Instructions for quetiapine fumarate sustained-release tablets

Quetiapine fumarate sustained-release tablets are used to treat schizophrenia. The following is the instruction manual of quetiapine fumarate sustained-release tablets compiled by me. Welcome to reading.

Product introduction of quetiapine fumarate sustained-release tablets Generic name: quetiapine fumarate sustained-release tablets

Manufacturer: AstraZeneca Pharmaceutical Co., Ltd.

Approval number: National Medicine Zhunzi J20 1400 13

Drug specification: 50mg*20 tablets.

Drug price: 0 yuan

Instructions for Quetiapine Fumarate Sustained-release Tablets Product Name (Silikang) Generic Name Quetiapine Fumarate Sustained-release Tablets

Chinese Pinyin Compound Code Abacus Liuping Huanshi Film

Quetiapine sustained-release tablets

Quetiapine fumarate is the main component.

Round, 1 1 mm, white, biconvex, coated tablets.

Indications for the treatment of schizophrenia.

Usage and dosage: twice a day, before and after meals.

Adults: The total daily dose for the first four days of treatment was 50 mg (day one), 100 mg (day two), 200 mg (day three) and 300 mg (day four) respectively. After the fourth day, the near dose gradually increased to the effective dose range, generally 300-450mg/ day. The dosage can be adjusted between 150-750mg/ day according to the patient's clinical response and tolerance.

Liver and kidney damage: the clearance rate of patients with liver and kidney damage decreased by about 25% after oral quetiapine. Quetiapine is widely metabolized in the liver, so patients with liver injury should use it with caution. For patients with kidney or liver damage, the initial dose of Sirecan should be 25mg/ day. Subsequently, the daily dose is increased by 25-50 mg until the effective dose is reached.

Pharmacology and toxicology

Quetiapine is a new atypical antipsychotic, which is a variety of neurotransmitter receptor antagonists. In the brain, quetiapine has a high affinity for 5- hydroxytryptamine (5-HT2) receptor, which is greater than that for dopamine D 1 and dopamine D2 receptor in the brain. Quetiapine has high affinity for histamine H 1 receptor and adrenergic a 1 receptor, and low affinity for adrenergic a2 receptor, but basically has no affinity for cholinergic muscarinic receptor or benzodiazepine receptor. If conditioned avoidance reflex is detected, the activity of quetiapine antipsychotic drugs is positive.

The results of pharmacodynamic animal experiments show that the possibility of predicting EPS shows that the dose of quetiapine that effectively blocks dopamine D2 receptor only leads to mild rigidity; Quetiapine selectively reduced the discharge of A 10 dopaminergic neurons in the midbrain limbic system, but had a weak effect on A9 neurons in substantia nigra striatum related to motor function. Quetiapine only has a slight effect on dystonia in monkeys allergic to nerve blockers.

Clinical Efficacy The results of three placebo-controlled clinical trials, including a trial of quetiapine with a daily dose of 75 ~ 750 mg, showed that the incidence of EPS caused by quetiapine was no different from that of placebo group or combined treatment group with anticholinergic drugs. Quetiapine does not produce sustained prolactin increase. The results of multi-fixed dose clinical trials showed that there was no difference in prolactin levels between different quetiapine dose groups and placebo group. Clinical trials show that quetiapine is effective in treating both positive and negative symptoms of schizophrenia. One trial compared with chlorpromazine and two trials compared with haloperidol showed that the short-term efficacy of quetiapine was equivalent to that of the control drug.

Toxicology study acute toxicity study Quetiapine has very low acute toxicity. After oral administration (500 mg/kg) or intraperitoneal injection (100 mg/kg), mice and rats have typical antipsychotic effects, including decreased activity, drooping eyelids, loss of righting reflex, salivation and convulsion.

pharmacokinetics

1. quetiapine is well absorbed and completely metabolized after oral administration. The main metabolites in human plasma have no obvious pharmacological activity.

2. Eating has no obvious effect on the bioavailability of quetiapine. The elimination half-life of quetiapine is about 7 hours. The binding rate of plasma protein was 83%.

