Speridan^® (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

An antipsychotic drug (neuroleptic), a benzisoxazole derivative. It also has sedative, antiemetic, and hypothermic effects. It is a selective monoaminergic antagonist. It has high affinity for serotonin 5-HT₂ receptors and dopamine D₂ receptors; it also 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. The antipsychotic effect is due to the blockade of dopamine D₂ receptors in the mesolimbic and mesocortical systems.

The sedative effect is due to the blockade of adrenergic receptors in the brainstem reticular formation; the antiemetic effect is due to the blockade of dopamine D₂ receptors in the trigger zone of the vomiting center; the hypothermic effect is due to the blockade of dopamine receptors in the hypothalamus. It reduces productive symptoms (delusions, hallucinations), automatism. It causes less suppression of motor activity and induces catalepsy to a lesser extent than classical antipsychotics (neuroleptics).

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

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

Pharmacokinetics

Absorption

When taken orally, it is absorbed rapidly and completely, and food does not affect the completeness and rate of absorption. C_max in plasma is reached in 1-2 hours.

Steady-state concentration of risperidone in the body is reached in most patients within 1 day, and of 9-hydroxy-risperidone within 4-5 days. Plasma concentrations of risperidone are proportional to the dose of the drug (within therapeutic doses).

Distribution

The drug is rapidly distributed, penetrates the CNS, and breast milk. V_d is 1.1 L/kg. Plasma protein binding (to alpha₁-glycoprotein and albumin) is 90% for risperidone and 77% for 9-hydroxy-risperidone.

Metabolism

It is metabolized by the CYP2D6 isoenzyme to the active metabolite, 9-hydroxy-risperidone (Risperidone and 9-hydroxy-Risperidone constitute the active antipsychotic fraction). Another metabolic pathway is N-dealkylation.

Excretion

The T_1/2 of risperidone is 3 hours, and the T_1/2 of 9-hydroxy-risperidone is 21 hours. 70% of the drug is excreted by the kidneys, of which 35-45% is in the form of the pharmacologically active fraction; 14% of the administered dose is excreted in the bile.

After a single dose, high levels of active plasma concentrations and slow excretion are observed in elderly patients and in patients with renal failure.

Indications

• Acute and chronic schizophrenia and other psychotic states with productive and/or negative symptoms;
• Affective disorders in various mental illnesses;
• Behavioral disorders in patients with dementia when symptoms of aggression (outbursts of anger, physical violence), activity disturbances (agitation, delirium) or psychotic symptoms are manifested;
• As adjunctive therapy (as a mood stabilizer) – behavioral disorders in adolescents over 15 years of age and adult patients with intellectual disability or mental retardation, in cases where destructive behavior (aggression, impulsivity, self-aggression) is predominant in the clinical picture of the disease;
• As adjunctive therapy in the treatment of mania in bipolar disorders.

ICD codes

Dosage Regimen

Tablets

For schizophrenia in adults and adolescents over 15 years of age, the drug is prescribed 1-2 times/day. The initial daily dose is 2 mg. On the 2nd day, the daily dose should be increased to 4 mg. Then the dose can either be maintained at the same level or individually adjusted if necessary. The optimal daily dose is 4-6 mg. In some cases, a slower dose increase and lower initial and maintenance doses may be justified.

When prescribing a daily dose of more than 10 mg, no higher efficacy was observed compared to lower doses. In this case, the development of extrapyramidal symptoms may be noted. Since the safety of doses above 16 mg/day has not been studied, doses above this level should not be used.

For elderly patients, the recommended initial dose is 500 mcg twice daily. The dose can be individually increased by 500 mcg per day up to 1-2 mg twice daily.

In patients with liver and kidney diseases, the recommended initial dose is 500 mcg twice daily. The dose can be gradually increased to 1-2 mg twice daily.

There is no information on the use of the drug for the treatment of schizophrenia in children under 15 years of age.

For drug abuse or drug dependence, the recommended daily dose of the drug is 2-4 mg.

For behavioral disorders in patients with dementia, the recommended initial dose is 250 mcg twice daily (an appropriate dosage form should be used). The dose can be individually increased by 250 mcg per day if necessary (no more often than every other day). For most patients, the optimal dose is 500 mcg twice daily. However, some patients are indicated to take the drug at a dose of 1 mg twice daily. After reaching the optimal dose, once-daily administration may be recommended.

For mania in bipolar disorders, the recommended initial dose of the drug is 2 mg once daily. If necessary, the dose can be increased by 2 mg per day, no more often than every other day. For most patients, the optimal daily dose is 2-6 mg.

For behavioral disorders in patients with intellectual disability, for patients weighing 50 kg or more, the recommended initial dose of the drug is 500 mcg once daily. If necessary, the dose can be increased by 500 mcg per day, no more often than every other day. For most patients, the optimal daily dose is 1 mg.

However, for some patients, a dose of 500 mcg/day is preferable, while some patients require an increase in dose to 1.5 mg/day.

For patients weighing less than 50 kg, the recommended initial dose of the drug is 250 mcg once daily. If necessary, this dose can be increased by 250 mcg per day, no more often than every other day. For most patients, the optimal dose is 500 mcg/day. However, for some patients, a dose of 250 mcg/day is preferable, while some require an increase in dose to 750 mcg/day.

