Active substanceZiprasidoneZiprasidone
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  • Zeldox®
    lyophilizate w / m 
    Pfizer Inc.     USA
  • Zeldox®
    capsules inwards 
  • Zipsil®
    capsules inwards 
    KRKA-RUS, LLC     Russia
  • Dosage form: & nbspcapsules
    Composition:

    1 capsule contains:

    Active substance:

    20 mg

    40 mg

    60 mg

    80 mg

    Ziprasidone hydrogen sulfate dihydrate

    26.50 mg

    53.00 mg

    79.49 mg

    105.99 mg

    which corresponds to ziprasidone hydrogen sulfate

    24.75 mg

    49.50 mg

    74.25 mg

    99.00 mg

    in terms of ziprasidone

    20.00 mg

    40.00 mg

    60.00 mg

    80.00 mg

    Excipients: Pregelatinized starch

    10.00 mg

    20.00 mg

    30.00 mg

    40.00 mg

    Povidone

    2.55 mg

    5.10 mg

    7.65 mg

    10.20 mg

    Magnesium stearate

    0.50 mg

    1.00 mg

    1.50 mg

    2.00 mg

    Lactose Monohydrate

    60.45 mg

    120.90 mg

    181.36 mg

    241.81 mg

    Composition of an empty gelatin capsule: Capsule body:

    Titanium dioxide (E171)

    0.456 mg

    0.576 mg

    0.732 mg

    0.912 mg

    Gelatin

    22,344 mg

    28.147 mg

    35.868 mg

    44.688 mg

    Indigo carmine dye (E132)

    -

    0.005 mg

    -

    -

    Iron colorant oxide yellow (E172)

    -

    0.072 mg

    -

    -

    Capsule cover: Titanium dioxide (E171)

    0.304 mg

    0.142 mg

    0.181 mg

    0.608 mg

    Indigo carmine dye (E 132)

    0.003 mg

    0.017 mg

    0.022 mg

    0.005 mg

    Iron colorant oxide yellow (E172)

    0.038 mg

    0.118 mg

    0.149 mg

    0.076 mg

    Gelatin

    14.855 mg

    18.923 mg

    24.048 mg

    29,711mg

    Description:

    Capsules 20 mg: Hard gelatin capsules No. 4: capsule body white, cap capsule, light green. The contents of the capsule are powder from light pink to brownish.

    Capsules 40 mg: Hard gelatin capsules No. 3: Capsule of light green color, lid capsule of dark green color. The contents of the capsule are powder from light pink to brownish.

    Capsules 60 mg: hard gelatin capsules No. 2: capsule body white, capsule cover dark green> color. The contents of the capsule are powder from light pink to brownish.

    Capsules 80 mg: hard gelatin capsules No. 1: capsule body white, cap capsule light green, color. The contents of the capsule are powder from light pink to brownish.

    Pharmacotherapeutic group:Antipsychotic agent (antipsychotic).
    ATX: & nbsp

    N.05.A.E.04   Ziprasidone

    Pharmacodynamics:

    Ziprasidone has a high affinity for type 2 dopamine receptors (D2) and a high affinity for serotonin 2A receptors (5HT2A). According to positron emission tomography (PET) data, 80% of serotonin 2A receptors and more than 50% of D2 receptors were blocked 12 hours after a single dose of 40 mg. Ziprasidone also interacts with serotonin 5HT2C, 5HT1D and 5HT1A receptors, and the affinity for these receptors is comparable or exceeds the affinity for D2 receptors. Ziprasidone has a moderate affinity for neuronal serotonin and norepinephrine transports, exhibits moderate affinity for histamine H1 and alpha1-adrenergic receptors. The affinity of ziprasidone for muscarinic M1 receptors is negligible.

    Ziprasidone is an antagonist of both receptors - serotonin 2A and dopamine D2. Ziprasidone also a potent 5HT2C and 5HT1D receptor antagonist and a 5HT1A receptor agonist. Suppresses the reverse neuronal seizure of norepinephrine and serotonin.
    Pharmacokinetics:

    Suction. After ingestion of ziprasidone with food, Cmax in blood plasma is usually achieved in 6-8 hours. Absolute bioavailability of 20 mg dose is 60%. Pharmacokinetic studies have shown that the bioavailability of ziprasidone during food intake rises to 100%, so the drug is recommended to be taken with meals.