Clinical trials have confirmed that taking quetiapine twice a day is effective. Positron emission tomography (PET) data further confirmed that the drug's occupation of 5-HT2 and D2 receptors could last for 12 hours after administration.

4. The pharmacokinetics of quetiapine is linear, and there is no gender difference.

5. The average clearance rate of quetiapine in the elderly is 30 ~ 50% lower than that of adults aged 18 ~ 65.

6. The average plasma clearance rate of quetiapine in patients with severe renal damage (creatinine clearance rate is lower than 30ml/min/ 1.73m2) and liver damage (stable alcoholic cirrhosis) can be reduced by about 25%, but the individual clearance rate is within the range of normal population.

7. The metabolism of quetiapine is relatively complete. After taking radiolabeled quetiapine, the original compounds in urine or feces only account for less than 5% of the unchanged drug-related substances. About 73% of radioactive substances are excreted in urine, and 265,438+0% are excreted in feces.

8. In vitro studies have confirmed that the main metabolic enzyme of quetiapine is CYP3A4 of cytochrome P450 enzyme system.

9. In a multi-dose clinical trial, the pharmacokinetics of quetiapine in healthy volunteers was evaluated before or during ketoconazole treatment. The results showed that the average Cmax and AUC of quetiapine increased by 235% and 522% respectively, and the corresponding average oral clearance rate decreased by 84%. The average half-life of quetiapine increased from 2.6 hours to 6.8 hours, but the average tmax remained unchanged.

Quetiapine and its metabolites are weak inhibitors of cytochrome P450 enzyme 1A2, 2C9, 2C 19, 2D6 and 3A4, but they only appear at the concentration of 10 ~ 50 times higher than the effective dose range of human body. According to these in vitro research results, quetiapine combined with other drugs is not easy to cause clinically significant drug inhibition related to cytochrome P450 enzyme.

Adverse reactions The most common adverse drug reactions (ADRs) of this product are drowsiness, dizziness, dry mouth, mild weakness, constipation, tachycardia, orthostatic hypotension and dyspepsia. Like other antipsychotics, syncope, malignant syndrome of antipsychotics, leukopenia, neutropenia and peripheral edema are related to this product. 1. See note. 2. Sleepiness may occur, usually in the first two weeks of treatment, which can be eliminated after continuous medication. 3. There are no reports of persistent severe neutropenia or agranulocytosis in the controlled clinical trials of this product. In post-marketing applications, leukopenia and/or neutropenia can be recovered after stopping the treatment of this product. Risk factors for leukopenia and/or neutropenia include low white blood cell count and a history of drug-induced leukopenia and/or neutropenia. 4. Mainly in the first few weeks of treatment. 5. In some patients taking this product, asymptomatic serum transaminase (ALT, AST) or? -GT level increased. This increase is usually recovered during the continuous processing of the product. 6. Like other antipsychotics with a 1 adrenaline blocking effect, this product may cause orthostatic hypotension (accompanied by dizziness), tachycardia and syncope in some patients; These events are more likely to occur during the initial dose increase period. When treated with this product, the level of thyroid hormone may decrease slightly in a dose-related manner, especially the total T4 and free T4. The decrease of total T _ 4 and free T _ 4 was the most significant in 2 ~ 4 weeks after quetiapine treatment, and there was no further decrease in long-term treatment. Almost all patients can recover their effects on total T4 and free T4 after stopping quetiapine, regardless of the course of treatment. Only at high doses, a small reduction in total T3 and T3 reversal was observed. The level of TBG did not change, and TSH generally did not increase correspondingly, indicating that this product will not cause clinically significant hypothyroidism. During quetiapine treatment, hyperglycemia and aggravation of pre-existing diabetes were rarely reported. Like other antipsychotics, this product may also cause weight gain, mainly in the first few weeks of treatment. Like other antipsychotics, this product may lead to prolonged QTc interval, but this change will not continue to increase in clinical trials (see precautions). There are reports of acute withdrawal reactions (see precautions).

