Buy Xeplion suspension 150 mg/1.5 ml syringe 1 pc.

Paliperidone

Brand Janssen Pharmaceuticals N.V.

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Available since: 2019-09-19

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Clinical Pharmacology

Cseplion is an antipsychotic (neuroleptic) drug.
Pharmacodynamics
Paliperidone palmitate is hydrolyzed to paliperidone. The latter is the central active antagonist of predominantly serotonin 5-HT_2Areceptors, as well as dopamine D₂receptors, adrenergic?₁- and?₂- receptors and H1-histamine receptors. Paliperidone does not bind to cholinergic m-receptors and adrenergic?₁- and?₂- receptors. The pharmacological activity of (+) and (-) enantiomers of paliperidone is quantitatively and qualitatively the same.

It is assumed that the therapeutic efficacy of the drug in schizophrenia is due to a combined blockade D₂ and 5-HT_2A -receptors.

Pharmacokinetics
Suction and distribution
Due to the extremely low solubility in water of paliperidone, palmitate after intramuscular injection slowly dissolves and is absorbed into the systemic circulation. After a single intramuscular injection, the concentration of paliperidone in the blood plasma slowly increases, reaching a maximum after 13-14 days (median) after administration to the deltoid muscle and 13-17 days after administration to the gluteal muscle. The release of a substance is detected as early as the 1st day and lasts for at least 126 days. The release characteristics of the active ingredient and the dosage regimen of the drug Xeplion ensure the long-term maintenance of the therapeutic concentration. After a single dose of 25–150 mg to the deltoid muscle, the maximum concentration (C_max) on average, 28% more than after administration to the gluteus muscle. At the beginning of therapy, the introduction of the drug into the deltoid muscle helps to quickly reach the therapeutic concentration of paliperidone (150 mg on the first day and 100 mg on the 8th day) than the introduction to the gluteal muscle. After repeated injections, the difference in effects is less obvious. The average ratio of the maximum and equilibrium concentrations of paliperidone after administration of 4 injections of the drug Xeplion at a dose of 100 mg in the gluteus muscle was 1.8, and after administration in the deltoid muscle - 2.2. With doses of paliperidone 25-150 mg, the area under the concentration-time curve (AUC) of paliperidone changed in proportion to the dose, and C_max at doses greater than 50 mg increased to a lesser extent than proportional to the dose.

The median half-life of paliperidone after administration of the drug Cseplion in doses of 25-150 mg ranged from 25 to 49 days.

After administration of the (-) - enantiomer of paliperidone, it is partially converted into (+) - enantiomer, and the ratio of AUC (+) - and (-) - enantiomers is approximately 1.6-1.8.

In a population analysis, the apparent volume of distribution of paliperidone was 391 L; paliperidone binds to plasma proteins by 74%.

Metabolism and excretion
One week after a single oral administration of 1 mg of the drug ¹⁴S-paliperidone with immediate release of the active component in the urine in unchanged form removes 59% of the administered dose; this indicates the absence of a significant metabolism of the drug in the liver. Approximately 80% of the administered radioactivity was detected in the urine and 11% in the feces. There are 4 known metabolic pathways of the drug in vivo, but none of them causes the metabolism of more than 6.5% of the administered dose: dealkylation, hydroxylation, dehydrogenation, cleavage of the benzisoxazole group. Although in vitro studies suggest a certain role for CYP2D6 and CYP3A4 isoenzymes in paliperidone metabolism, there is no evidence of the significant role of these isoenzymes in paliperidone metabolism in vivo. Population pharmacokinetic analysis did not reveal a noticeable difference in clearance of paliperidone after oral administration of the drug in people with an active and weak CYP2D6 metabolism. Studies using human liver microsomes in vitro have shown that paliperidone does not significantly inhibit drug metabolism with isoenzymes CYP1A2, CYP2A6, CYP2D6, CYP2E1, CYP3A4 and CYP3A5.

In in vitro studies, paliperidone showed the properties of the substrate P-glycoprotein, and in high concentrations the properties of a weak inhibitor P-glycoprotein. There are no relevant in vivo data, and the clinical significance of this information is unclear.

