How Safe Is Risperidone for the Elderly?

Risperidone tablets, the indications are 1. For the treatment of acute and chronic schizophrenia and other various psychotic states with obvious positive symptoms (e.g. hallucinations, delusions, mental disturbances, hostility, doubt) and obvious negative symptoms (e.g. unresponsiveness, apathy and social apathy, Few words). It can also reduce the emotional symptoms associated with schizophrenia (such as: depression, guilt, anxiety). For patients who are effective in the acute phase, this product can continue to exert its clinical effect in the maintenance phase. 2. Can be used to treat manic episodes of bipolar disorder, which are characterized by high mood, exaggeration or irritability, high self-evaluation, reduced sleep requirements, faster speech, thoughtfulness, distraction, or poor judgment (including disorders Or aggressive behavior).

Drug Name: Risperidone tablets

Drug type: Prescription medicines, essential medicines, medicines for medical workers' injuries
Use classification: Other antipsychotics

Risperidone tablet ingredients

Active ingredient: Risperidone Chemical name: 3- [2- [4- (6-fluoro-1,2-benzoisoxazol-3-yl) -l-piperidinyl] ethyl] -6,7 , 8,9, -tetrahydro-2-methyl-4H-pyrido [1,2-] pyrimidin-4-one chemical structural formula:

Molecular formula: C ₂₃ H ₂₇ FN ₄ O ₂
Molecular weight: 410.49

Risperidone Tablet Properties

1mg risperidone tablets are white film-coated tablets, white after removing the coating;
2mg risperidone tablets are light orange film-coated tablets, which are white after removing the coating.

Risperidone tablets indications

1. For the treatment of acute and chronic schizophrenia and other various psychotic states with obvious positive symptoms (e.g. hallucinations, delusions, mental disturbances, hostility, doubt) and obvious negative symptoms (e.g. unresponsiveness, apathy and social apathy, Few words). It can also reduce the emotional symptoms associated with schizophrenia (such as: depression, guilt, anxiety). For patients who are effective in the acute phase, this product can continue to exert its clinical effect in the maintenance phase.
2. Can be used to treat manic episodes of bipolar disorder, which are characterized by high mood, exaggeration or irritability, high self-evaluation, reduced sleep requirements, faster speech, thoughtfulness, distraction, or poor judgment (including disorders Or aggressive behavior).

Risperidone tablet specifications

(1) 1mg (2) 2mg

Risperidone tablets dosage

1. For people with schizophrenia who switch from using other antipsychotics to this product: When starting, the original antipsychotics should be gradually stopped. If the patient originally used long-acting antipsychotics, this product can be used instead of the next course of medication. Whether used anti-Parkinson's syndrome drugs need to be continued should be re-evaluated regularly.
Adult: 1 time or 2 times a day. The initial dose is 1 mg, and the dose is gradually increased to 2 to 4 mg per day within a period of about 1 week, and the dose can be gradually increased to 4 to 6 mg per day within the second week. Thereafter, this dose can be maintained unchanged or further adjusted according to personal circumstances. In general, the optimal dose is 2 to 6 mg per day. The daily dose generally does not exceed 10 mg.
2. The recommended starting dose for the treatment of bipolar disorder in manic episodes is 1 to 2 mg once daily, and the dose can be adjusted according to individual needs. The increase of the dose is 1 to 2 mg per day, and the increase of the dose is performed at least every other day or more days. The ideal dose for most patients is 2 to 6 mg per day. During all symptomatic treatments, the need for continued use of this product should be continuously evaluated.
3. Patients with impaired liver and kidney function The ability of patients with impaired renal function to clear antipsychotic drugs is lower than healthy adults; the concentration of free risperidone in the plasma of patients with impaired liver function has increased. Regardless of the indication, the initial and maintenance doses for patients with impaired renal function or for patients with impaired liver function should be halved, and dose adjustments should be slowed. Such patients should be cautious when using this product.

