Zeldox - instructions for use, doses, side effects, contraindications

Active substanceZiprasidoneZiprasidone

Similar drugsTo uncover

Zeldox®

lyophilizate w / m

Pfizer Inc. USA

Zeldox®

capsules inwards

Pfizer Manufakchuring Deutschland GmbH Germany

Zipsil®

capsules inwards

KRKA-RUS, LLC Russia

Dosage form: & nbsp

Lyophilizate for the preparation of solution for intramuscular injection.

Composition:

Lyophilizate:

Active ingredient: ziprasidone mesylate trihydrate 40.93 mg (equivalent to 30 mg ziprasidone).

Excipients: Cyclodextrin sodium sulfobutylate (SBECD) 441.49 mg.

Solvent:

Water for injection 1.4 ml (taking into account the necessary excess in 0.2 ml for a guaranteed withdrawal of 1.2 ml).

Description:

Lyophilizate: White or almost white lyophilizate;

Reconstituted solution: Clear colorless solution;

Solvent (water for injection): Transparent colorless liquid.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic).

ATX: & nbsp

N.05.A.E.04 Ziprasidone

Pharmacodynamics:

Ziprasidone is an antagonist of both serotonin receptors 2_a (5-HT_2a) type, and type 2 dopaminergic receptors (D₂), which determines the antipsychotic activity of the drug.

Ziprasidone is also a potent antagonist of 5-HT_2c, 5-HT₁_d and a potent 5-HT agonist_1Areceptors (the affinity of the drug for these receptors is comparable to that of D₂ receptors or exceeds it) and inhibits the reuptake of norepinephrine and serotonin in neurons. Serotonergic activity of ziprasidone and its effect on the reuptake of neurotransmitters in neurons are associated with antidepressant activity. Agonism of 5-HT_1Areceptors causes anxiolytic effects. Strong antagonism to 5-HT_2c receptors determines possible antipsychotic activity. Ziprasidone oppresses the reverse neuronal seizure of serotonin and norepinephrine. An affinity for H₁-gistaminovym and alpha₁adrenoreceptors. Antagonism to these receptors causes the possibility of developing drowsiness and orthostatic hypotension, respectively. Ziprasidone practically does not interact with m-holinoretseptorami (antagonism to these receptors is associated with memory impairment).

According to positron emission tomography (PET), the degree of blockade of serotonin receptors 2_a type at 12 hours after a single dose of the drug inside at a dose of 40 mg is 80%, and D₂ receptors - 50%.

A significant improvement in the state of psychomotor agitation is observed in patients after 15 minutes and is kept from 1 to 2 hours after administration of 10 mg of ziprasidone and from 30 minutes to 4 hours after the administration of 20 mg of ziprasidone.

Pharmacokinetics:

Bioavailability of ziprasidone with intramuscular injection is 100%.

After a single intramuscular injection, the serum concentration reaches a maximum in about 60 minutes or earlier. The average half-life period ranges from 2 to 5 hours. The concentration of the drug increases in accordance with the increase in the dose, and after a 3-day intramuscular application, cumulation is negligible.

The average systemic clearance of ziprasidone for intravenous administration is 7.5 ml / min / kg, and the volume of distribution is 1.5 l / kg. Ziprasidone more than 99% bind to serum proteins and the degree of binding does not depend on the concentration of the drug.

There are 3 ways of biotransformation of ziprasidone, which lead to the formation of 4 main metabolites - benzothiazolpiperazine (BITP) sulfoxide, BITP sulfone, ziprasidone sulfoxide and S-methyldihydrosiprasidone. Approximately 20% of the dose is excreted by the kidneys and approximately 66% by the intestine. The proportion of unchanged ziprasidone from the total drug and its metabolites in the serum is about 44%.

Isozyme CYP3A4 (the most important of the cytochromes P450) catalyzes the oxidative conversion of ziprasidone.S-methyldihydroziprasidone is formed as a result of 2 reactions catalyzed by aldehyde oxidase and thiolmethyltransferase.

Ziprasidone, S-methyldihydroziprasidone and ziprasidone sulfoxide have similar properties that can cause prolongation of the Q-T interval. S-methyldihydroziprasidone is excreted primarily by the intestine and by transformations catalyzed by the CYP3A4 isoenzyme. Ziprasidone sulfoxide is excreted by renal excretion and secondary metabolism under the action of the CYP3A4 isoenzyme.