Long-term use of Speridan^® in adolescents should be carried out under constant medical supervision.

Use in children under 15 years of age is not recommended.

Adverse Reactions

From the central and peripheral nervous system insomnia, agitation, anxiety, headache; sometimes – drowsiness, increased 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 due to the syndrome of inappropriate ADH secretion), tardive dyskinesia (involuntary rhythmic movements mainly of the tongue and/or face), neuroleptic malignant syndrome (hyperthermia, muscle rigidity, autonomic instability, impaired consciousness and increased CPK levels), 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, increase or decrease in 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 cycle disorders, 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.

Dermatological reactions dry skin, hyperpigmentation, itching, seborrhea.

Other arthralgia.

Contraindications

• Lactation period (breastfeeding);
• Hypersensitivity to the components of the drug.

With caution, the drug should be prescribed for diseases of the cardiovascular system (chronic heart failure, history of myocardial infarction, conduction disorders), dehydration and hypovolemia, cerebrovascular disorders, Parkinson’s disease, seizures (including history), severe renal or hepatic failure, drug abuse or drug dependence, conditions predisposing to the development of torsades de pointes tachycardia (bradycardia, electrolyte imbalance, concomitant use of drugs that prolong the QT interval), brain tumor, intestinal obstruction, cases of acute drug overdose, Reye’s syndrome (the antiemetic effect of risperidone may mask the symptoms of these conditions), pregnancy, in children under 15 years of age (efficacy and safety have not been established).

Use in Pregnancy and Lactation

The safety of risperidone in pregnant women has not been studied. During pregnancy, use is possible only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

Since Risperidone and 9-hydroxy-Risperidone are excreted in breast milk, if it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

With caution, the drug should be prescribed for severe hepatic insufficiency.

In patients with liver diseases, the recommended initial dose is 500 mcg twice daily. The dose can be gradually increased to 1-2 mg twice daily.

Use in Renal Impairment

With caution, the drug should be prescribed for severe renal insufficiency.

In patients with kidney diseases, the recommended initial dose is 500 mcg twice daily. The dose can be gradually increased to 1-2 mg twice daily.

Pediatric Use

Use in children under 15 years of age is not recommended.

Geriatric Use

Elderly patients are recommended an initial dose of 500 mcg twice daily. The dose can be individually increased by 500 mcg per day up to 1-2 mg twice daily.

Special Precautions

Transition from therapy with other antipsychotic drugs. In schizophrenia, at the beginning of treatment with Speridan^®, it is recommended to gradually discontinue previous therapy if clinically justified. If patients are switched from therapy with depot forms of antipsychotic drugs, it is recommended to start taking Speridan^® instead of the next scheduled injection. The need for continued therapy with antiparkinsonian drugs should be periodically assessed. Due to the alpha-adrenergic blocking action of risperidone, orthostatic hypotension may occur, especially during the initial dose titration period. If hypotension occurs, a dose reduction should be considered. In patients with cardiovascular diseases, as well as with dehydration, hypovolemia or cerebrovascular disorders, the dose should be increased gradually, according to the recommendations.

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 drugs should be considered. If neuroleptic malignant syndrome occurs, characterized by hyperthermia, muscle rigidity, autonomic instability, impaired consciousness and increased CPK levels, all antipsychotic drugs, including Risperidone, must be discontinued.

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

Patients should be advised to avoid overeating due to the possibility of weight gain.

During treatment, alcohol consumption should be avoided.

Effect on ability to drive vehicles and operate machinery

During treatment, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms drowsiness, sedative effect, depression of consciousness, tachycardia, arterial hypotension, extrapyramidal disorders, in rare cases – QT interval prolongation.

Treatment it is necessary to ensure a patent airway for adequate oxygenation and ventilation, gastric lavage (after intubation, if the patient is unconscious) and administration of activated charcoal in combination with laxatives. Symptomatic therapy aimed at maintaining vital body functions is carried out. There is no specific antidote.

To promptly diagnose possible cardiac arrhythmias, ECG monitoring should be started as soon as possible. Careful medical supervision and ECG monitoring are carried out until the symptoms of intoxication completely disappear.

Drug Interactions

Given that Speridan^® primarily affects the CNS, it should be used with caution in combination with other centrally acting drugs and with alcohol.

Speridan^® 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 noted. Similar effects may be observed with the use of other liver enzyme inducers.

Phenothiazines, tricyclic antidepressants and some beta-blockers may increase plasma concentrations of risperidone, but this does not affect the concentration of the active antipsychotic fraction.

Fluoxetine may increase the plasma concentration of risperidone, but to a lesser extent the concentration of the active antipsychotic fraction, so the doses of risperidone should be adjusted.

When using Speridan^® together with other drugs that are highly bound to plasma proteins, clinically significant displacement of any drug from the plasma protein fraction is not observed.

Hypotensive drugs enhance the severity of blood pressure reduction when used concomitantly with Speridan^®.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

The drug is dispensed by prescription.

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.