Finlepsin retard pills with prolonged action 200mg N50
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Active ingredients
Carbamazepine
Release form
Pills
Composition
Active ingredient: Carbamazepine. Concentration of active ingredient (mg): 200 mg
Pharmacological effect
The antiepileptic drug (a dibenzazepine derivative), which also has an antidepressant, antipsychotic and antidiuretic effect, has an analgesic effect in patients with neuralgia. The mechanism of action is associated with the blockade of potential-dependent sodium channels, which leads to stabilization of the membrane of overexcited neurons, inhibition of the occurrence of serial discharges of neurons and a decrease in the synaptic conduction of impulses. It prevents the re-formation of Na + -dependent action potentials in depolarized neurons. It reduces the release of the excitatory neurotransmitter amino acid glutamate, increases the reduced convulsive threshold of the central nervous system and, thus, reduces the risk of developing an epileptic seizure. Increases the conductivity of K +, modulates voltage-dependent Ca2 + channels, which can also contribute to the anticonvulsant effect of the drug. Effective with focal (partial) epileptic seizures (simple and complex), accompanied or not accompanied by secondary generalization, with generalized tonic-clonic epileptic seizures, as well as with a combination of these types of seizures (usually ineffective with small attacks - petit mal, absans and myoclonic seizures ). In patients with epilepsy (especially in children and adolescents), a positive effect on the symptoms of anxiety and depression, as well as a decrease in irritability and aggressiveness, was noted. The effect on cognitive function and psychomotor performance depends on the dose. The onset of the anticonvulsant effect varies from several hours to several days (sometimes up to 1 month due to autoinduction of metabolism). With essential and secondary trigeminal neuralgia, carbamazepine in most cases prevents the occurrence of pain attacks. Pain relief in trigeminal neuralgia occurs after 8-72 hours. In alcohol withdrawal syndrome, the threshold for convulsive readiness, which in this state is usually reduced and reduces the severity of the clinical manifestations of the syndrome (irritability, tremor, gait disturbances). Antipsychotic (anti-manic) action develops after 7-10 days, may be due to inhibition of dopamine and noradrenaline metabolism.
Pharmacokinetics
Absorption - absorption is slow, but complete (food intake does not significantly affect the rate and extent of absorption). After a single dose of the tablet, Cmax is reached after 12 hours. The average Cmax value of the unchanged active substance after a single dose of carbamazepine at a dose of 400 mg is about 4.5 μg / ml. The time to reach Cmax is 4-5 hours. The distribution of Css of the drug in plasma is achieved in 1-2 weeks (the speed of achievement depends on the individual metabolism: autoinduction of the liver enzyme systems, heteroinduction by other, at the same time, drugs) drug and duration of treatment. Significant interindividual differences in Css values in the therapeutic range are observed: in most patients, these values range from 4 to 12 mcg / ml (17-50 mcmol / l). Concentrations of carbamazepine-10,11-epoxide (pharmacologically active metabolite) make up about 30% of the concentration of carbamazepine. Binding to plasma proteins in children - 55-59%, in adults - 70-80%. The apparent Vd is 0.8-1.9 l / kg. In the cerebrospinal fluid and saliva, concentrations are created in proportion to the amount of active substance not bound to proteins (20–30%). It penetrates the placental barrier. Concentration in breast milk is 25-60% of that in plasma. Metabolism Metabolized in the liver, mainly along the epoxy pathway with the formation of the main metabolites: active - carbamazepine-10.11-epoxide and inactive conjugate with glucuronic acid. The main isoenzyme providing biotransformation of carbamazepine to carbamazepine-10,11-epoxide is cytochrome P450 (CYP3A4). As a result of metabolic reactions, the inactive metabolite 9-hydroxy-methyl-10-carbamoyl acridane is also formed. May induce its own metabolism. The concentration of carbamazepine-10,11-epoxide is 30% of the concentration of carbamazepine. Excretion of T1 / 2 after administration of a single oral dose is 25-65 hours (average 36 hours), after repeated administration depending on the duration of treatment - 12-24 hours ( due to autoinduction of the liver monooxygenase system). In patients receiving additional other anticonvulsant drugs-inductors of the monooxygenase system (phenytoin, phenobarbital) T1 / 2 averages 9-10 hours.After a single dose of carbamazepine inside 72% of the dose taken is excreted in the urine and 28% in the feces. About 2% of the dose is excreted in the urine as unchanged carbamazepine, about 1% as a 10,11-epoxy metabolite. Pharmacokinetics in special clinical situations In children, due to accelerated elimination, it may be necessary to use relatively higher doses of the drug per kg of body weight compared to with adults. There is no data on changes in the pharmacokinetics of carbamazepine in elderly patients.
