Instructions for use RISPOLEPT CONSTA
In patients who have not previously received risperidone, it is recommended to determine the tolerability of oral forms of risperidone before starting treatment with Rispolept Consta.
Rispolept Konsta is administered once every 2 weeks deep intramuscularly, using the sterile needle attached to the syringe. Injections should be done alternately into the right and left buttocks. The drug cannot be administered intravenously!
For adults
The recommended dose of Rispolept Konsta is 25 mg IM once every 2 weeks. Some patients require higher doses - 37.5 mg or 50 mg. In clinical studies, no increase in efficacy was observed with the 75 mg dose. The maximum dose should not exceed 50 mg once every 2 weeks.
For 3 weeks after the first administration of Rispolept Konsta (i.e., before the drug begins to act), the patient must take an effective antipsychotic drug.
The dose of the drug can be increased no more often than once every 4 weeks. The effect of such an increase in dose should be expected no earlier than 3 weeks after the first injection of the increased dose.
For elderly patients
The recommended dose is 25 mg IM once every 2 weeks. For 3 weeks after the first administration of Rispolept Konsta (i.e., before the drug begins to act), the patient must take an effective antipsychotic drug.
There are currently no data on the use of Rispolept Konsta in patients with impaired liver or kidney function.
. If it is still necessary to use Rispolept Konsta in this category of patients, then in the first week it is recommended to take 500 mcg of risperidone 2 times a day in oral dosage form. During the second week, the patient can take 1 mg 2 times a day or 2 mg 1 time a day. If the patient tolerates an oral dose of at least 2 mg well, then he can be administered 25 mg of Rispolept Konsta intramuscularly once every 2 weeks.
Rules for preparing the solution
To prepare a suspension from the Rispolept Konsta extended-release microgranules in the bottle, you can use only the solvent contained in a pre-filled syringe. The prepared suspension is administered intramuscularly only with a safe Needle-Pro needle. The components contained in the package must not be replaced with any other products. To ensure the full dose of risperidone is administered, the entire contents of the vial must be administered.
Remove the Rispolept Konsta package from the refrigerator and allow it to warm to room temperature before preparing the suspension.
1. Remove the colored plastic cap from the bottle containing the microgranules.
2. Open the blister pack and remove the Alaris Smart Site needle-free device by holding it by the white cap. Do not touch the sharp tip of the device.
3. Place the bottle on a hard surface. Using a top-down motion, press the tip of the pin of the needleless device to the center of the rubber stopper of the bottle until the device is firmly fixed on the bottle cap.
4. Wipe the attachment point of the device with the syringe (blue circle) with a suitable antiseptic before connecting it to the syringe.
5. The syringe has a white tip, consisting of two parts:
- white collar and glossy white cap. To open the syringe, hold the syringe by the white collar and break off the glossy white cap (the white cap must not be unscrewed). Remove the white cap along with the rubber tip inside it.
During all stages of assembly, hold the syringe only by the white collar located on the tip of the syringe. Be careful not to overtighten components during assembly as in this case, parts of the syringe may come off.
6. Holding the syringe by the white collar, insert the syringe into the blue circle of the device, press and turn clockwise to ensure that it is firmly connected to the device (do not twist). To prevent rotation, the “skirt” is held firmly while connecting the device to the syringe.
The syringe and device must be in line.
7. Inject the entire contents of the syringe (solvent) into the vial.
8. Holding the syringe plunger in the palm of your hand, shake the bottle vigorously for at least 10 seconds until a homogeneous suspension is formed. The mixing process can be considered complete when the suspension becomes homogeneous, thick, and milky in color. Microgranules may be visible in the liquid, but no dry microgranules should remain.
After preparation, the suspension should be used immediately, otherwise the suspension may separate.
9. Turn the bottle upside down and slowly suck the entire contents of the bottle into the syringe. For identification purposes, part of the label is separated from the bottle along the perforation line and glued to the syringe.
10. Holding the syringe by the white collar, unscrew the syringe from the device. Discard the bottle and needleless device.
11. Open the blister pack of the Needle-Pro needle. Do not touch the part of the needle attached to the syringe. Remove the needle from the package, holding it by the transparent case.
12. Hold the syringe by the white collar and attach the luer lock cannula of the orange Needle-Pro needle guard to the syringe by turning it slightly clockwise.
13. While continuing to hold the syringe by the white collar, pinch the clear needle sheath and secure the needle tightly into the Needle-Pro by pressing and turning clockwise.
Immediately before administration, the drug Rispolept Konsta must be resuspended, since after preparing the suspension in the vial, some of the microgranules may settle. To do this, shake the syringe vigorously until the microgranules are completely resuspended.
14. Remove the protective cap from the needle without rotating it. Do not bend the cap, because the luer lock connection may be damaged.
Lightly tap the syringe with your finger so that the air bubbles in it rise to the top. Remove air bubbles from the syringe by moving the piston forward, with the needle pointing vertically upward. The entire contents of the syringe are injected into the gluteal muscle.
The suspension cannot be administered intravenously.
Warning.
To avoid damage or contamination of the needle, do not:
- touch the needle with your hands while pressing the Needle-Pro device against the needle;
- disassemble the Needle-Pro device;
- try to straighten the Needle-Pro needle if it is bent;
- handle the needle protective casing carelessly; the tip of the needle should not be visible from the casing.
After injection, insert the needle into the safety (orange) Needle-Pro using one hand. To do this, carefully press the protective casing onto a table or any other flat surface. Once the guard is pressed down, the needle should fit firmly into it. Before discarding the needle, visually verify that the needle is securely seated in the Needle-Pro. Throw away the needle.
Rispolept Konsta por d/prig susp IM prolong d-ya 37.5 mg N1 (Johnson)
In patients who have not previously received risperidone, it is recommended to determine the tolerability of oral dosage forms of risperidone before starting treatment with Rispolept Consta®.
Use in elderly patients with dementia
The use of Rispolept Consta® has not been studied in elderly patients with dementia, as it is not indicated for this group of patients. Rispolept Konsta® is not intended for the treatment of behavioral disorders associated with dementia.
Increased mortality in older patients with dementia
In elderly patients with dementia, increased mortality was observed when treated with atypical antipsychotics compared with placebo in a meta-analysis of 17 controlled trials of atypical antipsychotics, including oral risperidone. In placebo-controlled studies of oral risperidone in this population, the incidence of death was 4.0% for patients taking risperidone compared with 3.1% for the placebo group. The mean age of patients who died was 86 years (range, 67–100 years). Data collected from two large observational studies show that older patients with dementia treated with typical antipsychotic medications also have a slightly increased risk of death compared with patients not treated. At present, insufficient data have been collected to accurately assess this risk. The reason for the increase in this risk is also unknown. Also unknown is the extent to which the increased mortality may be attributable to antipsychotic drugs rather than to the characteristics of this patient population.
Concomitant use with furosemide
In elderly patients with dementia, there was an increased mortality rate when taking furosemide and oral risperidone concomitantly (7.3%, mean age 89 years, range 75-97 years) compared with the risperidone alone group (3.1%, mean age 84 years , range 70-96 years) and the furosemide-only group (4.1%, mean age 80 years, range 67-90 years). An increase in mortality in patients taking risperidone with furosemide was observed in 2 of 4 clinical studies. Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) was not associated with an increase in mortality.
