Leptinorm - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 95/190 mg, corn starch 52.5 / 105 mg, microcrystalline cellulose (Avicel pH 101) 33/66 mg, hypromellose-2910 (5 cps) 4/8 mg, sodium lauryl sulfate 2/4 mg, microcrystalline cellulose (Avicel pH 102) 10/20 mg, silicon dioxide colloid 0.5 / 1 mg, magnesium stearate 1/2 mg;

Sheath: hypromellose-2910 (5 cps) 0.855 / 1.71 mg, hypromellose-2910 (15 cps) 0,855 / 1,71 mg, propylene glycol 0,515 / 1,03 mg, gitanium dioxide 1,066 / 1,96 mg, talc purified 0,685 / 1,37 mg, dye orange-yellow S 0.024 / 0 mg, indigo carmine dye (E132) 0/0.058 mg, quinoline yellow dye (E104) 0 / 0.162 mg.

Description:

Tablets 2 mg: Light orange, biconvex tablet of oblong form, film-coated, with risk on one side.

Tablets 4 mg: A green, biconvex tablet of oblong form, covered with a film membrane, with a risk on one side.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.X Other antipsychotics

N.05.A.X.08 Risperidone

Pharmacodynamics:

Risperidone - selective monoaminergic antagonist, has a high affinity for serotonergic 5-HT₂ and dopaminergic D₂-receptors; is also associated with α₁-adrenergic receptors and, somewhat weaker, with H_1-histaminergic and α₂-adrenergic receptors.

Risperidone has no tropism for cholinergic receptors.

Antipsychotic action due to blockade D₂-dopaminergic receptors of mesolimbic and mesocortical system.

Risperidone reduces the productive symptoms of schizophrenia; causes less inhibition of motor activity and to a lesser degree induces catalepsy than classical antipsychotics.

Balanced central antagonism to serotonin and dopamine probably reduces the propensity to extrapyramidal side effects and expands the therapeutic effect of the drug to include negative and affective symptoms of schizophrenia.

Clinical data

Schizophrenia

The efficacy of risperidone in the short-term treatment of schizophrenia was demonstrated in four studies lasting 4 to 8 weeks, which included 2,500 patients meeting the criteria for schizophrenia according to the system DSM-IV. In a 6-week placebo-controlled study with a titration dose of 10 mg / day 2 times a day risperidone was superior to placebo on a brief psychiatric evaluation scale (BPRS). In a 6-week placebo-controlled study using risperidone in four fixed doses (2, 6, 10 and 16 mg / day, 2 times a day), in the 4th group risperidone was more effective than placebo in the scale of assessment of positive and negative syndromes (PANSS).In an 8-week comparative study of five fixed doses of risperidone (1, 4, 8, 12 and 16 mg / day, 2 times a day), risperidone in groups of 4, 8 and 16 mg / day was more effective than risperidone 1 mg / day on the PANSS scale. In a 4-week, comparative placebo-controlled study of two fixed doses of risperidone (4 and 8 mg / day, once daily), risperidone in both groups was more effective than placebo on several points of the PANSS scale.

Manic episodes with bipolar disorder

The efficacy of risperidone in monotherapy of acute manic episodes in type I bipolar disorder was demonstrated in three double-blind, placebo-controlled studies involving about 820 patients with type I bipolar disorder, according to the scale DSM-IV. In these studies risperidone in doses of 1-6 mg / day (initial dose of 3 mg in two studies and 2 mg in one study) was statistically superior to placebo at the primary endpoint, that is, by changing the score on the scales of the Yang's mania (YMRS) in 3 weeks but in comparison with the initial one. The results for the secondary endpoints of efficacy are generally consistent with the results at the primary endpoint. Percentage of patients with a decrease> 50% of the score on a scale YMRS 3 weeks compared with the baseline was significantly higher for risperidone than in the placebo group.

The efficacy of risperidone, in combination with mood controllers in the treatment of mania, was demonstrated in two three-week, double-blind studies in approximately 300 patients meeting the criteria for type I bipolar disorder DSM-IV. In a 3-week study risperidone in doses of 1-6 mg / day, the initial dose of 2 mg / day, in combination with lithium or valproate was more effective than monotherapy with lithium or valproate in the incense primary primary endpoint, that is, by changing the score on the scoring scale YMRS compared with the original in 3 weeks.