Adverse effects of risperidone tablets

Clinical trial data < br In a clinical trial to evaluate the safety of this product, 9712 patients with different types of mental illness (including adults, dementia patients and children) received at least one dose of this product. Of these, 2626 patients received this product when participating in a double-blind, placebo-controlled trial. There are large differences in treatment status and duration, including inpatient and outpatients in double-blind, quantitative and non-quantitative, placebo or active controlled trials, and open-label trials, short-term (to 12 weeks) and long-term (to 3 years) ) Administration (cross classification).
Most adverse reactions were mild to moderate.
Double-blind, placebo-controlled trials-Adult patients reported adverse reactions in no less than 1% of patients in the risperidone group in 9 double-blind, placebo-controlled trials in which adult patients received risperidone for 3 to 8 weeks ( ADRs) are listed in Table 1.

* Parkinson's syndrome includes extrapyramidal disorders, musculoskeletal rigidity, Parkinson's syndrome, gear-like rigidity, temporary muscular palsy, bradykinesia, impaired motor function, mask face, muscle rigidity, and Parkinson's disease. Meditation cannot include meditation and restlessness. Dystonia includes dystonia and muscle spasms, involuntary muscle contractions, muscle contractures, eyeball rotation, and tongue muscle paralysis. Tremors include tremors and resting tremors of Parkinson's disease. Dyskinesias include dyskinesias and muscle twitches, chorea, choreography of dancing hands and feet.
Double-blind, placebo-controlled trial-Patients with Alzheimer's reported adverse reactions in less than 1% of patients in the risperidone group in 6 double-blind, placebo-controlled trials in which 6 patients with Alzheimer's received risperidone for 4 to 12 weeks The reaction is shown in Table 2. Table 2 only includes adverse reactions that are not listed in Table 1 or occur in Table 1 but occur twice or more frequently.

Double-blind, placebo-controlled trials-adverse reactions reported by no less than 1% of patients in the risperidone group in 8 double-blind, placebo-controlled trials of pediatric patients receiving risperidone for 3 to 8 weeks 3 In Table 3. Table 3 only includes adverse reactions that are not listed in Table 1 or occur in Table 1 but occur twice or more frequently.

Other clinical trial data Adverse reactions reported in less than 1% of patients in the risperidone group in double-blind, placebo-controlled trials in pediatric, adult and dementia patients, or other trials in double-blind, active control and open-label trials The adverse reactions reported by patients in the risperidone group are listed in Table 4.

Other adverse reactions related to risperidone reported from patients using risperidone microspheres for injection are as follows, excluding those related to the dosage form or route of injection.
Infections: lower respiratory infections, infections, gastroenteritis, subcutaneous abscesses, blood and lymphatic system: neutropenia, psychotic disorders: depressive nervous system: paresthesia, convulsions, eye: blepharospasm, ears and labyrinth: dizziness, heart: heartbeat Slow blood vessels: Hypertensive gastrointestinal tract: toothache, tongue cramps, skin and subcutaneous tissue: eczema, skeletal muscle, connective tissue and bone abnormalities: hip pain, whole body and administration site: pain study: weight loss, -glutamate transferase Elevation, elevated liver enzyme levels, poisoning and injury: falls <br Post- marketing experience < br The adverse events that were first identified as risperidone adverse reactions after marketing are shown in Table 5. Adverse reactions are classified by spontaneous reporting rate:
Very common
Common 1 / 100, and 1/10
Rarely 1 / 1000, and <1/100
Rare 1 / 10,000 and 1/1000
Very rare <1 / 10,000, including individual cases.
According to the frequency of spontaneous reporting, the above adverse reactions are listed in Table 5 according to their incidence.

a Includes thrombocytopenia, decreased platelet count, decreased platelet hematocrit, and decreased platelet products b Includes angioedema, acquired C1 esterase deficiency, edema of the mouth, eyelid edema, facial edema, hereditary angioedema, laryngeal edema, larynx Tracheal edema, ocular-respiratory syndrome, oral edema, periorbital edema, angioedema of the small intestine, tongue edemac Including QT interval prolongation after ECG correction, abnormal QT interval of ECG, prolongation of QT interval, QT interval Prolongation syndrome, congenital prolonged QT interval syndrome.

