Sifstad

Sifstad

pramipexole

Nhà sản xuất:

Stellapharm J.V.
Thông tin kê toa chi tiết tiếng Anh
Contents
Pramipexole.
Description
Each Sifstad 0.18 contains: Pramipexole (as pramipexole dihydrochloride monohydrate 0.25 mg) 0.18 mg.
Each Sifstad 0.7 contains: Pramipexole (as pramipexole dihydrochloride monohydrate 1 mg) 0.7 mg.
Sifstad tablets can be divided into equal doses.
Excipients/Inactive Ingredients: Mannitol, maize starch, povidone K30, colloidal anhydrous silica, magnesium stearate.
Action
Pharmacotherapeutic Group: Dopaminergic agents, dopamine agonists. ATC Code: N04BC05.
Pharmacology: Pharmacodynamics: Pramipexole is a non ergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes.
Parkinson's disease: The precise mechanism of action of pramipexole as a treament for Parkinson's disease is unknown, although it is believed to be related to its ability to stimulate dopamine receptors in the striatum.
Restless legs syndrome (RLS): The precise mechanism of pramipexole as a treatment for RLS is unknown. Although the pathophysiology of RLS is largely unknown, neuropharmacological evidence suggests primary dopaminergic system involvement. A mild striatal presynaptic dopaminergic dysfunction may be involved in the pathogenesis of RLS.
Pharmacokinetics: Pramipexole is readily absorbed from the gastrointestinal tract and peak plasma concentrations have occurred within about 2 hours in fasting patients and in about 3 hours when given with food. Oral bioavailability is reported to be about 90%. Pramipexole is widely distributed throughout the body and plasma-protein binding is less than 20%. Metabolism is minimal and more than 90% of a dose is excreted via renal tubular secretion unchanged into the urine. Elimination half-lives of 8 to 12 hours have been reported. On the basis of studies in rats, it is thought to be distributed into breast milk.
Indications/Uses
Sifstad is indicated in adults for treatment of the signs and symptoms of idiopathic Parkinson's disease, alone (without levodopa) or in combination with levodopa, i.e. over the course of the disease, through to the late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or "on off" fluctuations).
Sifstad is indicated in adults for symptomatic treatment of moderate to severe idiopathic restless legs syndrome in doses up to 0.54 mg of base (0.75 mg of salt).
Dosage/Direction for Use
Sifstad should be taken orally, swallowed with water, and can be taken either with or without food.
Parkinson's disease: The daily dose is administered in equally divided doses 3 times a day.
Initial treatment: Doses should be increased gradually from a starting dose of 0.264 mg of base (1 1/2 tablets Sifstad 0.18) per day and then increased every 5-7 days. Providing patients do not experience intolerable undesirable effects, the dose should be titrated to achieve a maximal therapeutic effect. (See Table 1.)


Click on icon to see table/diagram/image


If a further dose increase is necessary the daily dose should be increased by 0.54 mg of base (3 tablets Sifstad 0.18 or 3/4 tablet Sifstad 0.7) at weekly intervals up to a maximum dose of 3.3 mg of base (18 tablets of Sifstad 0.18 4 1/2 tablets Sifstad 0.7) per day. However, it should be noted that the incidence of somnolence is increased at doses higher than 6 tablets Sifstad 0.18 or 1 1/2 tablets Sifstad 0.7 per day.
Maintenance treatment: The individual dose of pramipexole should be in the range of 0.264 mg of base (1 1/2 tablets of Sifstad 0.18) to a maximum of 3.3 mg of base (18 tablets Sifstad 0.18 or 4 1/2 tablets Sifstad 0.7) per day.
During dose escalation in pivotal studies, efficacy was observed starting at a daily dose of 1.1 mg of base (6 tablets Sifstad 0.18 or 1 1/2 tablets Sifstad 0.7). Further dose adjustments should be done based on the clinical response and the occurrence of adverse reactions. It is recommended that the dose of levodopa is reduced during both the dose escalation and the maintenance treatment with pramipexole, depending on reactions in individual patients.
Treatment discontinuation: Abrupt discontinuation of dopaminergic therapy can lead to the development of a neuroleptic malignant syndrome. Pramipexole should be tapered off at a rate of 0.54 mg of base (3 tablets Sifstad 0.18 or 3/4 tablet Sifstad 0.7).  Thereafter the dose should be reduced by 0.264 mg of base (1 1/2 tablets Sifstad 0.18) per day.
Patients with renal impairment: The elimination of pramipexole is dependent on renal function. The following dose schedule is suggested for initiation of therapy: Patients with a creatinine clearance above 50 ml/min require no reduction on daily dose or dosing frequency.
In patients with a creatinine clearance between 20 and 50 ml/min, the initial daily dose of pramipexole should be administered in two divided doses, starting at 0.088 mg of base (1/2 tablet Sifstad 0.18) twice a day. A maximum daily dose of 1.57 mg of pramipexole base (9 tablets Sifstad 0.18 or 2 1/4 tablets Sifstad 0.7) should not be exceeded.
In patients with a creatinine clearance less than 20 ml/min, the daily dose of pramipexole should be administered in a single dose, starting at 0.088 mg of base (1/2 tablet Sifstad 0.18) daily. A maximum daily dose of 1.1 mg pramipexole base (6 tablets Sifstad 0.18 or 1 1/2 tablets Sifstad 0.7) should not be exceeded.
If renal function declines during maintenance therapy the pramipexole daily dose should be reduced by the same percentage as the decline in creatinine clearance, i.e. if creatinine clearance declines by 30%, then the pramipexole daily dose should be reduced by 30%. The daily dose can be administered in two divided doses if creatinine clearance is between 20 and 50 ml/min and as a single daily dose if creatinine clearance is less than 20 ml/min.
Patients with hepatic impairment: Dose adjustment in patients with hepatic failure is probably not necessary.
Paediatric population: The safety and efficacy of pramipexole in children below 18 years has not been established.
Restless legs syndrome: The recommended starting dose of pramipexole is 0.088 mg of base (1/2 tablet Sifstad 0.18) taken once daily 2-3 hours before bedtime. For patients requiring additional symptomatic relief, the dose may be increased every 4-7 days to a maximum of 0.54 mg of base (3 tablets Sifstad 0.18 or 3/4 tablet Sifstad 0.7) per day (as shown in Table 2). (see Table 2.)


