Invega, sustained release pills 9mg, 28pcs

Composition

1 tablet of prolonged action, coated, contains:

Active ingredient:

paliperidone 9 mg

. excipients:

macrogol 200 K,

macrogol 7000 K,

sodium chloride,

povidone (K 29-32),

hyethylose,

stearic acid,

butylhydroxytoluene,

iron oxide red,

iron oxide yellow,

macrogol 3350,

cellulose acetate (398-10),

white dye (hypromellose, titanium dioxide, lactose monohydrate, triacetin),

Carnauba wax.

Pharmacological action

Invega – antipsychotic.

Pharmacodynamics

Mechanism of action

Paliperidone is a centrally acting dopamine_D2-receptor antagonist, which also has a high antagonism against serotonin 5-HT2-receptors. In addition, paliperidone is an antagonist of α1-and α2-adrenergic receptors and H1-histamine receptors. Paliperidone has no affinity for cholinergic, muscarinic, and β1– and β2-adrenergic receptors. The pharmacological activity of the ( + ) and (−)- enantiomers of paliperidone is the same in qualitative and quantitative terms.

The antipsychotic effect is due to the blockade_{of D2}-dopaminergic receptors of the mesolimbic and mesocortical systems. 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 can reduce the propensity for extrapyramidal side effects and expand the therapeutic effect of the drug to cover the negative and productive symptoms of schizophrenia.

Paliperidone has an effect on the structure of sleep: it reduces the latency period before falling asleep, reduces the number of awakenings after falling asleep, increases the total duration of sleep, increases sleep time and increases the sleep quality index. It has an antiemetic effect, may cause an increase in the concentration of prolactin in the blood plasma.

Pharmacokinetics

Unless otherwise specified, the pharmacokinetic data presented in this section are based on data obtained for adult patients. The pharmacokinetic characteristics of paliperidone after oral use are proportional to the dose taken in the recommended therapeutic range (3-12 mg once a day).

Absorption rate

After taking a single dose of the drug, the concentration of paliperidone in plasma steadily increased, and_cmax was reached after 24 hours. In most patients, steady-state concentrations of paliperidone were reached after 4-5 days of taking the drug once a day. Paliperidone is the active metabolite of risperidone. Features of the release of the Active ingredient from Invega® provided smaller fluctuations in the maximum and minimum concentrations of paliperidone than those observed with conventional dosage forms (the concentration fluctuation index was 38% compared to 125% for conventional dosage forms).

After taking paliperidone tablets, the mutual conversion of (+) and (−) enantiomers occurs, and the ratio of AUC — AUC (+)/AUC (−)  The absolute bioavailability of paliperidone after oral use is 28% (23-33% with a confidence interval of 90%). After a single dose of 15 mg of paliperidone in the form of a long-release tablet together with a high-calorie fatty food_{, cmax} and AUC increased by an average of 42 and 46%, respectively, relative to the same indicators when taking the tablet on an empty stomach. In another study, after a single dose of 12 mg of paliperidone in the form of a prolonged-release tablet together with a high-fat, high-calorie food_{, cmax} and AUC increased by an average of 60 and 54%, respectively, relative to the same indicators when taking the tablet on an empty stomach. Thus, the presence or absence of food in the stomach while taking paliperidone can change the concentration of paliperidone in the blood plasma.

Distribution

Paliperidone is rapidly distributed in tissues and body fluids. Apparent V_D — 487 l. The degree of binding to plasma proteins is 74%. Paliperidone binds mainly to_α1-acid glycoprotein and albumin.

Biotransformation and elimination

1 week after taking one standard tablet containing 1 mg of paliperidone,59% of the dose was excreted unchanged in the urine; this indicates that paliperidone does not undergo intensive metabolism in the liver. About 80% of the drug was detected in the urine and about 11% in the feces. Four pathways of paliperidone metabolism are known in vivo, none of which covers more than 6.5% of the dose: dealkylation, hydroxylation, dehydrogenation, and benzisoxazole cleavage. In vitro studies have shown that cytochrome P450 isoenzymes CYP2D6 and CYP3A4 may play a role in paliperidone metabolism, but there is no evidence that they play a significant role in paliperidone metabolism in vivo. Despite the fact that the activity of the CYP2D6 isoenzyme varies significantly in the general population, population pharmacokinetic studies did not reveal significant differences in the apparent clearance of paliperidone in patients with active metabolism of substrates of the CYP2D6 isoenzyme and in patients with weak metabolism of substrates of the CYP2D6 isoenzyme. In vitro studies using microsomal preparations of heterologous systems have shown that the isoenzymes CYP1A2, CYP2A6, CYP2C9, CYP2C19 and CYP3A5 are not involved in the metabolism of paliperidone.