Risperidone tablets contraindications

Disabled in patients known to be allergic to this product.

Precautions for risperidone tablets

1. Patients with Alzheimer's Disease 1.1 Total Mortality A summary analysis of 17 controlled trials of several atypical antipsychotics including this product shows that the mortality of Alzheimer's patients in the atypical antipsychotic group is higher than that of the placebo group Increased. In placebo-controlled trials with this product in this population, the mortality rate for patients in this product group and in the placebo group was 4.0% and 3.1%, respectively. The average age of patients who died was 86 years (range, 67 to 100 years).
1.2 In combination with furosemide In placebo-controlled studies of patients with Alzheimer's disease, the mortality of patients taking risperidone and furosemide was higher than that of patients taking risperidone or furosemide, respectively. It was 7.3% (mean age 89 years, range 75-97 years), 3.1% (mean age 84 years, range 70-96 years) and 4.1% (mean age 80 years, range 67-90 years). In two of the four clinical trials, an increase in mortality was observed in patients taking furosemide and this product.
Although no clear pathophysiological mechanism has been found to explain this phenomenon, and the cause of death of patients is not the same, the risk benefit should be carefully evaluated when combining risperidone and furosemide in elderly patients. The increase in mortality did not occur in patients taking risperidone in combination with other diuretics. Because dehydration is an important lethal factor in patients with dementia, it should be avoided as much as possible.
2. Cerebrovascular accident (CAE)
In placebo-controlled studies in patients with dementia (mean age 85 years, range 73-97 years), adverse events (cerebrovascular accidents and transient cerebral ischemia), including death, were observed in the risperidone group The incidence of blood attacks was higher than in the placebo group.
3. Blocking activity on alpha receptors Because this product has blocking effects on alpha receptors, (orthostatic) hypotension may occur, especially during the initial dose adjustment phase of treatment. For patients with known cardiovascular disease (such as heart failure, myocardial infarction, conduction abnormality, dehydration, decreased blood volume, or cerebrovascular disease), this product should be used with caution, and the dose should be gradually increased according to the recommended dose (see Dosage and Administration), such as If hypotension occurs, dose reduction should be considered.
4. Tardive Dyskinesia / Extrapyramidal Symptoms (TD / EPS)
Similar to all other drugs with dopamine receptor antagonist properties, this product may also cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, mainly found on the tongue and face. It has been reported that the occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. Compared with other traditional antipsychotic drugs, this product causes fewer extrapyramidal symptoms, so compared with traditional antipsychotic drugs, This product has a lower risk of tardive dyskinesia. If symptoms of tardive dyskinesia appear, consider discontinuing all antipsychotics.
5. Antipsychotic Malignant Syndrome (NMS)
It has been reported that the use of traditional antipsychotic drugs may lead to malignant syndrome, which is characterized by high fever, muscle stiffness, tremors, disturbance of consciousness and elevated serum creatine phosphokinase levels, and myoglobinuria (striated muscle) Lysis) and acute renal failure. All antipsychotics, including this product, should be discontinued at this time.
For patients with Lewy body dementia or Parkinson's disease, the pros and cons should be weighed when prescribing antipsychotics (including this product), which may increase the risk of malignant syndrome. At the same time, the above groups have increased sensitivity to antipsychotic drugs. In addition to the extrapyramidal symptoms, they will also appear confused, dull, unstable and often fall.
6. Hyperglycemia and diabetes During the use of this product, there have been reports of exacerbation of hyperglycemia, diabetes and pre-existing diabetes. The high risk of diabetes inherent in schizophrenia and the increased incidence of diabetes in the normal population complicate the assessment of the correlation between the use of atypical antipsychotics and glucose abnormalities. Patients with diabetes in schizophrenia should monitor for hyperglycemia and symptoms of diabetes.
7. Significant weight gain has been reported. When using this product, weight monitoring should be performed.
8. QT interval, like other antipsychotics, should be given to patients with a history of arrhythmia, congenital QT interval prolongation syndrome, and in combination with drugs known to prolong QT interval.
9. Other traditional antipsychotic drugs will reduce the seizure threshold, so patients with epilepsy should use this product with caution.
Patients taking this product should avoid overeating, as this product may cause weight gain.
For the special dosages recommended for elderly patients, patients with impaired liver function, patients with impaired renal function, or patients with dementia, see the [Geriatric Drugs] and [Dosage and Administration] sections.
This product has an impact on activities that require alertness. Therefore, before understanding the patient's sensitivity to this product, it is recommended that the patient should not drive a car or operate a machine during treatment.
Keep them out of reach of children.