No pathophysiological mechanisms have been established to explain this observation. However, special care should be taken when prescribing the drug in such cases. Before prescribing, the risk/benefit ratio must be carefully assessed. There was no increase in mortality in patients taking other diuretics concomitantly with risperidone. Regardless of treatment, dehydration is a common risk factor for mortality and should be carefully monitored in older patients with dementia.
Adverse events from the cerebrovascular system
In placebo-controlled clinical trials, an approximately 3-fold increased risk of cerebrovascular adverse events was observed in patients with dementia taking certain atypical antipsychotic drugs. Pooled data from 6 placebo-controlled studies involving primarily elderly patients with dementia (age >65 years) demonstrate that cerebrovascular adverse events (serious and non-serious) occurred in 3.3% (33/1009) of patients treated with risperidone. and in 1.2% (8/712) of patients receiving placebo. The risk ratio was 2.96 (1.34, 7.50) with a 95% confidence interval. The mechanism by which this risk increases is unknown. An increased risk cannot be excluded for other antipsychotic drugs, as well as for other patient populations. Rispolept Konsta® should be used with caution in patients with risk factors for stroke.
Orthostatic hypotension
Risperidone has alpha-blocking activity and may therefore cause orthostatic hypotension, especially early in therapy. Clinically significant hypotension has been observed in the post-marketing period when used concomitantly with antihypertensive drugs. Risperidone should be used with caution in patients with known cardiovascular disease (eg, heart failure, myocardial infarction, conduction disturbances, dehydration, hypovolemia, or cerebrovascular disease). It is recommended to carefully evaluate the benefit/risk ratio when assessing the possibility of continuing therapy with Rispolept Consta®.
Blood disorders (leukopenia, neutropenia and agranulocytosis)
Cases of leukopenia, neutropenia and agranulocytosis have been reported when using antipsychotics, including the drug Rispolept Consta®.
Very rare cases of agranulocytosis (<1/10,000 patients) have been reported during post-marketing surveillance.
During the first few months of therapy, patients with a clinically significant decrease in white blood cell count or a history of drug-induced leukopenia or neutropenia should be monitored. The possibility of discontinuing Rispolept Consta® should be considered when the first signs of a clinically significant decrease in the number of white blood cells appear in the absence of other causative factors.
Patients with clinically significant neutropenia should be closely monitored for fever or other signs or symptoms of infection and treated promptly. Discontinue use of Rispolept Consta® in patients with severe neutropenia (neutrophil count <1x109/L) and monitor white blood cell counts until recovery.
Tardive dyskinesia and extrapyramidal disorders
Drugs with dopamine receptor antagonist properties can cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, mainly of the tongue and/or facial muscles.
The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. If a patient experiences objective or subjective symptoms indicating tardive dyskinesia, the advisability of discontinuing all antipsychotic medications should be considered.
Neuroleptic malignant syndrome (NMS)
Antipsychotics, including risperidone, may cause neuroleptic malignant syndrome (NMS), which is characterized by hyperthermia, muscle rigidity, instability of autonomic nervous system function, depression of consciousness, and increased serum concentrations of creatine phosphokinase. Myoglobinuria (rhabdomyolysis) and acute renal failure may also occur in patients with NMS. If a patient develops symptoms of NMS, all antipsychotic medications, including Rispolept Consta®, must be immediately discontinued.
Parkinson's disease and dementia with Lewy bodies
The prescription of antipsychotic drugs, including Rispolept Konsta®, to patients with Parkinson's disease or dementia with Lewy bodies should be carried out with caution, because Both groups of patients have an increased risk of developing neuroleptic malignant syndrome and increased sensitivity to antipsychotic drugs (including dullness of pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms). Parkinson's disease may worsen when taking risperidone.
Hypersensitivity reactions
Although the tolerability of oral forms of risperidone should be checked before initiating therapy with Rispolept Consta®, very rare cases of anaphylactic reactions have been reported during post-marketing use in patients who have previously tolerated oral forms of risperidone.
If hypersensitivity reactions occur, it is necessary to stop using the drug Rispolept Consta®, take the necessary supportive clinical measures and monitor the patient's condition until symptoms disappear.
Hyperglycemia and diabetes mellitus
Hyperglycemia, diabetes mellitus, and exacerbation of existing diabetes mellitus were observed during treatment with Rispolept Consta®. It is likely that weight gain prior to treatment is also a predisposing factor. Very rarely, ketoacidosis and rarely, diabetic coma can occur. All patients should be clinically monitored for symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia and weakness). Patients with diabetes mellitus should be regularly monitored for worsening glucose control.
Weight gain
During treatment with Rispolept Consta®, a significant increase in body weight was observed. It is necessary to monitor patients' body weight.
Hyperprolactinemia
Hyperprolactinemia is a common adverse reaction during treatment with risperidone. It is recommended to determine the concentration of prolactin in the blood in patients with signs of hyperprolactinemia (for example, gynecomastia, menstrual irregularities, anovulation, impaired fertility, decreased libido, erectile dysfunction, galactorrhea).
Based on the results of tissue culture studies, it has been suggested that cell growth in breast tumors may be stimulated by prolactin. Although clinical and epidemiological studies have not shown a clear association between hyperprolactinemia and antipsychotic drug use, caution should be exercised when prescribing risperidone to patients with a history of this. Rispolept Consta® should be used with caution in patients with existing hyperprolactinemia and in patients with possible prolactin-dependent tumors.
QT prolongation
QT prolongation has been observed very rarely during post-marketing surveillance. As with other antipsychotics, caution should be exercised when prescribing Rispolept Consta® to patients with known cardiovascular disease, family history of QT interval prolongation, bradycardia, electrolyte imbalance (hypokalemia, hypomagnesemia), as this may increase the risk of arrhythmogenic effects. ; and when used together with drugs that prolong the QT interval.
Convulsions
Rispolept Consta® should be used with caution in patients with a history of seizures or other medical conditions that may lower the seizure threshold.
Priapism
Priapism may occur with risperidone due to alpha-blocking effects.
Body temperature regulation
Antipsychotic drugs are associated with such undesirable effects as disruption of the body's ability to regulate temperature. Caution should be exercised when prescribing Rispolept Consta® to patients with conditions that may contribute to an increase in core body temperature, such as intense physical activity, dehydration, exposure to high external temperatures, or concomitant use of drugs with angiocholinergic activity.
Venous thromboembolism
Cases of venous thromboembolism have been reported with the use of antipsychotic drugs. Since antipsychotic drugs often carry a risk of developing venous thromboembolism, all possible risk factors should be identified before and during treatment with Rispolept Consta®, and preventive measures should be taken.
Intraoperative floppy iris syndrome (ISID)
ISDR was observed during surgery for the presence of cataracts in patients receiving therapy with drugs that have α1-adrenergic receptor antagonist activity, including the drug Rispolept Consta®.
ISDR increases the risk of complications associated with the organ of vision during and after surgery. The doctor performing such an operation should be informed in advance that the patient has taken or is currently taking drugs that have α1-adrenergic receptor antagonist activity. The potential benefit of discontinuing α1-adrenergic antagonist therapy before surgery has not been established and should be weighed against the risks associated with discontinuing antipsychotic therapy.
Antiemetic effect
An antiemetic effect was observed in preclinical studies of risperidone. The appearance of this effect in a patient may mask signs and symptoms of overdose of some drugs or conditions such as intestinal obstruction, Reye's syndrome, or brain tumor.
