Expiration date: 12/2026
Release form
Suspension for intramuscular introduction of the prolonged action, 100 mg/1ml
Composition
Active substance:
100 mg of paliperidone in 1 ml 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 injections.
Packaging
0.25, 0,50, 0,75, 1,00, 1,50 ml into the syringe from cycloolefinic copolymer. The kit formulation contains 2 needles for intramuscular injection (deltoid and gluteal muscle). Pre-filled syringe with the drug and 2 needles in a plastic tray, closed with plastic wrap, put together with the instructions for use in a cardboard box.
Pharmacological action
Xeplion - antipsychotic (neuroleptic).
Pharmacodynamics
Paliperidone palmitate is hydrolyzed to paliperidone. The latter is zentralredaktion mainly active antagonist of the serotonin 5-HT2A receptors and dopamine D2 receptors, adrenergic ?1.2 - receptors and H1-histamine receptors. Paliperidone is not associated with cholinergic m-receptors and adrenergic ?1.2 - receptors. The pharmacological activity of (+) and (-) enantiomers of paliperidone quantitatively and qualitatively the same.
It is expected that a therapeutic efficacy in schizophrenia due to the combined blockade of D2 and 5-HT2A receptors.
Pharmacokinetics
Absorption and distribution
Due to extremely low water solubility of paliperidone palmitate after intramuscular administration is slowly dissolved and absorbed into the systemic circulation. After a single intramuscular injection concentration of paliperidone in blood plasma increases slowly, reaching a maximum of 13-14 days (median) after injection in the deltoid muscle and 13-17 days after the injection in the gluteal muscle. The release of the substance is found in day 1 and persists for at least 126 days. Release characteristics of the active ingredient and the dosing regimen of the drug Xeplion provide long-term maintenance of therapeutic concentrations. After a single-dose 25 - 150 mg in the deltoid muscle maximum concentration (Cmax) is on average 28% more than after injection into the gluteal muscle. At the beginning of therapy the drug is administered in the deltoid muscle helps to achieve therapeutic concentrations of paliperidone (150 mg 1st day and 100 mg on the 8th day), than the introduction into the gluteal muscle. After multiple injections, the difference in impact 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 gluteal muscle was equal to 1.8, and after injection in the deltoid muscle is 2.2. At doses of paliperidone 25-150 mg, the area under the curve "concentration-time" (AUC) of paliperidone proportionally to the dose, and Cmax at doses of 50 mg and increased to a lesser extent than in proportion to dose.
The median half-life of paliperidone after administration of the drug Xeplion in doses of 25-150 mg ranged from 25 - 49 days.
After the injection of (-)-enantiomer paliperidone partially converted into (+)-enantiomer, and the ratio of AUC (+)- and (-)-enantiomers is about 1.6 to 1.8.
In population analysis, the apparent volume of distribution of paliperidone is 391 l equal to; paliperidone is associated with blood plasma proteins by 74%.
Metabolism and excretion
A week after a single oral administration of 1 mg 14C-paliperidone with an immediate release of the active ingredient in the urine in unchanged excreted 59% of the administered dose; this indicates the absence of significant metabolism of the drug in the liver. Approximately 80% of the administered radioactivity was detected in urine and 11% in feces. Known 4 ways of drug metabolism in vivo, but none of them leads to the metabolism of more than 6.5% of the administered dose: dezalkilirovania, hydroxylation, dehydrogenation, cleavage benzisoxazole group. Although in vitro studies suggest a role of isoenzymes CYP2D6 and CYP3A4 in the metabolism of paliperidone, the data about significant role of these isoenzymes in the metabolism of paliperidone in vivo no. Population pharmacokinetic analysis showed no notable differences in the clearance of paliperidone after oral administration of the drug people with an active and a weak CYP2D6 metabolism. Studies using human liver microsomes in vitro have shown that paliperidone does not substantially inhibit drug metabolism isoenzymes CYP1A2, CYP2A6, CYP2D6, CYP2E1, CYP3A4 and CYP3A5.