The final T_1/2 of paliperidone is about 23 hours.

In vitro studies have shown that paliperidone is a substrate of P-glycoprotein and weakly inhibits it in high concentrations. In vivo data are not available, and clinical significance is unknown.

Special groups

Patients with impaired liver function. Paliperidone is not extensively metabolized in the liver. In patients with mild to moderate hepatic impairment, there is no need to reduce the dose of paliperidone. The study, which included patients with moderate hepatic impairment (Child-Pugh class B), showed that in these patients, the plasma concentrations of unbound paliperidone were similar to those in healthy people. The use of Invega in patients with severe hepatic impairment has not been studied.

Patients with impaired renal function. The dose of paliperidone should be reduced in patients with moderate to severe renal impairment. Paliperidone excretion was studied in patients with varying degrees of renal impairment. Paliperidone elimination was found to decrease as creatinine clearance decreased. Total clearance of paliperidone was reduced by 32% in patients with mild renal impairment (Cl creatinine from 50 to 1/2 of paliperidone was 24,40 and 51 h in patients with mild, moderate and severe renal impairment, respectively; patients with normal renal function (Cl creatinine >80 ml/min), the figure was 23 h.

Teens. The systemic effects of paliperidone in adolescents were comparable to those in adults. The concentration of paliperidone in blood plasma in adolescents with body weight

Elderly patients. It is not recommended to change the dose of paliperidone depending on the patient’s age. The results of a pharmacokinetic study involving elderly patients aged 65 years and older showed that the apparent clearance of paliperidone at steady state after ingestion of Invega® in this group was 20% lower than in adult patients aged 18-45 years. However, after adjusting for age-related decreases in creatinine clearance, population analysis did not reveal the effect of age in schizophrenic patients on the pharmacokinetics of paliperidone.

Racial affiliation. No dose adjustment is required for patients of different racial backgrounds. Population pharmacokinetic analysis showed no racial differences in the pharmacokinetics of paliperidone when using Invega®. No differences in pharmacokinetics were found in the Japanese and Caucasian studies.

Gender. The recommended doses of paliperidone are the same for men and women. The apparent clearance of paliperidone after taking the drug in women is approximately 19% lower than in men. This difference is mainly due to differences in the fat-free component of body weight and creatinine clearance between men and women, since population studies, after adjusting for the fat-free component of body weight and creatinine clearance, did not reveal clinically significant differences in the pharmacokinetics of paliperidone in men and women taking the drug.

Smoking. It is not recommended to change the dose of paliperidone in smokers. In vitro studies using human liver enzymes have shown that paliperidone is not a substrate of the CYP1A2 isoenzyme, and therefore smoking should not affect the pharmacokinetics of paliperidone. In accordance with the results of in vitro studies, population-based studies did not reveal differences in the pharmacokinetics of paliperidone between smokers and non-smokers.

Indications

• schizophrenia, including in the acute phase in adult patients;
• prevention of exacerbations of schizophrenia in adults;
• treatment of schizophrenia in adolescents aged 12 to 17 years;
• treatment of schizoaffective disorders: as monotherapy or as part of a combination therapy with antidepressants and / or normotimics in adult patients.

Use during pregnancy and lactation

Currently, there are no data on the safety of using paliperidone during pregnancy in women and its effect on fetal development. The drug should not be prescribed during pregnancy, except in cases of extreme necessity from a clinical point of view. The effect of paliperidone on labor in women is not known.

The use of antipsychotic drugs in the third trimester of pregnancy was accompanied by reversible extrapyramidal symptoms in newborns.

Paliperidone is excreted in breast milk, so the drug should not be prescribed during lactation.