Risperidone also has a sedative, antiemetic and hypothermic effect. Sedative action is due to blockade of adrenoreceptors of the reticular formation of the brainstem; antiemetic effect - blockade of dopamine D₂receptors of the trigger zone of the vomiting center; hypothermic action - blockade of dopamine receptors of the hypothalamus.

Pharmacokinetics:

Suction. After ingestion risperidone completely absorbed, reaching the maximum concentrations in the plasma after 1-2 hours. Absolute oral bioavailability of risperidone is 70%.Food does not affect the absorption of the drug, so risperidone can be appointed regardless of the intake of food.

Distribution. Risperidone quickly distributed in the body. The volume of distribution is 1-2 l / kg. In the plasma risperidone binds to albumin and alpha₁acid glycoprotein. Risperidone is 90% bound by plasma proteins, 9-hydroxyrisperilone - by 77%.

Metabolism and excretion. Risperidone is metabolized by the isoenzyme CYP2D6 to 9-hydroxyrisperidone, which has a similar pharmacological effect. Risperidone and 9-hydroxyrisperidone constitute the active antipsychotic fraction. The CYP2D6 isozyme is susceptible to genetic polymorphism. Another way of metabolizing risperidone is N-dealkylation.

After ingestion risperidone is deduced with a half-life (T_1/2) about 3 hours. The half-life of 9-hydroxyrisperidone and the active antipsychotic fraction is 24 hours. A week after the application of the drug 70% of the dose is excreted by the kidneys, 14% - through the intestine. In the urine, the content of risperidone and 9-hydroxyrisperidone corresponds to 35-45% of the dose taken. The rest is made up of inactive metabolites.

Linearity. The concentration of risperidone in plasma is directly proportional to the dose taken in the therapeutic dose range.

Elderly patients and patients with hepatic and renal insufficiency

After a single dose of risperidone in elderly patients, the concentration of active antipsychotic fraction in plasma was on average 43% higher, the half-life lasted 38% longer, and the clearance decreased by 30%.

In patients with renal insufficiency, an increase in plasma concentration and a decrease in the clearance of the active antipsychotic fraction was observed on average by 60%.

In patients with hepatic insufficiency, the concentrations of risperidone in the plasma did not change, but the average concentration of the free fraction of risperidone increased by 35%.

Children

The pharmacokinetics of risperidone, 9-hydroxyrisperidone and the active antipsychotic fraction in children are comparable with the pharmacokinetics in adult patients.

Influence of sex, race and smoking

There is no effect of sex, race or smoking on the pharmacokinetics of risperidone or an active antipsychotic fraction.

Indications:

- Treatment of schizophrenia;

- treatment of manic episodes of moderate and severe severity,caused by bipolar disorder.

Contraindications:

- Hypersensitivity to risperidone or any other ingredient in the drug;

- Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

Carefully:

- Diseases of the cardiovascular system (chronic heart failure, suffered myocardial infarction, conduction disorders of the heart muscle);

- dehydration and hypovolemia; disorders of cerebral circulation;

- Parkinson's disease;

- convulsions and epilepsy (including in the anamnesis);

- severe renal or hepatic insufficiency (see section "Method of use and dose ");

- Drug abuse or drug dependence (see section "Method of administration and dose");

- conditions predisposing to the development of tachycardia such as "pirouette" (bradycardia, electrolyte imbalance, concomitant medication prolonging the QT interval);

- brain tumor, intestinal obstruction, cases of acute drug overdose, Reye's syndrome (the antiemetic effect of risperidone can mask the symptoms of these conditions):

- elderly patients with dementia;

- risk factors for thromboembolism of venous vessels;

- hyperglycemia;

- Pregnancy,

- disease of diffuse Levi bodies

- application in combination with furosemide.

Pregnancy and lactation:

There were no full-scale studies on the use of risperidone in pregnant women. In animal studies risperidone did not have teratogenic effect, but other types of toxic effects on the reproductive system were observed.

The potential risk to people is unknown. In the case of a woman taking antipsychotic drugs (including risperidone) in the third trimester of pregnancy, neonates have a risk of extrapyramidal disorders and / or withdrawal syndrome of varying severity. Symptoms that are characteristic of withdrawal may include agitation, hypertension, hypotension, tremor, drowsiness, respiratory disorders, and breastfeeding. Therefore, newborns whose mothers took risperidone in the third trimester of pregnancy, should be under careful medical supervision.

