DAFIDI 25 Southeast drug treats neurological diseases (10 blisters x 10 tablets)

Dosage form Box of 10 blisters x 10 tablets
Specifications Clozapin
Ingredient Southeast Pharmaceutical Production - Trading Joint Stock Company

Ingredient

Composition information	Content
Clozapin	25mg

Uses

indications

anti -treatment schizophrenia

is indicated in anti -treatment schizophrenia patients and severe schizophrenia patients, neurological adverse reactions that do not cure other mental dealers, including non -typical anti -psychotic drugs.

Definition of treatment is defined as a lack of clinical improvement in adequately, despite the full dose of at least two different anti -psychotic drugs, including non -typical anti -psychotic substances, regulations for appropriate time.

Mental disorders throughout the process of Parkinson's disease

Clozapin is also indicated in mental disorders that occur during the process of Parkinson's disease, in the case of standard treatment that failed.

Pharmacokology

Pharmacological group: Anti -psychotic agent.

ATC code: n05Ah02.

Clozapin is the first non -typical anti -psychotropic drug of the second generation and is the substance of dibenzodiazepin. The drug has many different pharmacological properties from the classic neurolysis drugs of phenothiazin or butyrophenen, such as less thinning surgery syndrome, less prolactin secretion.

Clozapin's anti -psychotic effects have not been completely clarified. This mechanism includes the participation of Serotoninergic, Adrenergic and Cholinergic neurotransmitter systems in the central nervous system and is related to the selective effect on the dopaminergic system in the border area. Clozapin has weak affinity associated with the receptor of dopamine (D1, D2, D3, D5) in the pattern and the back of the yen, but has a moderate or strong affinity for the D4 receptor. This makes the difference between clozapine and other classic anti -disorder medications (less effects of foreign tower, less prolactin secretion).

Alpha-commenergic receptor antagonistic effect explains a part of the sedative effect, muscle relaxation and other effects on the cardiovascular system 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, 5HT-3 receptors in the central nervous system and peripheral relevant partly to the deep sedative effect, effect on the negative evidence of schizophrenia and gain weight during the treatment with clozapine. Clozapin has a clear activity on Y-Aminobutyric Acid (GABA) which is a substance that inhibits dopaminergic neurons. Contrary to the effects of classic anti -disorder, clozapin increases the rotation of the gaba in the form of the pattern and the accubens. Increasing rotation and release of GABA in the form of pattern can reduce the non -tower reaction, while in the Accubens 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 wave, slowing the frequency of dominant alpha wave. In some patients, clozapin reduces the potential time and increases a lot of time to sleep in the eye.

Clozapin can inhibit strong bone marrow leading to grain leukocytes, even fatal. The grain leukemia is not clearly related to any patient's characteristics and cannot be predicted through dosage or treatment time. However, the highest rate is common in the first 6 months of clozapin treatment for patients over 50 years old.

pharmacokinetics

absorption:

After drinking, Clozapin absorbed quickly and almost entirely through the digestive tract (mainly in the sub -colon), but due to the one -step metabolism in the liver, the oral bioavail only reached 50 - 60%. Food does not affect the absorption of the drug. The concentration of medication in the blood reaches a maximum of 2.5 hours after taking the drug. Plasma drug concentration reaches a stable state after 7-10 days with a reminded dose, with an average peak concentration of 319 nanogam/ml achieved after the dose of 100 mg, 2 times/day. Pharmacological effects appear about 15 minutes 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 a few weeks, the maximum effect may need several months of treatment.

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 state of 1.6 liters/kg. Because the distribution is smaller than other psychotic drugs, clozapin is less stored in tissues. The ratio of binding with plasma protein is about 97%.

Metabolism:

Clozapin is metabolized in the liver before eliminating by n-demethylation reactions, n-oxidation, hydroxylation, 3'-carbon-oxygen, epoxy chemicals mainly through CYP1A2 and then concluded with glucuronic acid. Demethyl metabolites (Norclozapin) also retain a part of the activity of clozapin.

Era:

After taking the single dose of 75 mg, half -life eliminated in the plasma of Clozapin about 8 hours (ranging from 4 hours to 12 hours). Half life eliminated after the dose repeated 100 mg, 2 times/day in a stable state at about 12 hours (ranging from 4 to 66 hours). Clozapin is eliminated mainly in the form of metabolites, a small part (2-5%) in the form of intact through urine and feces.

Before taking DAFIDI 25 Southeast drug treats neurological diseases (10 blisters x 10 tablets)

How to use

Clozapin is used orally, can be taken at meals or away from meals.

