Composition, form of production and packaging
The tablets of the prolonged action, covered with a cover of white color, a capsular form, with an inscription "PAL 3"; The outlets can be visible or invisible when viewed visually.
1 tab.
paliperidone 3 mg
Auxiliary substances: macrogol 200K - 81.43 mg, macrogol 7000K - 73.7 mg, sodium chloride - 30 mg, povidone (K29-32) - 10 mg, hyetylose - 10.45 mg, stearic acid - 0.75 mg, butyl hydroxytoluene - 0.11 mg, iron oxide red - 1 mg, iron oxide yellow - 0.03 mg, macrogol 3350-1 mg, cellulose acetate (398-10) 44.55 mg, white dye (hypromellose, titanium dioxide, lactose monohydrate, triacetin) 33 mg, carnauba wax 0.03 mg .
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
30 pcs. - polyethylene bottles (1) - cardboard packs.
Tablets of prolonged action, covered with a cover of light orange color (a slight brownish tinge is permissible), capsular shaped, with the inscription "PAL 6"; The outlets can be visible or invisible when viewed visually.
1 tab.
paliperidone 6 mg
Auxiliary substances: macrogol 200K - 78.45 mg, macrogol 7000K - 73.7 mg, sodium chloride - 30 mg, povidone (K29-32) - 10 mg, hyetylose - 10.45 mg, stearic acid - 0.75 mg, butyl hydroxytoluene - 0.11 mg, iron oxide red - 1.01 mg, macrogol 3350-1 mg, cellulose acetate (398-10) 44.55 mg, beige dye (hypromellose, titanium dioxide, polyethylene glycol 400, iron oxide yellow, iron oxide red) - 18 mg, carnauba wax - 0.03 mg.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
30 pcs. - polyethylene bottles (1) - cardboard packs.
Tablets of prolonged action, covered with a pink coating (a grayish color is allowed), capsular shaped, with the inscription "PAL 9"; The outlets can be visible or invisible when viewed visually.
1 tab.
paliperidone 9 mg
Excipients: macrogol 200K - 75.45 mg, macrogol 7000K - 73.7 mg, sodium chloride - 30 mg, povidone (K29-32) - 10 mg, hyetylose - 10.45 mg, stearic acid - 0.75 mg, butyl hydroxytoluene - 0.11 mg, iron oxide black 0.01 mg, iron oxide red 1 mg, macrogol 3350-1 mg, cellulose acetate 398-10 44.55 mg, dye pink (hypromellose, titanium dioxide, polyethylene glycol 400, iron oxide red) 15 mg, carnauba wax - 0.03 mg.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
30 pcs. - polyethylene bottles (1) - cardboard packs.
The tablets of the prolonged action, covered with a cover of dark yellow color (grayish shade allowed), capsular shaped, with the inscription "PAL 12"; The outlets can be visible or invisible when viewed visually.
1 tab.
paliperidone 12 mg
Auxiliary substances: macrogol 200K - 72.43 mg, macrogol 7000K - 73.7 mg, sodium chloride - 30 mg, povidone (K29-32) - 10 mg, hyetylose - 10.45 mg, stearic acid - 0.75 mg, butyl hydroxytoluene - 0.11 mg, iron oxide red - 1 mg, iron oxide yellow - 0.03 mg, macrogol 3350-1 mg, cellulose acetate (398-10) - 44.55 mg, dye dark yellow (hypromellose, titanium dioxide, polyethylene glycol 400, iron oxide yellow) - 12 mg, carnauba wax - 0.03 mg.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
30 pcs. - polyethylene bottles (1) - cardboard packs.
The inscription on the tablets of all dosages is made in water-soluble black ink (hypromellose, iron oxide, black, purified water, isopropanol, propylene glycol).