    Distribution. The volume of distribution is approximately 1.1 l / kg. Ziprasidone more than 99% associated with blood proteins.

    Biotransformation and excretion. T1 / 2 ziprasidone after ingestion is 6.6 hours. The equilibrium state is reached within 1-3 days. The average clearance of ziprasidone administered intravenously is 5 ml / min / kg.Approximately 20% of the dose is excreted by the kidneys and 66% is excreted with bile through the intestine.

    When receiving therapeutic doses of 40 to 80 mg 2 times a day, the pharmacokinetic schedule of ziprasidone is linear.

    Ziprasidone is metabolized mainly in three ways, with the formation of four major circulating metabolites: benzothiazole piperazine (BITP) sulfoxide, BITP sulfone, ziprasidone sulfoxide and S-methyldihydroziprasidone. Unchanged ziprasidone is approximately 44% of the total drug circulating in the serum. In invivo studies, it has been established that conversion to S-methyldihydroziprasidone is the main route of drug metabolism. In vitro studies indicate that this metabolite is formed by reduction catalyzed by aldehyde oxidase, followed by S-methylation. There is also an oxidative metabolism, mainly involving the isoenzyme CYP3A4 and the potential participation of the CYP1A2 isoenzyme.

    In the invitro experiments, S-methyldihydroziprasidone and ziprasidone sulfoxide exhibited properties that could cause the prolongation of the QTc interval. S-methyldihydroziprasidone is mainly excreted from the body through the intestine by biliary excretion with minimal participation of the CYP3A4 isoenzyme.Ziprasidone sulfoxide is excreted by renal excretion and secondary metabolism catalyzed by the CYP3A4 isoenzyme.

    Special groups of patients. Pharmacokinetic screening of patients did not reveal significant pharmacokinetic differences in smokers and non-smokers.

    Given that renal clearance does not affect the overall clearance of ziprasidone, when it was used by patients with different renal function, there was no increase in its content in the blood.

    Exposure of 20 mg of ziprasidone 2 times / day for several days in patients with mild (creatinine clearance more than 60 ml / min), moderate (KK 30-60 ml / min) and severe renal insufficiency (the need for dialysis) respectively, 146%, 87% and 75% of the drug exposure in healthy volunteers (QC more than 70 ml / min). For mild to moderate liver failure (class A / B according to Child-Pugh classification) caused by cirrhosis, serum concentrations of ziprasidone after ingestion were 30% higher and T1 / 2 increased approximately 2 hours compared to healthy volunteers. The effect of liver failure on serum concentrations of metabolites is unknown.

    Indications:

    Schizophrenia and other psychotic conditions (treatment and prevention).

    Contraindications:

    • Hypersensitivity to ziprasidone or any component of the drug;
    • prolongation of QT interval on electrocardiogram (ECG), including congenital syndrome of elongated QT;
    • myocardial infarction (acute, acute stage);
    • decompensated chronic heart failure;
    • arrhythmia requiring the use of antiarrhythmic drugs IA and III classes;
    • simultaneous therapy with drugs that extend the QT interval: arsenic trioxide, halofantrine, levacetylmetadol, mesoridazine, thioridazine, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, dolasetron, mefloquine, sertindole or cisapride;
    • pregnancy, lactation;
    • age younger than 18 years;
    • congenital galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

    Carefully:

    Pronounced bradycardia, electrolyte disorders (hypokalemia, hypomagnesemia), bipolar disorder, elderly age (over 65 years), history of convulsions, severe hepatic insufficiency, risk of stroke, simultaneous use of alcohol, thrombosis, due to risk of thromboembolism.

    Pregnancy and lactation:

    The drug Zipsila® is not used in pregnancy and during breastfeeding.

    Dosing and Administration:

    Inside, with food.

    Treatment of schizophrenia

    The recommended dose is 40 mg 2 times / day.

    In the future, the daily dose can be changed in accordance with the clinical picture and course of the disease and brought to a maximum of -160 mg / day (2 times 80 mg). If necessary, the daily dose can be brought to maximum for 3 days.

    Prevention of schizophrenia

    Recommended minimum initial dose - 20 mg 2 times / day.

    Elderly patients (over 65 years of age)

    Dose adjustment is required for concomitant diseases and / or conditions limiting the use of ziprasidone (a minimum initial dose is recommended).

    Impaired renal function: correction of the dose is not required.

    Impaired liver function: the dose of the drug should be reduced.