Dosage

The dose of clozapin must be carefully corrected on each patient and the lowest dose used effectively. Dosage should be gradually increased and divided into doses of the day at the beginning of treatment to minimize ADR.

Dosage must be adjusted separately. For each patient, the lowest dose should be used effectively. For the dose that cannot be done/perform carefully and a division schedule is all necessary to minimize the risks of hypotension, convulsions and sedation.

Starting the treatment of clozapin must be limited to patients with leukemia ≥ 3500 / mm3 (3.5x109 / l) and an ANC ≥ 2000 / mm3 (2.0x109 / l) within the normal limit in the treatment regimen. Adjustment of the prescribed dosage in patients who also receive drugs with pharmacokinetics and pharmacokinetics with clozapin, such as benzodiazepine or serotonin inhibitors have selective reabsorption.

Transfer from an anti -psychotic therapy first to treat clozapin

Clozapin should not be used in combination with other anti -psychotic drugs. When treating clozapin is to start in a patient undergoing anti -psychotic therapy, it is recommended that other anti -psychotic drugs for the first time should stop because when reducing the dose down.

The following doses are recommended:

Dosage for adults over 16 years old:

Treatment of anti -anti -treatment mental treatment:

Start treatment: The first day of 12.5 mg (half of 25 mg), 1 or 2 times/day (older people 12.5 mg, 1 time/day), day 2: 25 - 50 mg, 1 or 2 times/day (older 25 - 37.5 mg, 1 time/day) then increase the dose gradually (add 25-50 mg/day for each increase; The dose of 300 mg/day, divided into several times (using a larger dose before bed, up to 200 mg). In case of necessity, additional dose may continue (add 50 - 100 mg after weeks) to achieve the common dose of treatment in the range of 250 - 400 mg/day (maximum 900 mg/day). Note that when the treatment is achieved, it is necessary to continue treating with the lowest doses effectively. After controlling the symptoms, it is necessary to carefully reduce the dose to the minimum maintenance dose effectively.

Maximum dose: To get full treatment benefits, some patients may need larger doses, in some cases may be up to 900 mg/day. The ability to increase side effects (during seizures) occurs at a dose of over 450 mg/day must be noted.

Maintenance dose: Once the treatment is achieved, it is necessary to continue treating with the lowest dose effectively. Treatment should be maintained for at least 6 months. If the daily dose does not exceed 200 mg, the drug should be used once a day in the evening.

End of treatment: In case of a plan to terminate clozapin treatment, the dose should gradually reduce the dose for 1 to 2 weeks before stopping. If sudden stopping the drug is necessary (for example, because Leucopoenia), the patient must be carefully monitored to prevent the recurrence of symptoms related to cholinergic recovery, such as sweating, headache, nausea, vomiting and diarrhea.

Note: In the case of treatment after stopping clozapin before, it is necessary to follow the distance of at least 2 weeks between the two treatments, starting with a dose of 12.5 mg, 1 or 2 times/day of the first day, the rapid dose increasing stage may be faster than the previous treatment period. However, it is necessary to be very cautious if there is a cardiac arrest or respiration before when using the starting dose.

Reduce the risk of relapse of suicide behaviors in schizophrenia patients or other psychosis:

Start: 12.5 mg, 1 or 2 times/day, then gradually increase the dose depending on the response of the patient (up 25 - 50 mg/day for each increase) to the dose of 300 - 450 mg/day after 2 weeks.

Moderate dose is about 300 mg/day (ranging from 12.5 mg to 900 mg/day). Treatment time should be extended for at least 2 years if the disease is not worse or the serious toxicity of the drug.

Treatment of psychosis, agitation appears in Parkinson's disease:

Start 12.5 mg/day before going to bed, then increase gradually depending on the response of the patient with a dose increased by 12.5 mg, an increase of 2 times/week. The usual dose ranges from 25 mg to 37.5 mg/day, used before going to bed (up to 50 mg/day). In the exception, the additional dose may continue (add 12.5 mg per week) to a maximum dose of 100 mg/day, divided 1-2 times.

Used for people in the following special group:

People with liver failure:

Patients with liver failure should be careful to drink clozapin regularly monitored for liver function tests.

Children:

Unresed research on children. The safety and effectiveness of clozapin in children and adolescents under 16 years old has not been determined. Children should not use this medicine.

Patient 60 years and older:

Starting treatment is recommended at a particularly low dose (12.5 mg for a first day), the next dose is limited to 25 mg/day.

Renal failure:

Do not use clozapin for patients with severe renal failure.

What do

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

Symptoms: unconsciousness, central neurological inhibition, tachycardia, hypotension, respiratory failure, pneumonia, increased salivation, sometimes seizures have been recorded.

