Torendo, 3 mg 20 pcs.

Torendo is an antipsychotic (neuroleptic).

Pharmacodynamics

Risperidone is an antipsychotic and also has sedative, antiemetic and hypothermic effects. Risperidone is a selective monoaminergic antagonist with strong affinity for serotonergic 5-HT2 and dopaminergic D2 receptors, it also binds to alpha1-adrenoceptors and with some less affinity for H1-histaminergic and alpha2-adrenergic receptors. It has no tropinity 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.

Reduces productive symptomatology (delirium, hallucinations), automatism. Causes less suppression of motor activity and is less likely to induce catalepsy than classical antipsychotics (neuroleptics).

The balanced central antagonism to serotonin and dopamine may reduce the risk of extrapyramidal symptomatology.

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

Pharmacokinetics

In oral administration, risperidone is completely absorbed (regardless of food intake) and maximum plasma concentrations are observed after 1-2 hours.

Risperidone is metabolized with participation of P-450 IID6 cytochrome to form 9-hydroxy-risperidone, which has similar pharmacological effects. Risperidone and 9-hydroxy-risperidone constitute an effective antipsychotic fraction. The further metabolism of risperidone consists of N-dealkylation. When administered orally, risperidone is excreted with a half-life of about 3 hours. The half-life of 9-hydroxy-risperidone and the active antipsychotic fraction has been found to be 24 hours.

In most patients the equilibrium concentration of risperidone is observed one day after the start of treatment. The equilibrium state of 9-hydroxy risperidone is in most cases reached 3-4 days after the start of treatment.
The concentration of risperidone in plasma is proportional to the dose of the drug (within therapeutic doses).

Risperidone is rapidly distributed in the body. The volume of distribution is 1-2 l/kg. In plasma risperidone is bound to albumin and acidic alpha-1-glycoprotein. The fraction of risperidone that is bound to plasma protein is 88% and 77%, respectively, in the case of 9-hydroxy-risperidone.

It is excreted by the kidneys – 70% (of which 35-45% as pharmacologically active fraction) and 14% with the bile. In single administration high levels of active plasma concentrations and slow excretion in elderly patients and patients with insufficient renal function are noted.

Indications

– Acute and chronic schizophrenia and other psychotic conditions with productive and/or negative symptoms.
– Affective disorders in various mental illnesses.
– Behavioral disorders in patients with dementia with symptoms of aggressiveness (outbursts of anger, physical violence), mental disturbances (agitation, delusions) or psychotic symptoms.
– As an adjuvant therapy in the treatment of mania in bipolar disorders.
– As an auxiliary treatment for behavioral disorders in adolescents over 15 years of age and adult patients with a reduced intellectual level or mental retardation, in cases where destructive behavior (aggression, impulsivity, self-aggression) is leading in the clinical picture of the disease.

Pharmacological effect

Torendo is an antipsychotic (neuroleptic).

Pharmacodynamics

Risperidone is an antipsychotic drug and also has sedative, antiemetic and hypothermic effects. Risperidone is a selective monoaminergic antagonist with pronounced affinity for serotonergic 5-HT2 and dopaminergic D2 receptors, also binds to alpha1-adrenergic receptors and, with slightly less affinity, to H1-histamine and alpha2-adrenergic receptors. Does not have tropism for cholinergic receptors.
The antipsychotic effect is due to the blockade of dopamine D2 receptors of the mesolimbic and mesocortical systems.

The sedative effect is due to the blockade of adrenergic receptors in the reticular formation of the brain stem; antiemetic effect – blockade of dopamine D2 receptors in the trigger zone of the vomiting center; hypothermic effect – blockade of dopamine receptors of the hypothalamus.

Reduces productive symptoms (delusions, hallucinations), automatism. Causes less suppression of motor activity and induces catalepsy to a lesser extent than classical antipsychotics (neuroleptics).

Balanced central antagonism of serotonin and dopamine may reduce the risk of extrapyramidal symptoms.

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

Pharmacokinetics

When taken orally, risperidone is completely absorbed (regardless of food intake) and maximum plasma concentration levels are observed after 1-2 hours.

Risperidone is metabolized by cytochrome P-450 IID6 to form 9-hydroxy-risperidone, which has similar pharmacological effects. Risperidone and 9-hydroxy-risperidone are an effective antipsychotic fraction. Further metabolism of risperidone involves N-dealkylation. When taken orally, risperidone is eliminated with a half-life of approximately 3 hours. The half-life of 9-hydroxy-risperidone and the active antipsychotic fraction has been found to be 24 hours.

In most patients, steady-state risperidone concentrations are observed one day after the start of treatment. The equilibrium state of 9-hydroxy-risperidone is in most cases achieved 3-4 days after the start of treatment.
The concentration of risperidone in plasma is proportional to the dose of the drug (within therapeutic doses).

Risperidone is rapidly distributed in the body. The volume of distribution is 1-2 l/kg. In plasma, risperidone is bound to albumin and alpha-1 acid glycoprotein. The fraction of risperidone that is bound to plasma protein is 88% and 77%, respectively, in the case of 9-hydroxy-risperidone.

Excreted by the kidneys – 70% (of which 35-45% in the form of a pharmacologically active fraction) and 14% with bile. With a single dose, high levels of active plasma concentrations and slow elimination are observed in elderly patients and patients with insufficient renal function.

Special instructions

In schizophrenia, when starting treatment with risperidone, it is recommended to gradually withdraw previous therapy if clinically justified. If patients are transitioning from depot antipsychotic therapy, it is recommended that risperidone be started instead of the next scheduled injection.

