When used inside during ziprasidone serum concentration of food normally reaches a maximum for 6-8 hours. Ziprasidone linear pharmacokinetics when receiving doses from 40 mg to 80 mg 2 times a day after meals. The absolute bioavailability of a dose of 20 mg after meals is 60%. When fasting jelfa omnadren ziprasidone absorption is reduced by 50%. The drug twice a day, usually leads to achieve equilibrium within 3 days. The duration of the retention of the equilibrium state depends on the dose.
In equilibrium, the final terminal half-life of ziprasidone after oral administration is 6.6 hours.
Clinically significant relationship pharmacokinetics of ziprasidone of age or gender, the presence of factors of smoking at intake were observed.
There were no significant changes in the pharmacokinetics of ziprasidone when administered in patients with severe and moderate renal impairment compared not identified with healthy patients. Increased if such patients the serum concentration of metabolites are unknown.
In patients with mild to moderate hepatic impairment (Child-Pugh A or B) against cirrhosis serum jelfa omnadren concentrations of ziprasidone after oral administration were 30% higher than in healthy patients and terminal half-life of about 2 hours more.
- hypersensitivity to ziprasidone or any inactive components of the drug;
- with known prolongation of the interval QT, including congenital long QT syndrome;
- recent myocardial acute myocardial infarction; decompensated heart failure;
- arrhythmias requiring admission antiarrhythmics IA and Class III (see Cautions.);
- pregnancy, lactation,
efficacy and safety of ziprasidone in patients aged less than 18 years have not been studied.Pregnancy and lactation Pregnancy Studies in pregnant women have not been conducted. In this regard, women of childbearing age should use an adequate method of contraception. Given the limited experience in humans of the drug, ziprasidone is not recommended during pregnancy except in cases where the expected treatment benefit to the mother justifies the potential risk to the fetus. Use in lactation It is not known whether ziprasidone appears in breast milk. In the treatment of ziprasidone women should be warned about the termination of breastfeeding.
Dosage and method of use of ziprasidone taken orally with meals (see. Pharmacokinetics). Adults The recommended starting dose is 40 mg 2 times a day. Subsequently the dose selected considering the clinical condition to a maximum daily dose of 160 mg (2 times 80 mg per day). If necessary, the daily dose may be increased to a maximum, for 3 days. Changes in the dose in the elderly (65 years and older), in patients with impaired renal function, in smoking patients is required. Application for violations of liver function in patients with mild or moderate severe hepatic insufficiency, it is advisable to reduce the dose of the drug. Experience with ziprasidone in patients with severe hepatic impairment is not present, so the drug in this group should be used with caution (see. Pharmacokinetics section).
Adverse events occur in more than 1% of patients treated with ziprasidone: asthenia, headache, constipation, dry mouth, dyspepsia, increased salivation, nausea, vomiting, agitation, akathisia, dizziness, dystonic reactions, extrapyramidal jelfa omnadren syndrome, hypertension, insomnia or drowsiness, tremor, blurred vision.
convulsions (less than 1% of patients treated with ziprasidone) rarely appear. Movement disorders Index (Movement Disorder Burden Score), reflecting the severity of extrapyramidal symptoms, in the application of ziprasidone significantly lower (p <0.05) than with haloperidol or risperidone. Comparable changes were observed on the scale of assessment of akathisia (Simpson Angus and Barnes akathisia scales) when using ziprasidone and placebo. Furthermore, the treatment with haloperidol and risperidone frequency akathisia and anticholinergics use was higher than in the treatment of ziprasidone.
Reported swing weight upwards on average 0.5 kg for receiving short (4-6 weeks) and downward by 1-3 kg with a long reception (during the year), compared with patients not taking the drug.
in the background maintenance therapy ziprasidone sometimes there was an increase in prolactin levels, but in most cases returned to normal without treatment discontinuation. Neuroleptic malignant syndrome (NMS) when using antipsychotics observed cases of NMS, which is a rare but potentially fatal complication. Clinical manifestations of NMS are fever (giperpereksiya), muscle rigidity, altered mental status, and autonomic instability (irregular heartbeat (arrhythmia) and the change in blood pressure, tachycardia, profuse sweating, heart rhythm disturbance). Additional signs may include raising the level of creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure. If a patient develops symptoms that can be attributed to the signs of NMS, or suddenly appeared high fever (giperpereksiya), not accompanied by the appearance of the other symptoms of NMS, you should immediately cancel all antipsychotic drugs, including ziprasidone.
The cases of NMS were observed in post-marketing use of Zeldoksa. Slow dyskinesia In long-term use as well as other ziprasidone antipsychotics risk of slow development of dyskinesias and extrapyramidal syndromes other remote. If signs of dyskinesias advisable to reduce the dose of ziprasidone, or cancel it. Other adverse events that were observed in post-marketing trials, ziprasidone: postural hypotension, tachycardia (including torsade de pointes), insomnia, skin rashes, allergic reactions, galactorrhea.
Data on overdose are limited to ziprasidone. The pre-registration clinical trials with oral medication proven to maximize dose (12,800 mg) in patients with apparent sedative effect of the drug, slow speech, and transient high blood pressure (200/95 mm Hg. Art.). No clinically significant changes in heart rate or functional changes were observed.
