Mebamrol S.P.M medicine for schizophrenia (5 blisters x 10 tablets)

Dosage form Box of 5 blisters x 10 tablets
Specifications Clozapine

Ingredient

Composition information	Content
Clozapine	100mg

Uses

indications

Mebamrol 100mg SPM is indicated in the following cases:

Schizophrenia anti -treatment:

Clozapin is indicated for anti -treatment mental patients and severe schizophrenia patients, non -nervous reactions that cannot be treated with other neurolithic drugs, including not typical neurolithic calves.

Defense resistance is determined when the clinical improvement responds to the use of at least two different doses of sedatives, including a typical non -typical sedative, prescribed during sufficient treatment.

Psychosis in the process of Parkinson's disease:

Clozapin is also indicated in neurological disorders that occur in the process of Parkinson's disease, in the case of treatment preparation.

Pharmacokic

ATC code: N05A H02

Clozapin is a neuroleptic/anti -psychotic drugs that are not the first typical of the second generation and is the substance of dibenzodiazepin. The drug has many different pharmacological properties from the classic neurolysis drugs that conducts phenothiazin or butyrophenon such as less tower syndrome, less prolactin secretion.

In pharmacological experiments, the drug does not promote the status quo or inhibit the repetitive behavior caused by apomorphin or amphetamine. It only works to block the weak dopamine receptor in the receptors D1, D2, D3 and D5, but shows high efficiency for D4 receptors. This makes a difference between clozapin and other classic anti -disruptive drugs (less effective effects, less prolactin secretion, causing less dysfunction).

Alpha-commenergic receptor antagonistic effect explains a part of the sedative effect, muscle relaxation and other effects on the cardiovascular effect of Clozapin. Clozapin also has anti -cholinergic effect, so it can cause dry mouth and delirium in some patients. 5HT-2 receptor antagonistic effects in the central nervous system, 5 HT-3 receptors in the central and peripheral nerves are partly related to the deep sedative effect, effectively on the negative symptoms of schizophrenia and gain weight during the treatment of clozapine. Clozapin has a clear effect on γ-aminobutyric acid (GABA) is a substance that inhibits dopaminergic neurons. Contrary to the effects of classic anti -peptic drugs, clozapin increases the rotation and release of gaba in the form of the pattern and the accubens multiplied. Increasing rotation and release of GABA in the pattern can reduce the non -tower reaction, while the Accubuns core may be related to anti -psychotic effects.

The drug also has antagonistic effects on the hypamine receptor in the central nervous system, causing sedative effects, lowering blood pressure and gaining weight. On the brain, Clozapin increases the activity of Delta and Theta waves, slowing down the dominant alpha wave frequency. In some patients, Clozapin reduces the potential time and increases a lot of time for fast eye sleep (REM). Clozapine epilepsy depends on the dose, usually accumulated after one year of using the drug in a dose of 600 - 900mg/day at about 5% of patients treated. If using clozapin below 300 mg/day, the rate of convulsions is about 1-2%.

It also shows Serotoninergic resistance. Clozapin can inhibit strong bone marrow leading to leukopenia and granulocytes (even death) occurs at the estimated rate of 0.7% - 3%. The grain leukemia is not clearly related to any patient's characteristics and cannot be predicted through dosage or time. However, the highest rate is common in the first 6 months of clozapin treatment for patients over 50 years old. The exact mechanism of grain leukemia due to Clozapin has not been clearly defined, but may be related to the immunity and toxic mechanism of the drug or the metabolic derivatives of the drug. Therefore, the use of clozapin must be restricted in patients with resistance to treatment or patients with psychosis in Parkinson's disease when other treatments fail and in people with regular hematometry tests can be done.

Pharmacokinetics

absorption

After drinking, Clozapin absorbed quickly and almost completely (90 to 95%) through the gastrointestinal tract (mainly in small pages); Both the speed and level of absorption are not affected by food. Clozapin is first metabolized in the liver, so oral bioavailability only reaches about 50 - 60%. Plasma drug concentration reaches a stable state after 7-10 days with a reminded dose, with an average concentration of 319 nanogam/ml achieved after a dose of 100mg, 2 times/day. There is a great variable between individuals in terms of drug concentration in plasma after taking the same dose. Pharmacological effects appear about 15 blessings after taking the drug and maintained for 4 - 12 hours later. In schizophrenia patients, sedative effects are evident within a few hours after taking the first dose, the maximum effect is achieved within 7 days. However, after starting treatment with clozapin, anti -psychotic effects are often slower, appearing within one to a few weeks, maximum effect may need several months of treatment. The concentration of the clozapin treatment in plasma is not clearly defined. The correlation between blood concentration and the effectiveness of clozapin's treatment has not been established.