In vitro studies have shown paliperidone properties of substrate for P-glycoprotein, but in high concentrations properties of a weak inhibitor of P-glycoprotein. Relevant data in vivo no, and the clinical significance of this information is unclear.
Generally, the concentration of paliperidone in blood plasma in the period of the load after intramuscular administration of the drug Xeplion lay in the same range as after administration of paliperidone prolonged action oral release of the active ingredient at doses between 6 and 12 mg. Used circuit load paliperidone maintains the concentration within this range even at the end midazolama interval (the 8th and 36th day). Individual differences in the pharmacokinetics of paliperidone after administration of the drug Xeplion different patients was less than after administration of paliperidone prolonged action oral. Because of the differences in the change of median concentration of paliperidone in blood plasma when using the two drugs should exercise caution in direct comparison of their pharmacokinetics.
A special category of patients
The liver dysfunction.
Paliperidone undergoes no significant metabolism in the liver. Although the use of the drug Xeplion in patients with impaired liver function or moderate severity has not been studied in these impaired hepatic function dose adjustment is not required. In the study, the use of oral paliperidone in patients with impaired liver function moderate (class b child-Pugh), the free concentration of paliperidone in plasma was the same as in healthy volunteers. In patients with impaired liver function severe the use of paliperidone has not been studied.
The impairment of renal function.
For patients with impaired renal function mild dose of paliperidone should be reduced; Xeplion not recommended for use in patients with impaired renal function moderate-to-severe. We have investigated the distribution of paliperidone after a single oral tablet of paliperidone prolonged action of 3 mg in patients with different degree of impairment of renal function. With a decrease in creatinine clearance (CC) the excretion of paliperidone weakened: when renal failure mild (QC 50-80 ml/min) - 32%, moderate severity (QC 30-50 ml/min), 64% in severe (QC 10-30 ml/min) – 71%, resulting in a AUC0-? increased compared with healthy volunteers, respectively 1.5, 2.6 and 4.8 times. On the basis of a small amount of data on the use of the drug Xeplion in patients with impaired renal function mild and the results of the simulation of pharmacokinetics, the recommended loading dose of paliperidone for these patients is 75 mg in the 1st and 8th day; thereafter, monthly (every 4 weeks) administered at 50 mg.
Elderly patients.
Age itself is not a factor, requiring dose adjustment. However, such a correction may be required due to age-related decrease in KK.
Race.
Population pharmacokinetic analysis of the results of the study of paliperidone for oral administration revealed no differences in the pharmacokinetics of paliperidone after administration of the drug by people of different races.
Paul.
Clinically important differences in the pharmacokinetics of paliperidone in men and women was not found.
The effect of Smoking on the pharmacokinetics of a 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 showed no differences in the pharmacokinetics of paliperidone in smokers and non-smokers people.
Xeplion, indications
The treatment of schizophrenia and prevention of recurrence of schizophrenia.
Contraindications
Hypersensitivity to paliperidone or to any component of the drug Xeplion.
Because paliperidone is an active metabolite of risperidone, Xeplion is contraindicated in patients with known hypersensitivity to risperidone.
C caution
Orthostatic hypotension
Having the activity of alpha-adrenoreceptor paliperidone some patients can cause orthostatic hypotension. Xeplion should be used with caution in patients with cardiovascular diseases (e.g., heart failure, heart attack, or myocardial ischemia, impaired cardiac conduction), cerebrovascular disorders or conditions predisposing to decrease blood pressure (e.g., dehydration, decrease blood volume, the use of antihypertensive drugs).
Cramps
Like other antipsychotics, Xeplion should be used with caution in patients with a history of seizures or other conditions that may decrease seizure threshold.