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Mechanism of action
Paliperidone is a centrally acting antagonist of dopamine D 2 receptors, which also has high antagonism against serotonin 5-HT 2A receptors. In addition, paliperidone is an antagonist of alpha 1 - and alpha 2 -adrenergic receptors and H 1 -gistamine receptors. Paliperidone does not have affinity for cholinergic, muscarinic, and beta 1 - and beta 2 -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 D 2 -dophaminergic receptors of the mesolimbic and mesocortical system. It causes less inhibition of motor activity and to a lesser degree induces catalepsy than classical antipsychotics (antipsychotics).
A balanced central antagonism to serotonin and dopamine can reduce the propensity to extrapyramidal side effects and expand the therapeutic effect of the drug to include negative and productive symptoms of schizophrenia .
Paliperidone has an effect on the structure of sleep: reduces the latent period before falling asleep, reduces the number of awakenings after falling asleep, increases the total duration of sleep, prolongs sleep time, and increases the index of sleep quality. Has antiemetic effect, can 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 the results of studies in adult patients.
The pharmacokinetic characteristics of paliperidone after oral administration are proportional to the dose taken in the recommended therapeutic range (3-12 mg 1 time / day).
Absorption
After taking one dose of the drug, the concentration of paliperidone in the plasma increased steadily, and the maximum concentration (C max ) was reached after 24 hours. In most patients, equilibrium concentrations of paliperidone were achieved after 4-5 days of drug administration once a day.
Paliperidone is an active metabolite of risperidone. Features of the release of the active ingredient from Invega В® provided smaller fluctuations of maximum and minimum concentrations of paliperidone than those observed with conventional dosage forms (38% concentration fluctuation index compared to 125% for conventional dosage forms).
After receiving the paliperidone tablets, the (+) and (-) enantiomers are mutually converted, and the ratio of the area under the AUC (+) / AUC (-) curve in the equilibrium state is approximately 1.6. The absolute bioavailability of paliperidone after oral administration is 28% (23% -33% with a confidence interval of 90%).
After a single administration, 15 mg of paliperidone in the form of a sustained release tablet together with fatty high-calorie foods Cmax and AUC increased, on average, by 42 and 46%, respectively, relative to the same indices when taking the fasting tablet. In another study, after a single administration, 12 mg of paliperidone in the form of a sustained release tablet together with fatty high-calorie foods Cmax and AUC increased, on average, by 60 and 54%, respectively, relative to the same indices when taking the fasting tablet. Thus, the presence or absence of food during the reception of paliperidone may alter the concentration of paliperidone in the blood plasma.
Distribution
Paliperidone is quickly distributed in tissues and body fluids. Apparent volume of distribution - 487 liters. The degree of binding to plasma proteins is 74%.Paliperidone binds primarily to the alpha 1- acid glycoprotein and albumin.
Biotransformation and elimination
One 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 found in urine and about 11% in feces.
There are four ways of metabolizing paliperidone 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 CYP2D6 and CYP3A4 isoenzymes may play a role in the metabolism of paliperidone, but evidence that they play a significant role in the metabolism of paliperidone in vivo has not been obtained. Although the activity of the CYP2D6 isoenzyme varies significantly in the general population, population pharmacokinetic studies have not revealed significant differences in the apparent clearance of paliperidone in patients with active metabolism of substrates of the CYP2D6 isoenzyme and in patients with a weak metabolism of CYP2D6 isoenzyme substrates. In vitro studiesusing 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 half-life of paliperidone is about 23 hours.
In vitro studies have shown that paliperidone is a substrate of P-glycoprotein and weakly inhibits it at high concentrations. In vivo data are not available, clinical significance is unknown.
Special Groups
Patients with hepatic impairment
Paliperidone does not undergo intensive metabolism in the liver. In patients with mild and moderate impairment of liver function, there is no need to reduce the dose of paliperidone. A study in which patients with moderate impaired hepatic function (class B Child-Pugh classification) participated showed that in these patients the concentrations of unbound plasma paliperidone were similar to those in healthy people. The use of Invega В® in patients with severe impairment of liver function has not been studied.