Leptinorm may be prescribed during pregnancy only in case of emergency, when the expected benefit of using the drug for a pregnant woman outweighs the potential risk to the fetus. If you need to stop taking the drug during pregnancy, you should cancel Pgradually.

In studies in animals risperidone and 9-hydroxyrisperidone penetrated into breast milk. It was also demonstrated that risperidone and 9-hydroxyrisperidone penetrate into human milk in small amounts.

Data on adverse events in infants who are breastfed are absent. Therefore, the issue of breastfeeding should be addressed in the light of the possible risk to the child. During the period of application of the drug, breastfeeding is not recommended.

Dosing and Administration:

Inside

Schizophrenia

Adults

Leptinorm can be given once or twice a day. The initial dose is 2 mg per day. On the second day, the dose can be increased to 4 mg per day. From this moment, the dose can either be kept at the same level, or individually correct if necessary.Usually the optimal dose is 4-6 mg per day. In some cases, a slower dose increase and lower initial and maintenance doses may be justified.

Doses above 10 mg per day did not show a higher efficacy compared with smaller doses and may cause extrapyramidal symptoms.

Due to the fact that safety of doses above 16 mg per day has not been studied, doses above this level can not be used.

Manic episodes associated with bipolar disorder

Adults

The recommended initial dose of the drug is 2 mg per day at one time. If necessary, this dose may be increased not less than 24 hours later on 1 mg per day. For most patients, the optimal dose is 1-6 mg per day.

The use of doses above 6 mg per day in patients with manic episodes has not been studied.

As with any other symptomatic therapy, the advisability of continuing treatment with Leptinorm should be regularly evaluated and confirmed.

Diseases of the liver and kidneys

In patients with kidney disease, the ability to excrete the active antipsychotic fraction is reduced compared to other patients.

In patients with liver disease, there is an increased concentration of free fraction of risperidone in the blood plasma.

The initial and maintenance dose in accordance with the indications should be reduced 2 times, increasing the dose in patients with liver and kidney disease should be slower. Leptinorm should be administered with caution in this category of patients.

Side effects:

The most frequently observed side effects (incidence ≥10%) were: parkinsonism, sedation / drowsiness, headache and insomnia.

Side effects are given with frequency distribution and systemic organ classes. According to the frequency of development, side effects were classified as follows: very often (≥1 / 10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10000, <1/1000), very rarely (<1/10000).

Infectious and parasitic diseases: often - pneumonia, bronchitis, upper respiratory tract infections, sinusitis, urinary tract infections, ear infections, influenza; infrequently - respiratory infections, cystitis, eye infections, tonsillitis, onychomycosis, viral infections, localized subcutaneous tissue infections, acrodermatitis.

Hematologic disorders and disorders of the lymphatic system: infrequently - neutropenia, a decrease in the number of leukocytes in the blood, thrombocytopenia, anemia, a decrease in hematocrit, an increase in the number of eosinophils in the blood; rarely - agranulocytosis.

From the immune system: infrequently - hypersensitivity; rarely anaphylactic reactionand.

From the endocrine system: often - hyperprolactinaemia¹, rarely - a violation of the secretion of antidiouric hormone, the detection of glucose in the urine.

Metabolic and nutritional disorders: often - weight gain, increased appetite, decreased appetite; infrequently - diabetes, hyperglycemia, polydipsia, weight loss, anorexia, increased cholesterol concentration in the blood; rarely - water intoxication, hypoglycemia; hyperinsulinemia, an increase in the concentration of triglycerides in the blood; very rarely diabetic ketoacidosis.

Mental disorders: very often insomnia²; often - sleep disorders, agitation, depression, anxiety; infrequently - mania, anxiety, confusion, decreased libido, nervousness; nightmarish dreams; lethargy, rarely - flattening of affect, anorgasmia.

From the nervous system: very often sedation / drowsiness, Parkinsonism², headache; often - akathisia², dystonia², dizziness, dyskinesia², tremor; infrequently - tardive dyskinesia, cerebral ischemia, lack of response to irritants, loss of consciousness, impaired consciousness, convulsions², fainting, psychomotor hyperactivity, imbalance, coordination disorder, postural dizziness, attention disturbance, dysarthria, taste sensations, taste distortion, kinesisia, paresthesia, rarely - malignant neuroleptic syndrome, cerebrovascular disorders, diabetic coma, head tremor.

