Index of drugs

Treatment of schizophrenia in adults. Treatment of manic and mixed moderate-severity episodes in bipolar disorder in adults, children and adolescents aged 10-17 years (the effectiveness of the drug in preventing the recurrence of bipolar disorder episodes has not been established).

1 hard capsules contain 40 mg or 80 mg of ziprasidone in the form of bisulphate. The preparation contains lactose.

Antipsychotic drugs. Zyprasidone has a high affinity for type 2 dopaminergic receptors (D.₂) and clearly greater affinity for type 2A serotonergic receptors (5HT_2A). It also works on 5HT serotoninergic receptors_2C, 5HT_1D and 5HT_1Awherein its affinity for the binding sites of these receptors is equal to or greater than the affinity for the D-type receptor₂. Has moderate affinity to neuronal transporters of serotonin and norepinephrine and to histamine H-type receptors₁ and α-type receptors₁. It does not show significant affinity for M-type muscarinic receptors₁. Ziprasidon is antagonistic to both 5HT serotonergic receptors_2Aas well as dopaminergic D receptors₂. It is believed that the antipsychotic effect is partly due to the association of the above antagonistic activities. Ziprasidone is also a potent 5HT receptor antagonist_2C and 5HT_1D and the 5HT receptor_1A and a factor inhibiting the reuptake of serotonin and norepinephrine in synapses. After oral administration of multiple doses of ziprasidone during a meal, the maximum concentration of the drug in the blood is observed after 6-8 hours. Absolute bioavailability after a meal the dose of 20 mg is 60%; it can increase by up to 100% in the presence of food. Ziprasidone binds to plasma proteins at> 99%. Zyprasidone used orally is undergoing extensive metabolic changes. It is transformed in three metabolic pathways to 4 major metabolites: benzisothiazolopiperazine sulphoxide (BITP), BITP sulphone, ziprasidone sulfoxide and S-methyl dihydrospyrazodone. Conversion into S-methyl dihydrospyrazide is the major metabolic pathway. Cytochrome P-450 enzymes, mainly CYP3A4, participate in the metabolism with the possible involvement of CYP1A2. It is excreted mainly in the form of metabolites, with urine (20%) and faeces (66%). Medium T_0,5 ziprasidone is 6.6 hours. In mild to moderate hepatic impairment (Child-Pugh grade A or B) caused by cirrhosis, oral blood levels were 30% higher and T_0,5 about 2 hours longer than in patients without liver failure.

Hypersensitivity to ziprasidone or other ingredients of the preparation. QT prolongation found. Congenital syndrome of prolonged QT interval. Fresh myocardial infarction. Uncompensated heart failure. Arrhythmias treated with antiarrhythmic agents from groups IA and III. Concomitant treatment with QT prolonging drugs such as antiarrhythmics from groups IA and III, arsenic trioxide, halofantrine, levometadyl acetate, mesoridazine, thioridazine, pimozide, spparfloxacin, gatifloxacin, moxifloxacin, dolasetron methylsulfonate, meflox, sertindole, cisapride.

Due to the risk of QT prolongation, caution is recommended in patients with significant bradycardia. Electrolyte abnormalities such as hypokalaemia and hypomagnesaemia should be corrected before starting treatment with ziprasidone. In patients with stable cardiac disease, ECG should be considered before starting treatment. If symptoms suggestive of cardiac arrhythmias occur during treatment, consideration should be given to whether or not there has been a malignant arrhythmia and to monitor cardiac function, including by ECG. If QTc> 500 ms is prolonged, it is recommended to discontinue the treatment. Data on the safety and efficacy of ziprasidone in the treatment of schizophrenia in children and adolescents are unknown. In the event of a neuroleptic malignant syndrome (NMS), antipsychotic agents should be discontinued immediately. If symptoms suggestive of tardive dyskinesia occur, dose reduction or discontinuation of ziprasidone should be considered.Caution is advised when treating patients with a history of seizures. In patients with severe hepatic impairment, the preparation should be used with caution. Due to the risk of adverse cerebrovascular events, the drug should be used with extreme caution in patients with risk factors for stroke. In elderly patients with dementia who received antipsychotics, there was a slightly increased risk of death compared to the untreated group - ziprasidone is not approved for use in the treatment of dementia-inducing psychoses. Due to the risk of venous thromboembolism (VTE), all possible VTE risk factors should be identified and appropriate preventive measures should be taken before and during treatment with ziprasidone. Ziprasidone may increase the concentration of prolactin; long-lasting hyperprolactinemia, when accompanied by hypogonadism, may lead to a decrease in bone mineral density and increase the risk of fractures. The preparation contains lactose - should not be used in patients with congenital galactose intolerance, Lapp lactase deficiency or impaired glucose-galactose absorption.