Patients with impaired renal function
The dose of paliperidone should be reduced in patients with moderate and severe renal dysfunction. Paliperidone excretion was studied in patients with varying degrees of renal dysfunction. It was found that the elimination of paliperidone decreased as the clearance of creatinine (CC) decreased. The total clearance of paliperidone was reduced by 32% in patients with mild renal impairment (QC 50 to <80 ml / min), 64% in patients with moderate renal impairment (QC 30 to <50 ml / min) and 71% in patients with severe renal dysfunction (CC 10 to <30 mL / min). The mean final half-life period of paliperidone was 24, 40 and 51 h in patients with mild, moderate and severe renal dysfunction, respectively; in people with normal renal function (KK-80 ml / min), this value was 23 hours.
Teens
The systemic effect of paliperidone on adolescents was comparable to that of adults. The concentration of paliperidone in blood plasma in adolescents with a body weight <51 kg is 23% higher than in adolescents with a body weight of? 51 kg, which is not clinically significant. Age does not affect the concentration of paliperidone in plasma.
Elderly patients
It is not recommended to change the dose of paliperidone depending on the age of the patient. The results of a pharmacokinetic study in which elderly patients aged 65 years and older participated, showed that the apparent clearance of paliperidone in the equilibrium state after taking Invega В® in this group was 20% lower than in adult patients aged 18-45 years. However, after making an adjustment to the age-related decline in creatinine clearance, population analysis did not reveal the effect of the age of schizophrenic patients on the pharmacokinetics of paliperidone.
Race
Dosage adjustments for patients of different race types are not required. Population pharmacokinetic analysis showed no racial differences in the pharmacokinetics of paliperidone when using Invega В® . There were no differences in pharmacokinetics in studies on Japanese and europoid.
Floor
The recommended doses of paliperidone are the same for men and women. The apparent clearance of paliperidone after taking the drug in women is about 19% lower than that of men. This difference is mainly due to differences in the fat-free body weight and creatinine clearance between men and women, since population studies, after adjusting for the non-fat 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 doses of paliperidone in smokers. In vitro studies using human hepatic enzymes have shown that paliperidone is not a substrate for the isoenzyme CYP1A2, and therefore smoking should not affect the pharmacokinetics of paliperidone. According to the results of in vitro studies , population studies have not revealed differences in the pharmacokinetics of paliperidone between smokers and non-smokers.
INDICATIONS
- schizophrenia, incl. in the acute phase in adults;
- prevention of exacerbations of schizophrenia in adults;
- treatment of schizophrenia in adolescents aged 12 to 17 years;
- therapy of schizoaffective disorders: as a monotherapy or as part of a combination therapy with antidepressants and / or normotimics in adults.
DOSING MODE
The drug is intended for oral administration. Tablets should be swallowed whole, squeezed with liquid, they can not be chewed, divided into parts or chopped.
Schizophrenia
Adults (over 18 years)
The recommended dose in 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 daily. There is a general tendency to increase the effect when using large doses of the drug. In case the dose increase is necessary, it is recommended to increase the dose by 3 mg per day at intervals of more than 5 days.
Adolescents (12-17 years old)
The recommended dose for 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 causes higher doses within the recommended range of 6-12 mg once daily. The dose increase is possible only after a clinical reassessment, with an increase in the dose of 3 mg per day at intervals of more than 5 days.
Schizoaffective disorder
Adults (over 18 years)
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 causes lower or higher doses within the recommended range of 6-12 mg once daily. An increase in the dose, if necessary, should be performed only after an assessment of the patient's clinical condition. If the dose is increased, it is recommended to increase the dose by 3 mg per day at intervals of more than 4 days.Supportive therapy in patients with schizoaffective disorders has not been studied.
Patients with hepatic impairment
In patients with mild to moderate liver function, no dose reduction is required. The use of Inveg В® in patients with severe impairment of liver function has not been studied.