Clinically significant dependence of the pharmacokinetics of ziprasidone on age or sex with oral administration was not noted.

Significant changes in the pharmacokinetics of ziprasidone in patients with severe and moderate impairment of kidney function when taken orally compared to healthy volunteers have not been identified.

In patients with mild or moderate impairment of liver function (Child-Pugh class A or B), the serum ziprasidone concentrations are 30% higher than in healthy volunteers and the half-life is approximately 2 hours longer with cirrhosis.

Indications:

Suppression of psychomotor agitation in patients with schizophrenia.

Contraindications:

increased sensitivity to ziprasidone or any other component of the drug;
prolongation of the Q-T interval in the history, including congenital syndrome of the extended interval Q-T;
acute and subacute stage of myocardial infarction;
heart failure in the stage of decompensation;
joint administration of drugs extending the Q-T interval, in particular antiarrhythmic agents of classes IA and III, arsenic anhydride, halofantrine, methadone, mesoridazine, thioridazine, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, dolasatron, mefloquine, sertindole or cisapride. (see section "Special instructions");
Patients with psychosis due to dementia.

The efficacy and safety of ziprasidone in patients under the age of 18 years and in elderly people over 65 years of age have not been established.

Carefully:

Elongation of the Q-T interval, myocardial infarction, unstable angina

It is believed that there is a relationship in the occurrence of Q-T lengthening and paroxysmal ventricular arrhythmia (torsade des pointes), which is potentially life-threatening (a similar effect is caused by some drugs, including antiarrhythmic drugs 1A and III class (seesection Contraindications)).

When observing the symptoms that confirm the occurrence of arrhythmia during the treatment with ziprasidone, a cardiac function examination should be performed. If the QTc interval exceeds 500 ms, it is recommended to stop treatment (see Contraindications section). There were rare cases of the occurrence of paroxysmal ventricular arrhythmia (torsade de pointes) in patients with multiple sour risk factors taking ziprasidone in the postmarketing period, although a causal relationship with the drug was not established.

Ziprasidone should be administered with caution to patients with the following risk factors that may aggravate the occurrence of such an arrhythmia:

bradycardia;

electrolyte imbalance;

use with other drugs that extend the Q-T interval.

Caution should be exercised when prescribing ziprasidone to patients who have recently undergone myocardial infarction, as well as to patients with unstable angina, as the efficacy and safety of ziprasidone in patients with these diseases has not been established.

Application for renal dysfunction

Intramuscularly with patients with impaired renal function ziprasidone should be used with caution, because cyclodextrin, as an auxiliary component of the drug, is able to be excreted by glomerular filtration.

Application for violations of liver function

Experience with ziprasidone in patients with severe hepatic insufficiency is absent, so the drug should be used cautiously in this group (see Pharmacokinetic properties section).

Convulsions

Care should be taken when treating patients with cramps in an anamnesis.

Diabetes

Patients with diabetes mellitus, after initiation of therapy with atypical antipsychotics, need regular monitoring of blood glucose concentrations. In the presence of risk factors for diabetes mellitus (in particular, obesity, the presence of diabetes in the family history) in patients who started treatment with atypical antipsychotics, it is necessary to determine the concentration of fasting blood glucose during the initiation of such therapy and periodically during it. It is necessary to monitor all patients taking atypical antipsychotics for manifestations of hyperglycemia, including polydipsia, polyuria, polyphagia and weakness.With the development of these manifestations against the background of taking atypical antipsychotics, it is necessary to determine the concentration of glucose in the blood on an empty stomach. In some cases, hyperglycemia is eliminated after the abolition of an atypical antipsychotic; however, some patients require the continuation of hypoglycemic therapy even after the withdrawal of the intended drug that caused the disorder.

Arterial hypotension.

Ziprasidone can provoke arterial hypotension, accompanied by dizziness, tachycardia and, in some patients, fainting, especially during the initial period of dose titration, which is probably due to its a₁adrenoblocking activity. Cases of syncope were noted in 0.6% of patients who received ziprasidone. Ziprasidone should be used with extreme caution in patients with cardiovascular pathology (with a history of myocardial infarction or coronary heart disease, heart failure or conduction disorders), cerebrovascular pathology or other conditions predisposing to arterial hypotension (dehydration, hypovolemia, and also receiving other antihypertensive agents ).

Aspiration pneumonia

Aspiration pneumonia is a frequent condition that occurs in elderly patients, in particular, with severe dementia due to Alzheimer's disease. Ziprasidone and other antipsychotics should be used with caution in patients at risk for aspiration pneumonia.

