Rispolettes, 4 mg 20 pcs.

Rispolept is an antipsychotic drug, a benzisoxazole derivative. It also has sedative, antiemetic and hypothermic effects.

Risperidone is a selective monoaminergic antagonist with high affinity for serotonin 5-HT2- and dopamine D2-receptors. It binds to α1-adrenoceptors and somewhat weaker to histamine H1-receptors and α2-adrenoceptors. It has no tropism to cholinoreceptors.

Antipsychotic action is caused by blockade of dopamine D2-receptors of mesolimbic and mesocortical system. Sedative action is caused by blockade of adrenoreceptors of reticular formation of brain stem; antiemetic action – by blockade of dopamine D2-receptors of trigger zone of vomiting center; hypothermic action – by blockade of dopamine receptors of hypothalamus.

Risperidone reduces the productive symptomatology of schizophrenia (delirium, hallucinations), aggression, automatism, causes less suppression of motor activity and is less likely to induce catalepsy than classical neuroleptics. Balanced central antagonism to serotonin and dopamine may reduce the propensity for extrapyramidal side effects and extend the therapeutic effect of the drug on the negative and affective symptoms of schizophrenia.

Risperidone may cause a dose-dependent increase in plasma prolactin concentrations.

Pharmacokinetics

Intake

After oral administration, risperidone is completely absorbed from the GI tract. Cmax in plasma is reached after 1-2 hours. Food has no effect on absorption of the drug, so Rispolet can be prescribed regardless of meals.

Distribution

Risperidone is rapidly distributed in the body. The Vd is 1-2 l/kg. In plasma, risperidone binds to albumin and alpha1-glycoprotein. Risperidone binds 88% to plasma proteins, 9-hydroxy-risperidone – 77%.

The Css of risperidone in the body is reached within 1 day in most patients.

The Css of 9-hydroxy-risperidone is reached within 4-5 days. Plasma concentrations of risperidone are proportional to the dose of the drug (within therapeutic doses).

Metabolism

Risperidone is metabolized in the liver with the participation of CYP2D6 isoenzyme to form 9-hydroxy-risperidone, which has pharmacological effects similar to risperidone. Risperidone and 9-hydroxy-risperidone constitute the active antipsychotic fraction. Another route of metabolism of risperidone is N-dealkylation.

Elevation

After oral administration in patients with psychosis, the T1/2 of risperidone from plasma is about 3 hr. The T1/2 of 9-hydroxy-risperidone and the active antipsychotic fraction is 24 hours.

After a week of taking the drug, 70% of the dose is excreted in the urine, 14% in the feces. In the urine, risperidone plus 9-hydroxy-risperidone make up 35-45% of the dose. Inactive metabolites make up the rest.

Pharmacokinetics in Special Clinical Cases

In elderly patients and patients with renal impairment, higher plasma concentrations and delayed excretion of risperidone were observed after a single oral administration.

In patients with hepatic impairment plasma concentrations of risperidone did not change.

Indications

Capitation of acute attacks and long-term maintenance therapy:

For mood stabilization in the treatment of mania in bipolar disorders (as adjunctive therapy).

Active ingredient

Composition

Active ingredient:

Spiridone;

Associates:

lactose monohydrate;

corn starch;

Hypromellose 2910 (15 mPa-s);

sodium lauryl sulfate;

MCC;

Magnesium stearate;

Colloidal silicon dioxide;

Film coating:

Hypromellose 2910 (5 mPa-s); propylene glycol; talc; titanium dioxide; Sunset Yellow dye (E110); quinoline yellow dye (E104); indigo carmine (E132)

How to take, the dosage

Ingestion, regardless of meals.

Schizophrenia

Adults. Risolept® may be administered 1 or 2 times a day. The initial dose of Risolette® is 2 mg/day. On the second day, the dose should be increased to 4 mg/day. From then on, the dose can either be maintained at the same level or individually adjusted if necessary. Usually the optimal dose is 4-6 mg/day. In some cases, a slower dose increase and lower starting and maintenance doses may be warranted.

Doses above 10 mg/day do not show greater efficacy than lower doses and may cause extrapyramidal symptoms. Because the safety of doses above 16 mg/day has not been studied, doses above this level should not be used.

Benzodiazepines may be added to Risolept® therapy if additional sedation is required.

Elderly patients. A starting dose of 0.5 mg per dose twice daily is recommended. The dose can be individually increased from 0.5 mg 2 times a day to 1-2 mg 2 times a day.

Adolescents over 13 years of age. A starting dose of 0.5 mg per dose once daily in the morning or evening is recommended. If necessary, the dose may be increased at least 24 hours later by 0.5-1 mg daily to the recommended dose of 3 mg/day if well tolerated. The safety of doses above 6 mg/day has not been studied.

Patients who have persistent somnolence are recommended to take half of the daily dose 2 times daily.

There is no information on the use of the drug for the treatment of schizophrenia in children under 13 years of age.

Behavioral Disorders in Patients with Dementia

The recommended starting dose is 0.25 mg per dose 2 times daily. The dose may be increased individually to 0.25 mg 2 times a day if necessary, no more often than every other day. For most patients, the optimal dose is 0.5 mg 2 times a day. However, some patients may require 1 mg twice daily.

Interaction

Rispolettes may act as an antagonist of levodopa and dopamine agonists.

When Rispolettes and carbamazepine are used concomitantly, a decrease in plasma concentration of the active antipsychotic fraction of risperidone was noted. Similar effects may be observed with the use of other hepatic enzyme inducers. When carbamazepine and other hepatic enzyme inducers are withdrawn, the dose of Rispolet should be reconsidered and, if necessary, reduced.