If you suspect an overdose, it is jelfa omnadren necessary to take into account the possible role of many drugs, if the patient is receiving concomitant therapy. Ziprasidone no specific antidote. In acute overdose should ensure airway and adequate ventilation and oxygenation of the lungs. Possible gastric lavage (after intubation if the patient is unconscious) and administration of activated charcoal together with a laxative.Possible seizures or dystonic reaction of the head and neck muscles after overdose may endanger aspiration with induced emesis. It is necessary to immediately start monitoring the function of the cardiovascular system, including continuous ECG recording to detect possible arrhythmias. Given that ziprasidone is largely bound to plasma proteins, hemodialysis is ineffective in the case of an overdose.
Interaction with other drugs and other forms of interaction antiarrhythmic agents of class IA and III, and other drugs causing prolongation of the interval, the QT (see section Special instructions. The interval QT). Drugs acting on the CNS / alcohol (see section Special instructions. Drugs acting CNS / alcohol). effect of ziprasidone to other drugs ziprasidone has no inhibitory effect on CYP1A2, CYP2C9 or CYP2C19. Ziprasidone concentration causing inhibition of CYP2D6 and CYP3A4 in vitro, at least 1000 times higher than the concentration of drug that could be expected in vivo. This indicates the absence probability clinically significant interaction between ziprasidone and drugs metabolized by these isoenzymes. Dextromethorphan In accordance with the results of in vitro studies and data of clinical trials on healthy volunteers showed that the ziprasidone had no mediated through isozyme CYP2D6 influence on the metabolism of dextromethorphan and the main metabolite Dextrorphan. Oral contraceptives The use of ziprasidone did not cause significant changes in estrogen pharmacokinetics (ethinyl estradiol, which is the substrate of CYP3A4) or components that contain progesterone. lithium ziprasidone has no effect on lithium pharmacokinetics when used together. Contact proteins ziprasidone is largely bound to plasma proteins . In in vitro studies of warfarin and propranolol, two jelfa omnadren drugs with high protein binding, did not affect the binding of ziprasidone plasma proteins, as well as ziprasidone did not affect the binding of these drugs plasma proteins. Thus, the ability of drugs interact with ziprasidone due to displacement from its association with plasma proteins, it is unlikely. The influence of other drugs on ziprasidone Ziprasidone is metabolized by aldehyde oxidase, and to a lesser extent of CYP3A4 isoenzyme. Clinically significant inhibitors or inducers of aldehyde known. The use of ketoconazole (400 mg / day) as a potential inhibitor of CYP3A4 resulted in an increase of approximately 35% AUC and C max ziprasidone.Similar effects are produced by ketoconazole are unlikely to have clinical significance. Primenenenie carbamazepine (200 mg twice daily) as an inducer of CYP3A4, led in turn to a decrease in indicators of ziprasidone at 36%. . These changes influenced karbomazepina hardly clinically significant cimetidine – a non-specific inhibitor of isoenzymes of CYP, had no significant effect on the pharmacokinetics of ziprasidone. Antacids The use of antacids containing aluminum and magnesium, had no effect on the pharmacokinetics of ziprasidone. Benztropine, propranolol, lorazepam – clinical trials of ziprasidone in patients treated with benztropine, lorazepam propranolol and showed no clinically significant effect of these drugs on the pharmacokinetic parameters ziprasidone concentration in serum.
Cautions QT interval Ziprasidone causes a mild to moderate prolongation of the interval QT. It is believed that there is a connection in the event of prolongation of the QT interval and paroxysmal ventricular arrhythmia (torsade de pointes), which is a potentially life-threatening (like effect causes some drugs, including antiarrhythmics IA and class III (see. section Contraindications)). There have been rare cases of such arrhythmias in patients with multiple mixed risk jelfa omnadren factors taking ziprasidone in the post-marketing use, although a causal relationship to drug intake has not been established. ziprasidone should be used with caution in patients with a lower listed risk factors that can aggravate the possibility of such arrhythmias:
- electrolyte imbalance,
- use with other drugs that prolong the interval QT.
If the QT interval greater than 500 ms, it is recommended to discontinue treatment (see. Section Contraindications). Cramps in the treatment of patients with seizures in history should be careful. Drugs acting on the CNS / alkogol ziprasidone has a primary effect on the CNS, therefore caution should be exercised when used in combination other centrally acting drugs, including agents acting on the dopaminergic and serotonergic systems. during treatment with ziprasidone alcohol is not recommended.
Effect on Driving and using technology
Like other antipsychotics, ziprasidone may cause drowsiness. This should warn patients who can drive a car or dangerous machinery.
By 7, 10 or 14 capsules in PVC / aluminum blister. 14, 20, 30, 50, 56, 60 or 100 capsules, together with instructions for use placed in a cardboard box (2 or 8 blisters 7 capsules; 1 or 4 blisters per 14 capsules, 2, 3, 5, 6 or 10 blister packs of 10 capsules).
Store at a temperature not exceeding 30 ° C. Keep out of the reach of children.
4 years. Do not use after the expiration date printed on the package.
Conditions of supply of pharmacies
on medical prescription.