Regulation of body temperature
With the use of neuroleptics bind the deterioration of the body's ability to reduce body temperature. Advised to exercise caution in the appointment of Xeplion patients who may be exposed to, increasing your body temperature such as heavy physical exertion, high ambient temperature, effects of drugs on activity of m-cholinergic antagonists, as well as dehydration.
Q-T Interval
As with other antipsychotics, caution should be exercised in the appointment of Xeplion patients with a history of arrhythmia or congenital prolonged Q-T interval, or taking drugs, lengthening the interval Q-T.
Given the effect of paliperidone on the Central nervous system (CNS), care should be taken to apply Xeplion 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 Xeplion older patients with dementia, patients with Parkinson's disease or dementia with Lewy bodies.
Method of application and doses
Patients, never taken oral paliperidone or risperidone administered orally or parenterally, before treatment with the drug Xeplion recommended for 2-7 days to check tolerability of paliperidone or oral risperidone.
It is recommended to start treatment with Xeplion with a dose of 150 mg 1st day and 100 mg after 1 week (both injection in the deltoid muscle). In the future, a recommended dose of 75 mg monthly; the dose may be increased or decreased in the range of 25-150 mg, depending on individual tolerability and/or efficacy. After the second dose of successive injections can be performed in the deltoid or gluteal muscle.
The maintenance dose can be adjusted on a monthly basis. This should take into account the prolonged release of the active ingredient of paliperidone palmitate, as the effect of changing the dose can fully manifest itself only a few months.
Skipping doses
Avoid skipping doses. The second load dose of paliperidone should enter through 1 week after the first dose. If this is not possible, you can enter it 2 days earlier or later. Similarly, the third and subsequent doses are recommended to enter every month, but if this is not possible, then injection can be done 7 days earlier or later.
Skipping doses (a term from 1 month to 6 weeks). After the start of treatment is recommended injections of the drug Xeplion monthly. If the last injection was less than 6 weeks, you should as soon as possible to enter another dose, equal to the previous one. After that, the drug administered monthly.
Skipping doses (a period of > 6 weeks to 6 months). If the last injection of the drug Xeplion has been more than 6 weeks, then resume treatment at a dose equal to the previous one, as follows:
ASAP is administered another dose in the deltoid muscle,
after 1 week introduce another (same) dose in the deltoid muscle,
resume injection in the deltoid or gluteal muscle at intervals of 1 month.
Skipping doses term (> 6 months). If the last injection of the drug Xeplion for more than 6 months, the treatment begins anew, as described above for treatment.
Method of application
Xeplion is intended only for intramuscular administration. The drug is slowly injected deep into the muscle. Injections should only be performed by a medical professional. The entire dose is administered at once; it is impossible to administer the dose over several injections. It is impossible to inject the drug into the blood vessels or subcutaneously. Avoid accidental contact with the blood vessel. To this end, before drug injection, the syringe plunger pulled back to check on the subject of entering the needle in a major blood vessel. If the syringe enters the blood, remove needle and syringe from the patient's muscles and dispose of them. Recommended needle size for conducting drug Xeplion in the deltoid muscle is determined by body weight of the patient. For patients with body weight ?90 kg is recommended, a long needle with grey body kit. For patients with body weight For administration of the drug Xeplion into the gluteal muscle is recommended, a long needle with grey body kit. Injections in the upper outer quadrant of the buttocks. Should be alternately administered in the right and left gluteal muscle. Concomitant use of Paliperidone palmitate and oral paliperidone or risperidone administered orally or parenterally has not been studied. Since paliperidone is the major active metabolite of risperidone, consideration should be given to the additive action of paliperidone when using these drugs simultaneously with the drug Xeplion.
Patients with impaired liver function
The use of the drug Xeplion in patients with impaired liver function have not been studied. Based on the results of the study of paliperidone for oral administration to patients with hepatic impairment mild or moderate severity dose adjustment is not required. The use of the drug Xeplion in patients with impaired liver functions severe not been studied.
