Zeldox

Zeldox is a neuroleptic (antipsychotic drug).

Indications Zeldox

Prescribed for psychosis and schizophrenia (as a treatment or as a preventive measure against exacerbations).

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Release form

Available in capsules. Volume 40 and 80 mg - 14 pcs. on a blister plate, 2 plates per package. Volume 60 mg - 10 pcs. on a blister, 3 blister plates per package.

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Pharmacodynamics

Ziprasidone has a high affinity for dopamine type 2 junctions (such as D2), but even higher affinity for serotonin type 2A junctions (such as 5HT 2A). Positron emission tomography showed that 12 hours after a single 40 mg dose, serotonin junctions were blocked (by more than 80%), as were D2 junctions (by 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. Insignificant compatibility is demonstrated with muscarinic M1 conductors.

Ziprasidone has also been shown to be an antagonist of serotonin type 2A (such as 5HT 2A) and dopamine type 2 (such as D2) pathways. According to this mechanism, the antipsychotic effect of the drug is partly due to this combination of antagonist properties. In addition, the active component of Zeldox is a potent antagonist of 5HT 2C and 5HT 1D pathways and a potent agonist of 5HT 1A pathways. It inhibits reuptake by norepinephrine and serotonin neurons.

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Pharmacokinetics

Absorption. The active substance reaches its peak concentration in the blood serum 6-8 hours after taking the drug in multiple doses with food. The bioavailability of a single dose of 20 mg after food is 60%. Research has shown that when ziprasidone is taken with food, its bioavailability can increase to 100%. That is why the drug should be taken with food.

The distribution volume is approximately 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 steady-state concentrations are reached approximately 1-3 days after initiation of therapy. The mean clearance rate of ziprasidone after intravenous administration is 5 mL/min/kg. About 20% of the drug is excreted in the urine, and about 66% in the feces.

The pharmacokinetics of ziprasidone remain linear when the drug is taken in the dosage range of 40-80 mg twice daily.

Following oral administration, the active substance is extensively metabolized. It is excreted unchanged in feces (<4%) and urine (<1%) in small amounts. The process of ziprasidone excretion occurs mainly via 3 putative metabolic pathways. As a result, 4 main circulating breakdown products are formed: benzisothiazole piperazine sulfoxide and benzisothiazole piperazine sulfone, and in addition ziprasidone sulfoxide with S-methyl-dihydroziprasidone. The unchanged active component is equal to 44% of the total number of drug derivatives in the blood serum.

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Dosing and administration

The medicine should be taken with food. The dosage is 40 mg twice a day. The dosage is then calculated based on the patient's clinical condition, increasing it to the maximum daily dose of 160 mg (80 mg twice a day). If necessary, the daily dosage can be increased to the maximum over 3 days.

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Use Zeldox during pregnancy

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

Contraindications

Among the contraindications:

• drug intolerance;
• the patient has recently suffered a myocardial infarction;
• prolongation of the QT interval (also the congenital form of long QT syndrome);
• decompensated form of heart failure in the chronic stage;
• arrhythmia, which requires taking antiarrhythmic drugs Ia, and in addition to this, class III;
• children and adolescents under 18 years of age.

Caution is required when using:

• severe liver failure (no experience of use);
• the patient has a history of seizures;
• bradycardia;
• lack of electrolyte balance;
• use of other drugs that prolong the QT interval.

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Side effects Zeldox

Side effects are quite rare. Among them are: headaches, dyspepsia, general weakness, constipation, and nausea with vomiting. In addition, dry mouth, increased salivation, dizziness, akathisia, psychomotor agitation, autonomic dysfunction, arterial hypertension, extrapyramidal syndrome. Drowsiness or, conversely, insomnia may also occur, along with convulsions, blurred vision, and tremor.

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

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

In case of prolonged use – dysfunction and other remote extrapyramidal syndromes.

In post-marketing testing, the following adverse reactions have been observed: tachycardia, skin rash, insomnia, and orthostatic hypotension.

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Overdose

Manifestations of overdose (ingestion of the maximum confirmed dose of 3240 mg): the patient experienced slow speech and a short-term increase in blood pressure (200/95 mm/Hg) – the sedative properties of the drug were evident.

There is no specific antidote. In case of acute drug overdose, unimpeded air passage through the respiratory tract and effective pulmonary oxygenation together with ventilation should be ensured. Gastric lavage (if the patient is unconscious, after intubation) and the use of activated charcoal together with laxatives may be necessary.

Due to possible muscular dystonia of the neck and head or convulsions, there may be a risk of aspiration during artificially induced vomiting.

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

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Interactions with other drugs

Antiarrhythmic drugs of classes Ia and III, as well as other drugs that provoke prolongation of the QT interval, in combination with Zeldox can cause a strong prolongation.

Ziprasidone does not inhibit CYP1A2, CYP2C9, or CYP2C19. The concentrations of the drug that are able to inhibit CYP3A4 and CYP2D6 in vitro are at least 1000 times higher than the concentration observed for the drug in vivo. Thus, it is clear that there are no clinically significant interactions of ziprasidone with drugs that are metabolized by these isoenzymes.

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

Does not change the pharmacokinetics of the substance ethinyl estradiol (a CYP3A4 substrate), and in addition to this, drugs that contain progesterone. Also does not affect the pharmacokinetic properties of Li+.

When combined with ketoconazole (at a dosage of 400 mg/day), the peak concentration of ziprasidone, as well as AUC, increases (by 35%).

In combination with carbamazepine (200 mg 2 times a day), the peak concentration and AUC of ziprasidone are reduced by 36%.

The pharmacokinetic properties of ziprasidone do not undergo significant changes when combined with antacid drugs (containing Al3+ and Mg2+), cimetidine, and also lorazepam and propranolol.

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Storage conditions

The preparation should be kept in a place protected from moisture and children. Temperature conditions should not exceed 30°C.

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Shelf life

The preparation should be kept in a place protected from moisture and children. Temperature conditions should not exceed 30°C.

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