Ophthalmic disorders: often - blurred vision, conjunctivitis; infrequent - photophobia, dry eyes, increased lacrimation, congestion hyperemia; rarely - glaucoma, involuntary sprains of eyeballs, crust formation on the edges of the eyelids, intraoperative syndrome of flabby (trembling) iris.

From the side of the ear and the labyrinth: infrequently - vertigo, noise in the ears, pain in the ear.

From the heart: often - tachycardia: infrequently - atrial fibrillation, atrioventricular block, conduction disorder of the heart, lengthening of the interval QT on the electrocardiogram (ECG), bradycardia, ECG deviations, palpitation; rarely - sinus arrhythmia;

From the side of the vessels: often - arterial hypertension; infrequently - lowering blood pressure, orthostatic hypotension, hot flashes; rarely - embolism pulmonary artery, deep vein thrombosis.

Respiratory, thoracic disorders and disorders of the mediastinum: often - shortness of breath, pain in the larynx and pharynx, cough; nosebleeds, nasal congestion; infrequently - aspiration pneumonia, congestion in the lungs, violation of the patency of the respiratory tract, wet wheezing, wheezing, dysphonia, respiratory failure; rarely - sleep apnea syndrome, hyperventilation.

From the gastrointestinal tract: often - abdominal pain, stomach discomfort, vomiting, nausea, constipation, diarrhea, indigestion, dry mouth, toothache; infrequently - incontinence, fecal matter, gastroenteritis, dysphagia, flatulence; rarely - pancreatitis, intestinal obstruction, edema of the tongue, cheilitis.

From the skin and subcutaneous tissues: often - a rash, erythema; infrequently urticaria, itching, alopecia, hyperkeratosis; eczema, dry skin, discoloration of skin, acne, acne, seborrheic dermatitis, skin damage; rarely - a drug rash, dandruff; very rarely - Quincke's edema.

From the osteomuscular system and connective tissue: often - muscle spasms, musculoskeletal pain, back pain, arthralgia; infrequently - an increase in the activity of creatine phosphokinase, violation of posture, stiffness in the joints, swelling of the joints, muscle weakness, pain in the neck; rarely rhabdomyolysis.

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

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

On the part of the reproductive system and mammary glands: infrequently - erectile dysfunction, ejaculation disorder, amenorrhea, menstrual cycle disorder², gynecomastia, galactorrhea, sexual dysfunction, chest pain, discomfort in the mammary glands, vaginal discharge; very rarely - priapism, menstrual cycle delay, breast enlargement, breast engorgement, discharge from the chest.

Common violations: often swelling², pyrexia, pain in the chest, asthenia, fatigue, pain; infrequently - edema of the face, influenza-like condition, fever, gait disturbance,thirst, discomfort in the chest, poor health, discomfort; rarely - hypothermia, lower body temperature, cold extremities, withdrawal syndrome, induration.

Hepatobiliary disorders: infrequently - an increase in the activity of transaminases, an increase in the activity of gamma glutamyltransferase, an increase in the activity of hepatic enzymes; rarely - jaundice.

Injuries, poisoning and complications of procedures: often - falling; infrequently - caused by the administration of the drug pain.

¹ - giperprolaktinemiya in some cases can lead to gynecomastia, menstrual disorders, amenorrhea and galactorrhea.

² - extrapyramidal disorders can manifest as: parkinsonism (hypersalivation, musculoskeletal stiffness, parkinsonism, drooling, rigidity of the "cogwheel" type, bradykinesia, hypokinesia, masculine face, muscle tension, akinesia, stiff neck, muscle rigidity, parkinsonian gait, glabellar reflex abnormalities, parkinsonian tremor disturbance) , akathisia (akathisia, anxiety, hyperkinesia and restless leg syndrome), tremor, dyskinesia (dyskinesia, muscle twitching, choreoathetosis, athetosis and myoclonus), dystonia.

The term "dystonia" includes dystonia, hypertension, torticollis, involuntary muscle contractions, muscle contracture, blepharospasm, eyeball movements, paralysis of the tongue, facial spasm, laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurototonus, spasm of tongue and trismus.