Patients with impaired renal function
The use of the drug Xeplion in patients with impaired renal function have not been studied systematically. In patients with impaired renal function mild (creatinine clearance from ? 50 to < 80 ml/min), it is recommended to start use of the drug Xeplion with a dose of 100 mg on day 1 and 75 mg in 1 week (both injection in the deltoid muscle). After this is administered at 50 mg monthly in the deltoid or gluteal muscle. Xeplion not recommended for use in patients with impaired renal function moderate or severe (creatinine clearance < 50 ml/min).
Elderly patients
In General, for elderly patients with normal renal function it is recommended that the same dose of the drug Xeplion that for younger patients with normal renal function. In elderly patients, renal function may be reduced, and in such patients, apply the above recommendations for patients with impaired renal function.
Teenagers and children
The safety and efficacy of the drug Xeplion in patients under 18 years has not been studied.
Other special categories of patients
Dose adjustment of the drug Xeplion depending on sex, race and Smoking patients is not required.
Application of pregnancy and breastfeeding
Pregnancy
The safety of the drug Xeplion intramuscular or oral paliperidone during pregnancy in humans is not established. With the use of high doses of paliperidone oral was a slight increase in mortality of fetuses in animals. Xeplion intramuscular injection had no effect on the pregnancy of rats, but high doses were toxic to pregnant females. The dose of paliperidone when administered of the drug Xeplion intramuscular injection that create concentrations exceeding the maximum therapeutic dose in humans, respectively, in 20-22 times and 6 times did not affect the offspring of laboratory animals. Xeplion can be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus. The influence of the drug Xeplion on labor and delivery 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.
Breastfeeding
In studies of paliperidone in animals and risperidone found in humans the excretion of paliperidone breast milk. Therefore, women receiving Xeplion should not breast-feed babies.
Side effects
Most unwanted side reactions (NDP) was weak or moderate.
Below are adverse reactions observed in patients. The frequency of adverse reactions were classified as follows: very common (?10%), frequent (?1% and < 10 %), uncommon (?0.1% and Infections: frequent infection of the upper respiratory tract.
Metabolic disorders: infrequent – decreased appetite, increased appetite.
Psychiatric disorders: very often – insomnia; often – agitation, nightmares; infrequently – anxiety.
Violations of the nervous system: very common – headache; common akathisia, dizziness, extrapyramidal symptoms, drowsiness; infrequent convulsion, dizziness postural, drooling, dysarthria, dyskinesia, dystonia, neuroleptic malignant syndrome, lethargy, oromandibular dystonia, parkinsonism, psychomotor hyperactivity, syncope.
Ophthalmic disorders: infrequent – oculogyric crisis, involuntary movement of the eyeball, the lack of visual perception.
Violations of the organ of hearing and balance: infrequent – vertigo. Violations by the cardiovascular system: often – increased blood pressure; infrequent - bradycardia, blockade feet beam Guisa, the syndrome of postural orthostatic tachycardia, tachycardia, orthostatic hypotension.
Gastrointestinal disorders: frequent pain in the upper abdomen, constipation, diarrhea, dry mucous membranes of the mouth, nausea, toothache, vomiting; infrequent abdominal discomfort, hypersecretion of saliva, stomach discomfort.
Violations of the musculoskeletal system and connective tissue: often – pain in the extremities.
Violations of the skin: infrequent generalized itching, rash.
Disorders reproductive system and breast: infrequent – amenorrhea, erectile dysfunction, galactorrhea, gynecomastia, irregular menstruation, sexual dysfunction.
Other: often – asthenic disorders, weakness, local reactions (pain, itching, induration at the injection site), the increase in body weight.
Changes in laboratory parameters:
infrequent - increase the concentration of serum prolactin, cholesterol and blood glucose.