Kidney and liver failure
Although Rispolept Consta® has not been studied in patients with renal or hepatic impairment, caution should be exercised when using the drug in such groups of patients.
Care must be taken to avoid accidental injection of Rispolept Consta® into a blood vessel.
Do not expose the drug to temperatures above 25 °C. In the absence of a refrigerator, Rispolept Konsta® can be stored at a temperature not exceeding 25 ° C for no more than 7 days before use.
After preparation of the suspension: the suspension is physically and chemically stable for 24 hours at 25 °C. From a microbiological point of view, it is advisable to use the suspension immediately after preparation. If the suspension is not used immediately after preparation, it can be stored for no more than 6 hours at a temperature of 25 °C. Risperidone may reduce the rate of mental and physical reactions, and therefore patients should be advised to refrain from driving a vehicle or operating machinery.
Incompatible combinations
Rispolept Konsta® must not be mixed or diluted with any other medicines or liquids other than the special solvent contained in the package.
Directions for use
Important information
The use of the drug Rispolept Konsta® requires strict adherence to the instructions for preparing the suspension to ensure accurate administration of the drug and avoid possible errors.
Remove the Rispolept Consta® package from the refrigerator and allow it to warm to room temperature for at least 30 minutes before preparing the suspension.
Do not heat in any other way.
The components of this kit are specially designed for the use of the drug Rispolept Konsta®. To prepare a suspension from the Rispolept Konsta® extended-release microgranules contained in the bottle, you can only use the solvent included in the kit.
The components contained in the package must not be replaced with any other products.
Do not store the suspension after preparation.
The drug should be administered immediately after preparing the suspension.
To ensure the full dose of risperidone is administered, the entire contents of the vial must be administered. The introduction of part of the contents of the bottle cannot ensure that the patient receives the required dose of the drug.
Do not reuse: This device is intended for one-time use only. Any attempt at subsequent reuse may adversely affect the integrity of the device itself or result in deterioration in its performance.
Kit components
1. Assemble the components.
Connect the needleless device to the bottle.
Remove the cap from the bottle.
Remove the colored plastic cap from the bottle.
Wipe the unopened bottle with an alcohol wipe and let dry.
Do not remove the gray rubber plug.
Prepare the needleless device.
Hold the sterile blister as shown in the picture. Pull back and remove backing paper.
Do not remove the needleless device from the blister.
To avoid contamination, do not touch the sharp tip of the device.
Connect the needleless device to the bottle
Place the bottle on a hard surface and hold the base of the bottle. Place the needleless device vertically on the bottle so that the sharp tip is positioned in the center of the rubber stopper. Using downward pressure, push the sharp tip of the needleless device through the center of the rubber stopper of the bottle until the device is securely attached to the top of the bottle.
Do not connect the needleless device at an angle, as the solvent may leak when poured into the bottle.
Connect the pre-filled syringe to the needleless device.
Remove the sterile blister.
Important!
Remove the sterile needleless device blister only when you are ready to remove the white cap from the syringe.
Keep the bottle upright to avoid leakage. Hold the base of the bottle and pull the blister to remove it.
Don't shake.
To prevent contamination, do not touch the luer lock.
Hold the syringe by the white collar.
Do not hold the syringe by the glass base.
Remove the cap.
Hold the syringe by the white collar and break off the white cap.
Do not unscrew or cut off the white cap.
To prevent contamination, do not touch the tip of the syringe.
The broken cap can be thrown away.
Connect the syringe and needleless device.
To prevent rotation during connection, hold the needleless skirt firmly.
Holding the syringe by the white collar, insert the tip of the syringe into the luer lock of the needleless device.
Do not hold the syringe by the glass base. This can lead to a white collar disconnect. Screw the syringe firmly onto the needleless device in a clockwise direction.
Avoid twisting. This may cause the syringe to fail.
2. Dissolve the microbeads
Enter solvent.
Inject the entire contents of the syringe with solvent into the bottle.
Important!
The contents of the bottle will now be under pressure. Hold the plunger of the syringe with your thumb.
Suspend the microbeads in the solvent.
Holding the syringe plunger with your thumb, shake the contents of the vial vigorously for at least 10 seconds until a homogeneous suspension is formed.
After proper mixing, the suspension becomes homogeneous, thick, and milky in color.
Microgranules may be visible in the liquid, but no dry microgranules should remain unwetted with solvent.
Proceed to the next step immediately as the suspension may separate.
Transfer the suspension into a syringe.
Turn the bottle upside down and SLOWLY draw the entire contents of the bottle into the syringe.
Remove the needleless device.
Hold the syringe by the white collar and unscrew the syringe from the needleless device.
Separate part of the label from the bottle along the perforation line and glue it to the syringe (for identification). Dispose of the bottle and needle-free device in accordance with local waste disposal regulations.
3. Attach the needle.
Select the appropriate needle.
Select the needle depending on the injection site (gluteal or deltoid).
Attach the needle.
Open the blister pack and grasp the base of the needle as shown in the picture.
While still holding the syringe by the white collar, secure the syringe tightly into the luer lock cannula of the needle guard by pressing and turning clockwise.
To prevent contamination, do not touch the luer lock of the guard.
Resuspend the microbeads.
Remove the blister completely. Immediately before administering the drug, it is necessary to resuspend the microgranules, since after preparing the suspension in the vial, some of the microgranules may settle. Shake the syringe vigorously.
Administer the drug.
Remove the transparent case from the needle
Pull the needle guard in the opposite direction from the syringe as shown in the figure. Holding the syringe by the white collar, remove the transparent case from the needle. DO NOT bend the case as it will... the luer lock connection may be damaged.
Remove any air bubbles.
Lightly tap the syringe with your finger so that the air bubbles in it rise to the top. Slightly push the plunger upward to remove air bubbles from the syringe and needle, holding the syringe so that the needle points vertically upward.
Administer the drug.
Immediately inject the entire contents of the syringe intramuscularly into the patient's gluteal or deltoid muscle.
The gluteal injection should be given in the upper outer quadrant of the gluteal region.
The suspension cannot be administered intravenously.
Place the needle in the safety device.
Using one hand, position the guard on a flat surface at a 45-degree angle. Quickly push down until the needle enters the guard.
Warning:
Don't use both hands.
Do not disassemble the needle guard.
Do not attempt to straighten the needle or touch the needle guard if the needle is bent or damaged.
Dispose of the needle properly.
Before discarding the needle, make sure that the needle is firmly secured in the needle guard.
Dispose of in accordance with local waste disposal regulations.
Also discard the unused needle provided in the kit.