Distribution

Clozapin and metabolites are rapidly distributed and abundant into tissues including central nerves. The distribution of the drug is about 4.65 liters/kg. In schizophrenia patients, the integral distributed in an average stability of 1.6 liters/kg due to the smaller distribution volt The ratio of binding with plasma protein is about 97%.

Metabolism

Clozapin is almost completely metabolized before elimination. Clozapin is metabolized in the liver before eliminating with N-Demethylation reactions, n-oxidation, hydroxylation, 3'-carbon-oxidation, epoxy-hemimony mainly through CYP1A2 and then concluded with glucuronic acid. Demethyl metabolites (Norclozapin) also retain a part of the activity of clozapin, pharmacological effects similar to clozapin, but weaker and shorter time.

Elimination

After taking the single dose, the plasma sale time of clozapin is about 8 hours (ranging from 4 - 12 hours). The sale time after using the dose repeats 100mg, 2 times/day in a stable state at about 12 hours (ranging from 4 - 66 hours).

Only a small amount of unmistakable drugs detected in urine and feces (2 - 5%), about 50% of the dose is eliminated in the form of metabolites in urine and 30% in feces.

Before taking Mebamrol S.P.M medicine for schizophrenia (5 blisters x 10 tablets)

How to use

oral tablets. Take the tablet with a glass of water.

Dosage

Dosage information

The dose must be adjusted according to each patient alone. For each patient, the lowest dose should be used effectively. For non -identified/unknown doses that cannot be done in a content, other content of this drug is available. Caution adjustment and dosage is necessary to minimize the risk of lowering blood pressure, convulsions and sedation.

Starting with clozapin treatment must be banned for patients with a total number of WBC ≥ 3500/mm3 (3.5x109/l) and ANC ≥ 2000/mm3 (2.0x109/l) within the normal standard limit.

The adjustment of patients is also taking drugs with pharmacokinetics interactions and pharmacokinetics with clozapin, such as benzodiazepine or selective serotonin reabsorption inhibitors.

changes from a sedative therapy first to clozapin

General recommendations that clozapin is not used with other sedatives. When treating clozapin is started in patients taking oral sedation, the first recommendation is to stop another sedative by gradually reducing the dose. The following doses are recommended:

Patients with anti -treatment schizophrenia:

Start treatment: 12.5 mg one or twice on the first day, followed by 25 mg one or twice on Monday. If tolerated well, the daily dose can be increased to 25 to 50 mg to achieve a dose of up to 300 mg/day for 2 to 3 weeks. After that, if required, the daily dose may be increased to 50 to 100 mg in half a week or, preferably, about weekly.

Dosage of treatment: In most patients, sedative effects can be expected in the range of 200 - 450 mg/day for use in subdivided doses. The daily daily dose can be divided unevenly, with large doses of sleep.

Maximum dose: To achieve a total therapeutic effect, some patients may require a larger dose, in this case, increasing the wise dose (not exceeding 100 mg) is acceptable to 900 mg/day. However, the possibility of harmful reactions (especially convulsions) occurs at a dose exceeding more than 450 mg/day must be memorized.

Maintenance dose: After maximum treatment effect, many patients are effective at lower doses. Therefore, adjustment adjustment is recommended. The treatment must be maintained for at least 6 months. If the daily dose does not exceed 200mg, once/day in the evening may be suitable.

End of treatment: In case of intention to stop treatment with clozapin, reduce the dose of 1-2 weeks more than the recommended period of 1-2 weeks. If the sudden stopping is necessary, the patient must be carefully observed with the appearance of the reaction of the lack of drugs.