A side effect of paliperidone oral
Below are side effects reported in the use of paliperidone for oral administration:
Violations by the immune system: anaphylactic reaction;
Violations of the nervous system: large and small seizures, tremor;
Violations by the cardiovascular system: atrioventricular block I degree, palpitations, sinus arrhythmia, sinus tachycardia, lowering blood pressure, myocardial ischemia;
Violations of the musculoskeletal system and connective tissue: muscle rigidity;
Violations of the reproductive system and mammary glands: priapism, discharge from the nipple;
Other: peripheral edema;
Changes in instrumental parameters: changes on the electrocardiogram (ECG);
Data on the safety of risperidone
Paliperidone is an active metabolite of risperidone. Character release of active substances and pharmacokinetics of paliperidone after administration of the drug Xeplion differ from those after oral preparations of risperidone with immediate release of the active substance or of risperidone for intramuscular introduction of the prolonged action. Information on the safety of risperidone for oral and risperidone for injection prolonged action obtained in clinical trials and through post-marketing monitoring of the use of drugs, is given in the instructions for medical use of these drugs.
Special instructions
The QT interval
Be careful with the use of paliperidone in patients with known cardiovascular disease or with prolonged QT interval in history and also in a joint application of medicines that may cause QT prolongation.
Neuroleptic malignant syndrome
When using antipsychotics, including paliperidone, was the development of neuroleptic malignant syndrome (NMS) characterized by hyperthermia, muscle rigidity, instability of autonomic nervous system, impaired consciousness and increased concentration of creatine phosphokinase in the blood serum. In addition, there may be myoglobinuria (rhabdomyolysis) and acute renal failure. When you have symptoms suggesting NMS, all antipsychotics, including Xeplion, cancel.
Tardive dyskinesia
The application of drugs having properties of antagonists of dopamine receptors, accompanied by the development of tardive dyskinesia characterized by rhythmic, involuntary movements primarily language and/or facial muscles. If you have symptoms of tardive dyskinesia should consider abolishing all antipsychotics, including Calion.
Hyperglycemia and diabetes
In the treatment of drug Xeplion were observed hyperglycemia, diabetes mellitus and exacerbation of existing diabetes mellitus. The relationship between the use of atypical antipsychotics and impaired 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 medications and the development of side effects associated with hyperglycemia is not fully installed. All patients needed to conduct clinical testing for the presence of symptoms of hyperglycemia and diabetes (see "Side effects").
The increase in body weight
In the treatment of atypical antipsychotics showed a significant increase in body weight. It is necessary to control body weight patients.
Hyperprolactinemia
Studies of tissue cultures indicate that the growth of breast tumors in humans can be stimulated by prolactin. Despite the fact that it is still in clinical and epidemiological studies has not been demonstrated a direct relationship with the use of antipsychotics, caution should be exercised in the use of paliperidone in patients with possible prolactin-dependent tumors.
Orthostatic hypotension
Having the activity of alpha-adrenoreceptor paliperidone some patients can cause orthostatic hypotension. Xeplion should be used with caution in patients with cardiovascular diseases (e.g., heart failure, heart attack, or myocardial ischemia, impaired cardiac conduction), cerebrovascular disorders or conditions predisposing to decrease blood pressure (e.g., dehydration, decrease blood volume, the use of antihypertensive drugs).
Cramps
Like other antipsychotics, Xeplion should be used with caution in patients with a history of seizures or other conditions that may decrease seizure threshold.
Renal failure
The concentration of paliperidone in plasma is increased in patients with impaired renal function. In patients with impaired renal function mild recommended dose adjustment. Xeplion not recommended for use in patients with impaired renal function moderate or severe (creatinine clearance < 50 ml/min)
Liver failure
The use of the drug Xeplion in patients with impaired liver function severe (class C child-Pugh) has not been studied. Be careful with the use of paliperidone in these patients.
Elderly patients with dementia
Cross analysis of the results of the studies showed increased mortality elderly patients with dementia treated with atypical antipsychotics, including risperidone, aripiprazole, olanzapine and quetiapine, compared with placebo. Among patients receiving risperidone and placebo, mortality was respectively 4% and 3.1%.
