Nantarid

Nantaride is an effective antipsychotic drug.

Indications Nantarida

Shown for:

• schizophrenia;
• manic episodes of moderate or severe nature that develop as a result of bipolar disorders.

Release form

Available in tablets. Volume 25 mg - 10 pieces per blister; inside a separate pack there are 3 blister plates. Volume 100 mg - 10 pieces per blister; inside one package there are 3 or 6 blister plates. Volume 200 mg - 10 pieces per blister; in a separate box there are 6 blister plates. Volume 300 mg - 10 tablets inside a blister plate; in one pack - 6 blisters.

Pharmacodynamics

Quetiapine has an atypical profile that is somewhat different from that of standard antipsychotics. In the case of prolonged use, the substance does not cause hypersensitivity of the dopamine (D2) receptor. Doses that allow blocking the D2 conductor are capable of provoking only weak catalepsy.

With constant use, the drug has a selective effect on the limbic structure, because it promotes depolarization of inhibition processes within mesolimbic neurons (but not within neurons containing nigrostriatal dopamine). The active substance only in minimal quantities provokes negative extrapyramidal motor manifestations and, most likely, is not capable of causing the development of late-stage dyskinesia.

In vitro test data showed that the processes of quetiapine metabolism via hemoprotein 450 are carried out with the help of the enzyme CYP3A4. It turned out that the active substance with its decay products weakly blocks the action of hemoprotein P450 1A2, as well as 2C9 with 2C19 and 2D6 with 3A4. But this can only happen at a concentration that can appear with an injection of a dose no less than 10-20 times higher than the standard daily dose (i.e., 300-450 mg).

The information obtained from in vitro tests shows that the possibility of significant blocking of drugs dependent on hemoprotein P450 and used in combination with quetiapine by the active substance is extremely unlikely. Experiments demonstrate that the active component is capable of inducing the activity of microsomal enzymes included in the structure of hemoprotein 450. At the same time, in specific drug interaction tests conducted in individuals with psychosis, no increase in the activity of hemoprotein 450 action (induced by quetiapine) was observed.

Pharmacokinetics

When taken orally, quetiapine is absorbed quite well and is also metabolized within the body. The main decay products found in plasma do not have a noticeable pharmacological effect. Combination with food does not affect the level of bioavailability of the substance. The half-life is approximately 7 hours. About 83% of the component is synthesized with plasma protein.

The pharmacokinetic properties of the drug are linear and do not differ depending on gender. The average clearance value in individuals with renal impairment (severe – CC <30 ml/min/1.73m2 ⁾ is reduced by 25%, although the individual clearance level remains in the range that is characteristic of healthy renal function.

A significant portion of quetiapine is metabolized in the liver. When the radiolabeled component is injected, less than 5% is excreted unchanged in the feces and urine. About 73% of the radioactive element is excreted in the urine, and the remaining 21% in the feces.

In individuals with liver dysfunction (at a stable stage of liver cirrhosis), the average clearance value of quetiapine is reduced by 25%. Since this component is mainly metabolized in the liver, its plasma indices should increase in individuals with problems in the functioning of this organ. As a result, it may be necessary to adjust the dosage of the drug in such patients.

Dosing and administration

The medicine should be taken orally - 1 tablet twice a day with or without food.

In case of schizophrenia, during the first 4 days of the course, it is required to drink 50 mg of the drug on the 1st day, 100 mg of the drug on the 2nd day, 200 mg on the 3rd day and 300 mg on the 4th day. Then the required daily dosage is set in the range of 300-450 mg. Depending on the effectiveness of the drug and its tolerability by the patient, the daily dose can be adjusted in the range of 150-750 mg. In case of schizophrenia, no more than 750 mg of the drug can be taken per day.

When eliminating manic attacks that develop against the background of bipolar disorders - during the first 4 days, the daily doses are 100 mg (day 1), 200 mg (day 2), 300 mg (day 3) and 400 mg (day 4). Then, on the 6th day, it is allowed to increase the daily dose to 800 mg. The dosage should be increased gradually - it cannot be increased by more than 200 mg per day.

Depending on the medicinal effect and tolerance of the drug, the daily dose may vary within the range of 200-800 mg. Often, the most effective dosage is within the range of 400-800 mg per day. In the process of treating manic attacks, it is allowed to take no more than 800 mg per day.

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Use Nantarida during pregnancy

There is no information on the effectiveness and safety of using drugs in pregnant women.

During pregnancy, the tablets can be used only in cases where the possible benefit from it for the woman exceeds the likelihood of side effects in the fetus. It should be borne in mind that withdrawal syndrome has been observed in newborns whose mothers were administered quetiapine.

It is unknown in what quantities the active substance is excreted in breast milk. For this reason, it is recommended to stop breastfeeding while using the medicine.

Contraindications

Among the contraindications of the drug:

• hypersensitivity to the active component or other additional elements of the drug;
• combined use with the following hemoprotein 450 ZA4 inhibitors: HIV proteases, antifungal drugs, nefazodone, clarithromycin with erythromycin, as well as azole derivatives;
• Since no studies have been conducted on the safety and effectiveness of using tablets in children, Nantaride is not prescribed for this group of patients.

