Sifrol 0.375mg Boehringer Treatment of Parkinson's disease (3 blisters x 10 tablets)

Dosage form Box of 3 blisters x 10 tablets
Specifications Pramipexole dihydrochloride monohydrate

Ingredient

Composition information	Content
Pramipexole dihydrochloride monohydrate	0.375mg

Uses

indications

Sifrol 0.375 mg Boehringer 3 x 10 is indicated in the following cases:

Treat the signs and symptoms of idiopathic Parkinson's disease. ))). This active ingredient has a complete intrinsic activity.

Pramipexole reduces patients' movement defects in Parkinson's disease by stimulating dopamine receptors in the pattern. Animal studies have shown pramipexole inhibiting synthesis, release and metabolism of dopamine.

On the volunteer, the decrease in the serve the dose dependents has also been recorded. It was observed that hypertension and heart rate in a clinical study on healthy volunteers, the dose of Sifrol 0.375 mg Boehringer 3 x 10 slow -released tablets are slowly adjusted faster (every 3 days) with recommended dose of up to 4.5 mg of salt. Such effects are not observed in research patients.

Pramipexole reduces signs and symptoms of Parkinson patients. Clinical trials with control include about 1800 patients using slow release tablets (or 2100 patients taking tablets) with the Hoehn and Yahr score of phase I - V treatment with Pramipexole. In addition, there are approximately 1,000 patients using slow release tablets (or about 900 patients taking tablets) during the progressive period, which has been treated with Levodopa therapy and has movement complications.

In the early and progressive stage of Parkinson's disease, Pramipexole's effectiveness in clinical trials with control is maintained for about 6 months. In the next open studies, the effect lasted for more than 3 years without signs of decline in treatment effectiveness.

In double -ended blind clinical trials that lasts 2 years of initial treatment with Pramipexole, significantly delaying the appearance of movement complications and minimizing recurrence compared to the starting treatment with Levodopa. The slow appearance of movement complications when treated with Pramipexole should be considered with a significant improvement in motor functions compared to Levodopa treatment (measured by the average change of the updrs scale). The new rate of illusion and drowsiness is higher in the stage of increasing the dose in the pramipexole group. However, there is no significant difference in the maintenance stage. This is the point to consider when treating with pramipexole for Parkinson patients.

Safety and effectiveness of Sifrol 0.375 mg Boehringer 3 x 10 slow -release tablets in the treatment of Parkinson's disease has been assessed in the multinational pharmaceutical development program including three controlled and random studies. Two tests are conducted in patients with Parkinson's early stage and one test conducted in Parkinson patients in the progressive stage.

The superiority of Sifrol 0.375 mg Boehringer 3 x 10 is slow release compared to the placebo described after 18 weeks of treatment based on both the main criteria (updrs scale of part II + III) and the key sub -criteria (CGI - I and PGI - I) in a double blind test, with a placebo comparison with 539 Parkon patients early in the early stages. The maintenance effect has shown in patients treated for 33 weeks. Sifrol 0.375 mg Boehringer 3 x 10 releasing tablets is slow than that of Pramipexole tablets release quickly when evaluating on the updrs scale of part II + III at week 33.

In a double clinical study, compared to the placebo, including 517 patients with Parkinson's disease, which has been treated simultaneously with Levodopa, showing the superiority of Sifrol 0.375 mg Boehringer 3 x 10 slow -released tablets slowly compared to the placebo after 18 weeks of treatment based on the main effective criteria (the updrs scale of part II+III) and the key sub -criteria (the time is not the key time (the non -response time ( Drugs).

Effectiveness and tolerance when switching from the Sifrol 0.375 mg Boehringer 3 x 10 tablets to the form of long -lasting release tablets at the same daily dose have been assessed in a double clinical study in early Parkinson patients.

The effect has been maintained at 87 of 103 patients switching to Sifrol 0.375 mg of Boehringer 3 x 10 slow -released tablets. Of these 87 patients, 82.8% of patients did not change the dose, 13.8% increased and 3.4% reduced the dose. In half of the number 16 patients do not meet the criteria for the efficiency of maintenance on the updrs scale of Part II + III, the change compared to the starting time is not clinically significant.

Only one patient switched to using Sifrol 0.375 mg Boehringer 3 x 10 slow release tablets is unwanted effects related to the drug and stopping the drug.