The use of the drug Xeplion in elderly patients with dementia has not been studied. Because paliperidone is an active metabolite of risperidone, it should be considered experience of application of risperidone. For elderly patients with dementia taking risperidone, there was an increased mortality in patients treated with furosemide and risperidone compared to the group receiving only risperidone and the group receiving only furosemide. Not established pathophysiological mechanisms to explain this observation. However, you should be very careful in appointing the drug in such cases. Not found increased mortality in patients simultaneously receiving other diuretics with risperidone. Irrespective of treatment, dehydration is a common risk factor for mortality and should be monitored carefully in elderly patients with dementia.
Violations of cerebral circulation
In placebo-controlled studies found a higher incidence of disorders of cerebral circulation (transient and stroke), including fatalities, in elderly patients with dementia treated with some atypical antipsychotics, including risperidone, aripiprazole and olanzapine, in comparison with the use of a placebo.
Leukopenia, neutropenia, agranulocytosis
Leukopenia, neutropenia and agranulocytosis was observed after the use of antipsychotics, including the use of the drug Xeplion. Agranulocytosis was noted very rarely during post-marketing observations. Patients with a clinically significant reduction in the number of leukocytes in the history of, or drug-dependent leukopenia/neutropenia it is recommended to conduct a complete blood count during the first months of therapy, discontinuation of treatment with the drug Xeplion should be considered 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 observed on the subject of rise in temperature or emergence of symptoms of infection and begin treatment immediately if you experience these symptoms. Patients with severe neutropenia (absolute neutrophil count less than 1 x 109/l) should discontinue use of the drug Xeplion as long as the white blood cell count is not normal.
Venous thromboembolism
When using antipsychotic drugs was observed cases of venous thromboembolism. Because patients taking antipsychotic medications often have a risk of venous thromboembolism, all possible risk factors should be identified before and during treatment with the drug Xeplion, and should be taken preventive measures.
Parkinson's disease and dementia with Lewy bodies
The physician should compare the risks and benefits of use of neuroleptics including Xeplion, in patients with Parkinson's disease or dementia with Lewy bodies, as both these categories of patients may be at increased risk of neuroleptic malignant syndrome (NMS) and the risk of increased sensitivity to antipsychotics. Manifestations of sensitivity may include confusion, blunting pain sensitivity, posture instability with frequent falls and extrapyramidal symptoms.
Priapism
There is evidence of the ability of drugs with properties of alpha-blockers to cause priapism. Priapism was under post-marketing monitoring of the use of paliperidone.
Effects on the regulation of body temperature
With the use of neuroleptics bind the deterioration of the body's ability to reduce body temperature. Advised to exercise caution in the appointment of Xeplion patients who may be exposed to, increasing your body temperature such as heavy physical exertion, high ambient temperatures, exposure to drugs with active m anticholinergics, as well as dehydration.
Antiemetic effect
In preclinical studies of paliperidone discovered antiemetic effect. The appearance of this effect in the patient may mask the signs and symptoms of overdose of certain drugs or, for example, conditions such as intestinal obstruction, Reye's syndrome or brain tumor.
Introduction
Intramuscular administration caution should be exercised to avoid accidental contact with the drug in the blood vessel.
Intraoperative flaccid iris syndrome (ISDR)
The ISDR was observed during surgical intervention on the presence of cataract in patients receiving therapy with drugs that are antagonists ?1-adrenergic receptors, such as Xelion.
The ISDR increases the risk of complications associated with the organ of sight, during and after surgery. Doctor performing such an operation, must be informed early that the patient has taken or is taking currently drugs that have the activity of antagonists ?1-adrenergic receptors. The potential benefits of therapy antagonists ?1-adrenergic receptors before surgery is not installed and must be assessed taking into account the risks associated with the abolition of therapy with antipsychotic drugs.
