Sizodon-Sun (Tablets) Instructions for Use

Marketing Authorization Holder

Sun Pharmaceutical Industries, Ltd. (India)

ATC Code

N05AX08 (Risperidone)

Active Substance

Risperidone (Rec.INN registered by WHO)

Dosage Forms

	Sizodon-Sun	Film-coated tablets, 1 mg: 10, 20 or 30 pcs.
		Film-coated tablets, 2 mg: 10, 20 or 30 pcs.
		Film-coated tablets, 3 mg: 10, 20 or 30 pcs.
		Film-coated tablets, 4 mg: 10, 20 or 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets orange in color, round, biconvex, with a score on one side.

Excipients: lactose, starch, microcrystalline cellulose, sodium benzoate, purified talc, magnesium stearate, colloidal silicon dioxide, sodium starch glycolate.

Coating composition Eudragit E-100, titanium dioxide, sunset yellow dye, polyethylene glycol 6000, sodium lauryl sulfate, isopropanol, acetone, purified water.

10 pcs. – aluminum blisters (1) – cardboard packs.
10 pcs. – aluminum blisters (2) – cardboard packs.
10 pcs. – aluminum blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Antipsychotic drug (neuroleptic)

Pharmacotherapeutic Group

Antipsychotic (neuroleptic) agent

Pharmacological Action

Antipsychotic agent (neuroleptic). It also has sedative, antiemetic and hypothermic effects. Sizodon-Sun is a selective monoaminergic antagonist with high affinity for serotonin 5-HT₂ and dopamine D₂ receptors, it also binds to α₁-adrenergic receptors and with somewhat less affinity to histamine H₁ 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 of the brainstem reticular formation; the antiemetic effect is due to the blockade of dopamine D₂ receptors of 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.

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

Pharmacokinetics

Absorption

After oral administration, Sizodon-Sun is completely absorbed from the gastrointestinal tract (regardless of food intake), C_max of risperidone in blood plasma is observed after 1-2 hours.

The plasma concentration of risperidone is proportional to the dose of the drug (within the range of therapeutic doses).

Distribution

In most patients, C_ss of risperidone is observed 1 day after the start of treatment. The steady state of 9-hydroxy-risperidone is reached in most cases 3-4 days after the start of treatment.

Risperidone is rapidly distributed in the body. V_d is 1-2 l/kg. Plasma protein binding (to albumin and acidic α₁-glycoprotein) is 88% for risperidone and 77% for 9-hydroxy-risperidone, respectively.

Metabolism

Risperidone is metabolized with the participation of the CYP2D6 isoenzyme to form 9-hydroxy-risperidone, which has a similar pharmacological action. Risperidone and 9-hydroxy-risperidone represent the effective antipsychotic fraction. Further metabolism of the drug consists of N-dealkylation.

Excretion

When the drug is taken orally, T_1/2 of risperidone is about 3 hours. It has been established that T_1/2 of 9-hydroxy-risperidone and the active antipsychotic fraction is 24 hours.

It is excreted by the kidneys – 70% (of which 35-45% in the form of a pharmacologically active fraction) and 14% with bile.

Pharmacokinetics in special clinical cases

With a single dose, high concentrations of the active substance and its active metabolite in the blood plasma and delayed excretion are noted in elderly patients and in renal failure.

Indications

• Schizophrenia (acute and chronic) and other psychotic conditions with productive and/or negative symptoms;
• Affective disorders in various mental illnesses;
• Behavioral disorders in patients with dementia with manifestations of aggressiveness (outbursts of anger, physical violence), with mental disorders (agitation, delusions) or psychotic symptoms;
• As an adjunctive therapy in the treatment of mania in bipolar disorders;
• As an adjunctive therapy for behavioral disorders in adolescents aged 15 years and older and in adult patients with intellectual disability or mental retardation, in cases where destructive behavior (aggressiveness, impulsivity, self-aggression) is the leading feature in the clinical picture of the disease.

ICD codes

Dosage Regimen

Schizophrenia

For adults and children over 15 years of age Sizodon-Sun can be prescribed 1 or 2 times a day.

The initial dose 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 individually adjusted if necessary. The optimal dose is usually 4-6 mg/day. In some cases, a slower dose increase and lower initial and maintenance doses may be justified.