It should be noted that there is a wider range of symptoms that do not always have extrapyramidal origin.

The term "insomnia" includes: a sleep disorder, an intrasomnia disorder; the term "convulsions" includes a large seizure; "menstrual cycle disorder" includes an irregular menstrual cycle, oligomenorrhoea; "edema" include: generalized edema, peripheral edema, mild edema.

Class Effects

As with other antipsychotics, very rare cases of augmentation of the tooth QT were observed in the post-marketing period of observation.

Other class-effects from the cardiovascular system, observed with the use of antipsychotics, which increase the prong QT, include: ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest and bidirectional ventricular tachycardia.

Venous thromboembolism

Cases of venous thromboembolism, including pulmonary embolism and cases of deep vein thrombosis, were observed with the use of antipsychotic preparations (the frequency is unknown).

Weight gain

In placebo-controlled studies in patients with schizophrenia, an increase in body weight of at least 7% at 6-8 weeks was observed in 18% of patients taking risperidone, and in 9% of patients taking placebo. In placebo-controlled studies in adults with schizophrenia, an increase in body weight of at least 7% at 6-8 weeks was observed in 18% of patients taking risperidone, and in 9% of patients taking placebo. In placebo-controlled clinical trials in patients with manic episodes, the number of cases of weight gain of 7% or more after 3 weeks of treatment was comparable in the group receiving risperidone (2.5%), and in the placebo group (2.4%), while in the active control group there was slightly more (3.5%).

In children with behavioral disorders during long-term clinical trials, the body weight increased by an average of 7.3 kg after 12 months of therapy. The expected increase in body weight in children 5-12 years old with normal development is 3-5 kg per year.

From the age of 12-16, the increase in body weight should be 3-5 kg per year for girls and about 5 kg per year for boys.

Additional information about side effects in special groups

Side effects that have been observed more frequently in elderly patients with dementia and in children than in adult patients are described below:

Elderly patients with dementia

Transient ischemic attack, stroke; urinary tract infections, peripheral edema, lethargy and cough.

Children

In general, the types of adverse reactions in children are similar to those observed in adult patients.

The following side effects were noted in children (5 to 17 years) with a frequency> 5% and at a frequency at least 2 times higher than the frequency observed in clinical trials in adults: drowsiness / sedation, fatigue, headache, increased appetite, vomiting, upper respiratory tract infections, nasal congestion, abdominal pain, dizziness, cough, pyrexia, tremor, diarrhea, enuresis.

Overdose:

Symptoms: drowsiness, sedation, depression, tachycardia, reduction arterial pressure, extrapyramidal symptoms.There was an extension of the QT interval and convulsions. Bi-directional ventricular tachycardia was noted with the simultaneous administration of an increased dose of risperidone and paroxetine. In case of an overdose, the possibility of an overdose from taking several drugs should be analyzed.

Treatment: should achieve and maintain free airway to ensure adequate intake of oxygen and ventilation, make a lavage (after intubation, if the patient is unconscious) and appoint Activated carbon together with a laxative. Immediately begin monitoring the ECG to identify possible arrhythmias.

Specific antidote does not exist, appropriate symptomatic therapy should be conducted.

Reduction of blood pressure and collapse should be eliminated by intravenous fluid infusions and / or sympathomimetic drugs.

In the case of development of acute extrapyramidal symptoms, anticholinergic drugs should be prescribed.

Continuous medical surveillance and monitoring should continue until the symptoms of intoxication disappear.

Interaction:

As in the case of other antipsychotic drugs, caution should be exercised when using Leptinorm together with drugs that increase the interval QT, such as antiarrhythmic drugs (eg, quinidine, disopyramide, procainamide, propafenone, amiodarone, sotalol), tricyclic antidepressants (amitriptyline), tetracyclic antidepressants (maprotiline), some antihistamines, other antipsychotic drugs, some antimalarial drugs (quinine, mefloquine), and drugs that cause electrolyte disorders (hypokalemia, hypomagnesemia), bradycardia, or suppressing the hepatic metabolism of risperidone. This list is not exhaustive.

Influence of risperidone on other medications

Risperidone should be used with caution in combination with other drugs and substances of central action, especially with alcohol, opiates, antihistamines and benzodiazepines because of the increased risk of sedation.