The need for continued therapy with antiparkinsonian drugs should be periodically assessed. Due to the A-blocking effect of risperidone, orthostatic hypotension may occur, especially during the initial dose titration period. If arterial hypotension occurs, dose reduction should be considered. In patients with diseases of the cardiovascular system, as well as in cases of dehydration, hypovolemia or cerebrovascular disorders, the dose should be increased gradually, as recommended.

The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. If signs and symptoms of tardive dyskinesia occur, discontinuation of all antipsychotic medications should be considered. If neuroleptic malignant syndrome, characterized by hypertension, muscle rigidity, instability of autonomic functions, impaired consciousness and increased CPK levels, occurs, all antipsychotic drugs, including risperidone, should be discontinued.

When carbamazepine and other liver enzyme inducers are discontinued, the dose of risperidone should be reduced. Patients should refrain from overeating due to the possibility of weight gain. The use of the drug in children under 15 years of age is not recommended. During treatment, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, as well as from drinking alcohol (ethanol).

Active ingredient

Risperidone

Composition

1 film-coated tablet contains:

active substance: risperidone 3 mg.

excipients:

cellactose*,

microcrystalline cellulose,

croscarmellose sodium,

silicon dioxide colloidal anhydrous,

sodium lauryl sulfate,

magnesium stearate.

shell:

Opadry OZN28785 white**, quinoline yellow dye E 104. * Cellactose is a spray-dried compound consisting of 75% alpha-lactose monohydrate and 25% cellulose powder, dry matter ** Opadry OZN28785 is a ready-made mixture of hypromellose, titanium dioxide, talc, propylene glycol

Pregnancy

The safety of risperidone in pregnant women has not been studied. During pregnancy, it can be used only if the positive effect justifies the possible risk.

Because risperidone and 9-hydroxy-risperidone are excreted in breast milk, women using the drug should not breast-feed

Contraindications

Lactation period.
– Children and adolescents up to 15 years of age (efficacy and safety have not been established).
– Hypersensitivity to the components of the drug.

The drug should be used with caution in diseases of the cardiovascular system (chronic heart failure, previous myocardial infarction, cardiac muscle conduction disorders), dehydration and hypovolemia, cerebrovascular accidents, Parkinson’s disease, seizures (including a history), severe renal or hepatic failure, drug abuse or drug dependence, conditions predisposing to the development of tachycardia of the “pirouette” type (bradycardia, electrolyte imbalance, concomitant use of drugs that prolong the QT interval), brain tumors, intestinal obstruction, cases of acute drug overdose, Reye’s syndrome (the antiemetic effect of risperidone may mask the symptoms of these conditions).

Side Effects

From the nervous system: insomnia, agitation, anxiety, headache, sometimes – drowsiness, fatigue, dizziness, impaired concentration, blurred vision, rarely – extrapyramidal symptoms (tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia), mania or hypomania, stroke (in elderly patients with predisposing factors), as well as hypervolemia (either due to polydipsia or the syndrome of inappropriate secretion of antidiuretic hormone), tardive dyskinesia (involuntary rhythmic movements mainly of the tongue and/or face), neuroleptic malignant syndrome (hyperthermia, muscle rigidity, instability of autonomic functions, impaired consciousness and increased levels of creatine phosphokinase), thermoregulation disorders and epileptic seizures.

From the digestive system: constipation, dyspepsia, nausea or vomiting, abdominal pain, increased activity of liver transaminases, dry mouth, hypo- or hypersalivation, anorexia and/or increased appetite, increased or decreased body weight.

From the cardiovascular system: sometimes orthostatic hypotension, reflex tachycardia or increased blood pressure.

From the hematopoietic organs: neutropenia, thrombocytopenia.

From the endocrine system: galactorrhea, gynecomastia, menstrual irregularities, amenorrhea, weight gain, hyperglycemia and exacerbation of pre-existing diabetes mellitus.

From the genitourinary system: priapism, erectile dysfunction, ejaculation disorders, anorgasmia, urinary incontinence.

Allergic reactions: rhinitis, rash, angioedema, photosensitivity.

From the skin: dry skin, hyperpigmentation, itching, seborrhea.

Other: arthralgia.

Interaction

Since risperidone acts primarily on the central nervous system, it should be used with caution in combination with other centrally acting drugs and ethanol. Risperidone reduces the effectiveness of levodopa and other dopamine agonists. Clozapine reduces the clearance of risperidone. When using carbamazepine, a decrease in the concentration of the active antipsychotic fraction of risperidone in plasma was observed.

Similar effects may be observed with other liver enzyme inducers. Phenothiazines, tricyclic antidepressants and some A-blockers may increase plasma concentrations of risperidone, but this does not affect the concentration of the active antipsychotic fraction. Fluoxetine may increase plasma concentrations of risperidone, but to a lesser extent the concentration of the active antipsychotic fraction, so doses of risperidone should be adjusted.

When risperidone is used simultaneously with drugs that are highly bound to plasma proteins, no clinically significant displacement of any drug from the plasma protein fraction is observed. Antihypertensive drugs increase the severity of the decrease in blood pressure caused by risperidone.

Overdose

Symptoms: drowsiness, sedation, depression of consciousness, tachycardia, arterial hypotension, extrapyramidal disorders, in rare cases, prolongation of the QT interval.

Treatment: it is necessary to ensure an open airway to ensure adequate oxygenation and ventilation, gastric lavage (after intubation, if the patient is unconscious) and the administration of activated charcoal in combination with laxatives. Symptomatic therapy aimed at maintaining vital body functions. For timely diagnosis of possible heart rhythm disturbances, it is necessary to begin ECG monitoring as soon as possible. Careful medical observation and ECG monitoring are carried out until the symptoms of intoxication completely disappear. There is no specific antidote.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Manufacturer

KRKA dd Novo Mesto, Slovenia