Zeldox
Zeldoks: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. In case of impaired liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Zeldox
ATX code: N05AE04
Active ingredient: Ziprasidone (Ziprasidone)
Manufacturer: PFIZER IRELAND PHARMACEUTICALS (Ireland)
Description and photo update: 18.10.2018
Prices in pharmacies: from 3198 rubles.
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Zeldox is an antipsychotic (neuroleptic) drug.
Release form and composition
Dosage forms:
- hard gelatin capsules with a "lock": size No. 4 - blue cap, white body with ZDX 20 inscription, size No. 4 - blue cap and body with ZDX 40 inscription, size No. 3 - white cap and white body with ZDX inscription 60, size 2 - blue cap, white body with ZDX 80 inscription, all caps - Pfizer inscription, the inscriptions are in black ink; inside capsules - crystalline loose powder of almost white color with a pink tint [in a blister: 20 mg or 80 mg - 7 pcs., in a cardboard box 2 or 8 blisters; 10 pcs., in a cardboard box 2, 3, 5, 6 or 10 blisters; 14 pcs., in a cardboard box 1, 2 or 4 blisters; 40 mg and 60 mg - 10 pcs., in a cardboard box 3 blisters (cardboard boxes with first opening control)];
- lyophilisate for the preparation of a solution for intramuscular (i / m) administration: almost white or white, after mixing with a solvent (colorless transparent liquid) - a colorless solution with a transparent structure (in a glass colorless bottle, in a cardboard box 1 bottle complete with 1 ampoule solvent).
1 capsule contains:
- active substance: ziprasidone hydrochloride monohydrate - 22.65 mg (ZDX 20), 45.3 mg (ZDX 40), 67.95 mg (ZDX 60) or 90.6 mg (ZDX 80), which is equivalent to 20 mg, 40 mg, 60 mg, or 80 mg ziprasidone;
- auxiliary components: pregelatinized corn starch, magnesium stearate, lactose monohydrate;
- composition of the capsule body and cap: gelatin, titanium dioxide;
- ink composition: Tek SW-9008 - ethanol, shellac, isopropanol, potassium hydroxide, propylene glycol, butanol, aqueous ammonia, water, iron dye black oxide.
Additionally as a part of capsules:
- capsule body 40 mg: indigo carmine;
- caps of capsules of 20 mg, 40 mg and 80 mg: indigo carmine.
1 bottle of lyophilisate contains:
- active substance: ziprasidone mesylate trihydrate - 40.93 mg, which is equivalent to the content of 30 mg of ziprasidone;
- auxiliary component: sodium sulfobutylate cyclodextrin (SBECD).
Solvent: water for injection.
Pharmacological properties
Pharmacodynamics
Ziprasidone is an antagonist of type 2A (5-HT 2A) serotonin receptors and type 2 dopaminergic receptors (D 2), a potent antagonist of 5-HT 2c, 5-HT ID and a powerful 5-HT 1A receptor agonist, this determines its antipsychotic effect.
Ziprasidone inhibits the reuptake of serotonin and norepinephrine in neurons.
The antidepressant activity of ziprasidone contributes to its effect on the reuptake of neurotransmitters in neurons and serotonergic activity.
The anxiolytic effects of the drug are due to the presence of 5-HT 1A receptor agonism. Antipsychotic activity is associated with pronounced antagonism to 5-HT 2c receptors.
Ziprasidone inhibits the reverse neuronal seizure of serotonin and norepinephrine, its affinity for alpha-adrenergic receptors and histamine H 1 receptors is noted. Antagonism to these receptors determines the possibility of orthostatic hypotension and drowsiness, respectively.
Ziprasidone almost does not interact with m 1 -cholinoreceptors, this can cause memory impairment.
12 hours after a single oral administration of the drug at a dose of 40 mg, the degree of blockade of aD2 receptors is 50%, of serotonin type 2 A receptors - 80% (data of positron emission tomography).
The antipsychotic effect when administered intramuscularly occurs after 1/4 hour and lasts for 1–2 hours after the administration of 10 mg and from 0.5 to 4 hours - 20 mg of ziprasidone solution.
Pharmacokinetics
The pharmacokinetics of ziprasidone capsules are linear when taken after meals in a daily dose of 80–160 mg.