Risperidone tablets for pregnant and lactating women

It is not clear whether this product is safe for pregnant women. Animal tests show that risperidone has no direct toxicity on reproduction, and only some indirect prolactin and central nervous system-mediated effects have been observed. This product has no teratogenic effect.
During the last trimester of pregnancy, fetuses exposed to antipsychotics (including risperidone) are at risk of developing extrapyramidal symptoms or withdrawal symptoms after birth, with varying degrees of severity. These symptoms include agitation, hypertonia, hypotonia, tremors, drowsiness, respiratory distress, and eating disorders.
For pregnant women, weigh the pros and cons before deciding whether to take this product.
Animal tests have shown that risperidone and 9-hydroxyrisperidone are excreted in animal milk. At the same time, human tests have also proven that this product will be excreted through breast milk, so women taking this product should not breastfeed.

Risperidone tablets for children

For schizophrenia, there is currently insufficient clinical experience for children under 15 years of age.
For conduct disorders and other behavioral disorders, there is currently insufficient clinical experience for children under 5 years of age.
For manic episodes of bipolar disorder, there is currently insufficient clinical experience in children and adolescents under 18 years of age.

Risperidone tablets for the elderly

Treatment of schizophrenia:
The recommended starting dose is 0.5 mg each time, twice daily, and the dose can be adjusted according to individual needs. The increase in dose was 0.5 mg each time, twice a day, until 1 to 2 mg, twice a day.

Risperidone tablets drug interactions

1. In view of the effect of this product on the central nervous system, caution should be exercised when combined with other drugs acting on the central system.
2. This product can antagonize the effects of levodopa and other dopamine agonists.
3. Clinically significant hypotension was observed when antihypertensive drugs were used in combination after marketing.
4. Caution should be used in combination with drugs known to extend the QT interval.
5. Carbamazepine and other CYP 3A4 liver enzyme inducers will reduce the plasma concentration of active ingredients of this product. When starting or stopping the use of carbamazepine or other CYP 3A4 liver enzyme inducers, the dose of this product should be re-determined.
6. Fluoxetine and paroxetine (CYP2D6 inhibitors) can increase the blood concentration of this product, but have less effect on the blood concentration of its antipsychotic active ingredient. When starting or stopping co-administration with fluoxetine or paroxetine, the doctor should re-determine the dose of this product.
7. Topiramate slightly reduces the bioavailability of risperidone and has no effect on the antipsychotic active ingredients in this product. Therefore, this interaction is essentially of no clinical significance.
8. Phenothiazine antipsychotics, tricyclic antidepressants and some beta-blockers will increase the blood concentration of this product, but will not increase the blood concentration of its antipsychotic active ingredients. Amitriptyline does not affect the pharmacokinetic parameters of risperidone or its antipsychotic active ingredient. Cimetidine and ranitidine can increase the bioavailability of risperidone, but have little effect on its antipsychotic active ingredients. Erythromycin (CYP3A4 inhibitor) does not affect the pharmacokinetic parameters of risperidone or its antipsychotic active ingredient. The cholinesterase inhibitors galantamine and donepezil have no significant effect on the pharmacokinetic parameters of risperidone or its antipsychotic active ingredient.
9. There is no clinically significant replacement of plasma proteins when taken with other highly protein-bound drugs.
10. This product has no significant effect on the pharmacokinetic parameters of lithium, sodium valproate, digoxin or topiramate.
11. For the content of increased mortality in patients with Alzheimer's disease treated with furosemide, please refer to the [Precautions] section.
12. Food does not affect the absorption of this product.