If you overdose, you need to contact the doctor, pharmacist or the closest hospital emergency room immediately, bring the remaining pills and the box if possible.

What to do when you forget a dose? If the time is close to the next dose, skip the forgotten dose and take the next dose to the normal plan. Do not double the dose.

Side Effects

Common, ADR> 1/100:

Cardiovascular: tachycardia, chest pain, hypertension, hypotension, unconsciousness. Chemistry: Constipation, weight gain, nausea, vomiting, increased salivation, discomfort/feeling of burns at the epigastric area, anorexia, diarrhea. Seeds.

Arrhythmia (ventricular and atrial), slow rhythm, hepatitis, jaundice, interstitial nephritis, muscle weakness syndrome, narrow -angle glaucoma, malignant neuropular syndrome, heat lowering, seizure state.

Rare, 10 000

Anemia, hyperglycemia.

Very rare, ADR

Intractive coma, osmotic boosting coma, triglyceride, cholesterol hyperactivity, late dysplasia, heart disease, muscle disease, thrombocytopenia, Stevens Johnson syndrome, diverse skin on the skin.

Notice the doctor with 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

Designing epilepsy. Severe (such as myocarditis). liver.

Caution when using

granulocyte loss:

The risk of granulocytes (the number of leukemia

Restricting the use of clozapin in patients with WBC> 3500/mm2 (3.5 x 109/l) and neutral leukocytes ≥ 2000/mm2 (2.0 x 109/l) and monitor the number of WBC and neutral leukocytes weekly for the first 18 weeks of treatment and then at least 4 weeks.

Before starting treatment with clozapin patients need to be tested for blood (see "neutral leukocytes") and health check. Patients with a history of heart disease or abnormal symptoms of heart need to be examined by specialists.

Patients who have stopped using clozapin due to WBC anemia or neutral leukemia, must not continue with Hozapin.

Eosinophilia:

In the case of eosin leukemia, clozapin should be discontinued if the number of eosinophilia> 3000 mm3 (3.0 x 109/l) continues to be treated when eosinophilia drops below 1000/mm3 (1.0x109/l).

Platelet reduction:

In case the patient has a platelet reduction, stop using Dafidi 25 if the number of platelets drops below 50000/mm3 (50 × 109/l).

cardiovascular disorders:

Hypotension posture, with or without fainting, may appear in the early stages of clozapin treatment. So closely monitor patients in this stage.

The risk of myocarditis and myocarditis can be life -threatening patients who have been reported when using clozapin. The risk of myocarditis usually occurs within the first 2 months of treatment. Therefore, it is necessary to examine thoroughly, make electrocardiograms to detect cardiovascular abnormalities before starting with clozapin treatment. For patients with cardiovascular abnormalities or a history of cardiovascular disease, only using clozapin after cautiously consider risks - benefits. It is necessary to suspect myocarditis or myocardial disease when the heart appears rapidly prolonged, especially within the first 2 months of treatment, accompanied by or not accompanied by chest drum, arrhythmia, chest pain and other signs of heart failure (idiopathic fatigue, shortness of breath, fast breathing). Stop clozapin immediately if suspected of myocarditis or myocarditis and transfer patients to treatment at cardiovascular specialist.

extends the QT range:

As well as other anti -mental disorders, be cautious when taking the drug in patients with cardiovascular disease or families with a history of extension of QT. Precautions when used at the same time with the drug extends the QT.

Myocardial infarction: can occur when using clozapin.

Effects on cerebral vessels: Clozapin should be used cautiously in patients at risk of stroke.

anti -cholinergic effect:

Be cautious when using clozapin for patients at risk of constipation, intestinal obstruction (History of colon or colon surgery, patients being treated with other anti -cheolinergic drugs), patients with prostate hypertrophy, narrow -angle glaucoma patients due to the anti -cholinergic effect of clozapin can aggravate these diseases.

epilepsy:

Be cautious when using clozapin for patients with a history of epilepsy, head injury or being treated with drugs that can reduce epilepsy threshold due to convulsions depending on the dose that may appear during the treatment with clozapin.

Blood lipid disorders:

Unwanted lipid changes have been observed in patients treated with typical anti -psychotic drugs, including clozapin.

Weight gain:

Weight gain has been recorded when using non -typical anti -psychotic drugs, including clozapin. Clinical monitoring is recommended.

Be cautious when using clozapin for diabetes patients with diabetes or glucose metabolism disorders, tight monitoring of blood glucose concentration due to the ability to increase blood sugar of clozapin, sometimes accompanied by ceton acidosis, coma increasing osmotic pressure has been reported.