Side effects Nantarida

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

• manifestations affecting the lymph and hematopoietic system: the most common symptom is leukopenia. Occasionally, eosinophilia develops, and in isolated cases, neutropenia;
• immune system organs: hypersensitivity often occurs;
• pathological manifestations affecting the nutritional system and metabolic processes: diabetes mellitus or hyperglycemia develops occasionally;
• NS organs: headaches, drowsiness and dizziness often occur. Syncope is also very common. Epilepsy attacks occur occasionally. Late dyskinesia develops occasionally;
• CVS organs: tachycardia develops most often. There are also reports of prolongation of the QT interval, ventricular arrhythmia, and also sudden unexplained death, as well as cardiac arrest with polymorphic ventricular tachycardia (the so-called Torsade de Pointes), which are associated with the use of neuroleptics and are characteristic of this category of drugs; in addition, orthostatic collapse occurs;
• respiratory system: the development of a runny nose is common;
• Gastrointestinal tract: constipation and dyspeptic symptoms are common, as well as dryness of the oral mucosa;
• bile ducts and liver: jaundice occasionally occurs. Isolated cases – hepatitis develops;
• subcutaneous layer and skin: Quincke's edema or Stevens-Johnson syndrome develops occasionally;
• mammary glands and reproductive organs: priapism is occasionally observed;
• General disorders: a mild form of asthenia or peripheral edema may often be observed. Rarely, a malignant form of neuroleptic syndrome develops;
• diagnostic and laboratory test data: often an increase in plasma transaminase values (AST together with ALT) and weight gain are observed. Rarely, an increase in GGT, total cholesterol, and in addition triglycerides (in a fasting state) is possible.

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Overdose

There is only limited information on drug overdose. There are reports of individuals taking up to 20 g of the drug, but even in such cases there were no reports of death. Recovery also occurred without complications. Cases of death, prolongation of the QT interval, and coma are extremely rare.

Typically, patients develop drowsiness, tachycardia, sedation, and a decrease in blood pressure - these manifestations occur due to the enhancement of the pharmacological properties of the drug.

Quetiapine has no specific antidote. In the case of severe poisoning, it is necessary 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 (clear the airways), and in addition, the required pulmonary ventilation with oxygenation. At the same time, constant monitoring of the cardiovascular system and maintenance therapy using medications are necessary. Constant monitoring with medical supervision should be carried out until the patient has fully recovered.

Interactions with other drugs

Since the active component of the drug has a primary effect on the central nervous system, it is necessary to combine it with other drugs that act on this system with caution. It is also necessary to refrain from drinking alcoholic beverages.

Combined administration of the drug with liver enzyme inducers (for example, carbamazepine) can significantly reduce the systemic effects of quetiapine.

Special care should be taken when using drugs that prolong the QT interval in combination (including neuroleptics, antiarrhythmic drugs (categories IA and III), mesoridazine with halofantrine, pimozide with levomethadyl acetate, thioridazine, moxifloxacin and gatifloxacin with sparfloxacin, as well as mefloquine, cisapride, dolansetron mesylate and sertindole).

Caution is required when taken simultaneously with risperidone, as well as drugs that provoke electrolyte imbalance (thiazide diuretics - development of hypokalemia), because they increase the likelihood of developing arrhythmia in a malignant form.

The process of biotransformation of the active component of the drug in the hemoprotein 450 system is mainly carried out by the enzyme type P450 CYP3A4. The combination of 25 mg of quetiapine with ketoconazole, an inhibitor of the CYP3A4 element, contributed to an increase (5-8 times) in the AUC level. Because of this, combining the drug with inhibitors of the CYP3A4 element is prohibited. Quetiapine should also not be taken with grapefruit juice.

To determine the pharmacokinetic properties of quetiapine in individuals taking the drug multiple times, it was given before treatment with carbamazepine (an inducer of microsomal liver enzymes) and during the course itself. Due to increased clearance, the AUC level of quetiapine, which was used alone, decreased to 13% (average), but in some patients this indicator was more significant. As a result of this interaction, its plasma values decreased, which may also affect the effectiveness of Nantarid.

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

People who use drugs that induce microsomal liver enzymes are allowed to use Nantaride only in cases where the attending physician believes that the possible benefit from its use will exceed the need to cancel the use of the inducer. It is also necessary to take into account that any changes in the course of therapy with a microsomal inducer are carried out gradually. If necessary, it is necessary to replace it with a drug that does not have such properties (for example, use sodium valproate).

Combined use with individual antidepressants (imipramine, which is an inhibitor of the CYP2D6 element, as well as fluoxetine, an inhibitor of the CYP3A4 elements, as well as CYP2D6), does not have a noticeable effect on the pharmacokinetic properties of quetiapine.

No noticeable effect on the pharmacokinetics of the drug was observed in combination with the following antipsychotics - haloperidol and risperidone. However, in the case of combination with thioridazine, the clearance rates of quetiapine increased by 70%.

No changes in the pharmacokinetic characteristics of quetiapine were observed when co-administered with lithium and cimetidine.

Combination with sodium valproate has little effect on the pharmacokinetic properties of both drugs (from a medicinally significant point of view).

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Storage conditions

The tablets should be kept out of the reach of small children. Temperature indicators - maximum 30°C.

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Shelf life

Nantaride is permitted to be used for a period of 2 years from the date of release of the drug.