Stalevo Novartis medicine for Parkinson treatment (100 tablets)

Dosage form Box of 100 capsules
Specifications Levodopa, Carbidopa, Entacapona

Ingredient

Composition information	Content
Levodopa	150mg
Carbidopa	37.5mg
Entacapona	200mg

Uses

Indications

Stalevo® is indicated in the following cases:

Treatment of patients with Parkinson and there are movement fluctuations at the end of the dose at the end of the dose that is not stable when treated with levodopa /Dopa decarboxylase inhibitors (DDC).

Pharmacokological

According to the current knowledge, the symptoms of Parkinson's disease are related to dopamine decrease in the form of pattern. Dopamine does not pass through the blood -brain barrier. Levodopa - the precursor of dopamine, passing through the bloody barrier and reducing the symptoms of the disease. Because Levodopa is strongly metabolized on the periphery, only a small dose reaches the central nervous system when Levodopa is used without metabolic enzyme inhibitors.

Carbidopa and Benserazide are peripheral DDC inhibitors that reduce the conversion of levodopa into dopamine on the peripheral, resulting in increasing the amount of levodopa in the brain. When Levodopa's carboxyl reduction is reduced when used in combination with DDC inhibitors, LEVODOPA dose can be used lower and the adverse reaction rate such as reduced nausea.

Due to the inhibition of carboxyl reduction by DDC inhibitors, Comt becomes the main metabolic line catalyst for the transformation of Levodopa to 3 - O - Methyldopa (3 - OMD) is a harmful metabolic substance. Entacapone is a major comt inhibitor acting on the periphery, specific, with reversible, designed to be used in combination with Levodopa. Entacapone slows down the Levodopa clearance from the bloodstream leading to an increase in the area under the curve (AUC) in the pharmacokinetic chart of Levodopa. The result is clinical response to each levodopa dose increased and lasted.

Evidence of Stalevo's therapeutic effect is based on two studies of Phase III double blindness, of which 376 patients with Parkinson's disease have movement fluctuations at the end of the dose used Entacapone or placebo with each dose of Levodopa/DDC inhibitors. The daily "turn" time whether or not to use Entacapone has been recorded in the patient's monitoring book. In the first study, Entacapone increased the "daily" daily time of 1 hour 20 minutes (1 hour 56 minutes, the 95% 45 -minute CI trusted range) compared to the original level. This corresponds to an increase of 8.3% in the "daily" time ratio. Corresponding, the daily "shortcut" reduction is 24% in Entacapone and 0% in the placebo group. In the second study, the average daily "turning" time ratio increased by 4.5% (7.97%, 95% CI confidence interval of 0.93%) compared to the original level. This is considered an average increase of 35 minutes on the "daily" time. Corresponding, daily "turning" time is reduced by 18% for Entacapone and 5% for placebo. Because the effect of Stalevo tablets is equivalent to Entacapone 200 mg tablets are used in combination with carbidopa/levodopa preparations on the market in the market at corresponding doses, these results can also be applied to describe the efficiency of Stalevo.

pharmacokinetic

The general characteristics of the active ingredient

absorption/distribution

There is a significant change in each patient and between patients with the absorption of Levodopa, Carbidopa and Entacapone. Both Levodopa and Entacapone are absorbed and excreted quickly. Carbidopa is absorbed and eliminated slightly slower than Levodopa. When used separately without 2 other active ingredients, Levodopa's bioavailability is 15 - 33%, Carbidopa is 40 - 70% and Entacapone is 35% after a dose of 200 mg. Most neutral amino acid meals can slow down and reduce the absorption of Levodopa. Food does not significantly affect the absorption of Entacapone. The distribution of both Levodopa (eg 0.36 - 1.6 liters/kg) and Entacapone (eg 0.27 liters/kg) is moderately low; No data for carbidopa.

Levodopa is connected to plasma proteins with only small amounts (about 10 - 30%), while Carbidopa binds about 36%and Entacapone is strongly bond (about 98%), mainly with serum albumin. At the treatment concentration, Entacapone does not replace the place of other strong active ingredients (eg warfarin , salicylic acid, phenylbutazone or diazepam), nor is it replaced by any significant level because any of these substances in the treatment concentration or higher.