In general, the concentration of paliperidone in the blood plasma during the period of loading after intramuscular administration of the drug Xeplion was in the same range as after taking paliperidone with prolonged action orally with the release of the active component in doses between 6 and 12 mg. The paliperidone loading scheme used maintains the concentration in this range even at the end of the inter-dose interval (8th and 36th day). Individual differences in the pharmacokinetics of paliperidone after administration of the drug Cseplion in different patients were less than after oral paliperidone intake of prolonged action. Because of the difference in the nature of the change in the median paliperidone concentration in the blood plasma when using two drugs, caution should be exercised when directly comparing their pharmacokinetics.

Special categories of patients
Liver dysfunction.
Paliperidone does not undergo substantial metabolism in the liver. Although the use of the drug Xeplion in patients with mild or moderately impaired liver function has not been studied, with such violations of the liver function, dose adjustment is not required. In the study, oral paliperidone administration in patients with moderate hepatic impairment (Child-Pugh class B) plasma free paliperidone concentration was the same as in healthy volunteers. In patients with severe hepatic impairment, paliperidone has not been studied.

Impaired renal function.
For patients with mild renal impairment, the dose of paliperidone should be reduced; Kseplion is not recommended for use in patients with impaired renal function of moderate severity and severe. The distribution of paliperidone after a single oral dose of paliperidone pills with a prolonged action of 3 mg was studied in patients with varying degrees of renal dysfunction. With a decrease in creatinine clearance (CK), paliperidone clearance was weakened: in cases of impaired renal function of mild severity (CK 50-80 ml / min) - by 32%, with moderate severity (CK 30-50 ml / min) - by 64%, with severe (CK 10-30 ml / min) - by 71%, resulting in AUC0-? increased compared with healthy volunteers, respectively, 1.5, 2.6 and 4.8 times. Based on a small amount of data on the use of the drug Xeplion in patients with impaired renal function of mild severity and from the results of pharmacokinetics simulation, the recommended loading dose of paliperidone for such patients is 75 mg on the 1st and 8th day; thereafter, 50 mg is administered monthly (every 4 weeks).

Elderly Sick
Age itself is not a factor requiring dose adjustment. However, such a correction may be required due to an age-related decrease in QA.

Race.
Population pharmacokinetic analysis of the results of the study of paliperidone for oral administration did not reveal differences in paliperidone pharmacokinetics after administration of the drug by people of different races.

Floor.
No clinically significant differences in paliperidone pharmacokinetics between men and women were found.

The effect of smoking on the pharmacokinetics of the drug.
According to studies using human liver microsomes in vitro, paliperidone is not a substrate of CYP1A2, so smoking should not affect the pharmacokinetics of paliperidone. In accordance with these in vitro data, population pharmacokinetic analysis did not reveal differences in paliperidone pharmacokinetics in smokers and non-smokers.

Indications

Treatment of schizophrenia and prevention of recurrence of schizophrenia.

Composition

Active substance: 100 mg of paliperidone in 1 ml of suspension (equivalent to 156 mg of paliperidone palmitate).
Excipients: polysorbate 20, macrogol 4000 (polyethylene glycol 4000), citric acid monohydrate, sodium hydrogen phosphate, sodium dihydrogen phosphate monohydrate, sodium hydroxide, water for injection.

Paliperidone is marketed under different brands and generic names, and comes in different dosage forms:

Brand name	Manufacturer	Country	Dosage form
Xeplion	Janssen Pharmaceuticals N.V	Belgium	suspension
Invega	Janssen Pharmaceuticals N.V	Belgium	pills

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Dosage and Administration

In patients who have never taken paliperidone orally or risperidone orally or parenterally, it is recommended to check the tolerability of paliperidone or risperidone orally within 2-7 days before starting treatment with Xeplion.
It is recommended to start treatment with Kseplion with a dose of 150 mg on the first day and 100 mg after 1 week (both injections into the deltoid muscle). Further recommended dose of 75 mg per month; The dose may be increased or decreased in the range of 25-150 mg, depending on individual tolerance and / or effectiveness. After the second dose, subsequent injections can be carried out in the deltoid or gluteal muscle.
Maintenance dose can be adjusted monthly. This should take into account the long-term release of the active ingredient from paliperidone palmitate, since the effect of changing the dose can fully manifest only after a few months.
Skip dose
Avoid skipping doses. The second loading dose of paliperidone is recommended to be administered 1 week after the first dose. If this is not possible, then it can be entered 2 days earlier or later. Similarly, it is recommended to administer the third and subsequent doses monthly, but if this is not possible, the injection can be given 7 days earlier or later.
Skip the dose (from 1 month to 6 weeks). After starting treatment, it is recommended to inject the drug Xeplion on a monthly basis. If less than 6 weeks have passed since the last injection, another dose equal to the previous one should be administered as soon as possible. After that, administer the drug monthly.
Skip the dose (period from> 6 weeks to 6 months). If more than 6 weeks have passed since the last injection of the drug Xeplion, then resume treatment at a dose equal to the previous one, as follows:

