Rezalen (Tablets) Instructions for Use

ATC Code

N05AX08 (Risperidone)

Active Substance

Risperidone (Rec.INN WHO registered)

Clinical-Pharmacological Group

Antipsychotic drug (neuroleptic)

Pharmacotherapeutic Group

Antipsychotic agent (neuroleptic)

Pharmacological Action

Antipsychotic agent (neuroleptic), a benzisoxazole derivative. It has a high affinity for serotonin 5-HT₂ and dopamine D₂ receptors. It binds to α₁-adrenergic receptors and, with somewhat lower affinity, to histamine H₁ receptors and α₂-adrenergic receptors. It has no affinity for cholinergic receptors.

Although Risperidone is a potent D₂ antagonist (which is considered the primary mechanism for improving the positive symptoms of schizophrenia), it causes less suppression of motor activity and induces catalepsy to a lesser extent than classical neuroleptics.

Due to the balanced antagonism to serotonin and dopamine receptors in the CNS, the likelihood of developing extrapyramidal side effects is reduced.

Risperidone may induce a dose-dependent increase in plasma prolactin concentration.

Pharmacokinetics

After oral administration, Risperidone is completely absorbed from the gastrointestinal tract, with C_max in plasma reached within 1-2 hours. Food does not affect the absorption of risperidone.

The C_ss of risperidone in the body is reached in most patients within 1 day. The C_ss of 9-hydroxyrisperidone is reached within 4-5 days. Plasma concentrations of risperidone are proportional to the dose (within the range of therapeutic doses).

Risperidone is rapidly distributed in the body, with a V_d of 1-2 L/kg. In plasma, Risperidone binds to albumin and alpha₁-glycoprotein. The binding of risperidone to plasma proteins is 88%, and that of 9-hydroxyrisperidone is 77%.

Risperidone is metabolized in the liver by the isoenzyme CYP2D6 to form 9-hydroxyrisperidone, which has pharmacological activity similar to risperidone. The antipsychotic action is due to the pharmacological activity of risperidone and 9-hydroxyrisperidone. Another pathway of risperidone metabolism is N-dealkylation.

After oral administration in patients with psychosis, the T_1/2 of risperidone from plasma is 3 hours. The T_1/2 of 9-hydroxyrisperidone and the active antipsychotic fraction is 24 hours.

After 1 week of administration, 70% is excreted in the urine, 14% in the feces. In urine, the total content of risperidone and 9-hydroxyrisperidone is 35-45%. The remainder consists of inactive metabolites.

In elderly patients and in patients with renal insufficiency, increased plasma concentrations and delayed excretion of risperidone were observed after a single oral dose.

Indications

Treatment of schizophrenia (including first-episode acute psychosis, acute episode of schizophrenia, chronic schizophrenia); psychotic states with pronounced positive (hallucinations, delusions, thought disorders, hostility, suspicion) and/or negative (blunted affect, emotional and social withdrawal, poverty of speech) symptoms; to reduce affective symptoms (depression, guilt, anxiety) in patients with schizophrenia; prevention of relapse (acute psychotic states) in the chronic course of schizophrenia; treatment of behavioral disorders in patients with dementia when symptoms of aggressiveness (outbursts of anger, physical violence), mental activity disorders (agitation, delusions) or psychotic symptoms are manifested; treatment of mania in bipolar disorders (as a mood stabilizer as an adjunctive therapy).

ICD codes

Dosage Regimen

Tablets

Individual. When taken orally, the initial dose for adults is 0.25-2 mg/day, on the 2nd day – 4 mg/day. The dose can then be either maintained at the same level or adjusted if necessary. The optimal therapeutic dose, depending on the indications, is usually in the range of 0.5-6 mg/day. In some cases, a slower dose increase and lower initial and maintenance doses may be justified.

For schizophrenia in elderly patients, as well as in concomitant liver and kidney diseases, an initial dose of 500 mcg twice a day is recommended. If necessary, the dose can be increased to 1-2 mg twice a day.

Maximum dose: When using risperidone at a dose of more than 10 mg/day, no increase in efficacy is observed compared to lower doses, but the risk of developing extrapyramidal symptoms increases. The safety of using risperidone in doses above 16 mg/day has not been studied, so further dose increase is not allowed.

Adverse Reactions

From the central nervous system often – insomnia, agitation, anxiety, headache; possible – drowsiness, fatigue, dizziness, impaired concentration, blurred vision; rarely – extrapyramidal symptoms, (including tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia). In patients with schizophrenia, tardive dyskinesia, neuroleptic malignant syndrome, thermoregulation disorders, and seizures may occur.

From the digestive system constipation, dyspeptic symptoms, nausea, vomiting, abdominal pain, increased activity of liver enzymes.

From the reproductive system priapism, erectile dysfunction, ejaculation disorders, orgasm disorders.

From the cardiovascular system rarely – orthostatic hypotension and reflex tachycardia, arterial hypertension.

From the endocrine system galactorrhea, gynecomastia, menstrual cycle disorders, amenorrhea, weight gain.

From the hematopoietic system slight decrease in the number of neutrophils and/or platelets.

Allergic reactions rhinitis, skin rash, angioedema.

Other urinary incontinence.

Contraindications

Hypersensitivity to risperidone.

Use in Pregnancy and Lactation

Use during pregnancy is possible if the expected benefit of therapy for the mother outweighs the potential risk to the fetus. If it is necessary to use during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

For schizophrenia with concomitant liver diseases, an initial dose of 500 mcg twice a day is recommended. If necessary, the dose can be increased to 1-2 mg twice a day.

Use in Renal Impairment

For schizophrenia with concomitant kidney diseases, an initial dose of 500 mcg twice a day is recommended. If necessary, the dose can be increased to 1-2 mg twice a day.

Pediatric Use

Data on the safety of using risperidone in children under 15 years of age are not available.

Geriatric Use

For schizophrenia in elderly patients, an initial dose of 500 mcg twice a day is recommended. If necessary, the dose can be increased to 1-2 mg twice a day.

Special Precautions

Use with caution in patients with cardiovascular diseases (including heart failure, myocardial infarction, cardiac conduction disorders), as well as in dehydration, hypovolemia, or cerebrovascular disorders. In this category of patients, the dose should be increased gradually.

The risk of developing orthostatic hypotension is especially increased during the initial dose titration period. If hypotension occurs, a dose reduction should be considered.

Risperidone should be used with caution in combination with other centrally acting drugs.

When discontinuing carbamazepine and other liver enzyme inducers, the dose of risperidone should be reviewed and, if necessary, reduced.

During treatment, patients should be advised to avoid overeating due to the possibility of weight gain.

Data on the safety of using risperidone in children under 15 years of age are not available.

Effect on the ability to drive vehicles and operate machinery

During treatment, until individual sensitivity to risperidone is determined, patients should avoid driving and other activities requiring high concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use of inducers of microsomal liver enzymes, a decrease in the plasma concentration of risperidone is possible.

With simultaneous use with phenothiazine derivatives, tricyclic antidepressants, and beta-blockers, an increase in the plasma concentration of risperidone is possible.

With simultaneous use with carbamazepine, the plasma concentration of risperidone is significantly reduced.

With simultaneous use, Risperidone reduces the effects of levodopa and other dopamine receptor agonists.

With simultaneous use with fluoxetine, an increase in the plasma concentration of risperidone is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.