Metabolism and elimination

Levodopa is strongly metabolized into different metabolites, carboxyl reduction by dopa decarboxylase (ddc) and o - methylation by catechol - O - methyltranferase (COMT) are the most important lines.

Carbidopa is converted into two main metabolites excreted in urine in the form of glucuronide compounds and inunity. Carbidopa does not constantly account for 30% of the total excretion in the urine.

Entacapone is almost completely metabolized before being excreted in the urine (10 - 20%) and through bile/fertilizer (80 - 90%). The main metabolic line is glucuronideization of Entacapone and its active metabolites are CIS - Isomer accounts for about 5% of the total amount of plasma.

Levodopa's total clearance at 0.55 - 1.38 liters/hour/hour and Entacapone at 0.70 liters/kg/hour. The sale time (T1/2) is 0.6 - 1.3 hours for Levodopa, 2-3 hours for Carbidopa and 0.4 - 0.7 hours for Entacapone when each drug is used individually.

Due to the short selling time, there is no real accumulation of levodopa or Entacapone when used repeated.

Data from in vitro studies use liver's liver (urinary) preparations that show that the Entacapone inhibits Cytochrome P450 2C9 (IC50 ~ 4 μm). Entacapone shows weak or non -inhibition of other ISOENZE P450 (CYP1A2, CYP2A6, CYP2D6, CYP2E1, CYP3A and CYP2C19).

Characteristics in patients

Elderly

In elderly patients using Levodopa without carbidopa and entacapone, more absorption and slower elimination than young patients. However, when coordinated with Carbidopa, the same Levodopa absorption in both elderly patients and young patients, although the area under the curve (AUC) is still 1.5 times higher in the elderly due to the reduced DDC activity and the clearance is lower due to age. There is no significant difference in the AUC of Carbidopa or Entacapone between younger people (45 - 64 years old) and the elderly (65 - 75 years old).

Gender

Levodopa's bioavailability is significantly higher in women than men. In pharmacokinetic studies for Stalevo, Levodopa's bioavailability is higher than in women than men, mainly due to weight differences, while there is no gender difference for Carbidopa and Entacapone.

Before taking Stalevo Novartis medicine for Parkinson treatment (100 tablets)

How to use

Stalevo medicine is taken orally.

Each tablet is taken with or not with food.

Each tablet contains a dose of treatment and should only take whole tablets.

Dosage

The optimal daily dose must be determined by careful standard Levodopa in each patient.

The best daily dose should be optimized by using one of the four existing tablets (50/12.5/200 mg, 100/25/200 mg, 150/37.5/200 mg or 200/50/200 mg levodopa/carbidopone/entacapone).

Using only one stalevo tablet per dose.

Patients taking less than 70 - 100 mg of carbidopa/day are more likely to be nausea and vomiting. While not having much experience with a total dose of over 200 mg of Carbidopa/day, the maximum dose recommended by Entacapone is 2000 mg/day and therefore the maximum stalevo dose for stalevo content of 50/12.5/200 mg, 100/25/200 mg and 150/37.5/200 mg is 10 capsules/day (equivalent to 375 mg Carbidopopa/day). The maximum daily levodopa dose is used in the form of Stalevo not exceeding 1500 mg.

Stalevo treatment starts

switch to Stalevo in patients who are currently untreated with Entacapone: stop the monoamine oxidase inhibitors (Mao) not selected at least 2 weeks before starting stalevo treatment. Stalevo can be used simultaneously with the recommended dose of the manufacturer of selective Mao inhibitors for Mao Type B (eg Selegiline HCl).

Start taking Stalevo with the dose corresponding to the current dose in some patients with Parkinson's disease and there are movement fluctuations at the end of the dose at the end of the dose but unstable when being treated with Levodopa/DDC inhibitors DDC release standard. It is not recommended to transfer directly from Levodopa/DDC inhibitors to Stalevo for patients with motor disorders or use Levodopa dose over 800 mg/day that should be used as a separate medicine and adjust the dose of Levodopa if necessary, before switching to Stalevo.

