Ziprasidon

When ATH:
N05AE04

Pharmacological action

Antipsychotics (anxiolytic). It has a high affinity for dopamine D₂-receptors and considerably more pronounced affinity for serotonin 5-HT_2A-Receptor. Also interacts with serotonin 5-HT_2FROM-, 5-HT_ID-, 5-HT_1A-receptors; drug affinity for these receptors with an affinity comparable to D₂-receptors or exceeds. It has moderate affinity for the expressed neuronal serotonin and norepinephrine transporters, as well as the histamine H₁-рецепторам и a₁-adrenoceptor. Antagonism at these receptors is associated respectively with sleepiness and orthostatic hypotension.

Ziprasidone practically does not interact with muscarinic m₁-receptors, antagonism which is associated with memory impairment.

Ziprasidone is an antagonist as a serotonin 5-HT_2A-receptors, and dopamine D₂-receptors. The antipsychotic activity, apparently, partly due to blockade of both types of receptors.

Ziprasidone is a potent antagonist of 5-HT_2FROM-, 5-HT_ID-, 5-HT_1A-receptor and inhibits reuptake of norepinephrine and serotonin neurons. Ziprasidone serotonergic activity and its effect on the reuptake of neurotransmitters in neurons associated with antidepressant activity. Блокада 5-HT_1A-receptors results in an anxiolytic effect of ziprasidone. Expressed antagonism to 5-HT_2FROM-receptors determines the antipsychotic activity.

Pharmacokinetics

The pharmacokinetics of ziprasidone linear when taken in doses of 40 to 80 mg 2 times / day after meals. When taken into ziprasidone with meals C_max It reached within 6-8 no. The absolute bioavailability of a dose 20 mg when given after a meal is 60%, in the fasting state is reduced by the absorption of ziprasidone 50%.

At reception 2 times / day equilibrium state is reached within 3 days. Duration Retention equilibrium dose dependent. V_d at equilibrium – 1.5 l / kg. Plasma protein binding is 99% and does not depend on the concentration of.

If ingestion of ziprasidone is largely metabolized, unchanged in the urine and feces displayed a small fraction of the dose (<1% and <4% respectively). In equilibrium, the T_1/2 is 6.6 no, clearance of ziprasidone at / introduction – 7.5 ml / min / kg. It is believed, that there 3 biotransformation way ziprasidone, which lead to the formation of four main metabolites – benzizotiazolpiperazin (BITP) sulfoxide, BITP sulfone, зипрасидона сульфоксида и S-метилдигидрозипрасидона. About 20% excreted in the urine and about 66% – with feces. The proportion of unchanged total of ziprasidone drug and its metabolites in serum is about 44%. CYP3A4 catalyzes the oxidative conversion of ziprasidone. S-metilgidroziprasidon formed by 2 Reactions, catalyzed by aldehyde oxidase and tiometiltransferazoy.

Ziprasidon, S-metildigidroziprasidon sulfoxide, ziprasidone and possess similar properties, that may make the elongation QT interval. S-metildigidroziprasidon write mainly from faeces, as well as being exposed to further metabolism involving CYP3A4, ziprasidone sulfoxide appears kidneys and also with the participation of CYP3A4 metabolized.

In patients with mild or moderate impaired hepatic function (class a or b on a scale Child-Pugh) against the background of cirrhosis: concentration in blood serum were on 30% higher, than in healthy patients, a T_1/2 in the final phase of approximately 2 h more.

Testimony

Prevention and treatment of schizophrenia and other mental disorders.

Dosage regimen

Is the inside. The recommended dose for adults is 40 mg 2 times / day. If necessary, the daily dose can be increased up to the maximum for 3 days. The maximum daily dose – 160 mg (by 80 mg 2 times / day).

In patients with mild or moderate acute human liver dose is recommended to reduce.

Side effect

From the central and peripheral nervous system: asthenia, headache, extrapyramidal syndrome, insomnia or drowsiness, tremor, blurred vision, psychomotor agitation, akathisia, dizziness, dystonic reactions; rarely – convulsions.

With long-term use:, like other antipsychotic means, There is a risk of development of dyskinesias and other remote extrapyramidal syndromes. When signs of psoriasis it is advisable to reduce the dose or discard it:.

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

Other: possible increase in prolactin levels, arterial hypertension, a small increase in body mass index, postural hypotension, tachycardia, skin rash.

Contraindications

Increase the QT interval (incl. congenital long QT syndrome), recently moved myocardial infarction, decompensated heart failure, Arrhythmia, requiring the admission of antiarrhythmics class IA and III, pregnancy, lactation (breast-feeding), hypersensitivity to zipracidonu.

Pregnancy and lactation

Use in pregnancy is contraindicated, except, when the intended benefits to the mother outweighs the potential risk to the fetus. If necessary, use during lactation should stop breastfeeding.

Women of childbearing age should use adequate contraception during treatment due to the lack of clinical data on the safety of pregnancy:.

Cautions

When symptoms, which can be attributed to the grounds of the CSN or unexpectedly high body temperature, not accompanied by other symptoms of CSN, You should immediately cancel antipsihoticalkie, including ziprasidone.

(C) to apply caution in patients with bradycardia, electrolytic disorders, tk. This can lead to longer QT interval or the development of paroxysmal ventricular tachycardia. If the QT interval is greater than 500 Ms, We recommend that you cancel the ziprasidone.

To apply caution in patients with a history of instructions for apnoea.

Experience of application: in patients with severe hepatic insufficiency is missing.

The efficacy and safety of: in patients under the age of 18 years unknown.

Effects on ability to drive vehicles and management mechanisms

To apply caution in patients, engage in potentially hazardous activities, require increased attention and psychomotor speed reactions. Patients should be warned of the possible occurrence of sleepiness in the face of the reception:.

Drug Interactions

In a joint application: medicines, causing QT prolongation (including antiarrhythmics I A and class III), increases the risk of fracture QT interval and paroxysmal ventricular tachycardia (the combination is contraindicated).

When coupled with drugs:, have a depressing effect on the CNS, Perhaps a mutual enhancement of this action (combination requires caution).

Application of ketoconazole in the dose 400 mg / day (CYP3A4 inhibitor) leads to an increase in the concentration of serum: approximately 40%. The concentration of S-metildigidroziprasidona in serum is increased by 55% at the time of admission ketokonazola.