Effect on driving and operating machinery
Xeplion can break the execution of actions requiring concentration and psychomotor speed reactions, and can affect vision. Therefore, patients should be advised not to drive vehicles and moving machinery until their individual sensitivity.
Drug interactions
Paliperidone may increase Q-T interval, so it should be used with caution in combination with other drugs, increasing the Q-T interval (antiarrhythmic drugs, including quinidine, procainamide, amiodarone, sotalol; antipsychotic drugs (chlorpromazine, thioridazine); antibiotics including Gatifloxacin, moxifloxacin.
Since Paliperidone palmitate is hydrolyzed to paliperidone, the assessment of the possibility of drug interaction should be taken into account the results of studies of paliperidone for oral administration.
The ability of the drug Xeplion to affect other drugs
It is not expected that paliperidone will show a clinically significant pharmacokinetic interaction with drugs, metaboliziruemah isoenzymes of cytochrome P450. Studies using human liver microsomes in vitro have shown that paliperidone is not significantly weaken the metabolism of substances by the isoenzymes CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4 and CYP3A5. Therefore, it is not expected that paliperidone will be clinically important to reduce the clearance of drugs, metaboliziruemah these isoenzymes. Also it is not expected that paliperidone will be the properties of the inductor isozymes, vol.K. in vitro studies paliperidone did not induce activity of isoenzymes CYPA2, CYPC19 or CYP3A4. Paliperidone in high concentrations is a weak inhibitor of P-glycoprotein. However, in vivo data in this regard is not, and the clinical significance of this phenomenon is unknown.
Given the effect of paliperidone CNS should be used with caution Xeplion in combination with other drugs and Central action of alcohol. Paliperidone may weaken the effect of levodopa and agonists of dopamine receptors. Because of the ability of the drug Xeplion to cause orthostatic hypotension may be additive amplification of this effect when using the drug Xeplion in conjunction with other drugs that are capable of doing.
The ability of other drugs affect Xeplion
Paliperidone is not a substrate of the isoenzymes CYP1A2, CYP2A6, CYP2C9, CYP2C19 and CYP3A5. This suggests a weak probability of interaction with inhibitors and inducers of these isoenzymes. Although in vitro studies indicate the possibility of minimal involvement of CYP2D6 and CYP3A4 in the metabolism of paliperidone, currently there is no evidence that these enzymes can play a significant role in the metabolism of paliperidone in vitro or in vivo. In vitro studies indicate that paliperidone is a substrate for P-glycoprotein.
Paliperidone to a limited extent, metabolized by the CYP2D6 isoenzyme. The study of the interaction of paliperidone for oral administration with an active inhibitor of CYP2D6 by paroxetine in healthy volunteers is not detected clinically significant changes in the pharmacokinetics of paliperidone.
Reception of paliperidone sustained release of the active component (1 per day) orally simultaneously with carbamazepine (200 mg 2 times a day) resulted in a reduction in average Cmax and AUC of paliperidone by approximately 37%. This decrease is largely attributable to the increase paliperidone renal clearance by 35%, probably due to activation of renal P-glycoprotein by carbamazepine. A very small decrease in the number of drug output through the kidneys in unchanged form, suggests that carbamazepine affects only weakly mediated through hepatic metabolism or bioavailability of paliperidone. When you start taking carbamazepine, the dose of the drug Xeplion should be reviewed and, if necessary, to increase. On the contrary, the abolition of carbamazepine, the dose of the drug Xeplion should be reviewed and, if necessary, to reduce. Paliperidone at physiological pH is a cation and is mainly excreted unchanged through the kidneys – half by filtration and by active secretion. The simultaneous use of trimethoprim, which inhibits active transport of cations in the kidney, did not affect the pharmacokinetics of paliperidone.
The use of the drug Xeplion together with risperidone
The use of the drug Xeplion together with risperidone has not been studied. Because paliperidone is an active metabolite of risperidone when concomitant use of the drug Xeplion and risperidone should take into account the increase in the concentration of paliperidone in plasma.