Contraindications

It is contraindicated in patients with hypersensitivity to paliperidone, risperidone, as well as any auxiliary ingredient of the drug.

With caution: convulsive conditions in the anamnesis and diseases that reduce the threshold of convulsive readiness. Like other antipsychotics, paliperidone should be used with caution in patients with a history of seizures or other conditions that reduce the threshold of seizure readiness.

Dysphagia and narrowing of the gastrointestinal tract lumen (possibility of obstruction). Invega ® Tablets they do not deform and almost do not change their shape in the gastrointestinal tract, and therefore they should not be prescribed to patients with severe narrowing of the gastrointestinal lumen (pathological or iatrogenic), as well as to patients who suffer from dysphagia or who have difficulty swallowing tablets. There are rare reports of gastrointestinal obstruction symptoms associated with ingestion of non-deformable dosage forms with controlled release of the Active ingredient. Paliperidone also belongs to such dosage forms, and therefore it can only be prescribed to those patients who can swallow the tablets whole.

Elderly patients with dementia. The efficacy and safety of paliperidone have not been evaluated in elderly patients with dementia. A meta-analysis of 17 placebo-controlled trials found that elderly patients with dementia who received atypical antipsychotic medications such as risperidone, aripiprazole, olanzapine, and quetiapine had a higher mortality rate compared to patients who received placebo. Placebo-controlled trials involving elderly patients with dementia demonstrated an increased incidence of cerebrovascular adverse events (strokes and transient ischemic attacks), including fatal ones, in patients treated with certain atypical antipsychotic medications, including risperidone, aripiprazole, and olanzapine, compared with patients who received placebo.

Parkinson’s disease and dementia with Lewy bodies. Physicians should carefully weigh the possible risks and potential benefits when prescribing antipsychotic medications, including paliperidone, to patients with Parkinson’s disease or Lewy body dementia, as such patients may have an increased risk of developing neuroleptic malignant syndrome (NMS) or increased sensitivity to antipsychotic medications. Manifestations of this hypersensitivity include, in addition to extrapyramidal symptoms, confusion, blunted reactions, and postural hypotension with frequent falls.

Side effects

Infections: often-upper respiratory tract infections, nasopharyngitis; infrequently-urinary tract infections, acrodermatitis, bronchitis, subcutaneous fat inflammation, cystitis, ear infections, flu, onychomycosis, pneumonia, respiratory tract infections, sinusitis, tonsillitis.

From the immune system: infrequently — anaphylactic reaction, hypersensitivity.

From the hematopoietic and lymphatic system: infrequently-anemia, decreased hematocrit, neutropenia, decreased white blood cell count; rarely-thrombocytopenia; very rarely-agranulocytosis.

From the endocrine system: infrequently-hyperprolactinemia; very rarely-inadequate ADH secretion.

From the side of metabolism and nutrition: infrequently – increased CPK activity, anorexia, hyperglycemia; rarely-diabetes mellitus, hypoglycemia, water intoxication; very rarely-diabetic ketoacidosis.

Mental disorders: often — insomnia (including primary and secondary insomnia), mania; infrequently-nightmares, sleep disorders, depression.

Nervous system disorders: very often-headache; often-akathisia, dystonia, dysarthria, increased muscle tone, Parkinsonism, sedation, drowsiness, tremor, drooling; infrequently-cerebrovascular disorders, postural dizziness, dyskinesia, convulsions, fainting, impaired attention, hypesthesia, loss of consciousness, paresthesia, psychomotor hyperactivity, tardive dyskinesia, hypokinesia, opisthotonus.

Antipsychotic drugs, including paliperidone, are known to cause NMS, which is characterized by hyperthermia, muscle rigidity, instability of the autonomic nervous system, depression of consciousness, increased CPK activity, myoglobinuria, rhabdomyolysis, and acute renal failure.

From the side of the visual organs: infrequently-conjunctivitis, dry eyes, photophobia, lacrimation; with unknown frequency-flabby iris syndrome (intraoperative).

Hearing disorders and labyrinth disorders: infrequently — ear pain, vertigo, ringing in the ears.