Psychiatry Psychiatry and psychopharmacotherapy named after. P.B. Gannushkina No. 05 2004
Introduction
The choice of drug for long-term therapy of patients with schizophrenia is determined by many factors. For example, its ability to effectively influence productive and negative symptoms for a long time and prevent the development of exacerbations is important; its tolerability and ease of administration, including for working patients, are also important. Some of the listed properties are possessed by durable (long-lasting) forms of antipsychotics, therapy with which in some patients can be limited to one injection every 2–4 weeks. Deposited forms of antipsychotics appeared in the 60s of the 20th century and quickly occupied a certain significant niche in the treatment of mental disorders. Clinical indications for the use of long-acting forms of antipsychotics are quite broad and include the presence of residual post-attack symptoms in patients, the need to prevent relapses of the disease, patient non-compliance with the treatment regimen, and resistance to tablet forms due to individual characteristics. Long-acting drugs have a number of objective advantages compared to conventional pharmaceutical forms (tablets, injection solutions, etc.). The pharmacokinetic features of prolonged forms provide a more constant and stable concentration of the drug in the blood, make it possible to titrate the effective dose of the drug to a minimum, and the absence of daily fluctuations in the concentration of the drug in the blood associated with taking the next dose ensures good tolerability of therapy. Compared to tablet forms, prolongs have slightly greater clinical efficacy also due to the lack of “absorption metabolism” associated with the absorption of the active substance from the gastrointestinal tract when taken orally [2, 24, 32, 34, 36]. Another objective advantage of long-acting drug therapy is complete control over patient compliance with the therapy regimen. A number of studies have convincingly shown [37] that independent manipulations by patients with schizophrenia to reduce the daily dose of a prescribed antipsychotic or premature cessation of treatment lead to serious consequences (exacerbations, hospitalization, loss of work). Continuity and duration of antipsychotic treatment have a significant impact on relapse prevention [18, 20, 22]. Thus, premature cessation of therapy in patients with the first episode of schizophrenia increases the risk of recurrence of an acute psychotic state fivefold. Other authors [10, 19] have shown that the risk of developing an exacerbation of schizophrenia after cessation of treatment increases by 10% monthly, and in 80% of patients an exacerbation occurs during the first year without therapy, which, in addition to the direct deterioration of the patient’s mental state, social, work and family maladjustment leads to an increase in suicidal risk and a significant increase in the cost of therapy [11, 42]. Specially conducted studies have also shown the presence of subjective preferences for prolonged forms both among patients and among practicing psychiatrists, especially in conditions of long-term therapy [4, 35]. Thus, 77% of patients consider injections a more effective treatment method than taking pills, and 87% prefer these forms of treatment either as monotherapy or in combination with pills. However, despite the benefits, the use of stored antipsychotics began to decline progressively after the advent of atypical antipsychotics, which cause virtually no extrapyramidal side effects. In addition, atypical antipsychotics with long-term use are superior to traditional antipsychotics in anti-relapse efficacy and anti-negative effect, which was, for example, shown in a long-term comparative study of risperidone and haloperidol [9]. The situation that has arisen in recent years with the choice of an antipsychotic for long-term anti-relapse therapy, when, on the one hand, there is clear evidence of the clinical advantages of atypical drugs, and on the other, the undoubted positive properties of durable forms, makes the emergence of a prolonged form of an atypical antipsychotic, Consta, especially relevant. combining both those and other advantages.
Dosage form and method of application
Konsta technology is based on the use of special patented microspheres that have been shown to be safe from a medical point of view, in which risperidone is dispersed in a specific biodegradable polymer. This polymer has been used for a long time in other branches of medicine - transplantology, traumatology and has certain stable properties, which allows it to uniformly release the drug, in this case risperidone, for several weeks and act as its carrier. Microspheres containing risperidone are dissolved in a special aqueous solvent, which cannot be replaced by water for injection or other solvents. The advantages of this technology are significantly less painful injections compared to oil solutions of deposited forms of traditional antipsychotics, which are conjugates of the active substance with fatty carboxylic acids. After injection of Consta, the carrier polymer begins gradual biodegradation into glycolic and lactic acids, releasing risperidone into the blood at a constant rate. The polymer breakdown products (lactic and glycolic acids) undergo further complete metabolic destruction - to carbon dioxide and water and are excreted from the body without residue [39]. The mechanism of release of risperidone from the polymer includes 3 stages. At stage 1 - hydration, which lasts 2-3 weeks after injection, a significant amount of risperidone does not yet enter the blood. Only a small amount of the drug is absorbed directly from the surface of the microspheres. During this period, the concentration of risperidone in the blood plasma is low, which means that it is necessary to continue previous therapy after the first injection of Consta for another 2-3 weeks. At stage 2 - diffusion, the breakdown of the carrier polymer begins and, consequently, the active release of risperidone into the blood. This process begins 3 weeks after injection, reaches a peak by the 4th week and continues, gradually weakening, until the 6th week after injection. At stage 3 - erosion, which occurs by the 7th week after injection of the consta, the polymer completely disintegrates into lactic and glycolic acids and is eliminated from the body without a residue. The concentration of risperidone in the blood decreases rapidly during this period. The processes of hydration, diffusion and erosion of microspheres create the characteristic pharmacokinetic profile of the consta. In the first 3 weeks after injection, there is a latent period with low concentrations of the drug in the blood. At 4–6 weeks after injection, the therapeutic concentration of risperidone in the blood is determined with a maximum between 4 and 5 weeks, and after the 6th week the level of the drug in the blood begins to decline rapidly. Special studies [26, 27, 39] determined that injections of Consta should be carried out every 2 weeks, and a constant concentration of the drug in the blood (steady state) will be achieved after 4 injections (8 weeks of therapy). A comparative study of the pharmacokinetic profiles of tableted risperidone and Consta [12, 13, 27] shows that after reaching the equilibrium concentration of drugs in the blood, when using Consta, smoother fluctuations in the concentration of risperidone are observed (on average 30% lower) than when taking tablets, with one on the other hand, and on the other hand, a slightly lower average concentration of risperidone when using Consta provides a qualitative clinical effect, the same as when taking a larger amount of risperidone in tablets, apparently due to the high stability of the concentration of the prolonged drug in the blood. In addition, when using Consta, the lower average effective concentration and the absence of concentration peaks associated with taking tablets ensure good tolerability of therapy. Monitoring the concentration of consta in the blood during a year of therapy did not reveal signs of drug accumulation [14, 15]. The drug “Konsta” is a large white powder (microspheres with risperidone), packaged in vials for a single injection and requiring storage at certain temperatures (2–8 ° C, refrigerator), which, immediately before injection, is mixed with a special aqueous solvent and administered to the patient intramuscularly, into the gluteal muscle. Konsta is used in dosages of 25, 37.5 and 50 mg intramuscularly every 2 weeks. For most patients, a maintenance dose of 25 mg every 2 weeks is recommended. For patients receiving rispolept in a daily dose of more than 4 mg, the starting dose of Consta can be 37.5 mg every 2 weeks. The maximum dose is 50 mg once every 2 weeks. When transferring from the tablet form of risperidone to Consta, it should be taken into account that if the daily dose of the drug is less than 4 mg, the patient should be prescribed a prolonged form at a dose of 25 mg every 2 weeks. The decision to increase the dose is made no earlier than 4 weeks from the start of treatment with Consta, which is due to the pharmacokinetic characteristics of the drug, the clinical effect of which develops 3 weeks after the injection. For the same reason, after the first injection, the patient continues to take risperidone tablets or solution in the full daily dose for another 3 weeks. If it is necessary to increase the dose of Consta, similar to the period of initiation of therapy, the patient is prescribed additional risperidone in tablets at a dose of up to 4 mg/day for a 3-week period after the injection until the period when the clinical effect of a higher dose of the prolonged drug begins. The dose of Consta can be increased by no more than 12.5 mg at a time. Patients who are prescribed risperidone for the first time should begin treatment with the drug in tablet form or in solution for 2-3 days to check individual tolerance before the first injection of consta. In elderly patients (over 65 years of age), the maximum dose of Consta is 25 mg every 2 weeks. There are currently no data on the use of Consta in patients under 18 years of age. Patients with chronic renal or liver failure may be prescribed Consta in cases where rispolept in a daily dose of 2 mg is well tolerated by them. An overdose of Consta is unlikely, given the specifics of its use; the clinical signs in this case are the same as with an overdose of risperidone in other pharmaceutical forms. A significant positive difference between Consta, determined by the characteristics of pharmacokinetics and elimination, from other long-acting antipsychotics is the drug’s lack of ability to slowly accumulate in fatty tissues, which excludes this mechanism for the development of overdose [39]. When using Consta, you should take into account the possible drug interactions characteristic of risperidone. The drug is an antagonist of levodopa and other drugs that enhance dopaminergic transmission. Carbamazepine (a powerful inducer of the cytochrome P-450 enzyme system) leads to a significant decrease in the pharmacologically active fraction of the drug in the blood. Phenothiazines, tricyclic antidepressants, b-blockers can lead to a slight increase in the concentration of risperidone in the blood, fluoxetine and paroxetine have the same effect.