Pregnancy and lactation:

Application in pregnancy

Women of reproductive age should use a reliable method of contraception. Given the limited experience of using the drug in humans, ziprasidone It is not recommended to prescribe during pregnancy, except when the expected benefit of treatment for the mother justifies the possible risk to the fetus.

Application when breastfeeding

It is not known whether ziprasidone with breast milk. In the treatment of ziprasidone, women should be cautioned against stopping breastfeeding.

Dosing and Administration:

Only for intramuscular injection. Do not administer intravenously!

Adults

The recommended dosage is from 10 mg to 20 mg (maximum 40 mg / day). Doses of 10 mg can be administered every 2 hours; a dose of 20 mg can be administered every 4 hours (maximum 40 mg / day).The efficacy of ziprasidone for intramuscular administration for more than 3 days has not been studied.

If long-term therapy is required, the patient should be transferred from the intramuscular injection as soon as possible to receive ziprasidone capsules inside.

Application for violations of liver function

In patients with hepatic insufficiency, the dose should be reduced in proportion to the severity of the disease.

Application for smokers

Dose changes in smokers are not required.

Instructions for preparing a solution.

The contents of the vial are dissolved in 1.2 ml of the supplied water for injection; the concentration of the resulting solution is 20 mg of ziprasidone per ml. The vial is shaken until the powder is completely dissolved. You can use only a transparent solution that does not contain visible inclusions. From each vial, you should only take one dose of the drug, and the remainder must be poured.

Side effects:

The most frequent adverse reactions were nausea, sedation, dizziness, pain at the injection site, headache and drowsiness.

All unwanted reactions are listed with the distribution by class and frequency: very often (> 1/10), often (> 1/100, but <1/10), infrequently (> 1/1000, but <1/100) and rarely <1/1000).

The undesirable reactions listed below could also be associated with concomitant pathology and / or concomitant medications.

Disorders from food and metabolism: infrequently - anorexia.

Disorders of the psyche: infrequently - agitation, antisocial behavior, psychotic disorder, sleep disturbance, tics, anxiety, personality disorders, speech disorders.

Impaired nervous system: Often - akathisia, dizziness, dystonia, headache, sedation, drowsiness. Infrequent - muscle rigidity as a "cogwheel", postural dizziness, dysarthria, dyskinesia, dyspraxia, parkinsonism, tremor, hypertension, paresthesia, extrapyramidal syndrome.

Heart Disease: infrequently bradycardia, tachycardia.

Disturbances from the organs of hearing and balance: infrequently - vertigo.

Disorders from the vascular system: often - increased blood pressure. Infrequent - hyperemia, orthostatic hypotension. Rarely, vasodilation.

Disturbances from the respiratory system, chest and mediastinal organs: infrequently - laryngospasm, rhinitis, chest pain.

Disorders from the gastrointestinal tract: often - nausea, vomiting. Infrequent - constipation, diarrhea, dryness of the oral mucosa. Rarely - rectal bleeding, dyspepsia, dental diseases, abdominal pain.

Disturbances from the skin and subcutaneous tissue: Infrequently - a hyperhidrosis, a furunculosis.

Disturbances from the musculoskeletal system and connective tissue: often - rigidity of muscles. Rarely, pain in the back.

Disorders from the kidneys and urinary tract: rarely - dysmenorrhea.

General disorders and complications at the site of administration: often - asthenia, burning at the injection site, pain at the injection site. Infrequent - the "withdrawal" syndrome, fatigue, flu-like syndrome, discomfort at the injection site, irritation at the injection site, fever.

Laboratory and instrumental data: infrequently - lowering blood pressure, increasing the activity of liver enzymes.

The most frequent cardiovascular adverse events reported in clinical studies of intramuscular administration of fixed doses of ziprasidone were dizziness (10 mg - 11%, 20 mg - 12%), tachycardia (10 mg - 4%, 20 mg - 4%), postural dizziness (10 mg - 2%, 20 mg - 2%), orthostatic hypotension (20 mg - 5%) and reduction of blood pressure (10 mg - 2%).

In pre-registration clinical studies of intramuscular administration of fixed doses of ziprasidone, an increase in blood pressure was noted in 2.2% of patients receiving the drug at a dose of 10 mg; In addition, an increase in blood pressure was registered in 2.8% of patients who received ziprasidone in a dose of 20 mg.