    Side effects:

    Classification of incidence of side effects (World Health Organization): very often> 1/10; often> 1/100, <1/10; infrequently> 1/1000, <1/100; rarely> 1/10000, <1/1000; very rarely <1/10000, including single messages.

    From the cardiovascular system: infrequently - palpitations, tachycardia, hypertensive crisis, increased blood pressure (BP), orthostatic hypotension,fainting; rarely - isolated systolic or diastolic hypertension, labile blood pressure.

    From the sense organs: often - impaired vision; -only: photophobia; rarely - pain in the ears, amblyopia, itching and dryness of the conjunctiva, discomfort in the eyes.

    From the digestive system: often - nausea, vomiting, constipation, indigestion, dryness of the oral mucosa, increased salivation; infrequently - diarrhea, dysphagia, gastritis, discomfort in the abdomen, swelling of the tongue, flatulence;

    Metabolic and nutritional disorders: infrequent - increased appetite; rarely - hypocalcemia.

    From the musculoskeletal system: often - rigidity of muscles; infrequently - muscle cramps, pain in the limbs, stiffness of the joints; rarely - trimester.

    From the nervous system: very often - drowsiness, akathisia; often - dystonia, extrapyramidal disorders, tardive dyskinesia, parkinsonism (including rigidity of the "cogwheel" type, bradykinesia, hypokinesia), tremor, dizziness, sedation, headache, anxiety, agitation, insomnia; -nonly: generalized tonic-clonic convulsions, ataxia, dysarthria, oculogic crisis, attention disturbance, hypertension,tremor, sensory disturbances (hypesthesia, paresthesia), lethargy, agitation, anxiety disorders, sensation of "coma in the throat", sleep disturbance (nightmares), mania, hypomania; rarely - serotonin syndrome, malignant neuroleptic syndrome, panic attacks, depressive syndrome, bradyphrenia, affective disorders; very rarely - torticollis, paresis of the facial nerve, akinesia, hyperkinesia, restless legs syndrome;

    From the genitourinary system: rarely - urinary incontinence, dysuria, enuresis, erectile dysfunction, increased erection, galactorrhea, gynecomastia, anorgasmia, priapism.

    From the respiratory system: infrequently - dyspnoea.

    From the skin: infrequently - angioedema, urticaria, skin rash, acne; rarely - psoriasis, allergic dermatitis, alopecia, erythema, papular rash.

    Laboratory indicators: infrequently - increased activity of "hepatic" enzymes in the blood; rarely - prolongation of the QT interval on the ECG, increased lactate dehydrogenase activity, eosinophilia, lymphopenia.

    Common violations: often asthenia, weakness; -nonly: violations of gait.

    Other: thromboembolism, including thromboembolism of the pulmonary artery, deep vein thrombosis, the incidence of which is not established.

    Overdose:

    The maximum, confirmed, single application of ziprasidone was 12800 mg. In this case, extrapyramidal disorders and lengthening of the interval QT446 msec were noted. (without any known complications or negative effects on the cardiovascular system). In general, the most common symptoms in overdose are extrapyramidal disorders, drowsiness and anxiety.

    Reduced pain sensitivity, convulsions or dystonic reactions in the head and neck area, due to an overdose, may create a risk of aspiration with induced vomiting.

    Treatment: there is no specific antidote.

    In case of acute overdose, it is necessary to provide airway patency, adequate ventilation and oxygenation of the lungs. Possible gastric lavage (after intubation, if the patient is unconscious) and the use of activated carbon in combination with laxatives. It is necessary to monitor the functions of the cardiovascular system, including continuous registration of the ECG in order to identify possible arrhythmias.

    Hemodialysis is ineffective.

    Interaction:

    Pharmacokinetic and pharmacodynamic studies with ziprasidone and drugs,extending the interval QT, were not carried out. It is impossible to exclude the additive effect of ziprasidone and these drugs. Concerning ziprasidone can not be used simultaneously with drugs that extend the QT interval (antiarrhythmic drugs IA and III classes, arsenic trioxide, halofantrine, levocetylmetadol, mesoridazine, thioridazine, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, dolasetron, mefloquine, sertindole or cisapride).

    An in vivo study with dextromethorphan showed that ziprasidone does not have an indirect effect through the isoenzyme CYP2D6 on the metabolism of dextromethorphan and its main metabolite dextrorphan.