Clinical efficacy and tolerability
In the period from 1999 to 2003, at least 40 clinical studies of consta were conducted on several thousand patients suffering from schizophrenia and schizoaffective disorder.
The effectiveness and tolerability of the drug were assessed both during long-term anti-relapse therapy and at the stage of follow-up treatment in the post-attack period [3, 6–8, 12–15, 21, 23, 30, 31, 38, 39, 40, 41]. Several studies have also been conducted assessing changes in the quality of life of patients with schizophrenia when transferred to Consta [16, 17] and a comparative pharmacoeconomic study [1]. The results obtained in the studies we found are quite uniform. In general, it has been shown that Consta leads to a significant reduction in productive and negative symptoms, has a pronounced anti-relapse effect and is well tolerated. Moreover, 3 studies were conducted using a double-blind, placebo-controlled technique with a high degree of reliability of the results from the point of view of evidence-based medicine. In a 12-week multicenter, randomized, double-blind, placebo-controlled study conducted by J. Kane et al. (2003) in the USA, 400 patients suffering from predominantly paranoid schizophrenia, less often undifferentiated and disorganized forms, received Consta in doses of 25, 50, 75 mg every 2 weeks or placebo (100 patients in each therapeutic group) [23]. The main criterion for the effectiveness of therapy was the reduction of the total PANSS score [25] during therapy (patients were examined every 2 weeks). To the responders, i.e. Patients with a good clinical effect were defined as patients whose total score reduction exceeded 20%. Every 2 weeks, the dynamics of positive and negative symptoms were also assessed on the corresponding subscales. Extrapyramidal side effects were taken into account using the ESRS scale [5]. In addition, the patients’ reaction to the injection itself was assessed objectively and subjectively (pain on a 100-point scale, the presence of local reactions in the form of redness, formation of compactions or infiltrates). The following results were obtained. 68% of patients in the placebo group and 51–52% in the const group stopped participating in the study prematurely. In the first 2 weeks of the study, the rate of patient dropout was equal in all groups, then patients receiving Consta were less likely to drop out of the study than those receiving placebo (Kaplan-Meier analysis). The reasons for discontinuation of therapy did not differ between groups. At the end of the study, the differences in the reduction in total PANSS scores between all groups receiving Consta and the group receiving placebo were statistically significant. Thus, in patients receiving 25 mg of Consta, the total score decreased by 27% (from 81.7 ± 3.5 to 59.6 ± 3.4 points), in patients receiving 50 mg of Consta - by 19.7% (from 82.3±3.9 to 66.1±3.4 points), 75 mg consta - by 18.6% (from 80.1±3.5 to 65.2±3.3 points), then as in patients receiving placebo - only by 8.3% (from 82±3.4 to 75.2±3.2 points). 17% of patients receiving placebo were classified as responders at the end of therapy, whereas when using Consta (in increasing dosages), responders were 47, 48 and 39%, respectively. The dynamics of positive and negative symptoms, assessed by the corresponding subscales, also statistically reliably indicate the advantages of Consta in all dosages over placebo. Side effects were noted equally frequently both in patients receiving Consta in various dosages and in patients in the placebo group. The most common symptoms are headache (15–20%), agitation (15–20%), insomnia (13–16%), dyspepsia (7–9%), drowsiness (5–10%), rhinitis (4–14%). ), constipation (5–7%), vomiting (3%). A slight increase in body weight of patients was also noted; the differences between Consta and placebo in this regard were statistically significant. This side effect was dose-dependent - for example, when using 25 mg of Consta, an increase in body weight occurred on average by 0.5 kg, when using 50 mg - by 1.2 kg, and by 1.9 kg in patients receiving 75 mg of the drug. In the group receiving placebo, there was a decrease in the weight of patients by an average of 1.4 kg. The severity of extrapyramidal symptoms on the ESRS scale before the start of the study was assessed in patients on average as mild (since they had already received neuroleptic therapy previously), and it did not change during the study in any of the groups. There were no statistically significant differences in this side effect between placebo and Consta. Extrapyramidal disorders were noted in 13% of patients receiving placebo, 10% of patients receiving 25 mg of Consta, 24% of patients with a dose of 50 mg of Consta, and 29% of patients with a dose of 75 mg. 13% of patients in the placebo group, 12% in the group of patients taking 25 mg of the drug, and 23% of patients in the groups receiving 50 and 75 mg of the drug needed antiparkinsonian correctors. Consta injections were minimally painful and were not accompanied by complications, which corresponded to good subjective tolerability of the procedure by patients. In another 12-week double-blind study, the efficacy and tolerability of Consta was compared with risperidone tablet form in 527 patients with schizophrenia in remission [6]. There were no statistically significant differences in clinical effectiveness (in terms of the ability to reduce psychopathological symptoms assessed using the PANSS and Clinical Global Impression - CGI scales) between dosage forms. The total score on the PANSS scale decreased by an average of 7.5% during consta therapy, and by 8.7% when taking risperidone tablets. Side effects were noted in 61 and 59% of patients, respectively, and were the same in both groups. According to the authors, the results of this study indicate that in addition to equal clinical effectiveness and tolerability, the transfer of patients from the tablet form of risperidone to intramuscular injections of Prolong should be tolerated by patients quite easily and proceed without reducing the effectiveness of treatment. The results of several open-label clinical studies are also of significant interest due to the large patient samples. Thus, in 474 patients with schizophrenia and schizoaffective psychosis in remission, the anti-relapse efficacy and tolerability of Consta were studied in a long-term (1 year of therapy) open clinical trial [30, 31]. Konsta was used in doses of 25, 50 and 75 mg every 2 weeks. The results of the study show that a statistically significant reduction in psychopathological symptoms on the PANSS scale (total score) occurred in all treatment groups. An analysis of the characteristics of clinical action, carried out according to the 5-factor model of schizophrenia [29], showed significant effectiveness of 25 mg of Consta in relation to all 5 factors, 50 mg of Consta in relation to 4 factors (positive, negative symptoms, disorganization of thinking and anxiety/depression) and 75 mg consta in relation to only 2 factors (positive and negative symptoms). The number of hospitalizations during the one-year therapy with consta was small, and, in addition, there was a tendency for the anti-relapse effect to increase as the duration of therapy increased. Thus, the average number of re-hospitalizations during the year was 16%, while in the first 3 months of therapy, an exacerbation developed in 38% of the rehospitalized patients, and in the last 3 months – in 12%. There was also a reduction in the average time of re-hospitalization by more than 3 times. The data obtained are consistent with the results of an open clinical study of the effectiveness of Consta with one-year use [37] in patients with schizophrenia, which confirmed an increase in the anti-relapse effect of the drug as the duration of therapy increases. In addition, a pharmacoeconomic effect was noted, which was explained by a significant decrease in patient visits to outpatient consultation offices (70% of requests for consultations occurred at the beginning of the study and 30% at its end). Therapy was well tolerated in all groups; only 5% of patients stopped therapy due to side effects. The severity of extrapyramidal symptoms constantly decreased during therapy, with hyperkinesis