Click on icon to see table/diagram/image


Patient's response should be evaluated after 3 months treatment and the need for treatment continuation should be reconsidered. If treatment is interrupted for more than a few days it should be re-initiated by dose titration carried out as previously mentioned.
Treatment discontinuation: Since the daily dose for the treatment of restless legs syndrome will not exceed 0.54 mg of base (3 tablets Sifstad 0.18 or 3/4 tablet Sifstad 0.7) pramipexole can be discontinued without tapering off.
Patients with renal impairment: The elimination of pramipexole is dependent on renal function. Patients with a creatinine clearance above 20 ml/min require no reduction in daily dose.
The use of pramipexole has not been studied in haemodialysis patients, or in patients with severe renal impairment.
Patients with hepatic impairment: Dose adjustment in patients with hepatic failure is not required.
Paediatric population: Pramipexole is not recommended for use in children and adolescents below 18 years due to a lack of data on safety and efficacy.
Overdosage
Symptoms: There is no clinical experience with massive overdosage. The expected adverse reactions would be those related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, hyperkinesia, hallucinations, agitation and hypotension.
Treatment: There is no established antidote for overdose of a dopamine agonist. If signs of central nervous system stimulation are present, a neuroleptic agent may be indicated. Management of the overdose may require general supportive measures, along with gastric lavage, intravenous fluids, administration of activitated charcoal and electrocardiogram monitoring.
Contraindications
Hypersensitivity to pramipexole or to any ingredient in the formulation.
Special Precautions
Hallucinations: Hallucinations are known as a side effect of treatment with dopamine agonists and levodopa. Patients should be informed that (mostly visual) hallucinations can occur.
Dyskinesia: In advanced Parkinson's disease, in combination treatment with levodopa, dyskinesia can occur during the initial titration of pramipexole. If they occur, the dose of levodopa should be decreased.
Mania and delirium: Patients should be regularly monitored for the development of mania and delirium. Patients and carers should be made aware that mania and delirium can occur in patients treated with pramipexole. Dose reduction/tapered discontinuation should be considered if such symptoms develop.
Ophthalmologic monitoring: Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.
Sudden onset of sleep and somnolence: Pramipexole 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 uncommonly. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with pramipexole. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore a reduction of the dose or termination of therapy may be considered. Because of possible additive effects, caution should be advised when patients are taking other sedating medicinal products or alcohol in combination with pramipexole.
Impulse control disorders: Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including pramipexole. Dose reduction/tapered discontinuation should be considered if such symptoms develop.
Patients with psychotic disorders: Patients with psychotic disorders should only be treated with dopamine agonists if the potential benefits outweigh the risks. Co-administration of antipsyhotic medicinal products with pramipexole should be avoided.
Severe cardiovascular disease: In case of severe cardiovascular disease, care should be taken. It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of postural hypotension associated with dopaminergic therapy.
Neuroleptic malignant syndrome: Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy.
Augmentation: Reports in the literature indicate that treatment of restless legs syndrome with dopaminergic medicinal products can result in augmentation.
Effects on ability to drive and use machines: Pramipexole can have a major influence on the ability to drive and use machines. Hallucinations or somnolence can occur. Patients being treated with pramipexole and presenting with somolence and/or 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 effect on pregnancy and lactation has not been investigated in humans. Pramipexole was not teratogenic in rats and rabbits, but was embryotoxic in the rat at matemotoxic doses. Pramipexole should not be used during pregnancy unless clearly necessary, i.e. if the potential benefit justifies the potential risk to the foetus.