The drug in doses of more than 10 mg/day does not show higher efficacy compared to lower doses and may cause extrapyramidal symptoms. Since the safety of the drug in doses of more than 16 mg/day has not been studied, this dose should not be exceeded.

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

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

For liver and kidney diseases, the recommended initial dose is 500 mcg twice a day. This dose can be gradually increased to 1-2 mg per dose twice a day.

For patients with drug abuse or drug dependence, the recommended dose of the drug is 2-4 mg/day.

Behavioral disorders in patients with dementia

The recommended initial dose is 250 mcg twice a day (an appropriate dosage form should be used). The dose can be increased if necessary by 250 mcg twice a day, no more often than every other day. For most patients, the optimal dose is 500 mcg twice a day. However, some patients are shown to take 1 mg twice a day.

Once the optimal dose is reached, once-daily administration may be recommended.

Mania in bipolar disorders

The recommended initial dose of the drug is 2 mg once a day. If necessary, the dose can be increased by 2 mg/day, no more often than every other day. For most patients, the optimal dose is 2-6 mg/day.

Behavioral disorders in patients with mental retardation

For patients weighing 50 kg or more, the recommended initial dose of the drug is 500 mcg once a day. If necessary, this dose can be increased by 500 mcg/day, no more often than every other day. For most patients, the optimal dose is 1 mg/day. However, for some patients, 500 mcg/day is preferable, in other cases an increase in dose to 1.5 mg/day is required.

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

Long-term treatment of adolescents with Sizodon-Sun should be carried out under constant medical supervision. The use of the drug 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 syndrome of inappropriate ADH secretion), 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 CPK levels), thermoregulation disorders, 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 reproductive system: priapism, erectile dysfunction, ejaculation disorders, anorgasmia.

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

Use in Pregnancy and Lactation

There are no clinical data on the safety of Sizodon-Sun during pregnancy. The use of the drug during pregnancy is possible only if the intended benefit to 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, the issue of stopping breastfeeding should be decided.

Use in Hepatic Impairment

The drug should be used with caution in severe hepatic insufficiency. In such cases, dose adjustment is required.

Use in Renal Impairment

The drug should be used with caution in severe renal failure. In such cases, dose adjustment is required.

Pediatric Use

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

Geriatric Use

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

Special Precautions

Transition from therapy with other antipsychotic drugs. In schizophrenia, at the beginning of treatment with Sizodon-Sun, it is recommended to gradually discontinue previous therapy if clinically justified. If patients are switched from therapy with depot forms of antipsychotic drugs, then it is recommended to start taking Sizodon-Sun 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 Sizodon-Sun, 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, instability of autonomic functions, impaired consciousness and increased CPK levels, all antipsychotic drugs, including Sizodon-Sun, should be discontinued.

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

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

During treatment, patients should avoid alcohol consumption.

Effect on the ability to drive vehicles and mechanisms

During treatment, patients should avoid driving vehicles and other activities that require high concentration and speed of psychomotor reactions.

Overdose

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

Treatment it is necessary to ensure a clear 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 the vital functions of the body is indicated.

To timely 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. There is no specific antidote.

Drug Interactions

Given that Sizodon-Sun acts primarily on the central nervous system, it should be used with caution in combination with other centrally acting drugs and with ethanol.

Sizodon-Sun reduces the effectiveness of levodopa and other dopamine agonists.

Clozapine reduces the clearance of risperidone.

With the simultaneous use of carbamazepine and Sizodon-Sun, 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 can increase the concentration of risperidone in the blood plasma, but this does not affect the concentration of the active antipsychotic fraction of the drug.

Fluoxetine may increase the concentration of risperidone in the blood plasma, but to a lesser extent the concentration of the active antipsychotic fraction, so dose adjustment of Sizodon-Sun is required with this combination.

When using Sizodon-Sun in combination with other drugs characterized by a high degree of binding to plasma proteins, clinically significant displacement of any drug from the plasma protein fraction is not observed.

Antihypertensive drugs increase the severity of blood pressure reduction against the background of Sizodon-Sun use.

Storage Conditions

The drug should be stored out of the reach of children, in a dry, light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 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.