Risperidone tablets overdose

When symptoms of acute overdose occur, consideration should be given to whether there are factors caused by the combination of other drugs.
In general, the reported symptoms and signs of overdose are caused by an extension of its pharmacological effects, including lethargy and sedation, tachycardia and hypotension, and extrapyramidal symptoms. Prolonged QT interval and epilepsy have been reported during drug overdose. Twisted ventricular tachycardia has been reported in combination with paroxetine in excess.
When overdose is rescued, airway patency should be maintained, sufficient oxygen and good ventilation should be ensured, gastric lavage (if the patient is unconscious should be intubated), and activated carbon and laxatives should be considered, and cardiovascular monitoring should be performed immediately This includes continuous ECG monitoring to detect possible arrhythmias. There is no specific remedy for this product. Therefore, appropriate supportive care should be used. Hypotension and circulatory failure can be corrected by intravenous infusion or appropriate measures such as sympathomimetic drugs. Once severe extrapyramidal symptoms occur, anticholinergics should be given, and close medical monitoring and monitoring should be continued until the patient recovers.

Risperidone tablets pharmacology and toxicology

1. Pharmacological effects Risperidone is a selective monoaminergic antagonist with high affinity for the 5HT ₂ receptor, D ₂ receptor, ₁ and ₂ receptors, and H ₁ receptor. It also has antagonistic effects on other receptors, but is weaker. Low to moderate affinity for 5HT _1C , 5HT _1D and 5HT _1A , weak sigma receptor sensitivity to D ₁ and haloperidol, and no affinity to M receptor or ₁ and ₂ receptors.
Like other drugs for schizophrenia, the mechanism by which risperidone treats schizophrenia is unclear. The therapeutic effect is believed to be the result of a combined effect of antagonism on the D ₂ receptor and the 5HT ₂ receptor. Antagonism of receptors other than D ₂ and 5HT ₂ may be related to other effects of risperidone.
2. Toxicology long-term toxicity: In a juvenile rat toxicity study, increased mortality and delayed physical development were found. In a 40-week study of juvenile dogs, it was found that they had delayed sexual maturity. Using a dose close to the maximum human dose (6 mg / day) will not affect bone development in adolescents; only at 4 times (calculated as AUC) or 7 times (calculated as milligrams per square meter) people Only then will the effect be observed.
Genotoxicity: Ames reverse mutation test, mouse lymphocyte aberration test, in vitro rat liver cell DNA repair test, mouse in vivo micronucleus test, fruit fly sex-related recessive lethal test, human lymphocyte or Chinese hamster cell chromosome aberration test None of the risperidone was found to be potentially mutagenic.
Reproductive toxicity: In the study of reproductive toxicity in Wistar rats, risperidone is 0.16 to 5 mg / kg (in mg / m ² , which is 0.16 to 4.9 times the maximum recommended human dose, and the maximum recommended human dose is 10 mg / day, see Usage and dosage part) reduce the number of mating times without affecting fertility. This effect occurred only in female rats, and no effect of mating behavior was observed in general reproductive toxicity tests administered to male rats only. In the subchronic study of Beagle dogs, when the dose of risperidone was 0.31 to 5 mg / kg (mg / m ² , 1.0 to 16.2 times the maximum recommended human dose), sperm motility and concentration decreased, and serum testosterone levels at the same dose Dose correlation decreased. After discontinuation of the drug, serum testosterone levels and sperm parameters were partially recovered, but remained at low levels. No effects were observed in rats or dogs.
Risperidone doses were 0.63 to 10 mg / kg, 0.31 to 5 mg / kg on SD and Wistar rats and New Zealand rabbits (calculated as mg / m ² , which are 0.6 to 6 times the maximum human dose and 0.4 respectively). 6 times). Compared with the control group, no increase in the incidence of deformities was observed. At doses of 0.16 to 5 mg / kg (in mg / m ² , 0.16 to 4.9 times the maximum human recommended dose, respectively), the pups died 4 days before lactation in rats. It is unknown whether these deaths were due to direct effects on the fetuses or pups, or the effects on the female rats.
No no-effect doses were observed that caused an increase in rat pup mortality. In a perinatal reproductive toxicity study, at 2.5 mg / kg (in mg / m ² , 2.4 times the maximum human recommended dose), stillbirths of rat pups increased. In a rat cross-raising study. Toxic effects on fetuses or puppies are reduced live pups at birth, increased numbers of dead pups, and reduced birth weight of pups related to the dose administered to the mother. In addition, there was an increase in pup mortality on the first day of life related to the dose administered to the mother rats, regardless of whether the pups were cross-bred. Risperidone may have a detrimental effect on maternal behavior, and the weight gain and survival rate of the pups raised from the administered female mice produced by the control animals were reduced (days 1 to 4 of lactation). These effects were all observed in the 5 mg / kg (in mg / m ² , 4.9 times the maximum recommended human dose) dose group.
Risperidone can be transported through the placenta into rat pups.
Carcinogenicity: 0.63, 2.5 and 10 mg / kg of risperidone were administered to mice and rats, respectively (in mg / kg, 3.8, 15, and 60 times the maximum recommended human dose, respectively; mice were given mg / m ² (Calculated as 0.3, 1.2, and 4.9 times the maximum recommended dose for humans, and 0.6, 2.4, and 9.8 times the maximum recommended dose for humans in mg / m ² , respectively), and the administration cycles were 18 months and 25 months, respectively. . Male mice did not reach the maximum tolerated dose. The results showed a statistically significant increase in pituitary adenomas, endocrine pancreatic adenomas, and breast adenocarcinomas. Antipsychotic drugs can cause prolonged prolactin levels in rodents. Prolactin levels were not measured in the risperidone carcinogenicity test, but measurements in subchronic toxicity studies showed that the same dose of risperidone as in the carcinogenicity test could increase prolactin levels in mice and rats 5 to 6 times. When long-term administration of other antipsychotic drugs, increased tumors of the breast, pituitary, and pancreas are found in rodents and are thought to be mediated by prolactin. The correlation between the occurrence of prolactin-mediated endocrine tumors and human risk in rodents is unknown.