It should not be used during pregnancy unless clearly necessary. If you need to stop treatment during pregnancy, the drug should not be withdrawn suddenly. Women of childbearing potential should be advised to use effective contraception during treatment with ziprasidone. Pregnancy is not recommended if the expected benefit to the mother does not outweigh the potential risk to the fetus. Newborns exposed to antipsychotics (including ziprasidone) during the third trimester of pregnancy are at risk of developing adverse reactions of various degrees of severity and duration including extrapyramidal symptoms and / or withdrawal - neonates should be carefully monitored. The drug should not be used during breast-feeding; If the use of ziprasidone is necessary, breast-feeding should be discontinued.

Common: restlessness, dystonia, akathisia, extrapyramidal disorder, parkinsonism (including symptom of the toothed wheel, slowness of movement, hypokinesis), tremor, dizziness, sedation, drowsiness, headache, blurred vision, nausea, vomiting, constipation, indigestion, dryness oral mucosa, excessive salivation, musculoskeletal stiffness, weakness, fatigue. Uncommon: increased appetite, agitation, anxiety, tightness in the throat, nightmares, generalized tonic-clonic convulsions, tardive dyskinesias, dyskinesias, salivation, ataxia, speech disorders, forcible vision with eye rotation, impaired concentration, excessive need sleep, hypoesthesia, paresthesia, lethargy, palpitations, tachycardia, photophobia, dizziness, tinnitus, hypertensive crisis, hypertension, orthostatic hypotension, hypotension, dyspnoea, sore throat, diarrhea, dysphagia, gastritis, discomfort in the gastrointestinal tract , swelling of the tongue, thickening of the tongue, flatulence, urticaria, rash, maculopapular rash, acne, musculoskeletal discomfort, muscle spasm, limb pain, stiffness of the joints, increased liver enzymes, chest discomfort, gait disturbances, pain, thirst. Rarely: rhinitis, hypocalcaemia, panic attacks, depressive symptoms, mental retardation, shallower affect, anorgasmia, torticollis, paresis, immobility, increased tension, restless legs syndrome, lymphopenia, increased eosinophils, QT prolongation on the ECG, amblyopia, vision disorder, eye pruritus, dry eye mucosa, ear pain, systolic hypertension, diastolic hypertension, blood pressure fluctuations, hiccups, gastro-oesophageal reflux, loose stools, psoriasis, allergic dermatitis, alopecia, face edema, erythema, rash follicular, skin irritation, lacrimation, urinary incontinence, dysuria, erectile dysfunction, increased erections, galactorrhea, gynecomastia, abnormal liver function tests, fever, feeling hot, increased lactate dehydrogenase activity. Frequency unknown: insomnia, mania, hypomania, neuroleptic malignant syndrome, serotonin syndrome, face drooping,torsade de pointes, fainting, venous thromboembolism, hypersensitivity, angioneurotic edema, involuntary urination, priapism, neonatal withdrawal syndrome, anaphylactic reaction. The most common side effects (reported with a frequency of> 10%) in children and adolescents with bipolar disorder were: sedation, drowsiness, headache, fatigue, and nausea. The frequency, type and severity of adverse reactions in this patient population were generally similar to those found in adult patients. Administration of ziprasidone in the pediatric group with bipolar disorder was associated with mild to moderate dose-related QT interval prolongation, which was also observed in adult population studies. In clinical studies in the pediatric group with bipolar disorder, there were no cases of tonic seizures and hypotension.

Orally.Adults. For the treatment of exacerbation of schizophrenia and manic episode in bipolar disorder: 40 mg twice daily. This dose may be increased depending on the clinical condition of the patient, up to a maximum of 80 mg twice daily. If indicated, the maximum recommended dose can be used from the 3rd day of treatment. The safety profile of doses> 160 mg / day has not been confirmed. For maintenance treatment of patients with schizophrenia, the lowest effective dose should be used; in many cases a dose of 20 mg 2 times a day is sufficient.Special groups of patients. In elderly patients, a lower starting dose is not usually indicated, but consideration should be given to administering such a dose to patients> 65 years of age if there is clinical justification. No dose adjustment is required in patients with renal insufficiency. In patients with hepatic impairment, a dose reduction should be considered.Children and youth. In the treatment of acute conditions in the course of bipolar disorder in children and adolescents (aged from 10 to 17 years): 20 mg in a single daily dose on day 1 of treatment. On the following days, zypryzodone should be administered in 2 divided doses, with the daily dose gradually increased over a period of 1-2 weeks, until the target values ​​reach 120-160 mg / day in patients with bw. ≥45 kg or 60-80 mg / day in patients with an <45 kg. In the later period, the doses should be selected based on the individual clinical condition in the range of 80-160 mg / day in patients with bw. ≥45 kg or 40-80 mg / day in patients with an <45 kg. In the clinical trial, an uneven distribution of divisional doses was allowed, with the morning dose being 20 mg or 40 mg lower than the evening dose. The safety profile of ziprasidone in doses> 160 mg / day for children of the month has not been confirmed. ≥45 and> 80 mg / day for children at <45kg. The drug should be taken during a meal.