Start treatment: In patients who have the period of temporary suspension of treatment from the last dose of clozapin for more than 2 days, the treatment must be started to be 12.5 mg again for a time or twice on the first day. If this dose is well tolerated, capable of adjusting the dose to the point of faster treatment is recommended for the start of treatment. However, in any patient who has respiratory arrells or cardiac arroxes first with the original dose, but can be successfully adjusted to the treatment dose, the adjustment must be performed very carefully.

Mental disorders occur in the process of Parkinson's disease, in the case of treatment preparation:

Start treatment: The starting dose does not exceed 12.5 mg/day, used in the evening. The next dose increase must increase by nearly 12.5 mg, with a maximum of 2 times a week reaches a maximum of 50 mg, the dose cannot be achieved until the end of the second week. The best daily total amount must be given in the form of single dose in the evening.

Treatment dose interval: The average dosage is usually 25 and 37.5 mg/day. In case the treatment lasts at least a week at a dose of 50 mg failure, to provide a response to treatment, the dose may be carefully increased by increasing 12.5 mg/week.

Maximum dose: 50 mg/day dose is exceeded only in exceptions, and never exceeded the maximum dose of 100 mg/day. The increase in the dose must be limited or postponed if the hypotension is standing, the sedation is excessive or confusing. Blood pressure must be monitored in the first week of treatment.

Maintenance dose: When there is a decrease in comprehensive mental symptoms for at least 2 weeks, increasing Parkinson's medicine can be indicated in normal movement state. If this method causes recurrence of mental symptoms, clozapin dose may be increased by an increase of 12.5 mg/week to a maximum of 100 mg/day, used in a dose or divided in half.

End of treatment: gradually reducing the dose with about 12.5 mg more than a cycle of at least 1 week (preferably 2) is recommended. The treatment must be stopped in the case of neutrophils or neutropenia. Eye leukemia. In this case, careful mental monitoring is essential because the symptoms can recreate very quickly.

For people with liver failure: Use cautious clozapin along with regular monitoring of liver function tests.

For people with renal failure: Do not use clozapin for severe kidney failure.

Children: Not for children under 16 years old.

For patients aged 60 and older: Starting treatment is recommended in special low doses (12.5 mg for a time on the first day), the next dose increase is limited to 25 mg/day.

What do

do when using overdose? In children, overdose when using 50 - 200 mg has also caused medium to severe poisoning levels (changing the mind, increasing muscle tone, symptoms of the tower).

Symptoms: Drop, delusion, loss of reflexes, coma, confusion, hallucinations, anxiety, delirium, overseas symptoms, excessive reflexes, convulsions; Increase salivation, pupils, blurred vision, Thermolability; lower blood pressure, faint, fast pulse, arrhythmia; Inhaling pneumonia, shortness of breath, inhibition or respiratory failure.

How to handle: There is no antidote specialized for clozapin. Gastric and/or activated carbon within 6 hours after taking the medication. The abdominal separation and hemorrhage seemingly ineffective. Treatment of total condition under continuous monitoring, respiratory price, electrolyte balance monitoring and acid-base. The use of epinephrin must be avoided in the treatment of hypotension because the ability to create 'Epinephrin is reversed'. Phyistigmin can be used if there is signs of severe cholinergic poisoning.

Strict medical monitoring is necessary for at least 5 days by the possibility of slow reactions.

What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double doses to compensate for missed dose.

Side Effects

Blood and lymphatic system

Development of leukemia and grain leukemia is an inherent risk for clozapin treatment. Despite the overall recovery when stopping treatment, granulocytes can cause

Infections and can be fatal. Because the immediate treatment is required to prevent the growth of grain leukemia threats life, the WBC counting monitoring is mandatory.

Metabolic and nutrition disorders

Glucose tolerance is reduced and/or developed or worsen diabetes

is reported rare during clozapin treatment. In very rare cases, severe hyperglycemia, sometimes increases the concentration of keton in the body with high blood sugar levels, causing dehydration, which has been reported in some patients treated with Ciczapin without a history of hyperglycemia. The level of glucose returns to normal in most patients after stopping clozapin and in some cases of recurring blood sugar at the beginning of treatment.

Although most patients with risk factors for diabetes are not insulin depend on, hyperglycemia also see in some patients without known risk factors.

