Zeldox capsules 60mg, 30pcs

Composition

Active ingredient:

ziprasidone hydrochloride monohydrate;

Auxiliary substances:  

lactose monohydrate,

pre-gelatinized corn starch,

magnesium stearate;

Capsule body and cap:

titanium dioxide; Indigo Carmine (except for the dosage of 60 mg); gelatin

Pharmacological action

Zeldox is an antipsychotic drug (neuroleptic).

It has a high affinity for dopamine D2 receptors and a significantly more pronounced affinity for serotonin 5-HT2A receptors; it also interacts with serotonin 5-HT2C,5-HT1A and 5-HT1D receptors.

It has a moderate affinity for neuronal transporters of serotonin and norepinephrine, as well as for H1-histamine and alpha-1-adrenergic receptors (which is associated with the development of drowsiness and orthostatic hypotension).

Practically does not interact with m-cholinergic receptors. The antipsychotic activity of the drug is partly due to the blockade of dopaminergic and serotonin receptors.

The serotonergic activity of ziprasidone and its effect on the reuptake of neurotransmitters in neurons are associated with antidepressant activity. Blockade of 5-HT1A receptors causes anxiolytic effects.

Strong antagonism to 5-HT2C receptors determines antipsychotic activity. The degree of blockade of serotonin 5-HT2A receptors 12 hours after a single oral dose of 40 mg – 80%, and D2-receptors-50%.

Indications

Schizophrenia and similar mental disorders (treatment and prevention of exacerbations).

Use during pregnancy and lactation

Use during pregnancy Studies in pregnant women have not been conducted. In this regard, women of reproductive age should use a reliable method of contraception. Given the limited experience of using the drug in humans, ziprasidone is not recommended for use during pregnancy.

Breast-feeding use It is not known whether ziprasidone is excreted in breast milk. When treating with ziprasidone, women should be warned about stopping breastfeeding.

Contraindications

• prolongation of the QT interval (including congenital long QT syndrome);
• recent acute myocardial infarction;
• decompensated heart failure;
• arrhythmias requiring the use of class IA and III antiarrhythmics;
• pregnancy;
• lactation (breastfeeding);
• hypersensitivity to ziprasidone or any inactive component of the drug.

Side effects

From the central nervous system and peripheral nervous system:  asthenia, headache, extrapyramidal syndrome, insomnia or drowsiness, tremor, blurred vision, psychomotor agitation, akathisia, dizziness, dystonic reactions. Seizures were extremely rare (less than 1% of patients treated with ziprasidone). The Movement Disorder Burden Score, which reflects the severity of extrapyramidal symptoms when using ziprasidone, is significantly lower (p

Neuroleptic Malignant Syndrome (NMS):  Cases of NMS, which is a rare but potentially fatal complication, have been reported with antipsychotic medications. Clinical manifestations of NMS include increased body temperature (hyperpyrexia), muscle rigidity, changes in mental status, and instability of the autonomic nervous system (arrhythmia, changes in blood pressure, tachycardia, profuse sweating, and cardiac arrhythmia). Additional signs may include elevated CPK levels, myoglobinuria (rhabdomyolysis), and acute renal failure. All antipsychotic medications, including ziprasidone, should be discontinued immediately if symptoms that can be attributed to signs of NMS appear, or if an unexpectedly high body temperature is not accompanied by the appearance of other symptoms of NMS.

Cases of NMS have been reported with post-marketing use of Zeldox.

Slow dyskinesia:  with prolonged use of ziprasidone, as with other antipsychotic drugs, there is a risk of developing slow dyskinesia and other long-term extrapyramidal syndromes. If signs of dyskinesia appear, it is advisable to reduce the dose of ziprasidone or cancel it.

From the digestive system:  constipation, dry mouth, dyspepsia, increased salivation, nausea, vomiting.

Other services:  during maintenance therapy with ziprasidone, an increase in prolactin levels was sometimes observed (in most cases it returned to normal without stopping treatment), arterial hypertension. Body weight fluctuation was reported in the direction of increasing by an average of 0.5 kg with short-term use (for 4-6 weeks) and in the direction of decreasing by 1-3 kg with long-term use (for a year) compared with patients who did not take the drug.

Interaction

When ziprasidone is co-administered with drugs that cause QT prolongation (including class IA and class III antiarrhythmics), the risk of QT prolongation and paroxysmal ventricular tachycardia increases (this combination is contraindicated).

When ziprasidone is co-administered with drugs that have a depressing effect on the central nervous system, this effect may be mutually enhanced (this combination requires caution).