most often noted - in 13, 12 and 12% of cases when using 25, 50 and 75 mg, respectively, an akinetic-rigid symptom complex - in 6, 7 and 8% of cases, and tremor - at 7, 4 and 4%. Tardive dyskinesia was observed in 0.6% of cases. After 1 year of therapy, body weight gain averaged 2.3 kg. The high clinical effect of Consta at a dosage of 25 mg is confirmed by the results of a double-blind, placebo-controlled study of the quality of life of patients with schizophrenia conducted by N. Nasrallah et al. (2004) [35]. It was shown that after 12 weeks of therapy with Consta at a dose of 25 mg, a statistically significant improvement in quality of life symptoms occurred in 7 of 8 domains of the social functioning scale (SF-36), while the improved indicators in most cases approached the norm, while the analysis of the effectiveness of Consta in general, without taking into account the dosages used, revealed improvements in only 5 domains. In an open-label clinical study of 166 patients suffering from schizophrenia and receiving long-term maintenance therapy with haloperidol decanoate, flupenthixol decanoate, fluphenazine decanoate and zuclopenthixol decanoate, it was shown that their transfer to const therapy was easily tolerated and not only did not lead to a temporary deterioration in the clinical condition, but often occurs when changing therapy, but is also accompanied by a statistically significant decrease in the total score on the PANSS scale, as well as an improvement in scores on the Clinical Global Impression (CGI) and ESRS scales [40, 41]. The benefit of transferring patients suffering from schizophrenia and schizoaffective disorder from traditional durable antipsychotics to Consta was shown in a multicenter open study conducted by R. Lasser et al. (2003) [26]. 725 patients with schizophrenia and schizoaffective disorder who were in a state of drug remission with mild or residual symptoms of the disease and receiving maintenance therapy with long-acting forms of traditional antipsychotics were transferred to constu. The dynamics of the patients' condition was assessed for 1 year using the PANSS and ESRS scales. In 25.9% of patients after transfer to Konsta at different periods of therapy, there was a statistically significant decrease in the severity of symptoms on the PANSS scale. Symptoms decreased by more than 20% in 52% of patients, by more than 40% in 34% of patients, and by more than 60% in 16% of patients. Analysis of the dynamics of syndromes using a 5-factor model of schizophrenia showed a significant improvement in the condition of patients according to 4 factors. The greatest reduction was observed in relation to negative symptoms, and there were no differences in relation to the factor “excitement, hostility”. The severity of extrapyramidal symptoms was low at the beginning of the study (an average of 4.9±4.2 points on the ESRS scale) and significantly decreased 3 months after the transfer of patients to constu on all subscales, and by the end of the study the average total score was 2.8± 3.4. The methodological value of the study is limited by the fact that it was not carried out by comparing two identical samples, but by sequentially transferring a single group of patients from one type of therapy to another. Therefore, spontaneous trends in the course of the disease towards the formation of remission could have a significant impact on the results obtained. A comparative assessment of the long-term (2-year) pharmacoeconomic effectiveness of Consta, olanzapine and fluphenazine decanoate was carried out in a Spanish study by E. Baca et al. (2004) [1] using the Markov decision tree model. Significant economic advantages of Consta compared to other drugs were discovered, realized due to high anti-relapse efficacy and lower total direct costs. Some other similar studies have shown that the pharmacoeconomic effectiveness of Consta is largely determined by a reduction in the duration of hospital treatment and less workload on medical personnel [16]. Conclusion Among all the atypical antipsychotics currently used in the world, only risperidone (Rispolept) so far has an approved pharmaceutical form of prolonged action, which in practical psychiatry is an undeniable advantage when choosing a drug for long-term treatment. Special pharmacokinetic studies confirmed the stability of the concentration of the drug in the blood plasma during therapy, subject to repeated injections every 2 weeks, showed the absence of the effect of accumulation in adipose tissue, and the safety of its use in elderly patients and in cases of compensated renal and liver failure. Randomized controlled studies with a high degree of evidence show that Konsta, with long-term use in patients with schizophrenia, statistically significantly reduces not only productive and negative symptoms, but also affects the cognitive sphere, including specific thinking disorders, as well as affective, affective-delusional symptoms disorders. The drug also has a clear anti-relapse effect, which increases as the duration of therapy increases, and in the event of exacerbations, it reduces their duration and severity. At the same time, the severity of extrapyramidal disorders during long-term therapy tends to decrease and when used at a dose of 25 mg is not statistically significantly different from placebo, and at doses of 50 and 75 mg it is 2 times higher than when using placebo. In terms of recommended dosages, it has been shown that at a dose of 25 mg every 2 weeks, the drug is the most clinically effective in terms of the risk/benefit ratio. At the same time, high antipsychotic efficacy is observed (in 45% of patients, a reduction in psychotic symptoms occurs by more than 20%), with a level of side effects comparable to placebo, which is accompanied by a significant improvement in the social functioning of patients. However, it should be noted that the interpretation of the results of most studies conducted is limited due to their design. There were no comparison drugs in double-blind, placebo-controlled studies and, despite the high degree of evidence of effectiveness, it is not possible to determine the comparative features of the effect of the consta. And the results of the effectiveness of the drug obtained in open, uncontrolled studies are influenced by a large number of nonspecific reasons. The assessment of various aspects of the development of remission, in particular its quality and stability, deserves special consideration. In this regard, global indicators such as social functioning and quality of life of patients are important. In schizophrenia, these parameters do not directly correlate with the severity of productive or negative symptoms; according to the literature, the phenomena of stable or increasing neurocognitive deficit, as well as the conditions of the microsocial environment, including the intensity of adequate psychocorrection and social rehabilitation measures, are of greater importance. Thus, the drug “Consta” - a prolonged form of risperidone, is certainly a new achievement of the modern stage of antipsychotic pharmacotherapy, since it combines the advantages of the second generation of antipsychotics (atypical antipsychotics) and durable forms of neuroleptics, which have proven themselves both in our country and and abroad for long-term treatment of patients with schizophrenia. The originality of the drug is also determined by its special dosage form (microspheres), new to clinical psychopharmacology, which introduces a number of qualitative differences into the spectrum of its action and method of application. All this largely makes Konsta a unique drug and allows us to hope for achieving a new quality in the treatment of patients with schizophrenia and other chronic psychoses that require long-term continuous psychopharmacotherapy. At the same time, the experience of using Consta in our country is still very limited, and the features of its clinical action, for example, in relation to individual syndromes and forms of schizophrenia in the long term remain not clear enough. In addition, it is necessary to conduct domestic pharmacoeconomic studies, since direct extrapolation of foreign data is difficult due to significant differences in the organization of psychiatric care.