From the CCC side: infrequently-bradycardia, palpitation, AV block, conduction disturbances, ECG changes, QT interval increase, ischemia, hot flashes, increased blood pressure, decreased blood pressure. Blood pressure; rarely — atrial fibrillation; very rarely-deep vein thrombosis, pulmonary embolism.

From the gastrointestinal tract: often — nausea, diarrhea, constipation, upper abdominal discomfort, dyspepsia, increased appetite; infrequently-decreased appetite, lip inflammation, dysphagia, fecal incontinence, small bowel obstruction, flatulence, gastroenteritis, tongue edema, toothache, dysgeusia; very rarely — pancreatitis, intestinal obstruction.

Liver and biliary tract disorders: very rarely — jaundice.

Respiratory system disorders: infrequently-pharyngopharyngeal pain, nasal congestion, cough, shortness of breath, hyperventilation, wheezing; rarely — sleep apnea syndrome.

Musculoskeletal and connective tissue disorders: often — myalgia, musculoskeletal pain; infrequently-muscle spasms, back pain, arthralgia, joint stiffness, joint swelling, muscle weakness, neck pain.

Skin and subcutaneous tissue disorders: infrequently-rash, itching, acne, dry skin, eczema, erythema, seborrheic dermatitis, skin discoloration; rarely-angioedema, alopecia.

From the side of the kidneys and urinary tract: infrequently — dysuria, pollakiuria, urinary incontinence, urinary retention.

From the genitals and breast: infrequently-decreased libido, anorgasmia, nipple discharge, erectile dysfunction, gynecomastia, menstrual changes, sexual dysfunction, vaginal discharge, ejaculation disorders, breast engorgement; very rarely-priapism.

Influence on the course of pregnancy, postpartum and perinatal conditions: very rarely — withdrawal syndrome in newborns.

Other: often-weight gain; infrequently-weight loss, chills, facial edema, gait disorders, edema (including generalized, peripheral, mild), increased body temperature, fever, thirst; very rarely — hypothermia.

Laboratory tests: infrequently — an increase in GGT activity, an increase in liver enzyme activity, an increase in transaminase activity, an increase in cholesterol concentration in the blood, an increase in the concentration of triglycerides in the blood.

Interaction

Most likely, paliperidone does not enter into a clinically significant pharmacokinetic interaction with drugs that are metabolized by cytochrome P450 isoenzymes. In vitro studies using human liver microsomes have shown that paliperidone does not significantly inhibit the biotransformation of drugs metabolized with the participation of cytochrome P450 isoenzymes, including CYP1%%A%%4, CYP2%%A%%6, CYP2%%C%%8/9/10, CYP2D6, CYP2E1, CYP3A4 and CYP3A5. Therefore, there is no reason to assume that paliperidone will inhibit to a clinically significant extent the clearance of drugs that are metabolized by these enzymes. In addition, paliperidone most likely does not induce enzymes. At therapeutic concentrations, paliperidone does not inhibit P-glycoprotein, and therefore is not able to inhibit the transport of other P-glycoprotein preparations to a clinically significant extent. Given the fact that paliperidone acts primarily on the central nervous system, it should be used with caution in combination with other drugs of central action and with ethanol. Paliperidone can neutralize the effects of levodopa and other dopamine agonists. Due to the ability of paliperidone to cause orthostatic hypotension, an additive effect may occur when the drug is used simultaneously with other drugs that cause orthostatic hypotension.

Paliperidone is not a substrate of the isoenzymes CYP1% ^% A%^%2, CYP2%^%A%^%6, CYP2%^%C%^%9, CYP2%^%C%^%19 and CYP3%^%A%^%5. This indicates a low probability of its interaction with inhibitors or inducers of these enzymes.In vitro studies revealed minimal involvement of CYP2D6 and CYP3A4 isoenzymes in paliperidone metabolism, however, there is no evidence that these isoenzymes play a significant role in paliperidone metabolism in vitro or in vivo. Paliperidone, which is a cation at physiological pH values, is mainly excreted unchanged by the kidneys, with about half of the excretion accounted for by filtration and about half by active secretion. Concomitant use of paliperidone with trimethoprim, which is known to inhibit active renal transport of cationic drugs, did not affect the pharmacokinetics of paliperidone. The concomitant use of paliperidone and risperidone has not been the subject of scientific research. Paliperidone is an active metabolite of risperidone, and therefore, with simultaneous use of paliperidone and risperidone, it is possible to increase the concentration of paliperidone in blood plasma.