Nervous system disorders

The reactions are very often observed including drowsiness/sedation, and dizziness. Ciczapin can cause EEG changes, including the occurrence of a nose-to-see complex. It reduces the seizure threshold in the way depends on the dose and may promote convulsions or body convulsions. These symptoms are more likely to occur with rapid increase in doses and in patients with epilepsy previously existed. In these cases, the dose must be reduced and, if necessary, treated with anti -convulsions is started. Caraliazepin must be avoided because of its ability to inhibit the bone marrow function, and with other anti -convulsions drugs that must be considered for pharmacokinetics. In cases, patients treated with clozapin may have a delirium.

Very rare, chronic nervous system disorders have been reported in patients using clozapin that they have been treated with other sedatives. Patients with chronic nervous system disorders developed with other sedatives improved with clozapin.

Heart disorders

tachycardia and posture hypotension with or without interrupts may occur, especially in the first week of treatment. The regular and ability of hypotension is affected by the proportion and magnitude of the dose adjustment. Circulation failure is the result of deep hypotension, especially related to the adjustment of the attack dose, with serious consequences that can occur cardiac arrest or cloher, which has been reported to clozapin.

A few patients treated with Clozapin have ECG that changes similarly to the changes that are seen with other sedatives, including reduction of S-T and flat segment or reversing T waves, this returns to normal after stopping clozapin. The significant of the sieve of these changes is unknown. However, such abnormalities have been observed in patients with myocarditis, so this must be considered.

Cases of separation of arrhythmia, pericarditis and myocarditis have been told, some of which die. Most cases of myocarditis occurred in the first 2 months begins with clozapin treatment. Orchiditis usually occurs after treatment.

Nontilia has been reported along with some cases of myocarditis and pericarditis; It is not known, however, whether eucalyptus loves EOSIN is a reliable sign of heart inflammation or not.

Signs and symptoms of myocarditis or chronic heart disease do not know the cause of the tachycardia at rest, nervous, arrhythmia, chest pain and other symptoms and symptoms of heart failure (for example, unexplained fatigue, shortness of breath, shortness of breath), or symptoms of myocardial infarction. Other symptoms may appear on the above symptoms like the flu.

Sudden, unexplained death has occurred among patients with mental disorders using ordinary sedatives but also among mental disorders untreated. Such deaths have been reported very rare in patients using clozapin.

circuit disorders

Cases of rare congestion have been reported.

Respiratory system

Respiratory failure or respiratory stops occur very rare, with or without circulation.

digestive system

Constipation and increased salivation are too close, nausea and vomiting. Very rare intestinal obstruction can occur. Rarely, clozapin treatment may be associated with difficulty swallowing. The inhalation of food that can occur in patients with difficulty swallowing or as a result of acute overdose.

Liver disorders

Temporary, asymptomatic and rare liver enzyme, hepatitis and jaundice can occur. Very rare, fast liver necrosis has been reported. If jaundice develops, clozapin must be stopped. In rare cases, acute pancreatitis has been reported.

Renal disorders

Cases of separation of acute nephritis have been reported with clozapine treatment.

Reproductive and breast disorders

There are very rare reports on erection.

General disorders

Cases of dangerous neurological disorders due to the use of sedatives (NMS) have been reported in patients using clozapin both individually or in combination with lithium or CNS -oriented drugs.

Notify the physician 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

Mebamrol 100mg SPM drugs are contraindicated in the following cases:

Hypersensitivity to clozapin and any ingredients of the drug. Clozapin. or severe kidneys (for example: myocarditis). Progressive liver disease, liver failure. Concomitance with special sedatives should not.

Be cautious when used

This drug contains lactose monohydrate

Patients with rare genetic problems without galactose, lactase deficiency or glucose-galactose abutment should not be taken.

Nonflower tank

In case of eosinophilia, clozapin stops are recommended if the number of eosinophilia increases above 3000/mm3 (3.0x109/l); The treatment begins again only after the number of eosinophilia drops below 1000/mm3 (1.0x109/l).

platelet reduction

In case of platelet reduction, stop treatment with clozapin is recommended if the number of platelets is below 50000/mm3 (50x109/l).

Cardiovascular disorders

Hypotension, with or without fainting, may occur during clozapin treatment. Rarely, static capture can be long and can be added with cardiac arrest and/or respiratory arrest. Such issues are more likely to occur with simultaneous use of benzodiazepine or any other neurological drugs and during the initial adjustment process related to rapid doses; On very rare occasions, they can occur, even after the first dose. Therefore, patients started with Clozapin treatment required closely medical monitoring.