    Inhibitor of isoenzyme CYP3A4 ketoconazole (400 mg / day) increases serum ziprasidone concentration by less than 40%. With the expected Tmax ziprasidone concentration in the serum of S-methyldihydrosiprasidone increases by approximately 55%, and ziprasidone-sulfoxide by 8%. An additional prolongation of the QT interval was not observed. Changes in pharmacokinetics with the simultaneous use of potent inhibitors of the isoenzyme CYP3A4 have not been identified, so dose adjustment is not required.

    When ziprasidone is used with serotonergic drugs, it is possible to develop a serotonin syndrome. Symptoms of serotonin syndrome: confusion, agitation, fever, sweating, ataxia, hyperreflexia, myoclonus, and diarrhea.

    Cimetidine, a nonspecific inhibitor of the CYP isoenzyme, has no significant effect on the pharmacokinetics of ziprasidone.

    The use of antacids containing aluminum and magnesium does not affect the pharmacokinetics of ziprasidone.

    Benzathropine, propranolol, lorazepam do not affect the pharmacokinetic parameters of ziprasidone concentration in blood serum.

    Does not affect the pharmacokinetics of lithium.

    The simultaneous use of ziprasidone and carbamazepine at a dose of 200 mg twice daily for 21 days resulted in a decrease in ziprasidone concentration of approximately 35%.

    Given the directional effect of ziprasidone on the central nervous system, care must be taken when it is combined with other drugs that depress the central nervous system, including alcohol.

    The use of ziprasidone does not cause significant changes in the pharmacokinetics of estrogens (ethinylestradiol, CYP3A4 substrate) or progesterone.

    Special instructions:

    QT interval. Ziprasidone causes an easy or moderate, dose-dependent, prolongation of the QT interval. In this regard, the drug should not be used together with drugs that also extend the QT interval. In patients with severe bradycardia, caution should be exercised when using Zipsil®.

    Electrolyte disorders such as hypokalemia or hypomagnesemia increase the risk of developing a malignant arrhythmia, so they should be identified before starting ziprasdon therapy.

    If the length of the QT interval is more than 500 msec, it is recommended to stop the use of Zipsil®.

    Malignant neuroleptic syndrome (CNS). ZNS is a rare, potentially dangerous condition associated with the use of antipsychotics, including ziprasidone. Symptoms of the ZNS: increased body temperature (hyperpyrexia), muscle rigidity, changes in mental status and instability of the autonomic nervous system (arrhythmia, fluctuations in blood pressure, tachycardia, profuse sweating, heart rhythm disturbance). When identifying the NSA, it is necessary to immediately abolish the Zipsila® preparation.

    Late dyskinesia. Long-term use of ziprasidone may cause the development of tardive dyskinesia and other extrapyramidal disorders. Particularly predisposed to the development of these complications are patients with bipolar disorders. The incidence of these conditions increases with age, and also depends on the duration of treatment with ziprasidone. When signs and symptoms of tardive dyskinesia appear, you either need to reduce the dose or stop using Zipsil®.

    Convulsions. In patients with episodes of seizures in history, caution should be exercised with Zipsila®.

    Dysfunction of the liver. The experience with ziprasidone in patients with severe hepatic insufficiency is limited, so the drug should be used with caution in this group of patients.

    Increased risk of cerebrovascular disorders among people with dementia. Possible increased risk of cerebrovascular disorders in patients with dementia. The drug Zipsila® should be used with caution in patients with risk factors for stroke.

    When ziprasidone is used, it is possible to develop thromboembolism, incl.thromboembolism of the pulmonary artery and deep vein thrombosis, the incidence of which is not established.

    Effect on the ability to drive transp. cf. and fur:The drug Zipsil® can cause drowsiness, dizziness, tremor, sedation, anxiety, and other side effects, and therefore, during the use of the drug, it is necessary to refrain from driving and potentially dangerous activities that require concentration and speed of psychomotor reactions.
    Form release / dosage:

    Capsules 20 mg, 40 mg, 60 mg, 80 mg.

    Packaging:

    For 10 or 14 capsules per blister (contour cell pack).

    3, 6 or 9 blisters (10 capsules) per pack of cardboard along with instructions for use or 2 or 4 blisters (14 capsules) per pack of cardboard along with instructions for use.

    Storage conditions:

    At temperatures not higher than 30 ° C, in the original packaging.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use the drug after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-000210
    Date of registration:15.02.2011
    Date of cancellation:2018-02-09
    The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp09.02.2018
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