How to take, course of use and dosage

Inside, tablets should be swallowed whole, washed down with liquid, they should not be chewed, divided into parts or crushed.

Schizophrenia

Adults (over 18 years of age). The recommended dose for adults is 6 mg once a day, in the morning, regardless of food intake. A gradual increase in the initial dose is not required. In some patients, the therapeutic effect is caused by lower or higher doses within the recommended range of 3-12 mg once a day. There is a general tendency to increase the effect when using large doses of the drug. If an increase in the dose is necessary, it is recommended to increase the dose by 3 mg per day at intervals of more than 5 days.

Teenagers (12-17 years old). The recommended dose in adolescents is 3 mg once a day, in the morning, regardless of food intake. A gradual increase in the initial dose is not required. In some patients, the therapeutic effect is caused by higher doses within the recommended range of 6-12 mg once a day. An increase in the dose is possible only after a clinical reassessment, with an increase in the dose by 3 mg per day at intervals of more than 5 days.

Schizoaffective disorders

Adults (over 18 years of age). The recommended dose for adults is 6 mg once a day, in the morning. A gradual increase in the initial dose is not required. In some patients, the therapeutic effect is caused by lower or higher doses within the recommended range of 6-12 mg once a day. An increase in the dose, if necessary, should be made only after evaluating the patient’s clinical condition. If an increase in the dose is necessary, it is recommended to increase the dose by 3 mg / day at intervals of more than 4 days. Maintenance therapy in patients with schizoaffective disorders has not been studied.

Patients with impaired liver function. No dose reduction is required in patients with mild to moderate hepatic impairment. The use of Invega in patients with severe hepatic impairment has not been studied.

Patients with impaired renal function. For patients with mild renal impairment (Creatinine clearance ≥50, but not in patients with creatinine clearance

Elderly patients. For elderly patients with normal renal function (creatinine clearance ≥80 ml/min), the same doses of the drug are recommended as for adult patients with normal renal function. However, in elderly patients, renal function may be reduced, and in this case the dose of the drug should be selected according to the renal function of the individual patient (see “Patients with impaired renal function”). Caution should be exercised when using the drug in elderly patients with dementia due to the increased risk of stroke. The efficacy and safety of Invega® in patients over 65 years of age with schizoaffective disorders has not been studied.

Children and teenagers. The efficacy and safety of Invega® for the treatment of schizophrenia in children under 12 years of age has not been studied. The efficacy and safety of Invega for the treatment of schizoaffective disorders in patients under 18 years of age has not been studied.

Special patient groups

It is not recommended to change the dose of paliperidone depending on gender, age and whether the patient smokes or not.

Transfer of patients to treatment with other antipsychotic drugs

Currently, there are no systematically collected data on the transfer of patients from treatment with paliperidone to treatment with other antipsychotic drugs. The pharmacodynamics and pharmacokinetics of different antipsychotic drugs are not the same, and therefore doctors should carefully monitor the condition of patients when transferring them from one antipsychotic drug to another.

Overdose

Symptoms: Overall, the objective and subjective symptoms of paliperidone overdose represent enhanced pharmacological effects of this drug. Drugs, i. e. drowsiness and sedation, tachycardia and hypotension, prolongation of the QT interval and extrapyramidal symptoms. Bidirectional tachycardia and ventricular fibrillation were observed with an overdose of oral paliperidone. In case of acute overdose, it is necessary to take into account the possibility of toxic effects of several drugs.

When assessing the therapeutic needs of the patient and the effectiveness of overdose management, it should be remembered that Invega® is a drug with a prolonged release of the Active ingredient.

Treatment: generally accepted supportive measures should be implemented. Ensure and maintain good airway patency, as well as adequate oxygenation and ventilation. It is necessary to immediately organize monitoring of cardiovascular activity (ECG monitoring to detect possible arrhythmias). Arterial hypotension and collaptoid states are stopped by intravenous use of plasma-substituting solutions and / or sympathomimetic agents. In certain situations, gastric lavage is indicated (after intubation, if the patient is unconscious), the introduction of activated charcoal and laxatives. If severe extrapyramidal symptoms occur, m-holinoblockers should be administered. Monitoring of the patient’s condition and monitoring of basic physiological functions should be continued until the consequences of overdose are completely eliminated. There is no specific antidote for paliperidone.