“Question to the expert”: V.B. Dutov’s answers to questions about the Use of long-acting antipsychotics in the practice of outpatient psychiatric services
December 18, 2021, 11:50 Ivan Martynikhin
Dear colleagues,
In the ROP pro-Schizophrenia a section “ Question to an Expert ” has been opened, where everyone has the opportunity to directly ask questions regarding assistance to people with schizophrenia, leading domestic scientists and health care organizers. Today we are publishing answers to questions regarding the Use of long-acting injection antipsychotics in the practice of outpatient psychiatric services
Invited expert: Vladimir Borisovich Dutov – Candidate of Medical Sciences, chief physician of the St. Petersburg State Budgetary Institution “Psychoneurological Dispensary No. 1” (St. Petersburg), Associate Professor of the Department of Psychiatry and Narcology of Northwestern State Medical University named after I.I. Mechnikov. The institution headed by Vladimir Borisovich has accumulated extensive experience in the differentiated use of long-acting antipsychotics, both traditional and atypical.
Answers on questions
Question 1
Dear Vladimir Borisovich, based on your practice and the practice of your doctors, do you think that managing a patient on monotherapy with a long-acting antipsychotic helps to keep the patient in remission? And if not, what can you add? — Goremyko A.V., Moscow, PB No. 1
Answer:
Dear colleague! According to the literature, and in particular, according to the results of the PROSIPAL study, which involved 715 people, including 180 patients from many cities in Russia, it was shown that 85% of patients on Xeplion monotherapy did not have new exacerbations of schizophrenia for two years. Modern long-acting antipsychotic drugs suggest their use in the form of monotherapy, since they have a sufficient antipsychotic effect. Monotherapy is the most acceptable method, both from the point of view of the patient and from the point of view of the doctor, since the patient does not have the opinion that he is receiving a “hodgepodge of drugs”, and the doctor has a clear understanding of the essence of the treatment process, while compliance and confidence increase that the patient is actually receiving treatment.
In case of insufficient dosage of a long-acting antipsychotic, exacerbations are likely, and in this case it is possible to add tablet forms of the drug already used for a short time to therapy. For example, according to the experience of our doctors, with a standard dosage of Xeplion 75 mg once every 4 weeks, in case of exacerbation of existing chronic symptoms or the emergence of new phenomena, it is advisable to prescribe Invega followed by a transition to a higher dosage of Xeplion the next month. The combination of long-acting antipsychotic drugs with other drugs, such as oral antipsychotic drugs, is potentially possible, but is undesirable, since their combined use can lead to a significant increase in the risk of side effects, and data on the safety of their simultaneous use are limited.
In a situation where the proper antipsychotic effect from a long-acting antipsychotic drug is not observed, first of all, it is necessary to analyze whether the dosage of the drug prescribed to the patient is sufficient and, if necessary, increase the dosage of the drug on the day of the scheduled injection (up to this point it is permissible to increase the dosage of the drug by prescribing the same drug per os).
Thus, in our practice, we try to avoid simultaneous prescribing of two antipsychotic drugs to a patient, but combination with other groups is possible - tranquilizers, antidepressants, mood stabilizers. We believe that managing the patient on monotherapy with long-acting antipsychotics is sufficient to keep him in remission.
Question 2
What is the fate of piportil and imap? — Abdulkadyrov Abdulkadyr Omarovich, Khasavyurt, clinic
Answer:
Dear colleague! Today, piportil and imap are discontinued. Previously, these drugs were used mainly for inpatient treatment. At the same time, IMAP had a rather labor-intensive prescription regimen, and piportil had to be administered only in a glass syringe. Currently, they are almost completely ousted from the market by more modern antipsychotic drugs and we do not use them in our practice.
Question 3
Dear Vladimir Borisovich, please tell me, if my patient with schizophrenia receives several antipsychotics, how can he switch to injectable paliperidone in this case? Should we cancel everything and focus only on it or gradual cancellation? — Mikhail, St. Petersburg
Answer
Dear colleague! In this case, of course, it matters which antipsychotics we are talking about. In general, the instructions for using Xeplion detail the procedure for transferring from various antipsychotics. Thus, when switching from risperidone, the dose of the drug may be gradually reduced over one week due to the risk of withdrawal symptoms, such as insomnia. Our clinical experience and literature data have shown that the doses of olanzapine and quetiapine should be continuously reduced over 3-4 weeks, due to the risk of withdrawal symptoms accompanied by blocking of cholinergic, histaminergic and alpha-1-adrenergic receptors. When switching from aripiprazole and amisulpride, the first initiating injection of Xeplion is given the day after taking the last tablet. When transferring from Invega, standard initiation of Xeplion therapy is acceptable. The first injection of Xeplion is made the next day after taking the last Invega tablet. When transferring from Rispolept-Consta, usually immediately maintain a maintenance dose of Xeplion in a therapeutic dose corresponding to the previous dosage of Rispolept-Consta.
In any case, it is advisable to follow the instructions for use of medications. For patients who have never previously taken oral paliperidone, oral or injectable risperidone, tolerability with oral paliperidone or oral risperidone should be assessed before initiating treatment with Xeplion. At the beginning of treatment with Xeplion, previously used oral antipsychotic drugs, as mentioned above, can be gradually withdrawn, while the risk of developing so-called “rebound” psychoses must be taken into account, which necessitates the need to carefully monitor the patient’s current mental state. In our practice, transferring patients to injectable paliperidone therapy with gradual withdrawal of previous therapy takes on average about two weeks.
Question 4
Dear Vladimir Borisovich! My question is more about traditional long-acting antipsychotics. Using these drugs in your institution, are you trying to switch the patient from taking oral forms or are you more likely to use injections as an addition to therapy with tablet drugs? — Kuznetsov Sergey Alexandrovich, Rep. Komi, Komi Republican Psychiatric Hospital
Answer
Dear colleague! Oral forms are used in patients determined to take daily oral therapy. The dosage form of Xeplion, which allows it to be used once a month, unlike oral antipsychotics, provides confidence in patient compliance. This result is achieved due to regular visits to the doctor, improved adherence, a decent quality of life for the patient and due to the convenience of therapy, a decrease in the number of relapses and readmissions. In the vast majority of cases, monotherapy with an antipsychotic drug is the preferred choice in therapy and allows minimizing the possible risks of adverse events and treatment complications.
To date, combination therapy with antipsychotic drugs does not show a significant increase in effectiveness, but reliably leads to an increase in the number of complications from therapy. At our institution, we strive to follow current thinking and evidence-based approaches in the treatment of patients and avoid the combination of long-acting and oral antipsychotics in most cases. However, depending on the dynamics of the clinical picture, in some cases we add therapy with antidepressants or anxiolytics.
It is important to note that we make maximum use of atypical prolongations to form better and longer remissions in patients with dangerous tendencies, patients from the ADN and APLiN list. In this group of patients, the use of long-acting antipsychotics is a priority, which once again emphasizes the enormous importance of these drugs for outpatient practice.