When ziprasidone is taken orally during meals, its maximum concentration (C max) in the blood is reached within 6-8 hours. The absolute bioavailability of 20 mg of the drug when taken after meals is 60%, on an empty stomach - absorption is reduced by 50%.
Taking the drug 2 times a day allows you to reach an equilibrium state within 3 days. The duration of maintaining the equilibrium state is in direct proportion to the dose. V d (volume of distribution) at equilibrium is 1.5 l / kg.
When administered intramuscularly, the bioavailability of ziprasidone is 100%.
The serum concentration of the drug with a single intramuscular injection reaches a maximum after 1 hour and earlier, it increases in proportion to the dose increase, after three days of administration, the cumulation of the drug is insignificant.
The half-life of ziprasidone is 2–5 hours, the systemic clearance averages 7.5 ml / min / kg, and the volume of distribution is 1.5 l / kg.
Plasma protein binding does not depend on concentration and is 99%.
Oral administration of ziprasidone is metabolized to a large extent, less than 1% and 4% of the drug are excreted in the urine and feces unchanged, respectively. In the equilibrium state, the half-life (T 1/2) of ziprasidone is 6.6 hours.
As a result of the biotransformation of ziprasidone, 4 main metabolites are formed: S-methyldihydroziprasidone, benzisothiazolepiperazine (BITP) sulfoxide, BITP sulfone, ziprasidone sulfoxide, of which about 20% is excreted in the urine, 66% in the feces. The proportion of unchanged ziprasidone is about 44% of its total content and serum metabolites. The oxidative conversion of ziprasidone catalyzes CYP3A4. The formation of S-methyldihydroziprasidone occurs as a result of reactions catalyzed by aldehyde oxidase and thiomethyltransferase.
The prolongation of the QT interval may be due to the similarity of the properties of ziprasidone, ziprasidone sulfoxide and S-methyldihydroziprasidone.
S-methyldihydroziprasidone is mainly excreted in the feces, excretion of ziprasidone sulfoxide is performed by the kidneys, in addition, both substances undergo further metabolism with the participation of CYP3A4.
With the simultaneous use of ketoconazole (a CYP3A4 inhibitor) in a daily dose of 400 mg, the level of concentration of ziprasidone in the blood serum increases by approximately 40%, S-methyldihydroziprasidone - by 55%. Lengthening the interval QT c further occurs.
Age, gender, smoking, severe and moderate impairment of renal function with oral administration of ziprasidone do not affect the pharmacokinetics of the drug.
The concentration of ziprasidone in the blood serum with mild to moderate liver dysfunction (class A or B on the Child-Pugh scale) in the presence of cirrhosis increases by 30%, and the terminal half-life is longer by about 2 hours.
Indications for use
- capsules: prevention and treatment of mental disorders, including the treatment of negative and productive symptoms, affective disorders in schizophrenia;
- lyophilisate: relief of psychomotor agitation in schizophrenia.
Contraindications
- congenital long QT interval syndrome;
- simultaneous use of class IA and III antiarrhythmic drugs;
- period of pregnancy;
- breast-feeding;
- age up to 18 years;
- individual intolerance to the components of the drug.
Zeldox is used with caution in severe hepatic insufficiency. In addition, additional contraindications to the use of capsules:
- decompensated heart failure;
- prolongation of the QT interval;
- condition after a recent acute myocardial infarction.
Additional contraindications for the appointment of a lyophilisate:
- stage of decompensation of heart failure;
- a history of QT interval prolongation;
- subacute and acute stage of myocardial infarction;
- combination with drugs that prolong the QT interval: arsenous anhydride, methadone, halofantrine, mezoridazine, thioridazine, sparfloxacin, dolasetron, gatifloxacin, pimozide, moxifloxacin, sertindole, mefloquine or cisapride;
- psychosis due to dementia;
- age over 65.
Caution should be exercised when prescribing Zeldox lyophilisate with prolongation of the QT interval, myocardial infarction, unstable angina pectoris, bradycardia, electrolyte imbalance, in combination with drugs that prolong the QT interval.
Instructions for the use of Zeldoks: method and dosage
Capsules
The capsules are taken orally with meals.
Recommended dosage: initial dose - 40 mg 2 times a day, then the dose is adjusted, taking into account the clinical condition of the patient. The dose is increased gradually. Within 3 days, a single dose can be increased to 80 mg with a frequency of administration 2 times a day. The maximum daily dose is 160 mg.