Special instructions

of the NMS. Antipsychotic drugs, including paliperidone, are known to cause NMS, which is characterized by hyperthermia, muscle rigidity, instability of the autonomic nervous system, depression of consciousness, and increased serum concentrations of CPK. Myoglobinuria (rhabdomyolysis) and acute renal failure may also occur in patients with NMS. If a patient experiences objective or subjective symptoms of NMS, all antipsychotic medications, including paliperidone, should be discontinued immediately.

Tardive dyskinesia. Drugs that have the properties of dopamine receptor antagonists can cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, mainly of the tongue and / or facial muscles. If a patient experiences objective or subjective symptoms that indicate tardive dyskinesia, discontinuation of all antipsychotic medications, including paliperidone, should be considered.

Prolongation of the QT interval. As with other antipsychotic agents, caution should be exercised when prescribing Invega to patients with a history of cardiac arrhythmias, congenital QT prolongation, and when co-administered with drugs that prolong the QT interval.

Hyperglycemia and diabetes mellitus. Hyperglycemia, diabetes mellitus, and exacerbation of pre-existing diabetes mellitus were observed during treatment with Invega®. Establishing the relationship between the use of atypical antipsychotic drugs and glucose metabolism disorders is complicated by an increased risk of diabetes in patients with schizophrenia and the prevalence of diabetes in the general population. Given these factors, the relationship between the use of atypical antipsychotic drugs and the development of side effects associated with hyperglycemia is not fully established. In patients with an established diagnosis of diabetes mellitus, glucose levels should be monitored regularly. Patients with risk factors for diabetes (e. g., obesity, family history of diabetes) should have their fasting blood glucose monitored at the beginning of treatment and periodically during treatment. All patients should be clinically monitored for symptoms of hyperglycemia and diabetes mellitus. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should have their blood glucose monitored. In some cases, symptoms of hyperglycemia disappeared when atypical antipsychotic medications were discontinued, but some patients require antidiabetic treatment despite discontinuation of the drug.

Weight gain. When treated with atypical antipsychotics, a significant increase in body weight was observed. It is necessary to monitor the body weight of patients.

Hyperprolactinemia. Like other_D2-dopamine receptor antagonists, paliperidone increases prolactin levels, and this increase persists throughout the drug intake. The effect of paliperidone is comparable to that of risperidone, the drug that has the greatest effect on prolactin levels among other antipsychotic drugs. Hyperprolactinemia, regardless of the etiology, can inhibit the expression of GnRH of hypotolamus, which leads to a decrease in the secretion of gonadotropins by the pituitary gland.This, in turn, can inhibit reproductive function, weakening sexual steroidogenesis in women and men. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients treated with prolactin-enhancing drugs. Prolonged hyperprolactinemia associated with hypogonadism can lead to a decrease in bone density in women and men.

In vitro tissue culture studies have shown that approximately one-third of human breast cancer cases are prolactin-dependent. This should be taken into account when prescribing drugs that increase prolactin levels to patients with previously diagnosed breast cancer. Clinical and epidemiological studies conducted to date have not shown a link between the use of atypical antipsychotic drugs and the formation of tumors in humans. However, the available data are too limited to draw definitive conclusions.

Orthostatic hypotension. Paliperidone has alpha-blocking activity, and therefore may cause orthostatic hypotension in some patients. Paliperidone should be used with caution in patients with cardiovascular diseases (for example, heart failure, myocardial infarction or ischemia, cardiac muscle conduction disorders), cerebrovascular diseases, as well as conditions that contribute to arterial hypotension (for example, dehydration, hypovolemia and antihypertensive drug therapy).

Regulation of body temperature. Antipsychotic drugs are attributed to such an undesirable effect as a violation of the body’s ability to regulate temperature. Caution should be exercised when prescribing paliperidone to patients with conditions that may contribute to an increase in internal body temperature, such as intense physical activity, dehydration, exposure to high external temperatures, or simultaneous use of drugs with anticholinergic activity.