as soon as possible inject another dose into the deltoid muscle,
after 1 week, another (same) dose is injected into the deltoid muscle,
resume injections into the deltoid or gluteal muscle with an interval of 1 month.

Skip the dose (term> 6 months). If more than 6 months have passed since the last injection of the drug Xeplion, the treatment will be restarted, as described above to start treatment.
Mode of application
Xeplion is intended for intramuscular administration only. The drug is slowly injected deep into the muscle. Injections should be carried out only by a medical professional. The entire dose is administered at one time; Do not enter the dose for multiple injections. You can not enter the drug in the blood vessels or subcutaneously. Avoid accidental contact with a blood vessel. To do this, before the start of drug administration, the syringe piston is pulled back to check for a needle entering a large blood vessel. In the event that blood flows into the syringe, the needle and syringe should be removed from the patient's muscles and disposed of. The recommended needle size for administering the drug Xeplion into the deltoid muscle is determined by the patient's body weight. For patients with body weight ≥90 kg, a long needle with a gray casing from the kit is recommended. For patients with body weight. For the injection of the drug Xeplion into the gluteus muscle, a long needle with a gray body from the set is recommended. Injections should be carried out in the upper outer quadrant of the buttocks. It should alternately inject the drug in the right and left gluteus maximus. The simultaneous use of paliperidone palmitate and paliperidone orally or risperidone orally or parenterally has not been studied. Since paliperidone is the main active metabolite of risperidone, the possibility of additive action of paliperidone when using these drugs at the same time as Xeplion should be considered.
Patients with impaired liver function
The use of the drug Xeplion in patients with impaired liver function has not been studied.Based on the results of the study of paliperidone for oral administration, for patients with impaired liver function, mild or moderate severity of dose adjustment is not required. The use of the drug Xeplion in patients with severe hepatic impairment has not been studied.
Patients with impaired renal function
The use of the drug Xeplion in patients with impaired renal function has not been systematically studied. In patients with impaired renal function of mild severity (creatinine clearance ≥ 50 to <80 ml="" min="" it="" is="" recommended="" to="" start="" the="" use="" of="" drug="" xeplion="" with="" a="" dose="" 100="" mg="" on="" 1st="" day="" and="" 75="" after="" 1="" week="" both="" injections="" into="" deltoid="" muscle="" that="" 50="" administered="" monthly="" or="" gluteal="" kseplion="" not="" for="" patients="" moderate="" severe="" renal="" impairment="" creatinine="" clearance="" br="">Elderly Sick
In general, for elderly patients with normal renal function, the same dose of the drug Xeplion is recommended as for younger patients with normal renal function. In elderly patients, renal function may be reduced, and the above recommendations for patients with impaired renal function apply to such patients.
Teenagers and children
The safety and effectiveness of the drug Xeplion in patients younger than 18 years has not been studied.
Other special categories of patients
Dose adjustment of the drug Xeplion, depending on gender, race of patients and smoking is not required.