Dynamic pharmacokinetics

pramipexole are absorbed quickly and completely after drinking. Absolute bioavailability is greater than 90%.

In a test of phase I, when evaluating Pramipexole, fast release tablets and slow release tablets in hunger, minimum concentration and peak concentration in plasma (cmin, cmax) and area under the curve (AUC) of the same daily dose of Sifrol 0.375 mg Boehringer 3 x 10 Slowly release tablets slowly use one -time daily use Compression used 3 times a day is equivalent.

Use once a day Sifrol 0.375 mg Boehringer 3 x 10 Lesson release tablets slowly reduce the frequent oscillation of plasma pramipexole content for 24 hours compared to when using Sifrol 0.375 mg Boehringer 3 x 10 fast -release tablets quickly 3 times daily.

The peak concentration in plasma is achieved after about 6 hours after using Sifrol 0.375 mg Boehringer 3 x 10 release tablets once daily and after 1 to 3 hours after using Sifrol 0.375 mg Boehringer 3 x 10 tablets. The equilibrium achieved at the latest after 5 days of continuous treatment.

Use with food generally does not affect the bioavailability of pramipexole.

Eating high -fat food increases the peak concentration (CMAX) about 24% after single dose and about 20% after multiple doses and slow time to achieve peak concentration in healthy volunteers about 2 hours. The area under the total curve (AUC) is not affected when used with food. Increasing CMAX is considered to have no clinical significance. In the clinical studies of phase III to establish the safety and effectiveness of Sifrol 0.375 mg Boehringer 3 x 10 slow -release tablets, the patient is instructed to take the drug studied without paying attention to the meal.

The body weight does not affect AUC, but the impact on the distribution is and thus affects the cmax peak concentration. Reducing body weight by about 30kg, resulting in an increase in CMAX by about 45%. However, in phase III clinical studies in Parkinson patients, there is no clinical significance of weight on the effectiveness of treatment and the ability to tolerate Sifrol 0.375 mg Boehringer 3 x 10 slow release tablets.

Pramipexole shows that the livel pharmacokinetics and plasma concentrations are less changing in patients. In humans, Pramipexole binds to protein at a very low rate (

On humans, pramipexole is only transformed at a small level.

Pramipexole is excreted mainly through the kidneys in non -metabolic form. About 90% of the drug is marked with 14C excreted through the kidneys, while less than 2% is found in the feces. The total clearance of Pramipexole is about 500 ml/minute and the renal clearance is about 400 ml/min. The sale time (t leave) changes from 8 hours in young people to 12 hours in the elderly.

Before taking Sifrol 0.375mg Boehringer Treatment of Parkinson's disease (3 blisters x 10 tablets)

How to use

Sifrol 0.375 mg Boehringer 3 x 10 Slow release tablet: is a single oral preparation form of a single -time use of the day. Drink whole tablets with water, and do not chew, split or crushed. Can be used with or not with food and should be used daily at a certain time.

Dosage

Starting treatment

The dose increases slowly, the starting dose is 0.375 mg of salt daily, and then increasing the dose gradually every 5-7 days. If the patient does not experience uncomfortable side effects, gradually adjust the dose until the maximum treatment is achieved.

Sifrol tablet increase schedule for slow release tablets

week

Total daily dose (mg in salt)

0.375

0.75

1.50

However, it should be noted that the drowsiness rate will increase when the dose is higher than 1.5 mg/day (see the unwanted effect).

Patients who have used Sifrol tablets can switch to using Sifrol who release slowly after only 1 night, with the same daily dosage. After switching to Sifrol, slow release tablets, adjustable doses based on patient treatment response (see Pharmacological Pharmacuretic section).

Maintain treatment

Dosage for each patient should be in the range of 0.375 mg of salt to a maximum of 4.5 mg of salt daily. In the process of increasing the dose in key studies, the effectiveness is started at a dose of 1.5 mg of salt. Additional dose adjustment should be based on clinical response and the appearance of adultery effects.

In clinical trials, about 5% of patients are treated at lower doses of more than 1.5 mg of salt. In the treatment of Parkinson's progression, the dose higher than 1.5 mg of salt/day may be helpful for patients when planning to reduce the dose of Levodopa. Levodopa dose reduction is recommended in both cases of increasing dose or maintenance treatment for Sifrol 0.375 mg Boehringer 3 x 10 depending on the reaction of each patient.