Entacapone increases the effects of Levodopa, reducing the dose of Levodopa by 10 - 30% within a few days to the first few weeks after starting treatment with Stalevo, especially in patients with motor disorders. Levodopa can be reduced daily by increasing the dose distance and/or reducing the amount of levodopa per dose depending on the clinical condition of the patient.

If used in combination with other Levodopa products with Stalevo tablets, it should be as recommended for the maximum dose.

If stopping with Stalevo (Levodopa/Carbidopone/Entacapone) and transferring the patient to Levodopa treatment/DDC inhibitor without Entacapone, it is necessary to adjust the dose of other drugs to treat Parkinson's syndrome, especially Levodopa, to achieve sufficient concentration to control the symptoms of Parkinson syndrome.

Children and teenagers

Stalevo is not recommended for children under 18 years of age due to lack of data on safety and efficiency.

Elderly

No need to adjust the dose of Stalevo in elderly patients.

Hepatic failure

Be careful when taking Stalevo for patients with mild to moderate liver failure. May need to reduce the dose.

kidney failure

renal failure does not affect the pharmacokinetics of Entacapone. There are no specific studies on pharmacokinetics of Levodopa and Carbidopa in patients with renal impairment, so be careful when taking Stalevo for patients with severe renal failure including those who are treating hemolysis.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.

What to do when using overdose?

Symptoms

agitation, confusion state, coma, slow heartbeat, ventricular tachycardia, cheyne -stokes -style respiration, skin color, tongue, conjunctiva and urine are abnormal colors.

Handling

Patients were hospitalized, gastric lavage, and active carbon doses over time. Careful monitor the respiratory, circulatory and kidney systems.

In an emergency, call the 115 emergency center immediately or go to the nearest local health station.

What to do when you forget a dose? However, if close to the next dose, skip the forgotten dose and take the next dose at the time as planned. Note that it should not be used double the prescribed dose.

Side Effects

When using Stalevo , you may experience unwanted effects (ADR).

Common

Anemia , weight loss, appetite.

depression , hallucinations, confusion, abnormal dreams, anxiety, insomnia.

Parkinson's dysplasia (for example: slow movement), tremor, and the phenomenon of on -off, muscular disorder, mental decline (such as memory loss, memory loss), drowsiness, dizziness, blurred vision.

Members of ischemic heart disease other than myocardial infarction (for example angina), arrhythmia. Hypoglycemia, hypertension, shortness of breath, diarrhea, vomiting, constipation, indigestion, abdominal pain, discomfort, dry mouth, rash, increased sweating.

muscle pain, musculoskeletal, and connective tissue, muscle spasm, joint pain, diuretic, chest pain, peripheral edema, falling, changing body imbalance, weakness, fatigue.

Pulse control disorders: pathological gambling, increased libido, excessive sexual activity, spending or buying in an impulsive manner, eating too excessive and uncontrollable tea can occur in patients treated with dopamine copper and/or dopaminergic treatments containing levodopa, including Stalodo Regarding some individual cases with excessive daytime sleepiness and sudden onset of sleep.

Instructions on how to handle ADR

When experiencing side effects of the drug, it is necessary to stop using and notify the doctor or go to the nearest medical facility for timely treatment.

Warnings

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

Contraindicated

Stalevo medicine contraindicated in the following cases:

Knowing hypersensitivity to any ingredients of the drug.

Severe liver failure.

Glaucoma narrow angle.

Chromic cells.

Simultaneously used with a monoamine oxidase inhibitor (Mao - A and Mao - b) not selective.

Sent by a selective Mao - A inhibitor and a selective Mao -B inhibitor. This inhibitor must be stopped at least 2 weeks before starting treatment with Stalevo.

History of malignant syndrome due to sedative (NMS) and/or muscle patterns are not injured.

Be cautious when using

It is not recommended to use Stalevo to treat foreign towering reactions caused by drugs

Be cautious when treating stalevo for patients with ischemic heart disease, cardiovascular disease or severe lung disease, bronchial asthma, kidney disease, liver or hormonal, or a history of stomach or convulsions.

In patients with a history of myocardial infarction with atrial arrhythmia, nodia or ventricular arrhythmia, special monitoring of heart function during the initial dose adjustment period.