Adverse reactions

Most of the unwanted adverse reactions (LPR) were mild or moderate.
The following are unwanted reactions observed in patients. The incidence of adverse reactions was classified as follows: very frequent (≥10%), frequent (≥1% and <10%), infrequent (≥0.1% and Infections: frequent - upper respiratory tract infections.
Metabolic disorders: infrequent - decrease in appetite, increase in appetite.
Psychiatric disorders: very frequent - insomnia; frequent - arousal, nightmares; infrequent - anxiety.
Nervous system disorders: very frequent - headache; frequent akathisia, dizziness, extrapyramidal symptoms, drowsiness; infrequent - convulsions, postural dizziness, drooling, dysarthria, dyskinesia, dystonia, neuroleptic malignant syndrome, lethargy, oromandibular dystonia, parkinsonism, psychomotor hyperreactivity, syncope.
Ophthalmic disorders: infrequent - oculogy crisis, involuntary movement of the eyeball, blurred vision.
Violations of the organ of hearing and balance: infrequent - vertigo.Violations of the cardiovascular system: frequent - increase in blood pressure; infrequent - bradycardia, blockade of the bundle of the His bundle, postural orthostatic tachycardia syndrome, tachycardia, orthostatic hypotension.
Gastrointestinal disorders: frequent - pain in the upper abdomen, constipation, diarrhea, dryness of the oral mucosa, nausea, toothache, vomiting; infrequent abdominal discomfort, salivary hypersecretion, gastric discomfort.
Disorders of the musculoskeletal system and connective tissue: frequent - pain in the limbs.
Skin disorders: infrequent - generalized itching, rash.
Disorders of the reproductive system and mammary glands: infrequent - amenorrhea, erectile dysfunction, galactorrhea, gynecomastia, irregular menstruation, sexual dysfunction.
Other: frequent - asthenic disorders, weakness, local reactions (pain, itching, induration at the injection site), weight gain.
Changes in laboratory parameters:
infrequent - an increase in the concentration of serum prolactin, cholesterol and glucose in the blood.
Side effect of paliperidone for oral administration
The following side effects are listed, registered with the use of paliperidone for oral administration:
Immune system disorders: anaphylactic reaction;
Nervous system disorders: large and small convulsive seizures, tremor;
Violations of the cardiovascular system: atrioventricular block I degree, palpitations, sinus arrhythmia, sinus tachycardia, lowering blood pressure, myocardial ischemia;
Disorders of the musculoskeletal system and connective tissue: muscle rigidity;
Disorders of the reproductive system and mammary glands: priapism, nipple discharge;
Other: peripheral edema;
Changes in instrumental indicators: changes on the electrocardiogram (ECG);
Risperidone Safety Data
Paliperidone is the active metabolite of risperidone. The nature of the release of the active substance and the pharmacokinetics of paliperidone after administration of the drug Xeplion differ significantly from those after ingestion of risperidone with the immediate release of the active substance or risperidone for intramuscular administration of prolonged action. Information on the safety of oral risperidone and long-acting risperidone for injection, obtained in clinical studies and in the framework of post-marketing control of the use of drugs, is provided in the instructions for the medical use of these drugs.

Contraindications

Hypersensitivity to paliperidone or any component of the drug Xeplion.
Since paliperidone is the active metabolite of risperidone, Xeplion is contraindicated in patients with known hypersensitivity to risperidone.

With caution
Orthostatic hypotension
Possessing the activity of alpha-adrenergic blocker, paliperidone in some patients may cause orthostatic hypotension. Kseplion should be used with caution in patients with cardiovascular diseases (for example, heart failure, heart attack or myocardial ischemia, cardiac conduction disorders), cerebral circulation disorders or conditions that predispose to a decrease in blood pressure (for example, dehydration, a decrease in circulating blood volume, antihypertensive drugs).
Cramps
Like other neuroleptics, Kseplion should be used with caution in patients with a history of seizures or other conditions in which the seizure threshold can be reduced.
Regulation of body temperature
The use of antipsychotics is associated with a deterioration in the body's ability to lower body temperature. It is recommended to exercise caution when prescribing Xeplion to patients who may be exposed to increases in body temperature, for example, heavy physical exertion, high ambient temperature, exposure to drugs with m-cholinolytic activity, as well as dehydration.
Q-T Interval
As in the case of other neuroleptics, caution should be exercised in the appointment of the drug Xeplion to patients with a history of arrhythmia or congenital lengthening of the Q-T interval, or taking drugs that prolong the Q-T interval.
Given the effect of paliperidone on the central nervous system (CNS), Xseplion should be used with caution in combination with other drugs acting on the CNS and alcohol. Paliperidone may weaken the effect of levodopa and dopamine agonists.
Caution should be exercised in the appointment of the drug Xeplion to elderly patients with dementia, patients with Parkinson's disease or dementia with Levi bodies.