Indications
Epilepsy: partial seizures with elemental symptoms (focal seizures); partial seizures with complex symptoms (psychomotor seizures); large seizures, mainly focal genesis (large seizures during sleep, diffuse large seizures); mixed forms of epilepsy, trigeminal neuralgia, paroxysmal pain of an unknown cause arising from one side of the tongue, pharynx and soft palate (genuinous glossopharyngeal neuralgia), pain in peripheral nerve lesions in diabetes mellitus (pain in diabetic neuropathy); , as, for example, spasms of the facial muscles in trigeminal neuralgia, tonic convulsions, paroxysmal speech and movement disorders (paroxysmal dysarthria and ataxia), unpleasant sensations Nia (paroxysmal paresthesia), and episodes of pain, prevention of seizures during alcohol withdrawal syndrome, psychosis (mainly in manic-depressive states, hypochondriac depression). Secondary prevention of affective and schizoaffective psychosis. Preventive indication: to prevent the development of convulsive seizures with alcohol withdrawal syndrome finlepsin is used only in a hospital.
Contraindications
Finlepsin 200 retard is contraindicated for use in: presence of bone marrow damage, disturbances in the conduction of the heart (atrioventricular block), known hypersensitivity to the active substance, tricyclic antidepressant drugs or to one of the other components, as well as in acute intermittent porphyria (a certain hereditary in the exchange of porphyrins).Finlepsin 200 retard should not be used simultaneously with lithium preparations (see "Interactions with other drugs"). Since finlepsin 200 retard can provoke new or enhance existing special forms of seizures (so-called absans), it is not recommended to appoint it to patients suffering from these forms of seizures.
Precautionary measures
Do not exceed the recommended dose. With caution, the drug should be used for decompensated chronic heart failure, in violation of liver and / or kidney function, in elderly patients, in patients with chronic alcoholism (CNS depression increases, carbamazepine metabolism increases), in dilution hyponatremia (syndrome ADH hypersecretion, hypopituitarism, hypothyroidism, adrenal cortex insufficiency), with inhibition of bone marrow hematopoiesis on the background of medication (in history), with hyperplasia and prostate, increasing intraocular pressure; with simultaneous use with sedatives and hypnotic drugs.
Use during pregnancy and lactation
Women of reproductive age Finlepsin, whenever possible, is prescribed as monotherapy, in the minimum effective dose, since the frequency of congenital anomalies of newborns from mothers who took the combined antiepileptic treatment is higher than with monotherapy. When a pregnancy occurs, it is necessary to compare the expected benefit of therapy and possible complications, especially in the first trimester of pregnancy. It is known that children of mothers suffering from epilepsy are predisposed to disorders of fetal development, including malformations. Finlepsin can increase the risk of these disorders. There are isolated reports of cases of congenital diseases and malformations, including cleft vertebrae (spina bifida). Antiepileptic drugs increase folic acid deficiency, which is often observed during pregnancy, which may increase the frequency of birth defects in children, so before the planned pregnancy and during pregnancy, folic acid is recommended. In order to prevent hemorrhagic complications in the newborn, women in the last weeks of pregnancy , as well as newborns, it is recommended to prescribe vitamin K. Carbamazepine enters breast milk, so you should compare the benefits and Possible undesirable effects of breastfeeding in the context of ongoing therapy.With the continuation of breastfeeding in the background of taking Finlepsin should be monitored for the child in connection with the possibility of adverse reactions (eg, severe drowsiness, allergic skin reactions).