Question 5
Dear Vladimir Borisovich, I heard that in St. Petersburg there is a practice of prescribing Xeplion in an acute condition in order to subsequently treat the patient on monotherapy. Tell me, is this true and how to act in this case from a practical point of view? What is the algorithm? — Andrey Feklistov, Moscow
Answer
Dear colleague! According to the instructions for medical use of the drug Xeplion, its use in acute psychomotor agitation or in a severe psychotic state, when immediate control of symptoms is necessary, is not recommended by the manufacturer and, obviously, the drug cannot be used in inpatient or, especially, outpatient practice. This is due to the fact that Xeplion, after injection into the deltoid muscle, reaches its peak therapeutic concentration only after 14 days, and into the gluteal muscle only after 13-17 days. Accordingly, it will not be possible to achieve a quick and complete effect to relieve acute symptoms. Moreover, the introduction of Xeplion without a sensitivity test is inappropriate. In such cases, it is possible to “cover” in the first stages of treatment with standard injectable neuroleptics and benzodiazepines. It is optimal to initiate Xeplion therapy at the stage of inpatient treatment with adjustment of therapy and reaching a mental state when further treatment with the drug can be continued in the form of monotherapy in selected dosages. Thus, the active use of atypical prolongs to an even greater extent implies interconnection and continuity in the work of inpatient and outpatient care. If it is necessary to treat long-acting injectable drugs in patients with mild to moderate psychotic states who have previously responded to therapy with oral forms of paliperidone or risperidone, Xeplion can be used without prior stabilization with oral drugs of this group, which can be successfully implemented in outpatient clinics. Our institution has such experience with the use of Xeplion in the intensive care unit for psychiatric care.
Question 6
Dear Vladimir Borisovich, how many patients are on long-acting antipsychotics? And is it only patients with schizophrenia? — Andrey Feklistov, Moscow
Answer
Dear colleague! If by long-acting antipsychotics you mean drugs such as Rispolept-Consta, Xeplion, Trevicta, then we are trying to provide these drugs to the maximum number of patients who meet the selection criteria. These are young age, social safety, ability to work, first psychotic episode and others. We can say with absolute certainty that the ability to prescribe long-acting atypical antipsychotic drugs is a revolutionary acquisition, primarily for outpatient psychiatric care. This is the most preferred and increasingly relevant type of drug therapy for patients. Moreover, recently we have been making our choice in favor of modern atypical long-acting antipsychotic drugs, as they are better tolerated, effective, safe and form the necessary compliance in partnerships with patients, creating the basis for overcoming stigmatization. The instructions state the indications as: treatment of schizophrenia and prevention of relapse of schizophrenia in adult patients. Treatment of schizoaffective disorders as monotherapy or as part of combination therapy with mood stabilizers and antidepressants in adult patients.
Indeed, these drugs are now widely used to treat schizophrenia and schizoaffective psychosis. We believe that one of the most effective areas for the use of atypical prolongs should be the early treatment of initial schizophrenic symptoms within the framework of the first episode clinic, when the use of such an expensive but highly effective drug is most economically justified. There are recommendations for their use in the case of affective psychoses, but in these situations the issue is resolved individually. In our institution, prolongs are actively used in the intensive psychiatric care unit, day hospital and rehabilitation department. In addition, some patients suffering from schizophrenia, schizoaffective and schizoform disorders receive extended periods of treatment in local psychiatric care as part of free additional drug provision. In this case, the number of patients receiving long-acting antipsychotics as part of additional drug provision is determined by the availability of drugs in pharmacies.
Question 7
How do primary patients without an official diagnosis of schizophrenia (for example, with F23) receive expensive extensions from you?
Answer
Dear colleague! In St. Petersburg, for a long time, there has been a register of patients provided with medicines at the expense of the constituent entities of the Federation. The inclusion of patients in the register is determined by regulations and includes a wide range of mental disorders from F20 to F29. The availability of the drug in pharmacies that provide preferential additional drug coverage, in turn, depends on the amount of funding. Although prescribing atypical long-acting antipsychotics specifically to patients diagnosed with “acute and transient mental disorder” (F 23) may not be very appropriate, because mental disorders of this spectrum require recovery within 2-3 months.
In addition, in St. Petersburg, in accordance with the Order of the Health Committee, the work of interdistrict medical commissions has been organized, which coordinate the prescription of expensive drugs, including Xeplion and Trevicta, based on the submitted medical documentation, the clinical picture and the presence of appropriate criteria for prescribing the drug.
Question 8
How to transfer a patient from Clopixol Depot to Xeplion? Because Xeplion has an activating effect, whether Klopixol tablets should be left together with Xeplion or canceled at the same time.
Answer
Dear colleague! As stated in the instructions, for patients who have never previously taken oral paliperidone and oral or injectable risperidone, a tolerability study with oral paliperidone or oral risperidone should be conducted before starting treatment with Xeplion. At the beginning of treatment with Xeplion, previously used orally administered antipsychotic drugs can be gradually withdrawn, while, as already mentioned, it is necessary to take into account the risk of developing so-called “rebound” psychoses, which necessitates the need to carefully monitor the patient’s current mental state.
If the patient receives long-acting injectable antipsychotics, treatment with Xeplion begins immediately with a maintenance dose at the time of the next scheduled injection. Treatment with Xeplion should be continued once a month.
Other features of the transition and administration of Xeplion for various patient transfer schemes should be carefully read in the instructions for the medical use of Xeplion. So, when transferring from clopixol depot to xeplion, as well as from other typical depot antipsychotics (haloperidol decanoate, fluphenazine decanoate, and flupenthixol decanoate), we try to use xeplion on the date of the planned depot injection in a maintenance dosage without the initiation of therapy stage. At the same time, we prefer to conduct a tolerability test a few days before the intended injection (when clopixol is still working) (for example, with the drug Invega). A tolerability test is necessary if the patient has not previously taken oral paliperidone or oral or injectable risperidone. If necessary, the patient continues to receive clopixol tablets for some time with a gradual reduction in dosage and subsequent discontinuation.
Question 9
To whom do you prescribe Xeplion, and to whom do you prescribe Rispolept consta? How do you divide such patients? By symptoms? This is also an atypical prolongation.
Answer
Dear colleague! If we compare Xeplion and Rispolept-Consta, the antipsychotic effect of both drugs is approximately the same (high affinity for serotonin 5-HT2 receptors and dopamine D2 receptors). It is known that Xeplion has a low affinity for histamine receptors and therefore the sedative effect is practically absent. In turn, rispolept-consta, on the contrary, has a higher affinity for histamine receptors, which causes a moderate sedative effect and an effect on affective symptoms. Xeplion has a positive effect on sleep disorders, so it is more acceptable in patients with depressive symptoms (an antidepressant effect has been described). In our clinical practice, we actually noted that Xeplion has a more pronounced antidepressant effect, while Rispolept-Consta may be preferable for manic symptoms.
Today, in most cases, the choice of a drug for maintenance therapy is determined by its effectiveness and ease of use both for the doctor and, of course, first of all, for the patient himself. Therefore, when choosing a drug, we give preference to Xeplion. In cases where the frequency of injections is not critical for the patient and the clinical picture allows, rispolept-consta is prescribed. Of course, it is necessary to take into account the economic component and storage capabilities (rispolept-consta requires low-temperature storage, as well as certain cooking conditions). In addition, when prescribing Rispolept-Consta or Xeplion, we take into account the patient’s adherence to a particular therapy, our real economic capabilities and the availability of the drug in pharmacies.
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