Drug interactions

Paliperidone can increase the Q-T interval, so it should be carefully combined with other drugs that increase the Q-T interval (antiarrhythmic drugs, includingquinidine, procainamide, amiodarone, sotalol; antipsychotic drugs (chlorpromazine, thioridazine); antibiotics, incl. gatifloxacin, moxifloxacin.
Since paliperidone palmitate is hydrolyzed to paliperidone, the results of studies of paliperidone for oral administration should be taken into account when assessing the potential for drug interaction.
The ability of the drug Xeplion to influence other drugs
Paliperidone is not expected to exhibit clinically significant pharmacokinetic interactions with drugs metabolized by cytochrome P450 isoenzymes. Studies using human liver microsomes in vitro have shown that paliperidone does not significantly weaken the metabolism of the isoenzymes CYP1A2, CYP2A6, CYP2C8 / 9/10, CYP2D6, CYP2E1, CYP3A4 and CYP3A5. Therefore, it is not expected that paliperidone will clinically significantly reduce the clearance of drugs metabolized by these isoenzymes. It is also not expected that paliperidone will exhibit the properties of an isoenzyme inducer, since in in vitro studies, paliperidone did not induce the activity of CYPA2, CYPC19 or CYP3A4 isoenzymes. Paliperidone in high concentrations is a weak inhibitor of P-glycoprotein. However, there is no in vivo data in this regard, and the clinical significance of this phenomenon is unknown.
Given the effect of paliperidone on the central nervous system, Xseplion should be used with caution in combination with other drugs of central action and alcohol. Paliperidone may weaken the effect of levodopa and dopamine receptor agonists. Due to the ability of the drug Xeplion to cause orthostatic hypotension, an additive enhancement of this effect can be observed when using the drug Xeplion in conjunction with other drugs that have this ability.
The ability of other drugs to influence Xeplion
Paliperidone is not a substrate of isoenzymes CYP1A2, CYP2A6, CYP2C9, CYP2C19 and CYP3A5. This suggests a low probability of interaction with inhibitors and inducers of these isoenzymes. Although in vitro studies show the possibility of minimal involvement of CYP2D6 and CYP3A4 in paliperidone metabolism, there is currently no evidence that these enzymes can play a significant role in paliperidone metabolism in vitro or in vivo. In vitro studies indicate that paliperidone is a substrate of P-glycoprotein.
Paliperidone is to a limited extent metabolized by the CYP2D6 isoenzyme. In a study of the interaction of paliperidone for oral administration with an active CYP2D6 inhibitor paroxetine in healthy volunteers, no clinically significant change in paliperidone pharmacokinetics was found.
Acceptance of paliperidone with prolonged release of the active component (1 time per day) orally simultaneously with carbamazepine (200 mg 2 times a day) resulted in a decrease in mean C_max and paliperidone AUC by about 37%. This decrease is largely due to an increase in kidney clearance of paliperidone by 35%, probably due to activation of the kidney P-glycoprotein by carbamazepine. A very small decrease in the amount of the drug excreted through the kidneys in an unchanged form suggests that carbamazepine only slightly affects mediated through metabolism in the liver or the bioavailability of paliperidone. At the beginning of the use of carbamazepine, the dose of Xeplion should be reviewed and, if necessary, increased. On the contrary, when canceling carbamazepine, the dose of Xeeplion should be reviewed and, if necessary, reduced. Paliperidone at physiological pH is a cation and is mainly excreted unchanged through the kidneys - half by filtration, and half by active secretion. The simultaneous use of trimethoprim, which inhibits the system of active transport of cations in the kidneys, did not affect the pharmacokinetics of paliperidone.
Use of the drug Xeplion with risperidone
The use of the drug Xeplion together with risperidone has not been studied. Since paliperidone is an active metabolite of risperidone, with simultaneous use of the drug Xeplion and risperidone, an increase in plasma paliperidone concentration should be considered.

Pregnancy and Lactation

Pregnancy
The safety of the drug Xeplion intramuscularly or paliperidone orally during pregnancy in humans has not been established. When high doses of paliperidone were used, a small increase in fetal mortality in animals was orally observed. When intramuscularly administered Kseplion did not affect the course of pregnancy in rats, but its high doses were toxic to pregnant females. Doses of paliperidone when administered intravenously and intramuscular Xseplion, which create concentrations in excess of the maximum therapeutic dose in humans, respectively 20-22 times and 6 times, did not affect the offspring of laboratory animals. Xeplion can be used during pregnancy only if the intended benefit to the mother outweighs the potential risk to the fetus. The effect of the drug Xeplion on labor and labor in humans is unknown.
The use of neuroleptics in the last trimester of pregnancy is accompanied by the development of reversible extrapyramidal disorders in newborns.
Breast-feeding
In studies of the use of paliperidone in animals and risperidone in humans, excretion of paliperidone in breast milk was found. Therefore, women receiving Xeplion should not breastfeed.