Post-marketing data

Immune system disorders: allergic reactions (such as allergic dermatitis, angioedema, edema of the face, urticaria).

Disorders of the psyche: mania / hypomania.

Impaired nervous system: dystonia, paralysis / paresis of the facial nerve, serotonin syndrome (when used as a monotherapy or in combination with serotonergic drugs).

Heart Disease: tachycardia, flutter / torsade de pointes (see "With caution").

Vascular disorders: postural hypotension, fainting.

Disturbances from the gastrointestinal tract: dysphagia, edema of the tongue.

Disturbances from the skin and subcutaneous tissues: rash.

Disorders from the kidneys and urinary tract: enuresis, urinary incontinence.

Violations of the genitals and breast: priapism, galactorrhea.

Malignant neuroleptic syndrome (CNS): when using antipsychotic drugs, cases of CNS, which is a rare but potentially fatal complication, have been observed. Clinical manifestations of CNS are fever (hyperpyrexia), muscle rigidity, changes in mental status and signs of instability in the autonomic nervous system (fluctuations in heart rate or changes in blood pressure, tachycardia, profuse sweating, arrhythmias).

Additional signs may include increased activity of creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Diagnosis of this syndrome is difficult. It is necessary to exclude cases in which a serious illness is combined (for example, pneumonia, systemic infection, etc.) and the symptoms of extrapyramidal disorders, for which therapy was not performed or was inadequate. Other conditions that should be considered in differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary pathology of the central nervous system.If a patient develops symptoms that can be attributed to signs of the NSH, or if a high body temperature suddenly appears, not accompanied by the emergence of other symptoms of the NSA, all antipsychotics should be immediately discontinued, including ziprasidone, to carry out intensive symptomatic therapy and careful monitoring of the patient's condition, to administer serious complications for which it is possible to apply specific treatment. There is no general strategy for specific pharmacological therapy of NSA. If the patient needs further antipsychotic therapy after relief of symptoms of the NSH, consideration should be given to re-starting treatment with minimal doses.

It is necessary to carefully monitor the patient's condition, since there are reports of the resumption of symptoms of the NSA.

ZNS cases were noted in the post-marketing application of Zeldoke®.

Late dyskinesia: With prolonged use of ziprasidone, as well as other antipsychotics, there is a risk of developing tardive dyskinesia and other distant extrapyramidal syndromes.

It is assumed that this syndrome is more likely to develop in patients receiving long-term therapy with ziprasidone in high doses. In addition, with increasing dose and duration of therapy, the risk of irreversibility of this syndrome increases. Nevertheless, this complication is less likely to develop after a short course of therapy with low doses of the drug. Specific treatment of this syndrome is not known, but the symptoms may disappear completely or partially with the withdrawal of ziprasidone therapy. In turn, antipsychotic therapy can suppress (or partially suppress) the symptoms of tardive dyskinesia and, thus, mask the signs of this syndrome. Given this, ziprasidone in such a way as to minimize the risk of developing tardive dyskinesia. Long-term treatment should be used in patients with a chronic disease that responds to antipsychotics and for whom there is no alternative, safer therapy. In patients with prolonged treatment, the lowest effective doses of the drug should be used in the shortest courses,which will have a therapeutic effect. Periodically, assess the need for continued treatment. When there are signs of late dyskinesia, it is advisable to reduce the dose of ziprasidone or to cancel it. However, some patients may require continued therapy, despite the symptoms of tardive dyskinesia.

An increase in the incidence of death on the background of the use of neuroleptics in elderly patients with dementia, combined with psychosis.

In elderly patients with psychosis caused by dementia, the risk of death is increased with the use of some neuroleptics compared with placebo. The results obtained during the research of ziprasidone do not allow to conclude that the risk of death in elderly patients with psychosis caused by dementia increases, against the background of taking the drug. Nevertheless, ziprasidone It is not recommended for treatment of this category of patients. Most deaths were caused by cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) disorders. It is assumed that, like atypical antipsychotics, against the background of the use of typical antipsychotics, there may be an increase in mortality.It is not clear to what extent the increase in mortality is due to the use of atypical antipsychotics or to the particular patient.

Overdose:

Information about an overdose of ziprasidone is limited. In the case of a maximum confirmed dose of 12800 mg, extrapyramidal symptoms and lengthening of the Q-T interval up to 446 ms (without cardiac dysfunction) were noted. The main symptoms of overdose are extrapyramidal disorders, drowsiness, tremors and anxiety. If you suspect an overdose, you should consider the possibility of interaction of several drugs.