Risperidone may reduce the effectiveness of levodopa and other dopamine receptor agonists.If simultaneous use is required, especially at the terminal stage of Parkinson's disease, the minimum effective dose of each drug should be used.

When risperidone was used together with antihypertensive drugs in the postmarketing period, a clinically significant decrease in blood pressure was observed.

Risperidone does not have a clinically significant effect on the pharmacokinetics of lithium, valproate, digoxin, or topiramate.

The effect of taking other drugs on the drug Leptinorm

When carbamazepine was used, a decrease in the concentration of the active antipsychotic fraction of risperidone in plasma was noted.

Similar effects can be observed with the use of other isoenzyme inducers CYP 3A4 and P-glycoprotein (eg, rifampicin, phenytoin, phenobarbital).

With the appointment and after the withdrawal of carbamazepine or other isoenzyme inducers CYP 3A4 / P-glycoprotein should adjust the dose of the drug Leptinorm.

Fluoxetine and paroxetine, inhibitors of isoenzyme CYP 2D6, increase the concentration of risperidone in plasma, but to a lesser extent the concentration of the active antipsychotic fraction.

It is expected that other isoenzyme inhibitors CYP 2D6, such as quinidine, can change the concentration of risperidone in plasma in the same way.

At the appointment and after the abolition of fluoxetine or paroxetine, the dose of Leptinorm should be adjusted.

Verapamil, isoenzyme inhibitor CYP3A4 and P-glycoprotein, increases the concentration of risperidone and plasma.

Galantamine and donepezil do not have a clinically significant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.

The phenothiazine derivatives, tricyclic antidepressants and some β-adrenoblockers may increase plasma concentrations of risperidone, but this does not affect the concentration of the active antipsychotic fraction.

Amitriptyline does not affect the pharmacokinetics of risperidone and the active antipsychotic fraction.

Cimetidine and ranitidine increase the bioavailability of risperidone, but have a minimal effect on the concentration of the active antipsychotic fraction.

Erythromycin, isoenzyme inhibitor CYP 3A4, does not affect the pharmacokinetics of risperidone and the active antipsychotic fraction.

The joint use of psychostimulants (eg, methylphenidate) and risperidone in children does not change the pharmacokinetic parameters andefficacy of risperidone.

Not It is recommended that risperidone together with paliperidone because paliperidone is an active metabolite of risperidone, and the use of this combination can lead to an increase in the concentration of the active antipsychotic fraction.

In the combined use of furosemide and oral forms of risperidone the risk of mortality increases in elderly patients with dementia (see "Special instructions").

Special instructions:

Transition from therapy with other antipsychotic drugs

When schizophrenia, at the beginning of the use of the drug Leptinorm recommended gradually to cancel the previous therapy, if it is clinically justified. If the patient is transferred from antipsychotic drug depot therapy, then the use of Leptinorm should be started instead of the next scheduled injection. Periodically, the need to continue current therapy with antiparkinsonian drugs should be evaluated.

Application the elderly patients with dementesthe

In elderly patients with dementia in the treatment of atypical antipsychotics, there is an increased mortality compared with placebo in studies of atypical antipsychotics, including risperidone. When using risperidone for a given population, the incidence of fatalities was 4.0% for patients taking risperidone, compared with 3.1% for placebo. The average age of the deceased patients is 86 years (range 67-100 years).

Application in combination with furosemide

In elderly patients with dementia, there was an increased mortality in patients taking furosemide in combination with risperidone (7.3%, mean age 89 years, range 75-97 years) compared with the group taking only risperidone (3.1%, average age 84 years, range 70-96 years) and a group that only took furosemide (4.1%, average age 80 years, range 67-90 years).

There are no pathophysiological mechanisms that explain this observation. Nevertheless, special care should be taken when prescribing the drug in such cases.

Increased mortality in patients taking both furosemide and risperidone, was observed in two of four clinical trials. There was no increase in mortality in patients taking other diuretics simultaneously (mainly thiazide diuretics used in low doses) together with risperidone.Regardless of treatment, dehydration is a common risk factor for mortality and should be carefully monitored in elderly patients with dementia.

Cerebrovascular disorders

In patients with dementia, at treatment with atypical antipsychotics, there was a significant (approximately 3-fold) increase in the risk of developing cerebrovascular unwanted reactions in randomized placebo-controlled clinical trials.