Risperidone tablets pharmacokinetics

Risperidone can be completely absorbed after oral administration and reaches its peak blood concentration within 1 to 2 hours. Its absorption is not affected by food, so it can be taken alone or with food. In the body, risperidone is metabolized to 9-hydroxyrisperidone by CYP2D6, which has similar pharmacological effects to risperidone. Risperidone and 9-hydroxyrisperidone together constitute the antipsychotic active ingredient of this product. Another metabolic pathway of risperidone in the body is N-dehydrocarbon effect. The elimination half-life of risperidone is about 3 hours, and the elimination half-life of 9-hydroxyrisperidone and other active metabolites is 24 hours. Most patients reach the steady state of risperidone within 1 day, and reach the steady state of 9-hydroxyrisperidone after 4 to 5 days. Within the therapeutic dose range, the blood concentration of risperidone is directly proportional to the administered dose. After one week of treatment, 70% of the drug was excreted in urine, 14% of the drug was excreted in feces, and 35 to 45% of the excretion was risperidone and 9-hydroxyrisperidone, and the rest were inactive metabolites. . A single-dose study showed that elderly patients and patients with renal insufficiency had higher plasma concentrations of the active ingredient, and the clearance of active ingredients decreased by 30% in elderly patients and by 60% in patients with renal insufficiency. Risperidone plasma concentrations are normal in patients with liver dysfunction, but the unbound portion of risperidone in plasma increases by an average of about 35%. The pharmacokinetics of risperidone, 9-hydroxyrisperidone and other active metabolites in children are similar to those in adults.

Risperidone tablets storage

Store in a sealed container at 15-30 ° C.

Risperidone tablet packaging

Packed in aluminum-plastic board, 2 × 10 pieces / board / box.

Risperidone tablets expiration date

36 months.

Risperidone Tablets

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