Nantarid

Nantaride is an effective antipsychotic drug.

Indications of the nantarida

Indicated when:

• schizophrenia;
• manic attacks of moderate or severe nature, which develop as a result of bipolar disorders.

Release form

Produced in tablets. The volume of 25 mg - 10 pieces per blister; Within a single pack contains 3 blister plates. The volume of 100 mg - 10 pieces per blister; inside of one package 3 or 6 blister plates. The volume of 200 mg - 10 pieces on the blister; in a separate box contains 6 blister plates. The volume of 300 mg - 10 tablets inside the blister plate; in one bundle - 6 blisters.

Pharmacodynamics

Quetiapine has an atypical profile, which is slightly different from the profile inherent in standard antipsychotics. In case of prolonged use, the substance does not cause hypersensitivity to the dopamine (D2) receptor. Dosages that can block the conductor D2, can provoke only a weak intensity of catalepsy.

With constant intake, the drug has a selective effect on the limbic structure, because it contributes to the depolarization of inhibition processes within mesolimbic neurons (but not inside neurons that contain nigrostrial dopamine). The active substance only provokes negative extrapyramidal motor manifestations in minimal amounts and, most likely, is not able to cause the development of the late stage of dyskinesia.

In vitro tests have shown that the processes of quetiapine metabolism through hemoprotein 450 are carried out using the SURCA4 enzyme. It turned out that the active substance with its decomposition products to a small extent blocks the action of hemoprotein P450 1A2, as well as 2C9 with 2C19 and 2D6 with 3A4. But this can happen only at a concentration that can occur when a dose is injected, no less than 10-20 times higher than the standard daily (ie, 300-450 mg).

The information obtained from in vitro tests shows that the possibility of a noticeable blockage by the active substance of drugs dependent on the hemoprotein P450 and used in combination with quetiapine is extremely unlikely. The experiments demonstrate that the active ingredient is able to induce the activity of microsomal enzymes that are part of the hemoprotein 450 structure. At the same time, no specific activity of the hemoprotein 450 (induced by quetiapine) was observed in the specific drug interaction tests conducted in persons with psychosis.

Pharmacokinetics

When administered orally, quetiapine is well absorbed and metabolized internally. The main decay products found inside the plasma do not have a noticeable pharmacological effect. The combination with food does not affect the level of bioavailability of the substance. Half-life is approximately 7 hours. About 83% of the component is synthesized with a plasma protein.

Pharmacokinetic properties of drugs are linear and do not differ depending on gender. The average value of clearance in people with a disorder in the kidneys (in a severe degree - QC <30 ml / minute / 1.7Zm ² ) is reduced by 25%, although the individual clearance level continues to be in the range that is characteristic of healthy kidney work.

A significant part of quetiapine passes the metabolism inside the liver. When an ingredient labeled with a radionuclide is injected, less than 5% is excreted unchanged together with feces and urine. About 73% of the radioactive element is excreted in the urine, and the remaining 21% - with feces.

In persons with disorders in the work of the liver (with a stable stage of hepatic cirrhosis), the average value of the clearance of quetiapine substance is reduced by 25%. Because this component is mainly metabolized inside the liver, people with problems in the work of this body should increase its plasma performance. As a consequence, dosage adjustment in such patients may need to be adjusted.

Dosing and administration

The drug should be taken orally - in the amount of 1 tablet twice a day with food or whatever food.

For schizophrenia, during the first 4 days of the course, it is necessary to drink 50 mg of LS on the first day, 100 mg of the drug on the second day, 200 mg on the third day, and 300 mg on the fourth day. Further, the desired daily dosage is set in the range of 300-450 mg. In relation to the effectiveness of drugs and its tolerance to the patient, the daily dose can be adjusted in the range of 150-750 mg. At a schizophrenia for a day it is possible to accept no more than 750 mg of a medicine.

When eliminating manic attacks developing against bipolar disorders - during the first 4 days the daily dose amounts to - 100 mg (day 1), 200 mg (day 2), 300 mg (day 3) and 400 mg (4 th day). Further, on day 6, it is allowed to increase the daily dose to 800 mg. Increasing the dosage should be gradual - you can not increase it by more than 200 mg per day.

In accordance with the drug effect and the tolerability of drugs, the daily dose can vary between 200-800 mg. Often the most effective dosage is 400-800 mg per day. During the treatment of manic attacks, it is allowed to take no more than 800 mg per day.

[2]

Use of the nantarida during pregnancy

There is no information on the efficacy and safety of drug use in pregnant women.

In pregnancy, tablets can be used only in cases where the possible benefits for a woman exceed the probability of manifestations of fetal side effects. It is necessary to bear in mind that in newborns, whose mothers were administered quetiapine, there was a development of withdrawal syndrome.

It is not known in what quantities the active substance is excreted in breast milk. Because of this, it is recommended to abolish breastfeeding while using the medication.

Contraindications

Among the contraindications of drugs:

• hypersensitivity to the active component or other additional elements of the drug;
• combined use with the following inhibitors of hemoprotein 450 SA4: HIV proteases, antimycotic drugs, nefazodone, clarithromycin with erythromycin, and azole derivatives;
• because there has been no research into the safety and effectiveness of the use of tablets in children, Nantarid is not prescribed for this group of patients.

