Biotransformation: Metabolism of piribedil is intense, with two main metabolites: (a hydroxylated derivative and a dihydroxylated derivative).
Elimination: Piribedil is excreted essentially in the urine: 68% of the piribedil absorbed is excreted by the renal route in the form of metabolites and 25% is excreted in bile.
Pharmacokinetic/pharmacodynamics correlations: The tablet containing 50 mg of sustained-release piribedil allows in vivo gradual absorption and release of the active ingredient.
The kinetic studies conducted in humans show extension of the therapeutic coverage which exceeds 24 hours.
Urinary excretion is approximately 50% at the 24th hour and is total at the 48th hour.
Toxicology: Preclinical safety data: Subchronic or chronic administration of piribedil has been well-tolerated in animals. No teratogenic potential has been demonstrated for piribedil in animals. In vitro and in vivo tests have shown no genotoxic potential. No carcinogenicity studies have been conducted.
Indications/Uses
Treatment of Parkinson's disease: either as monotherapy, or combined with dopatherapy from the outset, or secondarily.
Dosage/Direction for Use
Posology: Treatment of Parkinson's disease: as monotherapy: 150 mg to 250 mg, i.e. 3 to 5 tablets daily, to be divided into 3 to 5 administrations per day.
as a supplement to dopatherapy: 1 to 3 tablets daily (approximately 50 mg of piribedil per 250 mg of L.Dopa).
These doses must be attained gradually: increase by one tablet every three days.
Discontinuation of treatment: Sudden discontinuation of dopamine agents may result in neuroleptic malignant syndrome. To avoid this risk the dose of piribedil must be reduced gradually until complete discontinuation of treatment.
Impulse control disorders: To avoid the risk of impulse control disorders, prescription of the minimum effective dose is recommended. Dose reduction or gradual discontinuation of treatment should be considered if such symptoms occur (see Precautions).
Kidney or liver failure: Piribedil has not been studied in these groups of patients. It is recommended to treat these patients with caution.
Paediatric population: The safety and efficacy of piribedil in children under the age of 18 years have not been established. There is no available data. There is no justified use of piribedil in the paediatric population for this indication.
Method of administration: Oral route.
The tablets should be swallowed, without chewing, with half a glass of water at the end of the meal.
Overdosage
Given the emetic effect of piribedil at very high doses, overdosage is unlikely with the tablet form.
The signs of overdose are: blood pressure instability (arterial hypertension or hypotension), digestive symptoms (nausea, vomiting).
These symptoms disappear on discontinuation of administration and with symptomatic treatment.
Contraindications
This medicine is contra-indicated in the following situations: hypersensitivity to piribedil or to any of the excipients listed in Description, cardiovascular shock, acute phase of myocardial infarction, in association with anti-emetic neuroleptics (see Interactions).
Special Precautions
Dyskinesia: In advanced stage Parkinson's disease, in conjunction with levodopa, dyskinesia may occur at the start of treatment with piribedil. In this case, the dose of piribedil should be reduced.
Orthostatic hypotension: Dopamine agonists are known to alter systemic blood pressure regulation resulting in postural orthostatic hypotension.
Monitoring of blood pressure is recommended, particularly at the start of treatment, given the risk of orthostatic hypotension associated with dopamine treatment.
Abnormal behaviour: Abnormal behaviour has been reported and may be associated with manifestations of confusion, agitation, aggression. Dose reduction or gradual discontinuation of treatment should be considered if such symptoms occur.
Sleep disorders: Piribedil has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson's disease.
Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported very rarely. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with piribedil. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore, a reduction of dosage or termination of therapy may be considered.
Given the age of the population treated, the risk of falls whether related to hypotension, sudden sleep onset or delirium, must be taken into account.
Impulse control disorders: The onset of impulse control disorders must be regularly monitored in these patients. The patients and those close to them must be informed of the behavioural symptoms of impulse control disorders such as: pathological gambling (compulsive gambling), hypersexuality, increased libido, compulsive spending or shopping, excessive consumption of food and compulsive food disorders, which may appear in patients treated with dopaminergic agonists including TRIVASTAL. A decrease of the doses or progressive discontinuation of the treatment must be envisaged if such symptoms appear.