Need to carefully monitor all patients treated with Stalevo about the appearance of mental changes (for example, hallucinations and psychosis), depression with suicide tendencies and behaviors that are not suitable to serious society. Be careful when treating patients before or now psychotic.

Concomitance anti -psychotic drugs with dopamine receptor blockers, especially D2 receptor antagonists, must be carefully conducted and patients need to be carefully monitored for the loss of Parkinson's resistance or symptoms of Parkinson's syndrome.

Patients with chronic wide -angle glaucoma can be treated with Stalevo with caution, provided that the internal pressure is well controlled and the patient is carefully monitored with changes in internal pressure.

Stalevo can cause hypotension. Therefore, it is necessary to be cautious when taking Stalevo for patients who are taking other drugs that can cause hypotension.

combination of Entacapone and Levodopa is associated with drowsiness and sudden onset of sleep in patients with Parkinson's disease, so be careful when driving or operating machinery.

In clinical studies, unexpected dopaminergic effects such as a more common dysfunction in patients who are using Entacapone and dopamine isomers (such as bromocriptine), Selegiline or Amantadine compared to placebo users with this combination. The dose of other drugs may be adjusted when Stalevo is used in patients who were not treated with entacapone.

Secondary pattern due to serious movement disorders or malignant syndrome caused by sedation (NMS) has been observed in patients with Parkinson's disease. Separate cases of Co Van Tieu Van have been reported when treated with Entacapone. Malignant syndrome caused by sedation, including muscle pattern and hyperthermia, characterized by movement symptoms (hard, muscle vibration, tremor), mental changes (for example, excitement, confusion, coma), hyperthermia, automatic nervous system disorders (fast heart rate, unstable blood pressure) and increased creatine phosphokinase in serum. In individual cases, only some of these symptoms and/or signs are clear. Early diagnosis is important for appropriate management of malignant syndrome due to sedative. A malignant syndrome of malignant syndrome includes muscle stiffness, hyperthermia, mental changes and increased creatine phosphokase in serum has been recorded when suddenly stopping Parkinson's syndrome medications. Special cases of malignant syndrome due to sedative have been reported, especially after sudden decrease or stop of entacapone.

When deemed necessary, Stalevo and other dopaminergic treatments must be conducted slowly and if the signs and/symptoms still occur slowly, although stopped slowly Stalevo, may need to increase the dose of levodopa.

Doctors prescribe caution when transferring patients from Stalevo to Levodopa/DDC inhibitors without Entacapone. When it is necessary, the replacement of Stalevo with Levodopa/DDC inhibitor does not have Entacapone should be proceeded slowly and may need to increase the dose of levodopa.

If the body anesthesia is needed, it is necessary to continue treating stalevo as long as the patient is allowed to use drinks and medication by oral. If the treatment temporarily stops the treatment, Stalevo may be started as soon as possible oral medication with daily dose is the same as the previous dose.

Recommended recommendations for liver function, hematopoietic system, cardiovascular & cautious during the long period of treatment with Stalevo

For patients with diarrhea, it is recommended to monitor weight to avoid excessive weight loss. Prolonged diarrhea or persistent diarrhea is associated with Stalevo may be a sign of colitis. In the case of prolonged diarrhea or persistent diarrhea, medication must be stopped and consider appropriate medical treatment and appropriate tests.

For patients with continuous loss of appetite, depression and weight loss for a relatively short time, it is necessary to consider general medical evaluation including liver function.

Patients must be monitored regularly on the progression of pulse control disorders. Patients and caregivers need to be aware that the signs of pulse control disorders include pathological gambling, increased libido, excessive sexual activity, spending or buying in an impulsive, excessive and uncontrolled tea that can occur in patients treated with dopamine beneficiaries and/or other Dopaminergic drug treatments containing levodopopvo. Recommendations to review the treatment if there are the above symptoms.

Levodopa/Carbidopa can cause false positive when using the urinary test and this reaction does not change when boiling urine. The use of oxidase glucose can produce false positive results when testing in urine.

Patients with rare genetic problems in tolerance of fructose, malposure - galactose or lack of sucrase - Isomaltase should not be used.

The ability to drive and operate machinery

impact on the ability to drive and operate machinery: Stalevo may have a great influence when driving and operating machinery.