Lactation: As pramipexole treatment inhibits secretion of prolactin in humans, inhibition of lactation is expected. The excretion of pramipexole into breast milk has not been studies in women. In rats, the concentration of active substance-related radioactivity was higher in breast milk than in plasma.
In the absence of human data, pramipexole should not be used during breast-feeding. Howevere, if its use is unavoidable, breast-feeding should be discontinued.
Adverse Reactions
In patients with Parkionson's disease: Very common (ADR ≥1/10): Nervous system: Dizziness, dyskinesia, somnolence.
Gastrointestial: Nausea.
Common (1/100 ≤ ADR <1/10): Psychiatric: Abnromal dreams, behavioural symptoms of impulse control disorders and compulsions, confusion, hallucinations, insomnia.
Nervous system: Headache.
Eye: Visual impairment including diplopia, vision blurred and visual acuity reduced.
Vascular: Hypotension.
Gastrointestinal: Constipation, vomiting.
General: Fatigue, peripheral oedema.
Others: Weight decrease including decreased appetite.
Uncommon (1/1000 ≤ ADR <1/100): Infections and infestations: Pneumonia.
Endocrine: Inappropriate antidiuretic hormone secretion.
Psychiatric: Binge eating, compulsive shopping, delusion, hyperphagia, hypersexuality, libido disorder, paranoia, pathological gambling, restlessness, delirium.
Nervous system: Amnesia, hyperkinesia, sudden onset of sleep, syncope.
Cardiac: Cardiac failure.
Respiratory, thoracic, and mediastinal: Dyspnoea, hiccups.
Skin and subcutaneous tissue: Hypersensitivity, pruritus, rash.
Others: Weight increase.
Rare (1/10,000 ≤ ADR <1/1000): Psychiatric: Mania.
In patients with restless legs syndrome: Very common (ADR ≥1/10): Gastrointestinal: Nausea.
Common (1/100 ≤ ADR <1/10): Psychiatric: Abnormal dreams, insomnia.
Nervous system: Dizziness, headache, somnolence.
Gastrointestinal: Constipation, vomiting.
General: Fatigue.
Uncommon (1/1000 ≤ ADR <1/100): Infections and infestations: Pneumonia.
Endocrine: Inappropriate antidiuretic hormone secretion.
Psychiatric: Behavioural symptoms of impulse control disorders and compulsions such as binge eating, compulsive shopping, hypersexuality, and pathological gambling, confusion, delusion, hallucinations, hyperphagia, libido disorder, paranoia, restlessness, mania, delirium.
Nervous system: Amnesia, dyskinesia, hyperkinesia, sudden onset of sleep, syncope.
Eye: Visual impairment including diplopia, vision blurred and visual acuity reduced.
Cardiac: Cardiac failure.
Vascular: Hypotension.
Respiratory, thoracic, and mediastinal: Dyspnoea, hiccups.
Skin and subcutaneous tissue: Hypersensitivity, pruritus, rash.
General: Peripheral oedema.
Others: Weight decrease including decreased appetite, weight increase.
Drug Interactions
Amantadine: May slightly decrease the oral clearance of pramipexole.
Cimetidine: Caused a 50% increase in pramipexole AUC and a 40% increase in half-life (N=12).
Other drugs eliminated via renal secretion: Co-administration of drugs that are secreted by the cationic transport system (e.g., cimetidine, ranitidine, diltiazem, triamterene, verapamil, quinidine, and quinine) decreases the oral clearance of pramipexole by about 20%, while those secreted by the anionic transport system (e.g., cephalosporins, penicillins, indomethacin, hydrochlorothiazide, and chlorpropamide) are likely to have a little effect on oral clearance of pramipexole.
Dopamine antagonists: Since pramipexole is a dopamine agonist, it is possible that dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of pramipexole.
Co-administration of antipsychotic medicinal products with pramipexole should be avoided, e.g. if antagonistic effects can be expected.
Caution For Usage
Incompatibilities: In the absence of incompatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage
Store in a well-closed container, in a dry place. Do not store above 30°C.
Shelf-life: 24 months from the date of manufacturing.
ATC Classification
N04BC05 - pramipexole ; Belongs to the class of dopamine agonist. Used in the management of Parkinson's disease.
Presentation/Packing
Tab 0.18 (white, flat, oval-shaped, scored on both sides) x 3 x 10's. 0.7 (white, flat, oval-shaped, engraved with cross on one side, plain on the other side) x 3 x 10's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in