Dosage and administration
Without the specific instructions of your doctor for Finlepsin 200 retard, the following dosage regimens are valid. Please adhere to the doses prescribed by your doctor, because otherwise finlepsin 200 retard will not have a therapeutic effect! the nature and severity of the picture of the disease. The dose is then slowly increased until the most effective maintenance dose is reached. The optimal dose of the drug for the patient, especially with combination therapy, is determined by its level in the blood plasma. According to accumulated experience, the therapeutic concentration of Finlepsin 200 retard in the blood plasma is 4–12 mcg / ml. Replacing one antiepileptic agent with Finlepsin 200 retard should be performed gradually, reducing the dose of the previously used drug. Whenever possible, antiepileptic drugs are used only for monotherapy. Over the course of treatment, observation by a medical specialist is established. The generalized dose range is 400–1,200 mg of Finlepsin 200 retards per day, which are distributed to 1–2 single doses per day. Exceeding the total daily dose of 1200 mg does not make sense. The maximum daily dose should not exceed 1600 mg, since higher doses may contribute to an increase in the number of side effects. In some cases, the dose required for treatment may significantly deviate from the recommended initial and maintenance dose, for example, due to accelerated metabolism due to induction of microsomal liver enzymes or due to drug interactions in combination therapy. Unless specifically instructed by the physician, follow the following indicative scheme of drug use ta: Anticonvulsant treatment In general, in adults, the initial dose of 1–2 retard pills (corresponding to 200–400 mg of carbamazepine) is slowly increased to a maintenance dose,equal to 4–6 retard pills (corresponding to 800– 1,200 mg of carbamazepine). In general, the maintenance dose of carbamazepine for children averages 10–20 mg / kg of body weight per day. The following dosing regimen is recommended. 200–300 mg are prescribed in the morning / evening in the evening, 200–600 mg, 400–600 mg 200–400 mg. 400–600 mg.TableFor children under 6 years of age, a table is available for initial and supportive treatment. etki not prolonged action. Due to the lack of experience gained with retard pills, they are not recommended for children at this age. Preventing the development of convulsive seizures during alcohol withdrawal syndrome in hospital conditions The average daily dose is 1 retard tablet in the morning, 2 retard pills are prescribed in the evening (corresponding to 600 mg of carbamazepine) . In severe cases, in the first days, the dose can be increased to 3 retard pills 2 times a day (corresponding to 1200 mg of carbamazepine). Finlepsin 200 retard should not be combined with sedative-hypnotic drugs. In accordance with the clinical requirements, however, if necessary, Finlepsin 200 retard can be combined with other substances used to treat alcohol withdrawal. During treatment, Finlepsin 200 retard should be regularly monitored in the blood plasma. Due to the development of side effects from the central and autonomic nervous system (see the phenomena of alcohol withdrawal in the section "Side effects") for patients establish a careful clinical observation. The trigeminal nerve neuralgia, genoa This glossopharyngeal neuralgia. The initial dose is 1–2 retard pills (corresponding to 200–400 mg of carbamazepine), which, up to complete disappearance of pain, increases by 2–4 retard pills (corresponding to 400–800 mg of carbamazepine), which are divided into 1–2 single doses per day. After that, in a certain part of the patients, treatment can be continued with a lower maintenance dose, which can prevent pain attacks of 1 retard tablet 2 times a day (equivalent to 400 mg of carbamazepine). In older and sensitive patients, finlepsin 200 retard is prescribed in the initial dose, component of 1 tablet retard 1 time per day (corresponds to 200 mg of carbamazepine). Pain in diabetic neuropathy The average daily dose is 1 tablet retard in the morning and 2 pills retard in the evening (corresponds to 600 mg carbama Yeping).In exceptional cases, Finlepsin 200 retard can be administered at a dose of 3 retard pills 2 times a day (corresponding to 1200 mg of carbamazepine). Epileptiform convulsions in multiple sclerosis. The average daily dose is 1-2 pills of retard 2 times a day (corresponding to 400-800 mg of carbamazepine) Treatment and prevention of psychosis. The initial dose, which, as a rule, is also sufficient as a maintenance dose, is 1–2 retard pills per day (corresponding to 200–400 mg of carbamazepine). If necessary, this dose can be increased to 2 retard pills 2 times a day (corresponding to 800 mg of carbamazepine). Indication Patients with severe cardiovascular diseases, liver and kidney damage, and older people are prescribed lower doses of the drug. take finlepsin 200 retard Tablets retard are provided with a dividing groove, they are taken during or after a meal, drinking a sufficient amount of liquid (for example, a glass of water). Tablets retard can be taken after prior disintegration and them in water (in suspension). The prolonged effect is maintained even after the disintegration of the tablet in water. In some cases, the distribution of a daily dose of 4–5 single doses per day has proved to be particularly effective. For this, the drug form of a non-prolonged action is best suited. How long you should take Finlepsin 200 retard The duration of use depends on the indication and the patient's individual response to the drug. The treatment of epilepsy takes a long time. A specialist doctor should decide on the transfer of the patient to Finlepsin 200 retards, the duration of use and the abolition of it in each individual case. In general, the dose of the medication can be tried to lower or completely stop the treatment no earlier than after a 2-3-year absence of seizures. The treatment is stopped by gradually lowering the dose of the drug for 1-2 years. In this case, children should take into account the increase in body weight. At the same time, the EEG indices should not deteriorate. When treating neuralgia, it was helpful to prescribe Finlepsin 200 retard in a maintenance dose, which is just enough to relieve pain, for several weeks. By carefully lowering the dose, it is necessary to ascertain whether spontaneous remission of the symptoms of the disease has occurred.With the resumption of painful attacks, treatment is continued with the same maintenance dose. The duration of treatment for pain in diabetic neuropathy and epileptiform seizures in multiple sclerosis is the same as in neuralgia. Prevention of manic-depressive phases is carried out for a long time.