Special instructions

QT Interval
Caution must be exercised when using paliperidone in patients with known cardiovascular diseases or with a prolonged QT interval in history, as well as with the joint use of drugs that can lead to a prolongation of the QT interval.

Malignant Neuroleptic Syndrome
The use of neuroleptics, including paliperidone, has registered the development of neuroleptic malignant syndrome (NMS), characterized by hyperthermia, muscle rigidity, instability of the autonomic nervous system, impaired consciousness and an increase in serum creatine phosphonase content. In addition, myoglobinuria (rhabdomyolysis) and acute renal failure may occur. If symptoms appear that suggest NNS, all antipsychotics, including Xeplion, are canceled.

Tardive dyskinesia
The use of drugs with dopamine receptor antagonist properties is accompanied by the development of tardive dyskinesia characterized by rhythmic, involuntary movements, mainly of the tongue and / or facial muscles. If symptoms of tardive dyskinesia appear, the possibility of withdrawing all antipsychotics, including Cseplion, should be considered.

Hyperglycemia and Diabetes
In the course of treatment with Cseplion, hyperglycemia, diabetes mellitus and exacerbation of existing diabetes mellitus were observed. Establishing the relationship between the use of atypical antipsychotics and glucose metabolism is complicated by an increased risk of developing 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. All patients should be clinically monitored for the presence of symptoms of hyperglycemia and diabetes mellitus (see the “Side Effects” section).

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

Hyperprolactinemia
Tissue culture studies indicate that human breast tumor growth can be stimulated by prolactin. Although a direct link with the use of antipsychotics has not been demonstrated in clinical and epidemiological studies so far, caution should be exercised when using paliperidone in patients with possible prolactin-dependent tumors.

Orthostatic hypotension
Possessing the activity of alpha-adrenergic blocker, paliperidone in some patients may cause orthostatic hypotension. Kseplion should be used with caution in patients with cardiovascular diseases (for example, heart failure, heart attack or myocardial ischemia, cardiac conduction disorders), cerebral circulation disorders or conditions that predispose to a decrease in blood pressure (for example, dehydration, a decrease in circulating blood volume, antihypertensive drugs).

Cramps
Like other neuroleptics, Kseplion should be used with caution in patients with a history of seizures or other conditions in which the seizure threshold can be reduced.

Renal failure
The concentration of paliperidone in plasma is increased in patients with impaired renal function. In patients with impaired mild renal function, dose adjustment is recommended. Kseplion is not recommended for patients with moderate to severe renal impairment (creatinine clearance <50 ml="" min="" p="">

Liver failure
The use of the drug Xeplion in patients with severe liver function disorders (class C on the Child-Pugh scale) has not been studied. Caution should be exercised when using paliperidone in these patients.

Elderly patients with dementia
A cross-sectional analysis of the study results showed an increased mortality rate in elderly patients with dementia who received atypical antipsychotics, including risperidone, aripiprazole, olanzapine and quetiapine, compared with placebo. Among patients receiving risperidone and placebo, mortality was 4% and 3.1%, respectively.

The use of the drug Xeplion in elderly patients with dementia has not been studied. Since paliperidone is the active metabolite of risperidone, the experience with risperidone should be considered. For elderly patients with dementia who take risperidone, increased mortality was observed in patients taking furosemide and risperidone compared with the group taking only risperidone and the group taking only furosemide. There is no established pathophysiological mechanisms explaining this observation. However, special care should be taken when prescribing the drug in such cases. No increase in mortality was found in patients who simultaneously took other diuretics along with risperidone. Regardless of treatment, dehydration is a common risk factor for mortality and should be carefully monitored in elderly patients with dementia.

Disorders of cerebral circulation
In placebo-controlled studies, an increased frequency of cerebral circulation disorders (transient and stroke), including fatal, was found in elderly patients with dementia who received some atypical antipsychotics, including risperidone, aripiprazole and olanzapine, compared with placebo.