Monitoring of standard blood pressure and lying state is necessary during the first weeks of treatment in Parkinson's patients. Analysis of safety data shows that the use of clozapine is related to the risk of increased heart muscle inflammation especially transparent, but not limited to, the first two months of the treatment. In some cases, myocarditis may die. Pericarditis/pericardial fluid and chronic heart disease for unknown cause are also reported related to the use of clozapin; These reports also include deaths. Chronic myocarditis or chronic heart disease do not know the cause of suspected diseases in the persistent tachycardia during rest, especially the first two months of the treatment, and/or beat the chest drum, arrhythmia, chest pain and other symptoms and symptoms of heart failure (for example, unexplained, shortness of breath, shortness of breath), or symptoms like myocardial infarction. Other symptoms may appear added to the above symptoms like the flu. If myocarditis or chronic heart disease do not know the cause of suspicion, the treatment of clozapin must be stopped immediately and the patient is immediately transferred to the heart specialized doctor.

Patients with myocarditis or chronic heart disease do not know the cause of being promoted by clozapin must not be used clozapin.

Myocardial infarction

In addition, there are too newspapers in the circulation process of myocardial infarction that may be death. Assessing the cause is quite difficult in most cases because severe heart disease has existed first and reasonable causes.

extends the range of qt

As with other sedatives, caution is advised in patients with known cardiovascular disease or family history of the QT. As with other sedatives, caution must be done when clozapin is prescribed with other drugs known to increase the QT range.

Issues that are harmful to the blood vessels

The risk of increasing approximately 3 times the problems that are harmful to the brain vessels have been seen in placebo trials that are randomly controlled in people with dementia with some second -generation sedative drugs. The mechanism for this increasing risk is not known. An increased risk cannot be excluded for other sedatives or other patients. Clozapin must be used with caution in patients with risk factors for stroke.

Risk of congestion

Because clozapin may be associated with clogging, the patient's fixation must be avoided. Venous cases (VTE) have been reported to sedatives. Because patients are treated with sedative drugs, there are often risk factors for VTE, all VTE risk factors must be determined in advance and during clozapine treatment and preventive measures.

SECRETS

Patients with a history of epilepsy must be closely observed during clozapin treatment because seizures related to the dose have been reported. In such cases, the dose must be reduced and if necessary, anti -seizure treatment must be started.

The anti -cholinergic effects

Clozapin has anti -anti -anti -cholinergic effects, they can cause unwanted reactions to the whole body. Careful monitoring is indicated in the case of prostate hypertrophy and narrow-angle glaucoma. Almost certainly reporting its anti -cholinergic properties, clozapin is associated with changing the degree of impairment of intestinal motility, the range from constipation to the intestine, the tightness of the stool and intestinal obstruction. On some rare occasions, these cases are death. Special care is needed in patients who are using the drugs at the same time, the drugs are known to cause constipation (especially drugs with anti -cholinergic properties such as some sedative drugs, antidepressants and Parkinson's treatment), with a history of colon or lower abdominal surgery because they can worsen this condition. The survival is constipation and being active.

Fever

During the course of clozapin treatment, patients may have temporary temperature increases over 38 ° C, with a peak in the first 3 weeks of treatment. This fever is often harmless. Occasionally, it may be related to the increase or decrease of the total number of WBCs. Patients with fever must be carefully evaluated to eliminate the possibility of bacterial infections or granulocytosis. When fever is high, the possibility of dangerous neurological disorders due to sedative use (NMS) must be considered. If the diagnosis of NMS, Clozapin must be stopped immediately and appropriate medical measures must be applied.

Metabolic changes

The second -generation sedative, including clozapin, is associated with metabolic bars, which can increase the risk of cardiovascular/brain vessels. These metabolic changes may include hyperglycemia, hyperlipidemia, and weight gain. While the second -generation sedative can cause some metabolic changes, each drug in this group has their specific summary.