Side effects
Observed side effects occurred more often with combined treatment than with monotherapy. Depending on the dose and mainly at the beginning of treatment, the following side effects may occur: Central nervous system / Mind Often there can be stupor of consciousness, dizziness of consciousness (drowsiness), dizziness, fatigue, disturbance of gait and movements (cerebellar ataxia) and headaches. Elderly patients may develop confusion and anxiety. In isolated cases, depressive mood, aggressive behavior, thought block, impoverishment, and perception disorders (hallucinations) and tinnitus are observed. When treating finlepsin 200 retard, latent psychosis can be activated. Rarely, involuntary movements, such as large-scale tremor, muscle contraction or twitching of the eyeball (nystagmus), can occur. In addition, in elderly patients and with brain lesions, disorders of coordinated motor acts may occur, such as involuntary movements in the rotary area in the form of grimaces (rotous dyskinesias), rotational movements (choreaathetosis). Individual cases of speech disorders, false sensations, muscle weakness, nerve inflammation (peripheral neuritis), as well as manifestations of paralysis of the lower limbs (paresis) and taste perception disorders have been reported. Most of these phenomena disappear by themselves after 8-14 days or after a temporary decrease doses. Therefore, if possible, finlepsin 200 retard is dosed out carefully, starting treatment with low doses, then gradually increasing them. Eyes In some cases, inflammation of the connective membrane of the eye (conjunctivitis), sometimes transient visual disturbances (disturbance of the eye, double vision, blurred vision) occurred.Cases of lens opacification have been reported. In patients with glaucoma, intraocular pressure should be measured regularly. Motor system In rare cases, pains in the joints and muscles (arthralgia, myalgia), and muscle spasms were observed. These phenomena disappeared after discontinuation of the medication. Skin and mucous membranesHereted cases of allergic skin reactions with or without fever, such as rare or frequent urticaria (urticaria), pruritus, sometimes coarse plate or scaly skin inflammation (exfoliative dermatitis, erythromus) , necrosis of superficial areas of the skin with blistering (Lyell’s syndrome), photosensitivity (photosensitization), reddening of the skin with polymorphic rashes in the form of spots and formation of nodes, with hemorrhages ( conjunctival erythema multiforme, erythema nodosum, Stevens-Johnson syndrome), petechial hemorrhages in the skin and lupus erythematosus (disseminated lupus erythematosus). In rare or rare cases, hair loss (alopecia) and sweating (diaphoresis) and circulatory lymphatic system have been observed. hypersensitivity in the treatment with Finlepsin 200 retard, in addition, the following blood picture disorders can occur: rarely or often an increase (leukocytosis, eosinophilia) or a decrease (leukopenia) in the number of leukocytes comrade, or platelets (thrombocytopenia) in the peripheral blood. According to the literature, the benign form of leukopenia most often appears (about 10% of cases are transient, and 2% of cases persistent). Isolated cases of blood diseases, sometimes even life-threatening patients like agranulocytosis, aplastic anemia, along with other forms of anemia (hemolytic , megaloblastic), as well as an enlarged spleen and lymph nodes. When leukopenia (most often neutropenia), thrombocytopenia, allergic rashes on the skin (exanthema) and retlapsin fever, cancel yut.Gastrointestinal tractIn some cases, loss of appetite, dry mouth, nausea and vomiting, rarely diarrhea or constipation. It was reported on isolated cases of abdominal pain and inflammation of the mucous membranes of the oropharyngeal cavity (stomatitis, gingivitis, glossitis).These phenomena disappear on their own after 8–14 days of treatment or after a temporary decrease in the dose of the drug. They can be avoided by the initial administration of low doses of the drug with their gradual increase. There are indications in the literature that carbamazepine can sometimes cause inflammation of the pancreas (pancreatitis). Liver and bile Sometimes changes in the performance of liver function tests are detected, in rare cases jaundice appears in isolated cases There are different forms of hepatitis (cholestatic, hepatocellular, granulomatous, mixed). Two cases of acute intermittent