Zeldox

Zeldox is an antipsychotic (antipsychotic drug).

Indications Zeldox

It is prescribed for psychoses and schizophrenia (as a remedy or as a preventive measure against exacerbations).

[1]

Release form

Available in capsules. The volume of 40 and 80 mg - 14 pcs. On the blister plate, 2 plates per pack. The volume of 60 mg - 10 pcs. On the blister, 3 blister packs per package.

[2], [3], [4]

Pharmacodynamics

Ziprasidone has a high affinity with dopamine type 2 conductors (such as D2), but this figure is even higher with serotonin type 2A conductors (such as 5HT 2A). As a result of positron emission tomography, it was found out that after 12 hours after using a single dose of 40 mg, serotonin conductors blocked (more than 80%), as well as D2 conductors (more than 50%).

Ziprasidone is able to interact with serotonin conductors of types 5HT 2C, as well as 5HT 1D with 5HT 1A. Compatibility with these conductors exceeds compatibility with D2 receptors. Moderate compatibility of the active substance is observed with neurons that move norepinephrine with serotonin, and in addition there is moderate compatibility with histamine H1 and α-1 conductors. Minor compatibility demonstrates with muscarinic M1 conductors.

It was also found that ziprasidone is an antagonist of serotonin type 2A conductors (such as 5HT 2A), as well as type 2 dopamine conductors (such as D2). In accordance with this mechanism, the antipsychotic effect of the drug is partly conditioned by a similar combination of antagonistic properties. Along with this, the active component of Zeldox is a potent antagonist of 5HT 2C conductors with 5HT 1D, as well as a potent agonist of 5HT 1A conductors. It inhibits the reuptake of norepinephrine and serotonin neurons.

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Pharmacokinetics

Absorption. The peak concentration in the blood serum active substance reaches 6-8 hours after the drug is used in multiple doses together with food. The indicator of bioavailability of a single dose of 20 mg after meal is 60%. As a result of the research, it was found that when using ziprasidone with food, its bioavailability can be increased up to 100%. That's why the medicine should be consumed with food.

The distribution volume is about 1.1 l / kg. The binding of the active substance to plasma proteins is more than 99%.

The half-life of ziprasidone is 6.6 hours, and the equilibrium concentration reaches about 1 to 3 days. From the moment of the beginning of therapy. The average indicator of the purification rate of ziprasidone in the case of IV use is 5 ml / min / kg. About 20% of the drug is excreted along with the urine, and about 66% - along with the feces.

The pharmacokinetics of ziprasidone remains linear when taking the drug in the dosage range of 40-80 mg 2 r. / Day.

After oral administration, an intensive metabolism of the active substance takes place. Unchanged, it is excreted with feces (<4%) and urine (<1%) in small amounts. The process of excretion of ziprasidone occurs mainly along the 3-rd prospective pathways of metabolism. As a result, 4 main circulating degradation products are formed: piperazine benzisothiazole sulfoxide and benzisothiazole piperazine sulfone, and in addition ziprasidone sulfoxide with S-methyl-dihydrosiprasidone. The unchanged active ingredient is equal to 44% of the total number of drug derivatives in the blood serum.

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Dosing and administration

You need to consume the medicine with food. The dosage is 40 mg twice daily. In the future, the dosage is calculated based on the clinical state of the patient, increasing it to the maximum allowable daily mark of 160 mg (80 mg twice daily). If necessary, the daily dosage can be increased to the maximum for 3 days.

[10], [11]

Use Zeldox during pregnancy

The drug is prohibited during pregnancy, and in case of treatment during lactation, breastfeeding should be stopped.

Contraindications

Among the contraindications:

• drug intolerance;
• The patient's recent myocardial infarction;
• the elongation of QT interval values (also the congenital form of the QT prolonged interval syndrome);
• decompensated form of heart failure in the chronic stage;
• arrhythmia, at which it is necessary to take antiarrhythmic drugs Ia, and in addition to this class III;
• children and adolescents under 18 years of age.

Caution in application is necessary when:

• severe liver failure (no experience of eating);
• presence in the patient's history of seizures;
• bradycardia;
• lack of electrolyte balance;
• use of other drugs that extend the value of the QT interval.

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Side effects Zeldox

Adverse reactions are rare. Among them are: headaches, dyspepsia, general weakness, constipation, and nausea with vomiting. In addition, dryness in the oral cavity, increased salivation, dizziness, akathisia, psychomotor agitation, autonomic dysfunction, arterial hypertension, extrapyramidal syndrome. There may also be drowsiness or vice versa insomnia, and with it cramps, blurred vision and tremors.

Approximately 0.4% of patients have weight gain (on average about +0.5 kg).

With maintenance treatment, hyperprolactinemia is possible (it usually can be eliminated without drug discontinuation).

In case of prolonged use - dysfunction and other distant extrapyramidal syndromes.

In postmarketing testing, there were side effects such as tachycardia, rashes on the skin, insomnia and orthostatic hypotension.

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Overdose

Manifestations of an overdose (ingestion of the maximum confirmed dose of 3240 mg): the patient was observed speech retardation and a brief increase in blood pressure (200/95 mm / Hg) - sedative properties of the drug appeared.

There is no specific antidote. In case of acute drug overdose, it is necessary to ensure unobstructed air permeability through the respiratory tract, as well as effective pulmonary oxygenation together with ventilation. It may be necessary to lavage the stomach (if the patient is unconscious, after intubation), and also the use of activated charcoal together with laxatives.

Due to possible muscular dystonia of the neck and head or seizures, a threat of aspiration may occur during artificially induced vomiting.

It is necessary to monitor the activity of the cardiovascular system (including the constant registration of the ECG to detect possible arrhythmia). The effectiveness of hemodialysis is low.

[12]

Interactions with other drugs

Antiarrhythmic drugs of classes Ia and III, and in addition other drugs that cause prolongation of QT interval values, in combination with Zeldox, can cause a strong elongation.

Ziprasidone does not inhibit CYP1A2, but also CYP2C9 or CYP2C19. Such substance concentrations that are capable of suppressing CYP3A4 with CYP2D6 in vitro are at least 1000 times higher than the concentration observed in the drug in vivo. Thus, it is obvious that the clinically noticeable interaction of ziprasidone with drugs, in the metabolism of which there are these isoenzymes, is absent.

The active substance does not create an indirect effect (via isoenzyme CYP2D6) on the processes of dextromethorphan metabolism together with its main product of decomposition (dextrofan).

Does not change the pharmacokinetics of the substance ethinyl estradiol (substrate type CYP3A4), but in addition to this medication, which contains progesterone. It also has no effect on the pharmacokinetic properties of Li +.

When combined with ketoconazole (at a dosage of 400 mg / day.), The peak concentration of ziprasidone and also AUC (by 35%) increase.

In combination with carbamazepine (200 mg 2 r./d.), The peak concentration and AUC of ziprasidone decrease by 36%.

Pharmacokinetic properties of ziprasidone do not undergo significant changes when combined with antacid drugs (with Al3 + and Mg2 + in the composition), cimetidine, and in addition lorazepam and propranolol.

[13], [14]

Storage conditions

Keep the drug in a place that is closed from moisture and access to children. Temperature conditions - no more than 30 ° C.

[15], [16],

Shelf life

Keep the drug in a place that is closed from moisture and access to children. Temperature conditions - no more than 30 ° C.

[17],