Should not be used simultaneously with other neuroleptic drugs.

Risk of thrombosis:

Cases of venous thromboembolism (VTE) have been reported with anti -psychotic drugs. VTE factors need to be determined before and during treatment with clozapin and preventive measures should be taken.

During Dafidi 25 treatment, the patient's body temperature may increase fleeting above 38 ° C, the highest incidence in the first 3 weeks of treatment. This fever is generally benign. Occasionally, it may be related to the increase or decrease of the number of white blood cells. Patients with fever should be carefully monitored to eliminate the possibility of infection or the growth of granulocytes. If there is a high fever, malignant neuropular syndrome (NMS) must be considered. If diagnosis has NMS, Dafidi 25 should stop immediately and have appropriate medical measures.

Not typical anti -psychotic drugs, including Dafidi 25, combined with metabolic changes that can increase the risk of cardiovascular/cerebrovascular disease. Metabolic changes include hyperglycemia, blood lipid disorders and weight gain.

Sudden stopping reaction has been reported after suddenly stop clozapin, so it is necessary to reduce the dose slowly. If the drug is discontinued suddenly (for example, an leukopenia), the patient must be monitored by the kidneys to avoid recurrent symptoms of neuron and symptoms related to Cholinergic recovery, such as sweating, headache, nausea, vomiting and diarrhea.

Lactose intolerance:

Dafidi 25 tablets contain lactose, so it should not be used for patients with Galact

Special subjects:

Be cautious when using clozapin for patients with a history of liver disease, avoiding patients with progressive liver disease or liver failure due to impaired liver function including hepatitis that has been reported related to the use of clozapin. It is necessary to test the liver function evaluation when nausea, vomiting, fatigue in patients are being treated with clozapin.

Be cautious when using Clozapin for children: The safety and effectiveness of clozapin has not been established in children under 16 years old. However, the drug has been used to treat schizophrenia does not respond to other drugs. Be careful due to the high risk of unwanted effect on hematology and the risk of seizures on children without a history of epilepsy. The risk of neutrophils reduction, epilepsy related to clozapin is higher than at this age.

Be cautious when using clozapin for the elderly: Patients aged 60 and older should start treatment at the lowest dose. Hypotension and tachycardia may occur when treated with clozapin. Patients aged 60 years and older, especially people with cardiovascular function, can be easily affected.

Increase the death rate in the elderly with dementia.

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

Clozapin can cause dizziness, dizziness, headache. Therefore, do not use the drug while driving and operating machinery.

Use drugs for women during pregnancy and lactation

should only use clozapin when really necessary and potential benefits are greater than the risk of risk.

Women who use clozapin should stop breastfeeding.

Drug interaction

Avoid coordination should not be coordinated: Clozapin should not be combined with drugs that inhibit bone marrow (carbamazepin, cotrimoxazol, chloramphenicol, penicilamine, antibacterial sulfamid, anticancer drugs, pyrazolone conductive painkillers like azapropazon, phenybutazon, an An Neurology prolonged use of injection or subcutaneous implant) due to increased risk of bone marrow inhibition; With droperidol due to increased risk of toxicity on the heart (extending the QT range, torsion, cardiac arrest); With Metoclopramide due to increased risk of outsurers of foreign tower syndrome.

Increases the effects and toxicity of clozapin: Concomitance Clozapin with benzodiazepine drugs may increase the risk of circulatory inhibition leading to cardiac arrest and respiration. Alcohol, enzyme inhibitors (IMAO), other central nervous system inhibitors (including opioid analgesics and benzodiazepine derivatives) increase the central nerve inhibitor when used with clozapine. Lithi can increase the possibility of malignant neuroleptic syndrome when used with clozapin. CYP450 inhibitors (caffeine, cimetidin, erythromycin, quinidin, some antidepressants such as fluvoxamine, paroxetin, fluoxetin, sertralin, phenothiazine derivatives, IC anti -arrhythmic drugs such as propafenon, flecainid, encainid, ciprofloxacin, ritonavir) Therefore can increase the effect and toxicity of clozapin.

Reduce the effect of clozapin: CYP450 induction drugs (phenobarbital, carbamazepin, phenytoin, rifampicin, omeprazol, nicotine) reduce blood levels so it can reduce the effect of clozapine.

Increases the effects and toxicity of some other drugs: Clozapin increases the effect (constipation, dry mouth, urinary retention, sedation, visual disorders) of anti -cholinergic drugs, increasing the lowering effect of anti -hypertension drugs.

Storage

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

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