Precautions: Use this product with caution in patients with known cardiovascular and cerebrovascular diseases or other hypotensive tendencies. This product may cause orthostatic hypotension, especially during the first administration; The above phenomenon is more common in elderly patients than in young patients. In clinical trials, quetiapine has nothing to do with prolonged QTC interval. However, like other antipsychotics, we should be cautious when quetiapine is combined with other drugs known to prolong QTC interval, especially in elderly patients. Epilepsy In clinical controlled trials, there is no difference in the incidence of epilepsy between patients taking this product and patients taking placebo. As with other antipsychotics, attention should be paid to the treatment of epileptic patients. Like other antipsychotics, delayed dyskinesia may also lead to delayed dyskinesia after long-term treatment with this product. If there are signs and symptoms of tardive dyskinesia, you should consider reducing the dosage of this product or stopping using it. Neuroblocker malignant syndrome will be accompanied by the treatment of antipsychotic drugs (including this product, see [adverse reactions]). Clinical manifestations include high fever, mental state change, muscular rigidity, autonomic nerve dysfunction and increased phosphokinase activity. If this happens, stop using this product and give appropriate treatment. Acute withdrawal reactions (including nausea, vomiting and insomnia) are rarely reported after large doses of antipsychotics are suddenly stopped. Psychotic symptoms may recur, and there are also reports of involuntary dyskinesia (such as akathisia, dystonia and dyskinesia). Therefore, it is recommended to stop taking drugs gradually. Influence on driving and operating machines. This product may cause drowsiness. Therefore, it is necessary to remind patients who operate dangerous machines, including driving vehicles. Interaction See Drug Interaction. When this product is combined with liver enzyme inducer such as carbamazepine, it can reduce the systemic absorption of quetiapine. Therefore, when this product is used together with liver enzyme inducer, the dosage of this product should be increased according to the clinical response. When combined with potent CYP3A4 inhibitors (such as azole antifungal agents and macrolide antibiotics), the plasma concentration of quetiapine can be significantly higher than that observed in clinical trials (see pharmacokinetics). Therefore, a lower dose of this product should be used in this case. Elderly or frail patients should be careful when taking medicine. All patients should consider the risk-benefit ratio before taking the medicine.

Contraindications are prohibited for patients who are allergic to any component of this product.

The safety and effectiveness of this product for children and adolescents have not been evaluated.

Medication for elderly patients

1. In clinical trials, there is not much experience in taking this product. Someone once ate 20g of this product, but it didn't kill him. The patient recovered completely without sequelae. In the post-marketing experience, it is very rare to report death or coma after taking too much of this product alone.

2. Generally speaking, the symptoms and signs reported by the drug overdose are the enhancement of the known pharmacological effects of the drug, namely drowsiness and sedation, tachycardia and hypotension.

3. Quetiapine has no specific antidote. Patients with severe poisoning should consider the possibility of multi-drug intervention, and suggest taking active monitoring measures, including opening good airway, ensuring adequate oxygen supply and breathing, and monitoring and maintaining cardiovascular system function.

4. Strict medical supervision and monitoring should be taken until the patient recovers.

The effectiveness and safety of this product for pregnant women and lactating women have not been confirmed (please refer to the toxicology-reproductive toxicity research section of pharmacology and toxicology for information about animal reproductive toxicity). Therefore, the product can only be used for pregnant patients if the benefits outweigh the potential risks. The excretion of quetiapine in human milk is not clear. Breast-feeding women should be advised to stop breastfeeding when taking quetiapine.

drug interaction

1. Because quetiapine mainly acts on the central nervous system, this product should be combined with other drugs or alcoholic beverages that act on the central nervous system.

2. The combination of this product and lithium salt preparation will not affect the pharmacokinetics of lithium.

3. When this product (quetiapine fumarate) is combined with sodium valproate, the pharmacokinetics of sodium valproate and quetiapine will not change clinically. Sodium valproate hemisodium is a stable coordination compound, which contains sodium valproate and valproic acid in the molar ratio of 1: 1.