Ziprasidone has no inhibitory effect on CYP1A2, CYP2C9 or CYP2C19. The concentrations of ziprasidone causing inhibition of CYP2D6 and CYP3A4 in vitro were at least 1000 times higher than the drug concentration that could have been expected in vivo. This indicates that there is no likelihood of a clinically significant interaction between ziprasidone and drugs metabolized by these isoenzymes.

In accordance with the results of in vitro studies and data from clinical trials in healthy volunteers, it was shown that ziprasidone did not have a CYP2D6-mediated effect on the metabolism of dextromethorphan and its main metabolite dextrophan.

Ziprasidone, when co-administered with oral hormonal contraceptives, did not cause significant changes in the pharmacokinetics of estrogen, or ethinyl estradiol (which is a substrate of CYP3A4), or progesterone-containing components.

Ziprasidone does not affect the pharmacokinetics of lithium when co-administered.

Ziprasidone is highly bound to plasma proteins. In vitro studies, warfarin and propranolol (drugs with a high degree of protein binding) did not affect the binding of ziprasidone to plasma proteins, and ziprasidone did not affect the binding of these drugs to plasma proteins. Thus, the possibility of drug interaction with ziprasidone due to displacement from plasma protein binding seems unlikely.

Ziprasidone is metabolized by aldehyde oxidase and, to a lesser extent, by CYP3A4. Clinically significant inhibitors or inducers of aldehyde oxidase are unknown.

Co-use with ketoconazole (400 mg / day) as with a potential CYP3A4 inhibitor, an increase of approximately 35% in the AUC and Cmax of ziprasidone, which is unlikely to be of clinical significance.

Co-use with carbamazepine (200 mg twice daily), as a CYP3A4 inducer, resulted in a 36% decrease in the AUC and Cmax of ziprasidone, which is unlikely to be of clinical significance.

When co-administered, cimetidine, a non-specific isoenzyme inhibitor, did not significantly affect the pharmacokinetics of ziprasidone.

Concomitant use of antacids containing aluminum and magnesium did not affect the pharmacokinetics of ziprasidone.

No clinically significant effect of concomitant use of benztropine, propranolol, and lorazepam on the pharmacokinetic parameters and serum concentrations of ziprasidone has been established in clinical studies.

How to take, course of use and dosage

Inside, while eating.

Adults. In the treatment of acute schizophrenia and bipolar disorder, the recommended starting dose is 40 mg twice daily. Subsequently, the dose is increased taking into account the clinical condition. The maximum daily dose is 160 mg (80 mg 2 times a day). If necessary, the daily dose can be increased to the maximum within 3 days. The average therapeutic dose of Zeldox® is 120 mg divided into 2 doses.

As maintenance therapy for schizophrenia, the minimum effective dose should be prescribed; in most cases, taking 20 mg of the drug 2 times a day is sufficient.

Dose adjustment in the elderly (65 years and older), patients with impaired renal function, and smokers is not required.

Overdose

-Symptoms: Information about overdose of ziprasidone is limited. In pre-marketing clinical trials, when taking the drug orally at the maximum confirmed dose (12800 mg), the patient showed extrapyramidal manifestations, prolongation of the QT interval to 446 msec (without cardiac dysfunction). The most common symptoms of overdose are: extrapyramidal disorders, drowsiness, tremor, anxiety.

– Treatment: if an overdose is suspected, it is necessary to consider the possible role of many drugs if the patient has received concomitant therapy. There is no specific antidote for ziprasidone. In case of acute overdose, airway patency and adequate ventilation and oxygenation should be ensured. Gastric lavage (after intubation, if the patient is unconscious ) and taking activated charcoal in combination with a laxative are possible.Possible convulsions or dystonic reactions of the head and neck muscles after an overdose may pose a risk of aspiration with induced vomiting. Cardiovascular function monitoring should be initiated immediately, including continuous ECG recording to detect possible arrhythmias. Given that ziprasidone is largely bound to plasma proteins, hemodialysis is ineffective in case of overdose.

Special instructions

Ziprasidone causes a slight prolongation of the QT interval, so Zeldox should be prescribed with caution in patients with bradycardia, electrolyte disturbances, as this may lead to prolongation of the QT interval or the development of paroxysmal ventricular tachycardia. If the QT interval exceeds 500 msec, we recommend canceling the Zeldox.

Caution should be exercised when using Zeldox in patients with a history of seizures. Use in pediatrics

The efficacy and safety of ziprasidone in patients under 18 years of age has not been studied.

Influence on the ability to drive motor vehicles and manage mechanisms

Patients who engage in potentially dangerous activities that require increased attention and speed of psychomotor reactions should exercise caution. Patients should be warned about the possible occurrence of drowsiness while taking Zeldox.

Form of production

Capsules

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

4 years

Active ingredient

Ziprasidone

Conditions of release from pharmacies

By prescription

Dosage form

Capsules