porphyria have been described. Hormonal, water and left exchangeHas been reported on individual cases of breast enlargement in men (gynecomastia) and spontaneous outflow of milk from the mammary glands in women (galactorrhea). Finlepsin 200 retard can affect thyroid function parameters (triiodothyronine, thyroxin, thyroid-stimulating hormone and free thyroxin), especially combining it with other antiepileptic drugs. Due to the effects of finlepsin 200 retard, which reduces the excretion of urine from the body (antidiuretic effect), a decrease can occur in rare cases sodium content in serum (hyponatremia), accompanied by vomiting, headache and confusion. There have been isolated cases of edema and weight gain. Finlepsin 200 retard can lower serum calcium levels. In isolated cases, this leads to a softening of the bones (osteomalacia). Respiratory disorders. Individual cases of hypersensitivity of the lungs to the drug, accompanied by fever, shortness of breath (dyspnea), pneumonia and pulmonary fibrosis, are described. (proteinuria), the appearance of blood in the urine (hematuria), reduced urine excretion (oliguria), in isolated cases, they develop up to kidney failure. Perhaps these disorders are due to its own antidiuretic effect of the drug substance. Sometimes there is dysuria, pollakiuria and urinary retention. In addition, there are cases of sexual disorders, such asimpotence and decreased sexual desire. Cardiovascular system In rare or isolated cases, mainly in the elderly or in patients with known cardiac dysfunction, reduced heart rate (bradycardia), cardiac arrhythmias, and worsening of coronary heart disease may occur. Rarely observed violations of the excitation in the heart (atrioventricular block), in isolated cases accompanied by syncope. In addition, in some cases, blood pressure is greatly reduced or increased. The fall in blood pressure mainly occurs when using the drug in high doses. In addition, vasculitis, thrombophlebitis and thromboembolism were observed. Hypersensitivity reactionsRedko develop slowed hypersensitivity reactions to the drug, occurring with fever, skin rash, inflammation of blood vessels, lymphadenopathy, pain in joints, altered number of leukocytes in peripheral blood, enlarged liver and spleen, changes in liver function tests, which can occur in different combinations, and also involve other organs in the process, such as the lungs, kidneys, pancreas, and myocardium. In rare cases, there was an acute generalized reaction and aseptic inflammation of the meninges with myoclonias and eosinophilia. If you notice any side effects that are not mentioned in this annotation, then please inform your doctor or pharmacist about this.
Overdose
Symptoms: usually reflect violations of the central nervous system, cardiovascular and respiratory systems. On the side of the central nervous system and sensory organs: depression of the central nervous system, disorientation, drowsiness, agitation, hallucinations, coma, blurred vision, slurred speech, dysarthria, nystagmus, ataxia, dyskinesia , hyperreflexia (at the beginning), hyporeflexia (later), convulsions, psychomotor disorders, myoclonus, hypothermia, mydriasis. From the cardiovascular system: tachycardia, decrease in blood pressure, sometimes - increase in blood pressure, violations of intraventricular conduction with advanced rhenium complex QRS, syncope, cardiac serdtsa.So respiratory system: respiratory depression, edema legkih.So the digestive system: nausea and vomiting,delayed evacuation of food from the stomach, decreased motility of the colon. From the urinary system: urinary retention, oliguria or anuria, fluid retention, hyponatremia. . Treatment: no specific antidote. Symptomatic supportive treatment in the ICU, monitoring of heart functions, body temperature, corneal reflexes, kidney and bladder functions, correction of electrolyte disorders are needed. It is necessary to determine the concentration of carbamazepine in the plasma to confirm the poisoning by this agent and assess the degree of overdose, gastric lavage, the appointment of activated carbon. Late evacuation of gastric contents can lead to delayed absorption on days 2 and 3 and the recurrence of symptoms of intoxication during the recovery period. Forced diuresis, hemodialysis, and peritoneal dialysis are ineffective, but dialysis is indicated with a combination of severe poisoning and renal failure. Young children may need blood transfusions.