Stop treatment

Sudden stopping dopaminergic therapy can lead to malignant syndrome due to anti -psychotic drugs. Therefore, Pramipexole should be reduced slowly at 0.75 mg of salt daily until the daily dose decreases to 0.75 mg of salt. After that, the dose should be reduced by 0.375 mg of salt daily (see the cautious part when used).

Dosage in patients with renal failure

Pramipexole elimination depends on the kidney function. The following is a dosage suggested at the beginning of treatment: patients with creatinine clearance of more than 50 ml/minute do not need to reduce the dose or the frequency of daily use.

In patients with creatinine clearance from 30 to 50 ml/min, starting at a dose of 0.375 mg of Sifrol 0.375 mg boehringer 3 x 10 tablets released slowly every day. Be careful and carefully assess the treatment and tolerance level before increasing the daily dose after a week. If the additional dosage is needed, the dose should be increased by 0.375 mg of salt for each week until the maximum dose is 2.25 mg of salt daily.

Do not recommend treatment in patients with creatinine clearance below 30 ml/min with Sifrol 0.375 mg Boehringer 3 x 10 because data is not available for this patient group. Should consider when using Sifrol 0.375 mg tablets in this case. The above recommendations should be obeyed if the renal function decreases during maintenance treatment.

Dosage in patients with liver failure

There is no need to reduce the dose in patients with liver failure because about 90% of the active ingredient is absorbed will be excreted through the kidneys. However, the effect of liver failure on pharmacokinetics of Sifrol 0.375 mg Boehringer 3 x 10 has not been studied.

Pediatric patients

Do not use Sifrol 0.375 mg Boehringer 3 x 10 for indications for treatment of Parkinson's disease in children.

What do

do when using overdose? Understanding events may be related to the pharmacological properties of dopamine, including nausea, vomiting, hyperactivity, hallucinations, agitation and hypotension. There is no antidote for dopamine overdose. If there are signs of central nerve stimulation, sedative drugs may be used. Overdose treatment with supportive measures such as gastric lavage, infusion, activated carbon, ECG measurement ...

What to do when you forget 1 dose? If more than 12 hours, you should skip the forgotten dose and the next dose should be used the next day according to the schedule of medication.

Side Effects

When using Sifrol 0.375 mg Boehringer 3 x 10, you may experience unwanted effects (ADR):

Very common: ADR> 1/10

Nervous system disorders: drowsiness, dizziness.

Digestive disorders: Nausea.

Common: 1/100

Mental disorders: abnormal dreams, expression of behavior of impulse control disorders and coercive impulses, chess, confusion, hallucinations, insomnia.

Disorders of the nervous system: headache.

Eye disorders: vision disorders including one -sided vision, blurred vision and vision loss.

Pleeing disorders: Hypotension.

Digestive disorders: constipation, vomiting.

Systemic disorders and at the position of use: Fatigue of peripheral edema.

Disorders of examination: Losing weight, including appetite.

Uncommon: 1/1000

Cardiovascular disorders: heart failure.

Disorders of infections and bacterial disorders: pneumonia.

Endocrine disorders: ADH secretion is not suitable.

Disorders of the nervous system: forgot, hyperactive, sudden sleep and fainting.

Mental disorders: Invisible eating, excessive shopping, delusional eating, increasing libido, sexual desire disorders, paranoia, pathological gambling, restless restlessness, delusion.

Skin and subcutaneous tissue disorders: increased sensitivity, itching, rash.

Disorders of examination: weight gain.

Respiratory, chest and medical disorders: shortness of breath, hiccups.

Do not know the frequency determination

Systemic disorders and at the position of use: cessation syndrome.

Nervous system disorders: head and neck.

Unwanted effects (≥ 5%) in Parkinson patients using Pramipexole more than the placebo group is vomiting, movement disorders, lower blood pressure, dizziness, drowsiness, insomnia, constipation, hallucinations, headaches and fatigue. The rate of drowsiness increases when the dose is higher than 1.5 mg of salt/day (see the dose and usage). The common side effect when used in combination with Levodopa is movement disorders. Hypotension at the beginning of treatment, especially when increasing the dose of pramipexole too fast.

Sleepy

The common side effect when treating with pramipexole is sleepy and uncommon is a state of too sleepy during the day and sudden falling asleep (see the warning and caution).