Hyperglycemia

Glucose tolerance decreases and/or develops or makes diabetes worse and is reported rare during clozapin treatment. The mechanism of this possibility is not known. Cases of severe hyperglycemia with Keton in the body increased or comatose due to high blood glucose has been reported very rare in patients without a history of hyperglycemia first, some of them died. When monitoring the available data, stop clozapin most overcoming the impaired glucose tolerance, and the reuse of clozapin causes this phenomenon. Patients who have been diagnosed with diabetes began to use second -generation sedatives must be monitored through the worse of glucose control. Patients with diabetes risk factors (for example, obesity, family history with diabetes) who start using second -generation sedatives must perform blood glucose tests quickly at the beginning of treatment and periodically during treatment. Patients develop symptoms of hyperglycemia during treatment with second -generation sedative drugs that must perform blood glucose tests quickly. In some cases, hyperglycemia is resolved when stopping the second generation sedative; However, some patients are required to continue treating diabetes despite suspicious stops. Clozapin's stopping must be considered in patients when medication control over hyperglycemia fails.

Hypermathy lipid

Unwanted changes in lipids in patients treated with second -generation sedatives, including clozapin. Clinical monitoring, including lipid reviews continue to standards and periodically in patients using clozapin, recommended.

weight gain

Weight gain has been observed with the use of second -generation sedatives, including clozapin. Clinical monitoring of the recommended volume.

The effects of feedback, reactions of drug shortages

The reactions of acute lack of drugs have been reported after the sudden suspension of clozapin, so the slowly stopped drug is recommended (1-2 weeks) and closely monitor patients during this time before stopping with clozapin treatment to avoid feedback of mental symptoms. If sudden stopping is necessary (for example, because of leukopenia), the patient must be carefully observed the recurrence of mental symptoms and symptoms related to the anti -cholinergic, such as sweating, headache, nausea and diarrhea.

Special patient

Hepatic failure: Patients with stable liver disorders that exist before they may use clozapin, but need to do regular liver function tests. Liver function tests must be performed in patients where these patients are likely to be able to impaired liver function, such as nausea, vomiting and/or anorexia, developing during the treatment of clozapin. If the increase in clinical values (more than 3 times UNL) or if jaundice symptoms occur, clozapin treatment must be stopped. It can be started again only when the results of liver function test are normal. In such cases, liver function must be closely monitored after reusing clozapin.

Patients aged 60 and older: Starting treatment in 60 -year -old patients and taller recommended at lower doses. Standing hypotension can occur by the treatment of clozapin and have a rapid vascular report, which may last. 60 -year -old and higher patients, especially patients with heart -damaged heart function, may be more sensitive to these effects. Patients in the age of 60 and higher are also especially sensitive to the anti -cholinergic effects of Clozapin, such as urinary retention and constipation.

Increasing mortality rate in memory loss

Data from major studies observed that the elderly people who have dementia are treated with sedatives are at risk of increased death, compared to those who are not treated. There is not enough data to make sure the accuracy of the risk and the cause of the risk of increasing is not known.

Clozapin is not accepted for the treatment of behavioral disorders related to dementia.

The effect of the drug on the ability to drive and operate machinery

Due to the ability of Clozapin to sedate and lower the seizure threshold, activities such as driving and operating machinery should avoid, especially during the weeks starting treatment.

Use drugs for women during pregnancy and lactation

Pregnant women

Because Clozapin, only clinical data is limited to drug use in pregnant women. Animal studies do not specify direct or indirect effects on pregnant women, the development of embryos/fetal embryos, birth or postpartum development. Precautions when used for pregnant women and consider danger to the beginning of this object.

Babies are exposed to sedative drugs (including clozapin) in the last 3 months of pregnancy with risks of harmful reactions including symptoms of outsider and/or stopping drugs that they may change harshly and during postpartum time. There are reports of anxiety, increased muscle strength, reducing muscle tension, tremor, drowsiness, respiratory failure, or eating disorders. As a result, newborns must be carefully monitored.

breastfeeding women

Animal studies show that clozapin is excreted in milk and has the effect of inhibiting the central nervous system in breastfeeding, so do not use clozapin for nursing women or not breastfeeding when required to treat the mother.

Interactive drug

Not used simultaneously

The drugs are known to inhibit the bone marrow function (carbamazepin, cotrimoxazol, chloramphenicol, penicilamine, antibacterial sulfamid, anticancer drugs, pyrazolone conductive painkillers such as azapropazol, phenylbutazone, neurological drugs that are injected with injection or implantation of non -subcuties. Increases the risk of bone marrow inhibition.