Interaction with other drugs
The simultaneous appointment of carbamazepine with CYP3A4 inhibitors may lead to an increase in its concentration in the blood plasma and the development of adverse reactions. The combined use of CYP3A4 inducers can lead to an acceleration of the metabolism of carbamazepine, a decrease in its concentration in the blood plasma and a decrease in the therapeutic effect; on the contrary, their cancellation may decrease the rate of biotransformation of carbamazepine and lead to an increase in its concentration. Increase the concentration of carbamazepine in plasma: verapamil, diltiazem, felodipine, dextropropoxyphene, viloxazine, fluoxetine, fluvoxamine, cimetidine, acetazolamide, zanazol, zaazol, zooper, zolazazine, fluoxetine, fluvoxamine, cimetidine, acelazamide, felodipine, dextropropoxyphene in high doses), macrolides (erythromycin, josamycin, clarithromycin, troleandomycin), azoles (itraconazole, ketoconazole, fluconazole), terfenadine, loratadine, isoniazid, propoxyphene, grapefruit juice, inhibitors virus proteases used in the treatment of HIV infection (for example, ritonavir) - correction of the dosage regimen or monitoring plasma carbamazepine concentration is required. Phelbamate decreases plasma carbamazepine concentration and increases carbamazepine-10,11-epoxide concentration, while serum felbamate. The concentration of carbamazepine is reduced by phenobarbital,phenyinum plasma proteins and an increase in the concentration of the pharmacologically active metabolite (carbamazepine-10,11-epoxide). When combined with Finlepsin and valproic acid, coma or confusion may occur in exceptional cases. Isotretinoin alters the bioavailability and / or clearance of carbamazepine and carbamazepine-10,11-epoxide (plasma concentration of carbamazepine is necessary). Carbamazepine may decrease plasma concentration. or even completely neutralize the effects), which may require dose adjustment for the following drugs: clobazam, clonazepam, digoxin ethosuximide, primidone, valproic acid, alprazolam, GCS (prednisolone, dexamethasone), cyclosporine, teteracyclines (doxycycline), haloperidol, methadone, oral medications containing estrogens and / or progesterone (selection of alternative methods of contraception is necessary), theophylline, oral anticoagulants (warfarin, phenoprocone, Ioophoxone, anesthetic agents (warfarin, fenprocone, anesthesia), theophylline, oral anticoagulants (warfarin, phenoprocone, and non-essential drugs (warfarin, phenfumone, anesthesia), theophylline, oral anticoagulants (warfarin, phenoprocone, and non-essential anti-inflammatory drugs (warfarin, phenfumone, anesthesia) , tricyclic antidepressants (imipramine, amitriptyline, nortriptyline, clomipramine), clozapine, felbamate, tiagabine, oxcarbazepine, protease inhibitors used in the treatment of HIV infection (indinavira, rit onavira, saquinavir), calcium channel blockers (a group of dihydropyridine, such as felodipine), cit, itraconazole, levothyroxine, midazolam, olanzapine, lymphocyte, risperidone, cit, tramadol, ziprasidone. With simultaneous use of carbamazepine and lithium preparations, the neurotoxic effects of both active substances can be enhanced. Tetracyclines can weaken the therapeutic effect of carbamazepine. topically with paracetamol increases risk of toxic effects on the liver and decreases the therapeutic efficacy (acceleration of metabolism of paracetamol) .Odnovremennoe assignment carbamazepine phenothiazine, pimozide, thioxanthenes, molindone, haloperidol, maprotiline,Clozapine and tricyclic antidepressants increase the inhibitory effect on the central nervous system and weaken the anticonvulsant effect of carbamazepine. MAO inhibitors increase the risk of hyperpiretic crises, hypertensive crises, seizures, and death (MAO inhibitors should be canceled, however, should be canceled; or, if the clinical situation allows, even for a longer period). Simultaneous administration with diuretics (hydrochlorothiazide, furosemide) may result to hyponatremia, accompanied by clinical manifestations. Relaxes the effects of non-depolarizing muscle relaxants (pancuronium). In the case of such a combination, it may be necessary to increase the dose of muscle relaxants, and careful monitoring of the patient’s condition is necessary due to the possibility of a more rapid cessation of the action of muscle relaxants. Carbamazepine reduces ethanol tolerance. Myelotoxic drugs increase the manifestation of the drug’s hematotoxicity. , folic acid, praziquantel, can y