Leukopenia, neutropenia, agranulocytosis
Leukopenia, neutropenia and agranulocytosis were observed with the use of antipsychotics, including with the use of the drug Xeplion. Agranulocytosis was observed very rarely during post-marketing observations. Patients with a clinically significant decrease in the number of leukocytes in history or drug-dependent leukopenia / neutropenia are recommended to have a complete blood count during the first months of therapy, discontinuation of treatment with Xeprion should be considered at the first clinically significant decrease in the number of leukocytes in the absence of other possible causes. Patients with clinically significant neutropenia are advised to be monitored for fever or symptoms of infection, and to begin treatment immediately when such symptoms occur.Patients with a severe form of neutropenia (the absolute number of neutrophils less than 1 x 109 / l) should discontinue the use of the drug Xeplion until the number of leukocytes is normalized.

Venous thromboembolism
When using antipsychotic drugs, cases of venous thromboembolism were noted. Since patients taking antipsychotic drugs often have a risk of developing venous thromboembolism, all possible risk factors should be identified before and during treatment with Xeplion, and preventive measures should be taken.

Parkinson's disease and dementia with Levi bodies
The physician must compare the risk and benefits of using antipsychotics, including Xseplion, in patients with Parkinson's disease or dementia with Lewy bodies, since in both these categories of patients, the risk of developing malignant neuroleptic syndrome (SNR) and the risk of hypersensitivity to neuroleptics may be increased. Manifestations of hypersensitivity may include confusion, dulling pain sensitivity, unstable posture with frequent falls, as well as extrapyramidal symptoms.

Priapism
There is evidence of the ability of drugs with the properties of alpha-blockers, to cause priapism. Priapism is registered as part of post-marketing control of paliperidone use.

Effect on body temperature regulation
The use of antipsychotics is associated with a deterioration in the body's ability to lower body temperature. It is recommended to exercise caution when prescribing Xeplion to patients who may be exposed to increases in body temperature, for example, heavy physical exertion, high ambient temperature, exposure to drugs with m and cholinolytic activity, as well as dehydration.

Antiemetic effect
In preclinical studies of paliperidone, an antiemetic effect was found. The appearance of this effect in a patient may mask the signs and symptoms of an overdose of certain drugs or, for example, conditions such as intestinal obstruction, Reye syndrome or a brain tumor.

Introduction
For intramuscular administration, care should be taken to avoid accidental ingestion of the drug in a blood vessel.

Intraoperative Flabby Iris Syndrome (ISDR)
ISDR was observed during surgery for the presence of cataracts in patients receiving therapy with drugs that are antagonists of? 1 -adrenoreceptors, such as Xseplion.

ISDR increases the risk of complications associated with the organ of sight, during and after surgery. The doctor performing this operation should be informed in advance that the patient has been taking or is currently taking medications that have antagonistic activity of? 1 -adrenoreceptors. The potential benefit of discontinuing therapy with antagonists? 1-adrenoreceptors before surgery has not been established, and should be evaluated taking into account the risks associated with the abolition of therapy with antipsychotic drugs.

Impact on driving and working with machinery

Cseplion can interfere with the performance of actions that require concentration of attention and quickness of psychomotor reactions, and can affect vision. Therefore, patients should be advised not to drive vehicles and moving machinery until their individual sensitivity has been established.

Overdosage

Since Xeplion is intended for administration by health workers, the likelihood of an overdose for patients is small.
Symptoms
In general, the expected signs and symptoms correspond to an increase in the known pharmacological tachycardia, a decrease in paliperidone, arterial, iepressure, drowsiness, lethargy, prolongation of the Q-T interval, extrapyramidal symptoms. In the case of acute overdose, the possibility of patients receiving several drugs should be considered.
Treatment
When assessing the need for treatment and rehabilitation of patients, one should take into account the long-term release of the active substance and the long half-life of paliperidone. There is no specific antidote for paliperidone. General supportive measures should be implemented, and the airway is permeable, maintain adequate ventilation of the lungs, and saturate the blood with oxygen. It should immediately begin monitoring the function of the cardiovascular system, including continuous monitoring of the ECG to detect possible arrhythmias. In the event of a decrease in arterial blood pressure and circulatory collapse, appropriate measures should be taken, for example, intravenous administration of solutions and / or sympathomimetics. With the development of severe extrapyramidal symptoms, anticholinergic drugs are used. The patient’s condition should be carefully monitored until recovery.