Phenothiazines, tricyclic antidepressants and some beta-adrenoblockers may increase plasma concentrations of risperidone when used concomitantly with Rispolettes, but this does not affect the concentration of the active antipsychotic fraction.

In concomitant use with Rispolet, fluoxetine may increase plasma concentrations of risperidone, but to a lesser extent the concentration of the active antipsychotic fraction.

When Rispolette is used concomitantly with other drugs with high plasma protein binding, there is no marked displacement of any drug from the plasma protein fraction that is clinically apparent.

Special Instructions

With caution, the drug should be used in patients with diseases of the cardiovascular system (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 orthostatic hypotension is particularly increased during the initial period of dose adjustment. If hypotension occurs, dose reduction should be considered.

The occurrence of tardive dyskinesia, characterized by involuntary rhythmic movements (predominantly of the tongue and/or face), has been reported with the use of drugs with dopamine receptor antagonist properties. The occurrence of extrapyramidal symptoms has been reported to be a risk factor for the development of tardive dyskinesia. Rispolette causes the occurrence of extrapyramidal symptoms to a lesser extent than classical neuroleptics. If symptoms of tardive dyskinesia occur, consideration should be given to withdrawing all antipsychotic medications.

With the use of classical neuroleptics, cases of MNS have been described, characterized by hyperthermia, muscle rigidity, instability of autonomic functions, impaired consciousness, and elevated CPK levels. All antipsychotic medications, including Rispolettes, should be discontinued if MNS develops.

With caution, Rispolettes should be prescribed to patients with Parkinson’s disease because it may theoretically worsen the course of this disease.

The classical neuroleptics are known to lower the seizure threshold. Taking this into account, Rispolette is recommended with caution in patients with epilepsy.

Risoleptic primarily affects the CNS, so it should be used with caution in combination with other centrally acting drugs.

Patients should be advised to refrain from overeating during treatment due to the possibility of weight gain.

Contraindications

With caution, the drug should be used in patients with diseases of the cardiovascular system (including chronic heart failure, myocardial infarction, conduction disorders.In patients with cardiovascular diseases (including chronic cardiac insufficiency, myocardial infarction, conduction disorders), dehydration, hypovolemia, stroke, Parkinson’s disease, seizures (including history), severe renal or hepatic failure, drug abuse or addiction, conditions predisposing to the development of pirouette tachycardia (bradycardia, electrolyte imbalance, concomitant use of drugs that prolong the QT interval), brain tumors, bowel obstruction, cases of acute drug overdose, Reye syndrome (because of the antiemetic effect of vomiting).Because the antiemetic effect of risperidone may mask the symptoms of these conditions), in pregnancy, patients under 15 years of age (because the safety and effectiveness of the drug has not been established).

Side effects

CNS disorders: insomnia, agitation, anxiety, headache; sometimes – drowsiness, fatigue, dizziness, concentration disorders, visual disturbances; rarely – extrapyramidal symptoms (tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia). In patients with schizophrenia, hypervolemia (either due to polydipsia or inadequate ADH secretion syndrome), tardive dyskinesia (involuntary rhythmic movements primarily of the tongue and/or face), MNS (hyperthermia, muscle rigidity, instability of autonomic functions, impaired consciousness and increased CPK levels), thermoregulatory disorders and seizures are possible.

Digestive system disorders: constipation, dyspepsia, nausea, vomiting, abdominal pain, increased liver enzyme activity, dry mouth, hypo- or hypersalivation, anorexia, increased appetite, weight gain or loss.

Cardiovascular system: orthostatic hypotension and reflex tachycardia, increased BP. Against the background of Rispolettes therapy the development of strokes has been described mainly in elderly patients with predisposing factors.

Hematopoietic system disorders: neutropenia, thrombocytopenia.

Endocrine system disorders: galactorrhea, gynecomastia, menstrual cycle disorders, amenorrhea; in single cases – development of hyperglycemia or worsening of diabetes.

Urogenital system disorders: priapism, erectile dysfunction, ejaculation disorders, anorgasmia, urinary incontinence.

Allergic reactions: rhinitis, skin rash, angioedema.

Dermatological reactions: dry skin, hyperpigmentation, itching, seborrhea, photosensitization.

Others: arthralgia.

Overdose

Symptoms: somnolence, sedation, tachycardia, arterial hypotension, extrapyramidal symptoms. Administration of up to 360 mg of the drug has been reported. The data suggest a wide range of safety of the drug. In rare cases of overdose, prolongation of the QT interval has been noted.

In case of acute overdose in combination therapy, the possibility of involvement of other drugs should be analyzed.

Treatment: ensure free airway to ensure adequate oxygen supply and ventilation. Gastric lavage (after intubation if unconscious) and administration of activated charcoal together with a laxative are indicated. ECG monitoring should be initiated immediately to detect possible cardiac rhythm abnormalities.

There is no specific antidote, appropriate symptomatic therapy should be given. In case of arterial hypotension and vascular collapse, IV infusion solutions should be administered and/or sympathomimetic drugs should be used. If acute extrapyramidal symptoms develop, anticholinergic drugs should be prescribed. Continuous medical observation and monitoring should be continued until symptoms of intoxication disappear.

Pregnancy use

The safety of Rispolettes in pregnant women has not been studied.

Risopoletin should be used in pregnancy only if the positive effects justify the possible risks.

Because risperidone and 9-hydroxy risperidone penetrate into breast milk, women using Rispolet should not breastfeed.

Similarities