Describe unwanted effects

Sleeping and suddenly falling asleep

Patients treated with Pramipexole have been reported to fall asleep in daily activities, including driving activities, which can sometimes lead to accidents. In which some cases do not record warning signs such as drowsiness, a common sign that occurs in patients using Pramipexole, and always happens before the patient falls asleep according to the current knowledge of sleep physiology. There is no clear correlation with treatment time. Some patients are taking other drugs that are sedated. In most cases of information available, the events do not record further after reducing the dose or termination of treatment.

Sexual disorders

Uncompleted

has unwanted effects that cause sex disorders when using pramipexole (increase or decrease).

Pulse control disorders and coercive behaviors

Patients treat Parkinson's disease with dopamine benefactors, including Sifrol 0.375 mg Boehringer 3 x 10, especially in high doses that have been reported on signs of pathological gambling, increased sexual desire and increased activity, generally recovering when reducing the dose or stopping treatment.

heart failure

In clinical studies and after -sales data, heart failure reports in patients treated with pramipexole. In an epidemiological study, Pramipexole is related to an increase in the risk of heart failure compared to patients who do not use Pramipexole. There is no explanation of a relationship between pramipexole and heart failure.

In a horizontal and controlled study study, there are 3,090 patients with Parkinson's disease, 13.6% of patients who use dopaminergic or dopaminergic therapy are symptoms of a impulse control disorder within the last 6 months. Observations include pathological gambling, compulsive shopping, insatiable eating, and forced sexual behavior (increasing sexual activity). The possible independent risk factors for impulse control disorders even when treated with dopaminergic and high doses of dopaminergic, younger patients (≤ 65 years), unmarried and family history have been reported as gambling behaviors.

Note the patient informs the doctor for unwanted effects when using the drug

Instructions on how to handle ADR

Notify the doctor the unwanted effects when using the drug.

Warnings

Before using the drug you need to read the instructions carefully and refer to the information below.

contraindicated

sensitive to the active ingredient or any component of the product

Be cautious when using

kidney failure

When prescribing Sifrol 0.375 mg Boehringer 3 x 10 for Parkinson patients with renal failure, the dose should be reduced as instructions in the dosage and usage section.

Illusion

The illusion is the known side effect of Dopamine and Levodopa. Patients need to be notified that the illusion may occur (mostly virtual market).

movement disorders

In Parkinson patients with progression, when treatment combined with Levodopa, dynamic disorder may be encountered at the beginning of the standard Sifrol 0.375 mg Boehringer 3 x 10. If this happens, Levodopa dose is needed.

muscle disorders

Parkinson patients may appear muscle disorders around the shaft such as bending heads and neck (Antullis), abnormal spinal bend when standing and walking (Camptocormia) or rare neurological disorders due to prolonged contact with anti -psychotic drugs (Pleurothototus) (PISA syndrome). Sometimes, the muscular disorder is noticed after starting treatment with dopamine agreed drugs including pramipexole, although there is no clear causal relationship. Muscle disorders can also occur several months after the beginning of treatment or adjustment of the drug. If the muscle hypertension occurs, it is necessary to reconsider and consider adjusting the dopaminergic medication regime.

Drowsy and drowsiness

Pramipexole is involved in drowsiness and sudden drowsiness, especially in Parkinson's patient. There is rarely falling off in daily activities that in some cases of unknown or no warning signs. Patients need to be notified and carefully advised when driving or operating machinery when treated with Sifrol 0.375 mg Boehringer 3 x 10. The patient has manifested drowsiness or falling asleep should restrict driving or operating machinery. Moreover, it is necessary to consider reducing the dose or can stop treatment.

Due to the combination effect, it is recommended that patients if they use sedatives or alcohol (alcohol) with pramipexole.

Pulse control disorders and coercive behaviors

Pathological gambling, increased sexual desire and sexual activity are also recorded in dopamine bronze treatment for Parkinson's patients, including Sifrol 0.375 mg Boehringer 3 x 10. Therefore, it is recommended for patients and caregivers to identify the possibility of acts of impulse control disorders and forced acts such as excessive and excessive chores (compulsive brand). Should consider reducing the dose/stopped drugs slowly.

Halfy and delirium

Should check periodically to detect the impellance and delirium in the patient. Patients and caregivers should be noted that the impellance and delusion may occur in patients treated with Pramipexole. Can consider reducing the dose/stop slowly if these symptoms start.