Sediments that have a long impact (capable of inhibiting bone marrow) must not be used simultaneously with clozapin because they cannot be removed from the body in situations when possible, for example neutropenia.

Alcohol is not used simultaneously with clozapin due to the ability to be sedated.

Droperidol is not used simultaneously with clozapin due to increased risk of heart toxicity (extending the QT, torsion, cardiac arrest).

Metoclopramid is not simultaneously with clozapin due to an increased risk of outsider syndrome.

The kidneys include the dose adjustment

Increases the effect and toxicity of clozapin:

Clozapin can increase the central effect of CNS inhibitors such as anesthetic, antihistamine and benzodiazepine. Precautions are particularly recommended when treated with clozapin is started in patients taking benzodiazepin or any other psychiatric drugs. These patients are at risk of increased circulatory failure, in rare cases, may be severe and can lead to stopping and/or stopping steaming. It is unclear whether heart failure or respiratory failure can be prevented by adjusting the dose.

Alcohol, Mao Mao inhibitors (IMAO), other central nervous system inhibitors (including opiod analgesic and benzodiazepine derivatives) increase the central nervous inhibition effect when used simultaneously with clozapine. Because the ability of side effects, caution is essential when used simultaneously with drugs that have anti -cholinergic effects, hypotension, or respiratory inhibitors.

Due to the anti-alpha-adrenergic properties, Clozapin can reduce the effectiveness of norepinephrine hypertension or most alpha-adrenergic drugs and reverse the hypertension of Epinephrine.

Concentrated with drugs that inhibit the activity of some cytochrom P450 is the cytochrom P450 may increase clozapin levels, and clozapin's doses may need to be reduced to prevent unwanted effects. This is more important for selective serotonin. Some other Serotonin reabsorption inhibitors such as fluoxetin, paroxetin, to weaker levels, sertralin, phenothazin derivatives, IC anti -arrhythmic drugs such as propafenon, flecainid, encainid, ritonavir are CYP 2D6 inhibitors and as a result, the main dynamic pharmacy interactions with less likely to occur. Similarly, pharmacokinetic interactions with CYP 3A4 inhibitors such as antifungal drugs, cimetidin, erythromycin and protease inhibitors are not sure, although some have reported. Because the plasma concentration of clozapin is increased by caffeine and decreased by nearly 50% after a 5 -day cycle without caffeine, changing the dose of clozapin may be necessary when there is a change in the habit of drinking caffeine. In the case of sudden stopping smoking, plasma clozapin levels may increase, thus increasing harmful effects.

Cases reported on interactions between citalopram and clozapin, which may increase the harmful effects related to clozapin. The nature of this interaction has not been completely explained.

Reduce the effect of clozapin

Concentrated with drugs that promote cytochrom P450 enzymes can reduce clozapine levels in plasma, resulting in reduced efficiency. The drugs are known to promote the activity of cytochrom P450 enzymes and with interactions that have been reported to clozapin including carbamazepin (not used simultaneously with clozapin, due to its ability to inhibit bone marrow), phenytoin and rifampicin. The substances that promote CYP1A2 are known, like omeprazol, which can lead to reduced blood clozapin levels. The ability to reduce the effectiveness of clozapin is considered when it is used in combination with these drugs.

Other

Simultaneous use of lithium or CNS activity may increase the risk of developing dangerous neurological disorders due to sedative use (NMS).

Severe but rare reports of convulsions, including the strong development of convulsions in patients who are not epilepsy, and separate cases are delirious when clozapin is simultaneously used with Valproic acid that has been reported. These effects are probably due to pharmacological interaction, the mechanism of this has not been determined.

Be cautious to inform patients being treated simultaneously with other drugs inhibiting or promoting Isenzyme cytochrom P450. With 3 -round antidepressants, phenothiazine and 1C tube anti -dysplasia drugs, it is known to be associated with Cytochrom P450 2D6, so there are no clinical related interactions observed.

As with other sedatives, caution must be done when clozapin is prescribed with drugs that are known to increase the QTC range, or cause electrolyte imbalance.

Storage

Leave a cool place, avoid light, temperature below 30⁰C.

To be out of reach of children, read the user manual carefully before use.

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