Antiemetic effect. In preclinical studies, the antiemetic effect of paliperidone was revealed. This effect, if it occurs in humans, can mask the objective and subjective symptoms of overdose of certain drugs, as well as diseases such as intestinal obstruction, Reye’s syndrome and brain tumors.

Priapism. Drugs that have alpha-blocking effects can cause priapism. In post-marketing studies of paliperidone, priapism has been reported.

Suicide attempts. The possibility of suicide attempts is characteristic of mental illnesses, so treatment of high-risk patients should be carried out under close supervision. In these cases, Invega® should be prescribed in a minimum number of tablets to reduce the risk of overdose.

Leukopenia, neutropenia, agranulocytosis. Leukopenia, neutropenia, and agranulocytosis have been reported with antipsychotic medications, including Invega. Agranulocytosis was observed very rarely during post-marketing observations. Patients with a history of clinically significant white blood cell count reduction or drug-dependent leukopenia/neutropenia are recommended to undergo a complete blood count analysis during the first months of therapy; discontinuation of Invega® treatment should be considered at the first clinically significant white blood cell count reduction in the absence of other possible causes. Patients with clinically significant neutropenia should be monitored for fever or infection symptoms and start treatment immediately if such symptoms occur. Patients with severe neutropenia (absolute neutrophil count less than 1 * 109/l) should discontinue the use of Invega®. until the white blood cell count returns to normal.

Venous thromboembolism. Cases of venous thromboembolism have been reported with the use of antipsychotic drugs. Since patients taking antipsychotic medications are often at risk of developing venous thromboembolism, all possible risk factors should be identified before and during treatment with Invega® and preventive measures taken.

Intraoperative loose iris syndrome (ISDR). ISDR was observed during cataract surgery in patients receiving therapy with alpha_-1-adrenergic antagonist drugs. ISDR increases the risk of visual organ-related complications during and after surgery. The doctor performing such an operation should be informed in advance that the patient has taken or is currently taking drugs that have the activity of alpha_-1-adrenergic antagonists. The potential benefit of discontinuing alpha_-1-adrenergic antagonist therapy prior to surgery has not been established, and should be evaluated taking into account the risks associated with discontinuing antipsychotic therapy.

Pregnancy and child care. The patient should notify their doctor about pregnancy or its planning during treatment with Invega®. Caution should be exercised when prescribing Invega® to nursing mothers (see “Use during pregnancy and lactation”).

Alcohol consumption. Patients should avoid alcohol consumption during treatment with Invega®.

Conditions that lead to a decrease in the presence of the drug in the gastrointestinal tract. Conditions that lead to a decrease in the presence of the drug in the gastrointestinal tract, such as diseases associated with chronic diarrhea, can cause a decrease in the absorption of paliperidone.

Invega ® tablets are manufactured using osmotic release technology of the Active ingredient, in which osmotic pressure ensures the release of paliperidone at a controlled rate. The system, which looks like a capsule-shaped tablet, consists of an osmotically active three-layer core surrounded by an intermediate shell and a semi-permeable membrane. The three-layer core consists of two drug layers containing the drug substance and excipients, as well as an ejector layer containing osmotically active components. On the dome side of the drug layers, there are two laser-made discharge holes. In the gastrointestinal tract, the color membrane quickly dissolves, and water begins to enter the tablet through a semi-permeable control membrane. The membrane controls the level of water intake, and this in turn controls the level of drug release.

The hydrophilic polymers of the tablet core absorb water and swell, turning into a gel containing paliperidone, which is then pushed out through holes in the dome. The insoluble components of the tablet are eliminated from the body with the stool. Patients should not worry if they notice something that looks like a pill in the stool.

Influence on driving a car and working with mechanisms. Paliperidone can interfere with activities that require rapid mental reactions, and can also have visual effects, so patients should refrain from driving a car or working with mechanisms until their individual sensitivity to paliperidone is established.

Composition

Tablet Form of production

Storage conditions

At a temperature of 15-30 °C

Shelf life

2 years

Active ingredient

Paliperidone

Conditions of release from pharmacies

By prescription

Dosage form

Tablets