A generalized analysis of the results of six placebo-controlled studies of risperidone, mainly in elderly patients (over 65 years) with dementia, showed that cerebrovascular unwanted reactions (serious and non-serious, combined) occurred in 3.3% (33/1009) of patients who received risperidone and in 1.2% (8/712) of the patients receiving the placebo. The odds ratio is 2.96 (95% confidence interval). The mechanism of this increase in risk has not been studied. The possibility of an increased risk for other antipsychotics and other groups of patients can not be ruled out. Risperidone should be used with caution in patients with risk factors for stroke.

The risk of developing unwanted cerebrovascular reactions is significantly higher in patients with mixed or vascular dementia than in patients with Alzheimer's dementia. Therefore, patients with mixed or vascular dementia should not be prescribed risperidone.

It is necessary to assess the risks and therapeutic benefits of using risperidone in elderly patients with dementia, taking into account the prognostic risk factors for stroke in a particular patient. The patient and his environment should be warned about the need to report immediately the appearance of signs and symptoms of potential cerebrovascular unwanted reactions, such as sudden weakness or numbness in the face, upper and lower extremities, speech or vision impairment. In this case, all possible treatment options are urgently considered, including the abolition of risperidone. With persistent aggression in patients with Alzheimer's dementia risperidone appoint only for short-term use as an adjunct to non-pharmacological methods with their limited or ineffective, and if there is a risk of harm to the patient or third parties.

Need constant monitoring and evaluation of the patient's condition, as well as the rationale for continuing treatment with risperidone.

Orthostatic hypotension

In connection with α-adrenergic blocking action of risperidone may occur orthostatic hypotension, especially during the initial dose selection. Clinically significant reduction in blood pressure (BP) was observed with the combined use of risperidone with antihypertensive drugs. With a decrease in blood pressure, consideration should be given to reducing the dose.

Risperidone should be used with caution in patients with known cardiovascular diseases (heart failure, myocardial infarction, cardiac conduction disorder, dehydration, hypovolemia or cerebrovascular disorders) and the dose should be increased gradually according to the recommendations. It is recommended to evaluate the possibility of reducing the dose in the event of hypotension.

Leukopenia, neutropenia, agranulocytosis

Leukopenia, neutropenia and agranulocytosis were noted in the application of antipsychotic drugs, incl. when using risperidone.

Agranulocytosis was very rare during post-registration observations.

Patients with a clinically significant reduction in the number of leukocytes in the history or drug-dependent leukopenia / neutropenia recommended a complete blood test during the first months of therapy. It is necessary to determine the expediency of stopping therapy with Leptinorm at the first clinically significant decrease in the number of leukocytes in the absence of other factors that can lead to the development of leukopenia.

Patients with clinically significant neutropenia should be observed for fever or symptom onset of infection and begin treatment immediately if such symptoms are found.

Patients with severe neutropenia (absolute number of neutrophils less than 1 x 10⁹/ l) should stop using Leptinorm until the number of white blood cells is normalized.

Late dyskinesia / extrapyramidal disorders

Preparations with the properties of dopamine receptor antagonists, can cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, predominantly of the tongue and / or mimic muscles.There are reports that the occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. When signs and symptoms of tardive dyskinesia appear, consideration should be given to the abolition of all antipsychotics.

Malignant neuroleptic syndrome (CNS)

When a hazard is identifiedC, characterized by hyperthermia, muscle rigidity, instability of autonomic functions, impaired consciousness and increased activity of creatine phosphokinase (myoglobinuria (rhabdomyolysis) and acute renal failure may also occur), all antipsychotics, including Leptinorm, must be discontinued.

Parkinson's disease and dementia with Levi bodies

Care should be taken when prescribing antipsychotics, including Leptinorm, to patients with Parkinson's disease or dementia with Levy bodies. Risperidone can aggravate the course of Parkinson's disease. In both groups of patients, the risk of developing ZNC and increased sensitivity to antipsychotics (including extrapyramidic symptoms, as well as confusion, blunting of pain sensitivity, postural instability with frequent falls).