Psychotic disorders: Dopamine agonists may cause or worsen psychotic disorders such as delusion, delirium, hallucinations (see Interactions).
Dose reduction or gradual discontinuation of treatment should be considered if such symptoms occur.
Peripheral oedema: Peripheral oedema has been observed during the use of dopamine agonists. This should be taken into account when prescribing piribedil.
Neuroleptic malignant syndrome: Characteristic symptoms of neuroleptic malignant syndrome have been reported following sudden discontinuation of dopamine treatment (see Dosage & Administration).
Due to the presence of sucrose, this medicine is contra-indicated in case of fructose intolerance, glucose and galactose malabsorption syndrome or sucrase-isomaltase deficiency.
Effect on ability to drive and use machines: Patients being treated with piribedil and presenting with somnolence and/or an episode of sudden sleep episodes, must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. operating machines) until such recurrent episodes and somnolence have resolved.
Use In Pregnancy & Lactation
Pregnancy: The available data in mice show piribedil passes through the placental barrier, and is distributed in foetal organs.
In the absence of relevant data, the use of this drug during pregnancy and in women of childbearing age not using contraception is not recommended.
Lactation: In the absence of relevant data, the use of this drug during breastfeeding is not recommended.
Fertility: Studies conducted in animals have not shown any direct or indirect harmful effects on embryonic/foetal development, parturition or post-natal development.
Adverse Reactions
The following undesirable effects have been observed during treatment with piribedil and ranked under the following frequency: Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000), not known (cannot be estimated from the available data).
The following signs may appear: Gastrointestinal disorders: Common: minor gastrointestinal disorders (nausea, vomiting, flatulence), which may disappear particularly if the individual dose is adjusted (gastro-intestinal symptoms can be greatly reduced by stepwise uptitration (50mg increase every 2 weeks).
Psychiatric disorders: Common: psychic disorders such as confusion, hallucinations (visual, auditory, mixed) or agitation have been observed, which disappear when treatment is stopped.
Unknown frequency: aggression, psychotic disorders (delusion, delirium).
Impulse control disorders: Symptoms such as: pathological gambling (compulsive gambling), hypersexuality, increased libido, compulsive spending or shopping, excessive consumption of food and compulsive food disorders may appear in patients treated with dopaminergic agonists including TRIVASTAL (see Dosage & Administration and Precautions).
Nervous system disorders: Common: dizziness has been observed which disappears when treatment is stopped.
Unknown frequency dyskinesia.
Piribedil is associated with somnolence and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes.
Cardiovascular disorders: Uncommon: hypotension, orthostatic hypotension, unstable blood pressure causing syncope or malaise.
General disorders and anomalies at the administration site: Unknown frequency: peripheral oedema.
Risk of allergic reactions due the presence of Cochineal red A (E124).
Drug Interactions
Contraindicated combinations: Antiemetic neuroleptics: Reciprocal antagonism between the dopaminergic agent agonist and the neuroleptics.
Use an anti-emetic without extrapyramidal effects.
Inadvisable combinations: Antipsychotic neuroleptics (except clozapine): Reciprocal antagonism between the dopaminergic agent and the neuroleptics.
The dopaminergic agent can provoke or aggravate psychotic disorders. If a neuroleptic treatment is required in parkinsonian patients treated with dopaminergic agents, the latter must be gradually reduced until withdrawal (the sudden withdrawal of dopaminergic agents can expose to a "neuroleptic malignant neuroleptic syndrome" risk).
Tetrabenazine: Reciprocal antagonism between the dopaminergic agent and tetrabenazine.
Alcohol consumption: Alcohol increases the sedative effect of piribedil.
Impaired vigilance may make driving vehicles and the use of machinery dangerous.
Combinations to be taken into account: Other sedatives: Increase in central depression.
The impairment of alertness could make driving and using machines dangerous.
Caution For Usage
Incompatibilities: Not applicable.
Special precautions for disposal and other handling: No special requirements.
Storage
Store below 25°C.
Shelf life: 3 years.
MIMS Class
Antiparkinsonian Drugs
ATC Classification
N04BC08 - piribedil ; Belongs to the class of dopamine agonists. Used in the management of Parkinson's disease.
Presentation/Packing
SR tab 50 mg (coated) x 30's.
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