There is no specific ziprasidone antidote. In acute overdose, it is necessary to restore and maintain airway patency and provide adequate ventilation and oxygenation. The oppression of consciousness, the possibility of cramps or dystonic reaction of the neck muscles after an overdose create a threat of aspiration with induced vomiting. It is necessary to immediately begin monitoring the function of the cardiovascular system, including continuous registration of the ECG in order to identify possible arrhythmias. Given that ziprasidone is largely associated with plasma proteins, hemodialysis in case of an overdose is not indicated. The patient must remain under medical supervision until the symptoms of intoxication disappear completely.

Interaction:

Antiarrhythmic agents IA and class III and other drugs extending the Q-T interval

See "With caution" and "Contraindications".

Drugs acting on the central nervous system / alcohol

Ziprasidone has a depressing effect on the central nervous system, so care must be taken when it is used in combination with alcohol and other drugs that affect the central nervous system, including drugs acting on dopaminergic and serotonergic systems.

All studies on drug interaction were conducted using ziprasidone for oral administration.

The effect of other drugs on ziprasidone

Ziprasidone is metabolized by aldehyde oxidase and, to a lesser extent, isoenzyme CYP3A4. Clinically significant inhibitors or inducers of aldehyde oxidase are unknown. Inhibitor of isoenzyme CYP3A4 ketoconazole (at a dose of 400 mg / day) increased the concentration of ziprasidone in serum by less than 40%.The concentration of S-methyldihydrosiprasidone in serum at the expected time point Tmax of ziprasidone was increased by 55%. There was no additional elongation of the Q-T interval. The likelihood of a change in the pharmacokinetics of ziprasidone when co-administered with inhibitors of the isoenzyme CYP3A4 is small, so no correction of the doses of both agents is required in this case. The use of carbamazepine (200 mg twice daily), the inductor of the isoenzyme CYP3A4, leads, in turn, to a decrease in the area under the concentration-time curve (AUC) by 36%, which is also unlikely to be of clinical significance.

Cimetidine - has no significant effect on the pharmacokinetics of ziprasidone. Benzathropine, propranolol, lorazepam - do not have a clinically significant effect on the pharmacokinetic parameters of ziprasidone concentration in the serum.

Dextromethorphan

In accordance with the results of in vitro studies and clinical studies on healthy volunteers, it was shown that ziprasidone did not mediate through the isozyme CYP2D6 effect on the metabolism of dextromethorphan and its main metabolite dextrorphan.

Lithium

Ziprasidone does not affect the pharmacokinetics of lithium preparations when combined.

Connection with proteins

Ziprasidone is largely associated with plasma proteins. The binding of ziprasidone to blood plasma proteins in vitro did not change under the action of warfarin or propranolol - two drugs highly binding to plasma proteins; ziprasidone also did not change the binding of these drugs to human plasma proteins. Thus, the interaction of drugs with ziprasidone, caused by displacement from the bond with proteins, is unlikely.

Pharmaceutical properties

Incompatibility: The preparation should not be mixed with other preparations or solvents, except for water for injection.

Special instructions:

After relieving psychomotor agitation, it is advisable to transfer patients to oral intake of the drug.

As with intramuscular injection of other antipsychotics, deaths have been reported with ziprasidone, mainly in patients with multiple concomitant risk factors. Although there is no relationship between ziprasidone and these cases, caution should be exercised with intramuscular injection of Zeldox®.

It is recommended to monitor the concentration of potassium and magnesium in the blood plasma in patients with an increased risk of significant electrolyte disturbances, especially hypokalemia.

Hypokalemia (and / or hypomagnesemia) may increase the risk of prolonging the Q-T interval and arrhythmia. To hypokalemia, diuretics, diarrhea and other causes may result. Before continuing therapy in patients with low potassium and / or magnesium levels, these disorders should be eliminated. It is important to periodically monitor the content of electrolytes in the blood plasma in patients treated with diuretics during therapy with ziprasidone. Elongation of the QTc interval for a long time may also increase the risk of further lengthening and arrhythmia, but it is not known whether ECG is sufficient to detect such patients. Ziprasidone should be avoided in patients who have recently had myocardial infarction in patients with heart failure decompensation or heart rhythm disturbances.