Patients being treated with Stalevo are sleepy and/or having sudden onset of sleep must be proposed to avoid driving or participating in activities where the lack of alertness can cause them or others to be at risk of serious damage or death (eg operating machinery) until such recurrent attacks are over.

Levodopa, Carbidopa and Entacapone simultaneously can cause dizziness and hypotension. So be cautious when driving or operating machinery.

Pregnancy

should not use Stalevo during pregnancy.

Breastfeeding period

Women should not breastfeed when treated with Stalevo.

Drug interaction

Other drugs for Parkinson syndrome

So far, there has been no warning about interactions, which has to eliminate the use of standard Parkinson's syndrome treatment with stalevo therapy. High doses of Entacapone may affect the absorption of Carbidopa. However, the interaction with Carbidopa has not been observed with the recommended treatment regimen (200 mg of Entacapone up to 10 times/day). The interaction between Entacapone and Selegiline has been studied in repeated dose tests in patients with Parkinson's disease treated with Levodopa/DDC inhibitors and does not observe the interaction. When used with Stalevo, the daily Selegiline dose should not exceed 10 mg.

Because Stalevo contains Entacapone, should not be used simultaneously with Comtan (Entacapone).

Be cautious when the following active ingredients are simultaneously used with Levodopa therapy.

Hypertension medicine

Hypotension with symptomatic posture may occur when starting to take Levodopa in patients who are taking drugs to treat hypertension. May need to adjust the dose of hypertension.

Antidepressants

Rare reactions include hypertension and movement disorders that have been reported when used in combination with 3 -round antidepressants and Levodopa/Carbidopa. The interaction between Entacapone and Imipramine and between Entacapone and Moclobemide has been studied in single -dose tests in healthy volunteers. No observations of pharmacological interactions have been observed. A significant number of patients with Parkinson's disease has been treated in combination with Levodopa, Carbidopa and Entacapone with some active ingredients including Mao - A inhibitors, 3 -round antidepressants, Noradrenaline reabsorption inhibitors such as Desipramine, Moprotiline, Venlafaxine and drugs transformed by comt (for example, Catechol: Rimiterol, Rimiterol: Rimiterol, Rimiterol: Rimiterol: Rimiterol: Rimiterol: Rimiterol Isoprenaline, Adrenaline, Noradrenaline, Dopamine, Dobutamine, Alpha - Methyldopa, Apomorphine and Paroxetine). Not observed with pharmacological interaction. However, it is necessary to be cautious when using these drugs with Stalevo (see the contraindications and warnings).

Other active ingredients

Dopamine receptor antagonists (for example, some anti -psychotic and anti -vomiting drugs), Phenytoin and Papaverine can reduce Levodopa's treatment effect. Patients who are taking these drugs with Stalevo must be carefully monitored for loss of treatment.

Due to the affinity of Entacapone with Cytochrome P450 2C9 in vitro (see pharmacokinetics), Stalevo has the ability to prevent active ingredients whose metabolism depends on this isoenzyme, like S - Warfarin. However, in an interaction test on healthy volunteers, Entacapone does not change the concentration of S - Warfarin in plasma, while the area under the curve (AUC) for S - Warfarin increases an average of 18% [CI 90 11 - 26% reliable range]. International standardized ratio (INR) ratio increased by an average of 13% [CI 90 6 - 19% reliability range]. Therefore, the Inr control recommendation when starting to use Stalevo in patients using warfarin.

Other types of interactions

Because Levodopa competes with some amino acids, Stalevo absorption may be reduced in some patients who are using a protein -rich diet.

Levodopa and Entacapone can form chelate with iron in the digestive tract. Therefore, Stalevo and iron preparations should be used at least 2-3 hours apart.

Stalevo can be used for patients with Parkinson's disease using vitamin preparations containing pyridoxine hydrochloride (vitamine B6).

In vitro data

Entacapone attaches to the number II position with the albumin who is also the position associated with some other drugs, including diazepam and ibuprofen . According to In vitro studies, there is no expected significant occupancy at the treatment concentration of these drugs. So far there has been no warning about such interactions.

Storage

In a dry place, avoid light, temperature below 30 ° C.

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