In case of impaired renal function, in elderly patients or in smoking patients, dose reduction is not required.
With mild or moderate severity of liver dysfunction, it is advisable to reduce the dose of the drug.
Lyophilisate
Cannot be administered intravenously!
The ready-made solution of the lyophilisate is used only as an intramuscular injection.
The solution for injection is prepared by dissolving the contents of the vial with the supplied water for injection, after connection, the vial is shaken until the lyophilisate is completely dissolved. The concentration of the resulting solution corresponds to the content of ziprasidone in 1 ml - 20 mg.
Do not use the drug if there are visible inclusions in the solution.
The solution for each injection is prepared before direct administration, the rest of the drug in the vial is disposed of.
Recommended dosage: 10 mg every 2 hours or 20 mg every 4 hours. The maximum daily dose is 40 mg. The duration of the course of therapy is no more than 3 days.
The effectiveness of i / m administration of the drug for more than 3 days has not been established, therefore, if a longer use of Zeldox is required, the patient is transferred to taking capsules.
In case of impaired liver function, the dose is reduced in proportion to the severity of the disease.
No dose adjustment is required for smoking patients.
Side effects
- possible: against the background of long-term therapy - the development of distant extrapyramidal syndromes, including slow (or late) dyskinesia;
- rarely: a potentially fatal complication - neuroleptic malignant syndrome (NMS), its clinical manifestations include muscle stiffness, sudden increase in body temperature, change in mental status, arrhythmia, tachycardia, changes in blood pressure (BP), profuse sweating, heart rhythm disturbances, rhabdomyolysis, acute renal failure, increased blood levels of creatine phosphokinase.
In addition, adverse events while taking capsules recorded in clinical trials (> 1% of patients):
- from the nervous system: headache, dizziness, asthenia, extrapyramidal syndrome, insomnia, drowsiness, blurred vision, tremor, psychomotor agitation, dystonic reactions, akathisia; very rarely - convulsions;
- from the digestive system: dry mouth, nausea, vomiting, constipation, dyspepsia, increased salivation;
- others: arterial hypertension, increased prolactin levels (usually normalized without discontinuation of the drug); perhaps - an increase in body weight (by about 0.5 kg) with a course duration of 4-6 weeks or a decrease in weight by 1-3 kg during treatment during the year.
In post-marketing studies of ziprasidone in capsules, the following side effects were noted: tachycardia (including pirouette-type arrhythmias), postural hypotension, allergic reactions, insomnia, galactorrhea, skin rash.
Additional side effects, the occurrence of which is possible against the background of the use of a lyophilisate:
- mental disorders: infrequently - antisocial behavior, agitation, psychotic disorder, tics, insomnia;
- from the nervous system: often - headache, drowsiness, akathisia, dystopia, dizziness, sedation; infrequently - dysarthria, postural dizziness, "cogwheel" -type muscle rigidity, dyskinesia, dyspraxia, tremor, parkinsonism;
- from the vascular system: often - arterial hypertension; infrequently - orthostatic hypotension, hyperemia;
- from the side of the heart: infrequently - tachycardia, bradycardia;
- from the organs of hearing and balance: infrequently - dizziness;
- thoracic, mediastinal and respiratory disorders: infrequently - laryngospasm;
- from the digestive system: often - nausea, vomiting; infrequently - dry mouth, constipation, diarrhea;
- on the part of nutrition and metabolism: infrequently - anorexia;
- from the connective tissue and musculoskeletal system: often - muscle stiffness;
- dermatological reactions: infrequently - hyperhidrosis;
- laboratory tests: infrequently - lowering blood pressure, increasing the activity of liver enzymes;
- others: often - burning and / or pain at the injection site, asthenia; infrequently - fatigue, drug withdrawal, discomfort and / or irritation at the injection site, flu-like syndrome.
Overdose
Symptoms: after ingestion of the maximum confirmed dose (12 800 mg), the development of a sedative effect of the drug, speech retardation, and transient arterial hypertension were recorded. There were no clinically significant cardiac arrhythmias or functional changes.