Patients experiencing symptoms similar to the occurrence of paroxysmal ventricular arrhythmia (torsade de pointes) should be monitored for the condition of the cardiovascular system.Perhaps Holter monitoring can be useful.

In clinical studies, seizures were noted in 0.4% of cases. In many cases, patients had concomitant factors that could contribute to the development of seizures. As with other antipsychotics, caution should be exercised when using ziprasidone in patients with a history of seizures or with conditions that may reduce the convulsive threshold, such as Alzheimer's. It should be borne in mind that the conditions under which the convulsive threshold can be reduced are more typical for patients aged 65 years and older.

In clinical studies, there have been cases of development of leukopenia / neutropenia, as well as agranulocytosis (in some cases, with a fatal outcome).

Possible risk factors for the development of leukopenia / neutropenia include: an available reduction in the number of white blood cells, and a history of leukopenia / neutropenia induced by drugs. In these patient groups, a clinical blood test should be performed regularly during the first few weeks of therapy and if the first signs of abnormality appearthe number of white blood cells in the absence of other apparent causes, it is necessary to cancel ziprasidone therapy.

Patients with neutropenia should be closely monitored for the development of fever or other symptoms of the infection and, if they occur, appropriate treatment should be provided. In patients with severe neutropenia (absolute number of neutrophils <1000 m3), ziprasidone therapy should be discontinued and the number of white blood cells should be controlled until normal numbers are restored.

In 5% of cases in patients receiving ziprasidone, noted the development of rash / hives. In one sixth of these patients, this side effect led to the withdrawal of therapy. The occurrence of the rash was associated with the dose of ziprasidone, although this may also be due to a longer exposure to the drug in patients taking ziprasidone in high doses. Several patients reported symptoms of coexisting systemic diseases, for example, an increase in the number of white blood cells. In most patients, the symptoms went away with the use of antihistamines or glucocorticosteroids and / or after the drug was discontinued. All patients reported full recovery.If rashes occur and there is no other apparent cause, ziprasidone should be discontinued.

The possibility of suicidal attempts is characteristic for patients with psychotic or bipolar disorder. In this regard, careful monitoring of patients at high risk of this reaction is recommended. The patient should be prescribed the minimum amount of Zeldox® needed to reduce the risk of overdose.

When Zeldox® was used, cases of priapism were reported. As with other antipsychotics, this reaction does not depend on the dose of the drug and the duration of therapy. Severe cases of priapism may require surgical treatment.

When using antipsychotics, there were cases of impaired thermoregulation (a violation of the mechanism for reducing elevated body temperature). This effect was not observed in patients receiving ziprasidone, nevertheless caution should be exercised when using ziprasidone in patients with conditions predisposing to a rise in body temperature (for example, intensive physical exercise, exposure to high temperatures, use of drugs with anticholinergic action or condition dehydration).

Effect on the ability to drive transp. cf. and fur:

Like most psychotropic drugs, ziprasidone causes drowsiness and other side effects that may affect the ability to drive vehicles, etc. This should be prevented by patients who can drive a car or dangerous machinery.

Form release / dosage:

Lyophilizate for the preparation of a solution for intramuscular injection of 30 mg.

Packaging:

Lyophilizate: 30 mg of lyophilizate per 5 ml bottle of transparent colorless glass (type I) with a rubber stopper and an aluminum sealed cap with a plastic flip-off cap.

Solvent (water for injection) 1.4 ml in a vial of clear, colorless glass.

For 1 bottle and 1 ampoule together with instructions for use in a cardboard pack.

Storage conditions:

In the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

The bottle should be stored in the original carton.

Avoid freezing, to avoid damage to the ampoule with the drug's solvent.

Shelf life:

3 years. Do not use after the expiry date printed on the package.

The chemical and physical stability of the prepared solution was established for 24 hours at a temperature of up to 25 ° C and 7 days at 2-8 ° C. However, from the microbiological point of view, the drug solution should be used immediately or after no more than 24 hours of storage at 2 ° -8 ° C.

Terms of leave from pharmacies:On prescription

Registration number:П N015868 / 01

Date of registration:18.09.2009

The owner of the registration certificate: Pfizer Inc. Pfizer Inc. USA

Manufacturer: & nbsp

PHARMACIA & UPJOHN COMPANY USA

Representation: & nbspPfizer H. Si. Pi. CorporationPfizer H. Si. Pi. Corporation

Information update date: & nbsp12.08.2015

Illustrated instructions

Instructions

Zeldox® (Zeldox®)