Side effects of the nantarida

As a result of taking the medicine, the following side effects may occur:

• manifestations affecting lymph and hematopoietic system: the most common symptom is leukopenia. Occasionally eosinophilia develops, and in rare cases - neutropenia;
• organs of the immune system: often there is increased sensitivity;
• pathological manifestations affecting the food system and metabolism: single diabetes mellitus or hyperglycemia develops;
• organs of the National Assembly: often there are headaches, a feeling of drowsiness and dizziness. The development of syncope is also very common. Occasionally, epileptic seizures occur. A late form of dyskinesia develops;
• organs CAS: most often develops tachycardia. There are also reports of lengthening the QT interval, arrhythmia of the ventricles, and also about a sudden unexplained lethal outcome, as well as heart failure along with polymorphic ventricular tachycardia (the so-called Torsade de Pointes), which are associated with the use of neuroleptics and are specific for this category of drugs ; besides this, an orthostatic collapse occurs;
• respiratory system: common development of the common cold;
• organs of the digestive tract: the development of constipation and dyspeptic manifestations, as well as the dryness of the oral mucosa;
• bile duct and liver: occasionally jaundice occurs. Single - develops hepatitis;
• subcutaneous layer and skin: Quincke edema or Stevens-Johnson syndrome develops singly;
• breast and reproductive organs: priapism is occasionally observed;
• general disorders: often there may be a slight form of asthenia or peripheral puffiness. Occasionally, the malignant form of neuroleptic syndrome develops;
• data of diagnostic as well as laboratory tests: often increased plasma values of transaminases (AST with ALT) and weight gain. Sometimes it is possible to increase the GGT, total cholesterol, and in addition to triglycerides (in fasting state).

[1]

Overdose

There is only limited information about drug overdose. There are reports of individuals receiving up to 20 g of drugs, but in such cases there was no information about the death. Recovery also occurred without the development of complications. Extremely rare are cases of death, prolongation of the QT-interval, as well as coma.

Typically, patients develop drowsiness, tachycardia, sedation, as well as a decrease in the level of blood pressure - these manifestations arise because of the increased pharmacological properties of drugs.

Quetiapine does not have a specific antidote. With the development of severe poisoning, it is required to consider the option of combining several separate drugs, as well as performing urgent intensive therapy. It is necessary to ensure free access of air to the lungs (to release the airways), and in addition the required pulmonary ventilation with oxygenation. At the same time, continuous monitoring of the CAS operation and supportive therapy with the use of medications are necessary. Continuous monitoring with medical supervision should be carried out until the patient fully recover.

Interactions with other drugs

Because the active drug component has a primary effect on the central nervous system, it is necessary to carefully combine it with other drugs that are effective for this system. It is also necessary to refrain from drinking alcohol.

Combined medication with liver enzyme inducers (eg, carbamazepine) can significantly reduce the systemic effects of quetiapine.

It is necessary to use with particular attention the use of drugs that extend the QT interval (among them neuroleptics, antiarrhythmic drugs (categories IA and III), mesoridazine with halofantrine, pimozide with levometadil acetate, thioridazine, moxifloxacin and gatifloxacin with sparfloxacin, and mefloquine , cisapride, dolansetron mesylate and sertindole).

Caution is required when taking concomitantly with risperidone, as well as medications provoking electrolyte imbalance (thiazide diuretics - development of hypokalemia), because they increase the likelihood of arrhythmia in malignant form.

The process of biotransformation of the active component of the drug in the hemoprotein system 450 is mainly carried out using an enzyme type P450 SURCA4. The combination of 25 mg of quetiapine with the ketoconazole inhibitor of the SURCA4 element promoted an increase (in 5-8 times) of the AUC level. Because of this, combining the drug with inhibitors of the SURCA4 element is prohibited. You can not also take quetiapine, squeezed grapefruit juice.

To determine the pharmacokinetic properties of quetiapine in people taking the medicine many times, it was given before treatment with carbamazepine (is an inducer of microsomal hepatic enzymes), and also during the course itself. Because of the increased clearance, the level of Quetiapine AUC, which was applied singly, decreased to 13% (mean), but this indicator was more significant in individual patients. As a result of this interaction, its plasma values have decreased, which can also affect the effectiveness of Nantarid.

When combining drugs with phenytoin (is another inducer of microsomal hepatic enzymes), significantly (by 450%) increases the clearance rate of quetiapine.

People who use inductor drugs of microsomal hepatic enzymes are allowed to use Nantarid exclusively in cases when the attending physician believes that the possible use of his use will exceed the need to cancel the use of the inductor. It is also necessary to take into account that any changes in the therapy process with the help of the microsomal inducer are carried out gradually. If necessary, you need to replace it with a medicine that does not have similar properties (eg, use sodium valproate).

Combined use with individual antidepressants (imipramine, which is an inhibitor of element CUR2D6, as well as fluoxetine - an inhibitor of SURCA4 elements, as well as CYP2D6), has no significant effect on the pharmacokinetic properties of quetiapine.

There was no noticeable effect on the pharmacokinetics of drugs, and when combined with the following antipsychotics, haloperidol and risperidone. However, in the case of combination with thioridazine, the quetiapine clearance rates increased by 70%.

No changes in the pharmacokinetic characteristics of quetiapine were observed in the case of simultaneous administration with lithium and cimetidine.

The combination with sodium valproate has little effect on the pharmacokinetic properties of both of these drugs (from a drugically significant point of view).

[3]

Storage conditions

Keep the tablets in a place inaccessible to young children. Temperatures are a maximum of 30 ° C.

[4]

Shelf life

Nantarides are allowed to be used in the period of 2 years from the date of release of the medicine.