Treatment: there is no specific antidote, the possible effect of concomitant therapy should be considered. First of all, the patient should be provided with airway patency, adequate oxygenation and ventilation of the lungs, gastric lavage, the introduction of activated carbon in combination with laxatives. It is necessary to monitor the function of the cardiovascular system, including continuous electrocardiography to detect possible arrhythmias. Hemodialysis with an overdose of ziprasidone is ineffective.
special instructions
It is necessary to monitor the condition of patients with bradycardia and electrolyte disturbances. If the QT interval exceeds 500 msec, it is recommended to cancel Zeldox, since there is a high risk of developing paroxysmal ventricular tachycardia.
The capsules should be used with caution when treating patients with a history of convulsive conditions.
The primary effect of ziprasidone on the central nervous system (CNS) must be taken into account when prescribing the drug in combination with centrally acting drugs.
It is not recommended to consume alcohol during treatment.
Lyophilisate is used only to relieve psychomotor agitation, then the patient should be transferred to taking capsules.
Influence on the ability to drive vehicles and complex mechanisms
Since the effect of the drug can cause drowsiness in the patient, care should be taken when performing work requiring increased concentration of attention and high speed of psychomotor reactions, including driving.
Application during pregnancy and lactation
According to the instructions, Zeldoks is contraindicated to use during pregnancy, unless, in the opinion of the doctor, the intended benefits of therapy for the mother outweighs the potential threat to the fetus.
Women of reproductive age must use reliable methods of contraception.
If necessary, the use of the drug during lactation, breastfeeding should be discontinued.
Pediatric use
Prescribing the drug to patients under the age of 18 is contraindicated, since the safety and efficacy of ziprasidone in this category of patients have not been established.
With impaired renal function
In case of impaired renal function, a change in the dosage regimen for capsules is not required.
Caution should be used in the / m administration of the drug due to the ability of cyclodextrin to be excreted by glomerular filtration.
If liver function is impaired
With mild or moderate severity of liver dysfunction, it is advisable to reduce the dose of the drug. Due to the lack of experience with the use of ziprasidone in severe hepatic insufficiency, Zeldox is recommended to be used with caution in this category of patients.
Use in the elderly
Over the age of 65, the efficacy and safety of ziprasidone have not been established.
Drug interactions
With the simultaneous use of Zeldox:
- Class IA and III antiarrhythmics and other drugs that cause QT interval prolongation increase the risk of QT interval prolongation and paroxysmal ventricular tachycardia;
- drugs that have a depressing effect on the central nervous system can cause mutual reinforcement of the action;
- drugs metabolized by isoenzymes CYP1A2, CYP2C9 or CYP2C19 do not cause clinically significant interactions;
- lithium preparations, oral hormonal (containing estrogen, or ethinyl estradiol, or progesterone), contraceptive drugs do not significantly change their pharmacokinetics;
- warfarin, propranolol (agents with a high degree of binding to proteins) do not change their binding to plasma proteins and do not affect the binding to plasma proteins of ziprasidone;
- inhibitors of CYP3A4 (including ketoconazole at a daily dose of 400 mg) do not cause clinically significant interactions;
- CYP3A4 inducers (including carbamazepine at a daily dose of 400 mg) do not cause clinically significant interactions;
- nonspecific inhibitor of isoenzymes - cimetidine - does not significantly affect the pharmacokinetics of ziprasidone;
- antacids containing magnesium and aluminum do not affect the pharmacokinetics of the drug;
- benztropine, propranolol, lorazepam have no effect on serum concentration and pharmacokinetic parameters of ziprasidone.
Analogs
Analogs of Zeldox are: Serdolect, Zipsila, Sulpirid, Risperidone, Sertindol, Rileptid.
Terms and conditions of storage
Keep out of the reach of children.
Store at temperatures up to 30 ° C, the lyophilisate should be protected from light.
Shelf life: capsules - 4 years, lyophilisate - 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Zeldox
The few reviews about Zeldoks indicate the effectiveness of the drug, and the frequent development of side effects is also indicated.
The price of Zeldox in pharmacies
The price of Zeldox in capsules of 40 mg (30 pcs. In a package) is from 3689 rubles, 60 mg (30 pcs. In a package) - from 4159 rubles.
The cost of the drug in the form of a lyophilisate is unknown.
Zeldoks: prices in online pharmacies
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Drug name Price Pharmacy |
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Zeldox 40 mg capsule 30 pcs. RUB 3198 Buy |
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Zeldox 60 mg capsule 30 pcs. 4699 RUB Buy |
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Zeldox capsules 60mg 30 pcs. 5781 RUB Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
