Rispolettes, 1 mg/ml 30 ml

Rispolept is an antipsychotic drug, a benzizoxazole 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-adrenoreceptors and somewhat weaker to histamine H1-receptors and α2-adrenoreceptors. 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:

Risperidone 1 mg;

Supplementary substances:

tartaric acid;

benzoic acid;

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 Rispolettes® is 2 mg/day. On the second day, the dose should be increased to 4 mg/day. From this point on, the dose can either be maintained at the same level or adjusted individually 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 Rispolettes® 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.

Contraindications

With caution, the drug should be used in patients with cardiovascular diseases (including chronic heart failure, post-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, intestinal obstruction, in cases of acute drug overdose, Reye syndrome (because of the antiemetic effect of the vomiting effects of drugs).Because the antiemetic effect of risperidone may mask the symptoms of these conditions), in pregnancy, patients under the age of 15 years (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), thermoregulation 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 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 heart 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 the symptoms of intoxication disappear.

Similarities