Hyperglycemia and diabetes mellitus

It has been reported that when using risperidone, hyperglycemia, the development of diabetes mellitus, or exacerbation of existing diabetes mellitus can occur. It is likely that the previous increase in body weight is also predisposing to this factor. It is very rare to have ketoacidosis and rarely - a diabetic coma. All patients need to be clinically monitored for the presence of symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia and weakness). Patients with diabetes should be monitored regularly for impaired glucose control.

Weight gain

In the treatment with risperidone, a significant increase in body weight can be observed. It is necessary to monitor the body weight of patients.

Dipeprolactinemia

Studies on tissue cultures have shown that the growth of tumor cells in the mammary gland can be stimulated by prolactin. Leptinorm should be used with caution in patients with hyperprolactinemia and in patients with prolactin-dependent tumors.

Interval lengthening QT

Interval lengthening QT very rarely observed in the postmarketing period.

As with other antipsychotics, caution should be exercised when prescribing Leptinorm for patients with known cardiovascular diseases, lengthening the interval QT in a family history, bradycardia or electrolyte imbalance (hypokalemia, gmyopomniaemia), as this may increase the risk of arrhythmogenic effect, and also when combined with drugs that increase the interval QT.

Threshold of convulsive activity

Caution should be used to prescribe the Leptinorm to patients with history of epilepsy or other medical conditions in which the threshold of seizure activity may be reduced.

Priapism

Drugs that have alpha-adrenoblocking properties, including Leptinorm, can cause priapism.

Regulation of body temperature

Antipsychotic drugs attributed to such an undesirable effect as a violation of the ability of the body to regulate the temperature. Care should be taken when prescribing Leptinorm for patients with conditions that may contribute to an increase in internal body temperature, which include intense physical load, dehydration, exposure to high external temperatures, or simultaneous use of drugs with anticholinergic activity.

Antiemetic effect

In preclinical studies, the antiemetic effect of risperidone was identified. This effect, in the case of people, can mask the objective and subjective symptoms of an overdose of certain drugs, as well as diseases such as intestinal obstruction, Reye's syndrome and brain tumors.

Venous thromboembolism

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

Intraoperative syndrome of trembling iris (ISDR)

The ISDR was observed during the operative intervention for the presence of cataract in patients receiving therapy with preparations having the activity of antagonists α₁adrenoreceptors.

ISDR increases the risk of complications associated with the organ of vision, during and after an operation. The physician conducting such an operation should be informed in advance that the patient has taken or is currently taking drugs that have α antagonist activity₁adrenoreceptors.

The potential benefit of the abolition of α₁-adrenoceptors before surgical intervention is not established, and should be evaluated taking into account the risks associated with the abolition of antipsychotic drugs.

Children and teens

Before prescribing Leptinorm for children or adolescents with mental retardation, it is necessary to carefully evaluate their condition for the presence of physical or social causes of aggressive behavior, such as pain or inadequate demands of the social environment. The sedative effect of risperidone should be carefully monitored in this population because of the possible effect on learning ability. The change in the time of risperidone intake can improve the control of the effect of sedation on the attention of adolescents and children.

Due to the possible impact of prolonged hyperprolactinemia on the growth and sexual development in children and adolescents, regular clinical evaluation of the hormonal status, including measurement of height, weight, monitoring of sexual development, menstrual cycle and other possible prolactin-dependent affects, should be carried out.

During treatment, there should be a regular check of the presence of extrapyramidal symptoms and other movement disorders.

Effect on the ability to drive transp. cf. and fur:

The leptinorm may have an effect on activities requiring increased concentration of attention and quick reaction. Patients should be advised not to drive the car and from work with the mechanisms to determine their individual sensitivity to the drug.

Form release / dosage:

Tablets, film-coated, 2 mg and 4 mg.

Packaging:

10 tablets in a blister of three-layer PVC / LDPE / PVDC film and aluminum foil.

2, 3 or 6 blisters in a cardboard box together with instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005080/09

Date of registration:26.06.2009 / 23.06.2010

Expiration Date:Unlimited

The owner of the registration certificate:Torrent Pharmaceuticals Co., Ltd.Torrent Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

TORRENT PHARMACEUTICALS, Ltd. India

Representation: & nbspTORRENT PHARMACEUTICALS LTD. TORRENT PHARMACEUTICALS LTD. India

Information update date: & nbsp05.03.2018

Illustrated instructions

Instructions

Leptinorm (Leptinorm)