4. The combination of antipsychotic drugs risperidone or haloperidol will not significantly change the pharmacokinetics of quetiapine. However, the clearance rate of quetiapine will increase when this product is combined with thiazine.

5. Quetiapine does not induce the liver enzyme system related to antipyrine metabolism. However, in a multi-dose clinical trial, the pharmacokinetics of quetiapine was evaluated before or during treatment with carbamazepine, a known inducer of liver enzymes. The results showed that the combined use of carbamazepine significantly improved the clearance rate of quetiapine. Compared with quetiapine alone, this increase in clearance rate reduced the systemic absorption level of quetiapine (calculated by AUC) by 65438 03%. But in some patients, more significant effects can be observed. Due to this interaction, a lower plasma concentration may occur, so a higher dose of this product should be considered for each patient according to the clinical response. It should be noted that the maximum recommended daily dose of this product for the treatment of schizophrenia is 750mg/ day, so we can only consider continuing to use a higher dose after carefully evaluating the risks and benefits of individual patients.

6. The combination of this product with another microsomal enzyme inducer phenytoin can also increase the clearance rate of quetiapine. If quetiapine is combined with phenytoin or other liver enzyme inducers (such as barbiturates and rifampicin), the dosage of this product should be increased to maintain the effect of anti-psychotic symptoms. If phenytoin or carbamazepine or other liver enzyme inducers are stopped and non-inducers (such as sodium valproate) are used, the dosage of this product should be reduced.

7. Among cytochrome P450, CYP3A4 is the main enzyme that mediates quetiapine metabolism. Combination with cimetidine, a known P450 enzyme inhibitor, will not change the pharmacokinetics of quetiapine. Co-administration with imipramine (a known inhibitor of CYP2D6) or fluoxetine (a known inhibitor of CYP3A4 and CYP2D6) does not significantly change the pharmacokinetics of quetiapine. However, caution should be exercised if this product is combined with CYP3A4 strong inhibitors (such as azole antifungal drugs or macrolide antibiotics) (see Precautions and Pharmacokinetics).

The storage temperature should be lower than 30℃.

The validity period is 36 months.

Manufacturer AstraZeneca Pharmaceutical Co., Ltd.

AstraZeneca Pharmaceutical Co., Ltd. Sub-packaging Company

Efficacy and function of Siruikang: Siruikang is used to treat schizophrenia.

Common problems in the use of quetiapine fumarate sustained-release tablets: Is quetiapine fumarate sustained-release tablets useful for schizophrenia? Quetiapine fumarate sustained-release tablets are round, 1 1mm, white, biconvex and coated tablets, which are non-classical antipsychotics. So, is quetiapine fumarate sustained-release tablets useful for schizophrenia?

Schizophrenia is a group of serious mental diseases with unknown etiology, which usually occurs slowly or subacute in young adults. Clinically, it is often manifested as a syndrome with different symptoms, involving various obstacles such as perception, thinking, emotion and behavior, as well as uncoordinated mental activities. Patients are generally conscious and their intelligence is basically normal, but some patients will have cognitive impairment during the onset. The course of the disease is generally prolonged, which is characterized by repeated attacks, aggravation or deterioration. Some patients eventually suffer from depression and mental disability, but some patients can maintain complete recovery or basically complete recovery after treatment.

So, is quetiapine fumarate sustained-release tablets useful for schizophrenia? Quetiapine fumarate sustained-release tablets are a new atypical antipsychotic drug, which is a variety of neurotransmitter receptor antagonists. In the brain, quetiapine fumarate sustained-release tablets have higher affinity for 5- hydroxytryptamine (5-HT2) receptor than dopamine D 1 and dopamine D2 receptor in the brain. Quetiapine fumarate sustained-release tablets also have high affinity for histamine H 1 receptor and adrenergic a 1 receptor, and low affinity for adrenergic a2 receptor, but basically have no affinity for cholinergic muscarinic receptor or benzodiazepine receptor. Conditional avoidance reflex test showed that quetiapine fumarate sustained-release tablets were positive. Clinical trials show that quetiapine fumarate sustained-release tablets are effective for both positive and negative symptoms of schizophrenia.