Patients with mental disorders

Should only treat dopamine bronze drugs for patients with mental disorders if the benefits are higher than the risk.

It is not recommended to simultaneously use anti -psychotic drugs with pramipexole for example if the dopamine inhibitor effect is predictable.

Monitoring vision

It is necessary to check your vision periodically or when there is an abnormal vision.

Severe cardiovascular disease

Be careful in case of severe cardiovascular disease. Blood pressure monitoring should be monitored, especially when starting treatment, because of the general risk of hypotension posture related to dopaminergic therapy.

Malignant syndrome caused by psychotic drugs

The appearance of symptoms in malignant syndrome due to psychotic drugs is also recorded when the dopaminergic therapy suddenly stops dopaminergic therapy (see the dose and usage).

Cowdown syndrome

Certygia syndrome has been reported during or after stopping dopamine, including pramipexole. Risk factors may include high dopaminergic accumulation. The symptoms of quitting do not respond to Levodopa, and may include indifference, anxiety, depression, fatigue, sweating and pain. Before stopping the drug, it is advisable to notify the patient about the likelihood of cessation symptoms and need to closely monitor during and after the drug stopped. In the case of serious cessation symptoms, temporary reuse can be considered for the lowest doser at the lowest doses.

Traces in feces

Some patients have reported traces in feces that are like slow -release tablets Sifrol 0.375 mg Boehringer 3 x 10 in the feces. If the patient has such an observation report, the medical staff should re -evaluate the patient's response to the treatment.

The ability to drive and operate machinery

Sifrol 0.375 mg Boehringer 3 x 10 has a great impact on the ability to drive and operate machinery. Illusion or drowsiness may occur.

Patients using Sifrol 0.375 mg Boehringer 3 x 10 appear drowsiness and or sudden sleep should be warned to stop driving or participate in activities that if not alert, it will cause serious consequences for themselves or others (such as operating machinery) until solving the problem of drowsiness or sudden sleep.

Pregnancy

influence on pregnant and lactating women has not been studied in humans. Pramipexole does not have a monster on rats and rabbits, but has toxicity on rat embryos when using toxic doses for mice.

Do not use Sifrol 0.375 mg Boehringer 3 x 10 during pregnancy unless necessary, meaning only treatment if the benefits are higher than the risk for the fetus.

The period of breastfeeding

Because Pramipexole inhibits prolactin secretion on humans, can inhibit milk secretion. Pramipexole in breast milk has not been studied. In rats, the concentration of active substance - related to radioactive activity is determined in mother mouse milk higher than plasma. Due to lack of data on humans, Sifrol should not be used 0.375 mg Boehringer 3 x 10 during breastfeeding. However, if you cannot avoid using the drug during this time, stop breastfeeding.

Interactive drug

cohesion with plasma proteins

Pramipexole is associated with plasma proteins with very low rate (

Although interacting with anti -cholinergic drugs have not been studied, because cholinergic drugs have been eliminated due to biological changes, the ability to interact is very low. There is no pharmacokinetic interaction with Selegiline and Levodopa.

Inhibition/competition of active excretion lines through the kidneys

Cimetidine reduces the renal disposal of pramipexole by about 34%, perhaps due to inhibition of the transportation system of the cations (positive ions) in the renal tubules. Therefore, inhibitors or reducing the active excretion through the kidneys such as cimetidine, amantadine and mexiletine, can interact with pramipexole, result in reducing one or both medication clearance. It is necessary to consider reducing the dose of pramipexole when these drugs are used with Sifrol 0.375 mg Boehringer 3 x 10.

Simultaneously used with levodopa

When using Sifrol 0.375 mg Boehringer 3 x 10 along with Levodopa, Levodopa should be reduced, keeping the dose of other Parkinson's medications while increasing the dose of Sifrol 0.375 mg Boehringer 3 x 10.

Due to the possibility of a combination effect, careful recommendations for patients when using pramipexole simultaneously with other sedatives or alcohol (see warning and caution - influence on driving and operating machinery and unwanted effects).

Anti -psychotic drugs

It is not recommended to simultaneously use psychotic drugs with pramipexole, for example if the effects of antagonistic effects may occur.

Storage

Storage in the packaging, under 30 ° C.

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