Patients with impaired renal function
For patients with mild renal impairment (creatinine clearance (CK) ≥ 50, but <80 mL / min), the recommended initial dose is 3 mg once daily. This dose can be increased to 6 mg once a day after assessing the patient's condition and taking into account the tolerability of the drug. For patients with moderate or severe renal dysfunction (KK? 10, but <50 mL / min), the recommended dose is 3 mg once daily. The use of Invega ® in patients with CC <10 ml / min has not been studied, and therefore it is not recommended to prescribe the drug to these patients.
Elderly patients
For elderly patients with normal renal function (CC-80 ml / min), the same doses are recommended as for adult patients with normal renal function. However, in elderly patients, kidney function can be reduced, and in this case the dose of the drug should be selected according to the function of the kidney in a particular patient.Caution should be exercised when using the drug in elderly patients with dementia due to an increased risk of stroke.
The efficacy and safety of Invega В® in patients over 65 years of age with schizoaffective disorders has not been studied.
Children and teens
The efficacy and safety of Invega В® medicinal product for the treatment of schizophrenia in children younger than 12 years has not been studied. The efficacy and safety of Invega В® medicinal product for the treatment of schizoaffective disorders in patients younger than 18 years of age has not been studied.
Special patient groups
It is not recommended to change the dose of paliperidone depending on sex, age and whether the patient smokes or not.
Transfer of patients to treatment with other antipsychotic drugs
At present, there is no systematically collected data on the transfer of patients from paliperidone treatment to treatment with other antipsychotic drugs.Pharmacodynamics and pharmacokinetics in different antipsychotics are not the same, and therefore doctors should closely monitor the condition of patients when transferring them from one antipsychotic to another.
SIDE EFFECT
The undesirable effects observed in patients are listed below. The frequency of undesirable effects was classified as follows : very frequent (? 10%), frequent (? 1% and <10%), infrequent (? 0.1% and <1%), rare (? 0.01% and <0, 1%) and very rare (<0.01%).
Infections: frequent - infections of the upper respiratory tract, nasopharyngitis; infrequent - urinary tract infections, acarodermatitis, bronchitis, inflammation of subcutaneous fat, cystitis, ear infections, influenza, onychomycosis, pneumonia, respiratory infections, sinusitis, tonsillitis.
Immune system disorders : infrequent - anaphylactic reaction, hypersensitivity.
Disorders from the hematopoietic and lymphatic system : infrequent - anemia, a decrease in hematocrit, neutropenia, a decrease in the number of leukocytes; rare - thrombocytopenia; very rare - agranulocytosis.
Disorders from the endocrine system: infrequent - giperprolaktinemiya; very rare - inadequate secretion of antidiuretic hormone.
Disorders from the metabolism and nutrition : infrequent - increased activity of creatine phosphokinase, anorexia, hyperglycemia; rare - diabetes mellitus, hypoglycemia, water intoxication; very rare - diabetic ketoacidosis.
Mental disorders : frequent - insomnia (including primary and secondary insomnia), mania; infrequent - "nightmarish" dream, sleep disorders, depression.
Disorders of the nervous system : very often - headache; frequent - akathisia, dystonia, dysarthria, increased muscle tone, parkinsonism, sedation, somnolence, tremor, salivation; infrequent - cerebrovascular disorders, postural dizziness, dyskinesia, seizures, fainting, impaired attention, hypoesthesia, loss of consciousness, paresthesia, psychomotor hyperactivity, tardive dyskinesia, hypokinesia, opisthotonos.
It is known that antipsychotic drugs, including paliperidone may cause neuroleptic malignant syndrome (NMS), which is characterized by hyperthermia, muscular rigidity, instability of the autonomic nervous system, depression of consciousness, increased CPK activity, myoglobinuria, rhabdomyolysis, acute renal failure.
Violations by the organs of vision : infrequent - conjunctivitis, dry eye, photophobia, lacrimation; with unknown frequency: sagging iris (intraoperative) syndrome.
Violation of the organ of hearing and labririntnye disorders : rare - pain in the ears, vertigo, ringing in the ears.
Violations of the cardiovascular system: Infrequent - bradycardia, palpitations, atrioventricular block, conduction disorder, ECG changes, increasing the interval QT, ischemia, "flushing" of blood, blood pressure, lowering blood pressure; rare - atrial fibrillation; very rare - deep vein thrombosis, pulmonary embolism.
Disorders of the gastrointestinal tract : often - nausea, diarrhea, constipation, discomfort in the upper abdomen, dyspepsia, increased appetite; infrequently - decreased appetite, inflammation of the mouth, dysphagia, fecal incontinence, small bowel obstruction, flatulence, gastroenteritis, tongue swelling, toothache, dysgeusia; very rare - pancreatitis, intestinal obstruction.
Violations of the liver and biliary tract: very rare - the jaundice.
Violations of the respiratory system: Infrequent - pain in the pharyngeal-laryngeal area, nasal congestion, cough, shortness of breath, hyperventilation, wheezing; rare - sleep apnea.
Violations by musculoskeletal and connective tissue disorders: frequent - myalgia, musculoskeletal pain, infrequent - muscle cramps, back pain, arthralgia, joint stiffness, joint swelling, muscle weakness, pain in the neck.
Violations of the skin and subcutaneous tissue disorders: infrequent - rash, itching, acne, dry skin, eczema, erythema, seborrheic dermatitis, skin discoloration; rarely - angioedema, alopecia.
Violations of the kidneys and urinary tract: infrequent - dysuria, pollakiuria, urinary incontinence, urinary retention.
Violations by the genitals and breast : infrequent - decreased libido, anorgasmia, discharge from the nipples, erectile dysfunction, gynaecomastia, menstrual cycle changes, chest discomfort, sexual dysfunction, vaginal discharge, abnormal ejaculation, breast tenderness; very rarely - priapism.
Impact on the course of pregnancy, postpartum and perinatal conditions : very rare - syndrome "cancel" in the newborn.
Other : often - increase in body weight; infrequent - reduction of body weight, chills, face edema, gait disturbance, edema (including generalized edema, peripheral edema, mild edema), increased body temperature, fever, thirst, chest discomfort; very rare - hypothermia.
Laboratory Tests:infrequent - increasing the activity of gamma-glutamyl transferase, increased liver enzymes, increased transaminases, increase in blood cholesterol concentration, an increase in blood triglyceride concentration.
Information about the dose-related side effects is shown in Table 1.
Table 1. Adverse events registered in ≥2% of adult patients with schizophrenia receiving the drug Invega ® in clinical studies.
Body System / Adverse effects 3mg 1 time / day 6 1 mg once / day 9 1 mg once / day 12 mg 1 time / day Placebo
% % % % %
From the nervous system
Headache 11 12 14 14 12
dizziness June 5 4 5 4
extrapyramidal disorder 5 2 7 7 February
drowsiness March 5 7 5 3
akathisia 4 3 8 10 April
tremor 3 3 4 3 March
hypertension January 2 4 3 1
dystonia 1 1 4 1 April
sedation January 5 3 6 4
parkinsonism 0 <1 2 1 0
From the side of view
oculogyric crisis 0 0 2 0 0
From the side of the cardiovascular system
sinus tachycardia 9 4 4 7 4
tachycardia 2 7 7 7 3
bundle branch block legs 3 1 3 <1 2
atrioventricular block Istepeni 2 0 2 1 1
sinus arrhythmia 2 1 1 <1 0
orthostatic hypotension 2 1 2 4 1
Gastrointestinal disorders
vomiting 2 3 4 5 5
xerostomia 2 3 1 3 1
pain in the upper abdomen 1 3 2 2 1
hypersalivation 0 <1 1 4 <1
General disorders
asthenia 2 <1 2 2 1
exhaustion 2 1 2 2 1
Table 2. side effects recorded in ≥ 2% of adolescents (12-17 years) with schizophrenia receiving the drug Invega ® in clinical studies.
Body System / Adverse effects 1.5 mg 1 time / day 3 mg 1 time / day 6 1 mg once / day 12 mg 1 time / day Placebo
% % % % %
Disorders of the cardiovascular system
tachycardia September 6 0 6 0
Violations by the organs of vision
blurred vision 0 0 0 3 0
Gastrointestinal disorders
Dry mouth 0 0 0 3 2
hypersalivation 2 6 2 0 0
language edema 0 0 0 3 0
Vomiting 0 June 11 March 10th
General disorders
Asthenia 0 0 2 3 0
fatigue 4 0 2 3 0
Infections
nasopharyngitis 4 0 4 0 2
Laboratory Tests
increase in body weight 7 6 2 3 0
disorders of the nervous system
akathisia April 6 November 17 0
dizziness 2 6 2 3 0
extrapyramidal disorders Apr. 19 18 23 0
headache 9 6 4 14 4
lethargy 0 0 0 3 0
drowsiness September 13 20 26 4
language palsy 0 0 0 3 0
Disorders of the psyche
alarm 0 0 2 9 4
Violations of the genital organs, and breast
amenorrhea 0 6 0 0 0
galactorrhea 0 0 4 0 0
edema mammary 0 0 0 3 0
Disorders of the respiratory system
epistaxis 0 0 2 0 0
* Extrapyramidal disorders include: oculogyric crisis, muscle stiffness, musculoskeletal stiffness, stiffness in the neck, torticollis, trismus, bradykinesia, cogwheel rigidity, dyskinesia, dystonia, extrapyramidal disorder, hypertonia, hypokinesia, involuntary muscle contractions, parkinsonian gait, parkinsonism, tremors, and anxiety. Drowsiness includes sedation and somnolence hypersomnia. Insomnia includes initial insomnia and insomnia. Tachycardia includes tachycardia, sinus tachycardia, and increased heart rate. Hypertension includes hypertension and increasing blood pressure. Gynecomastia include gynecomastia and breast swelling.
Paliperidone is an active metabolite of risperidone, but on release profile and pharmacokinetic characteristics of the drug Invega В® significantly differs from risperidone dosage forms for oral administration with immediate-release formulations. Side effects reported with risperidone can be observed in the application of paliperidone.
Elderly patients
In clinical studies conducted with the participation of elderly patients with schizophrenia, the safety profile of the drug was the same as for younger patients. The drug Invega В® has not been studied in patients with dementia. In studies with other antipsychotic drugs were marked by an increase in the risk of death and cerebrovascular disorders. In elderly patients with dementia are at increased risk of stroke.
Other documented cases
of extrapyramidal symptom
In clinical studies carried out were no differences with placebo, 3 mg dosages and dosage of 6 mg. Dose-dependent extrapyramidal symptoms were reported at high doses of the drug Invega В®(9 mg and 12 mg). In clinical studies, schizoaffective disorders, extrapyramidal syndrome cases were detected with higher doses of the drug Invega В® , than placebo, for all groups of patients without apparent relationship with dosages. Extrapyramidal disorders included a pooled analysis and the following symptoms: dyskinesia, dystonia, hyperkinesia, Parkinsonism, and tremor.
Increased body weight
in clinical studies in schizophrenic patients, compared ratio cases weight gain of more than 7% from a constant weight. Approximately the same relation was observed while taking the drug Invega В® 3 mg and 6 mg compared with placebo, and a higher likelihood of weight gain was found for drug InvegaВ® 9 mg and 12 mg compared with placebo.
In clinical studies of patients with schizoaffective disorders in a higher percentage of patients receiving drug Invega В® (5%), it was observed increase in body mass over 7% in comparison with patients treated with placebo (1%). In this study, 27 patients were divided into two groups, weight gain of more than 7% when receiving low doses Invega preparation В® (3 mg and 6 mg) was 3% for patients treated with high doses of Invega preparation В® (9 mg and 12 mg) - 7%, and 1% - group where patients received placebo.
laboratory findings
In clinical studies in schizophrenic patients increased prolactin concentration in the serum was observed while taking the drug Invega В® in 67% of patients. Adverse reactions which may involve an increase in prolactin levels (e.g., amenorrhea, galactorrhea, gynecomastia) have been observed more than 2% of cases. The maximum value of the increase in the serum prolactin concentration were observed at the 15th day of treatment and remained above normal levels before the end of treatment.
class effects
When receiving antipsychotic drugs, can occur following side effects increase the interval QT, ventricular fibrillation (atrial fibrillation, ventricular tachycardia), sudden and unexplained death, heart failure and ventricular tachycardia type "pirouette" When receiving antipsychotics cases of venous thromboembolism have been identified, including cases of pulmonary embolism and cases of deep vein thrombosis.
CONTRAINDICATIONS
- Hypersensitivity to paliperidone, risperidone, or to any auxiliary ingredients of the drug.
With caution
Convulsive status and history of the disease, lowering seizure threshold
As with other antipsychotics, paliperidone should be used with caution in patients who have a history of seizures, or other disease that reduce the seizure threshold.
Dysphagia and narrowing of the lumen of the gastrointestinal tract (the possibility of obstruction)
Invega Tablets В®not deformed, and almost do not change their shape in the gastrointestinal tract, and therefore should not be administered to patients with a strong narrowing of the lumen of the gastrointestinal tract (pathologic or iatrogenic), as well as patients who suffer from dysphagia or who have difficulty swallowing pills. There are rare reports of symptoms of obstruction of the gastrointestinal tract associated with the ingestion of non-deformable formulations with controlled release of the active substance. Paliperidone also relates to such dosage forms, and so it can be given only to those patients who can swallow the tablets whole.
Elderly patients with dementia
The efficacy and safety of paliperidone were not evaluated in elderly patients with dementia. A meta-analysis of 17 placebo-controlled studies have shown that elderly patients with dementia treated with atypical antipsychotics such as risperidone, aripiprazole, olanzapine and quetiapine, had a higher mortality rate compared to those treated with placebo . Placebo-controlled trials involving elderly patients with dementia, cerebrovascular demonstrated increased frequency of adverse effects (stroke and transient ischemic attack), including: fatal, in patients treated with some atypical antipsychotics, which included risperidone, aripiprazole, and olanzapine, compared with patients who received placebo.
Parkinson's disease and dementia with Lewy bodies
Physicians should carefully weigh the risks and the potential benefit in the appointment of antipsychotic drugs, including paliperidone, patients suffering from Parkinson's disease or dementia with Lewy bodies, since such patients may be increased risk of developing neuroleptic malignant syndrome or increased sensitivity to antipsychotics. Manifestations of hypersensitivity include, in addition to extrapyramidal symptoms, confusion, dullness reaktsiyi postural hypotension with frequent falls.
PREGNANCY AND LACTATION
There is currently no data on the safety of paliperidone for pregnant women and fetal development. The drug may be used in pregnant women only if absolutely necessary, the potential benefit to the mother outweighs the potential risk to the fetus. Influence of paliperidone generic activities on women is not known.
If a woman taking antipsychotics (including paliperidone) during the third trimester of pregnancy, the newborn is at risk of extrapyramidal disorders, and / or the syndrome of "cancellation" of varying severity. These symptoms may include agitation, hypertension, hypotonia, tremor, somnolence, respiratory disorders and disruption of feeding. It is therefore necessary to carry out a special monitoring of the newborn. If you want to interrupt the treatment during pregnancy, it is necessary to reduce the dose gradually.
Lactation
Paliperidone at clinically relevant doses passes into breast milk, in connection with this drug should not be administered during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
For patients with moderate or severe renal impairment (creatinine clearance <50 mL / min), the recommended dose is 1 mg 3 times / day.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Patients with impaired liver function no dose reduction is required.
APPLICATION FOR CHILDREN
Efficacy and safety of Invega В® for the treatment of schizophrenia in children under 12 years of age has not been studied. Efficiency and baa
