Calculation of the rate of administration of dobutamine. Calculation of doses in various dosage forms

Excites dopamine, beta-adrenergic receptors (in low and medium doses) and alpha-adrenergic receptors (in high doses). Improvement in systemic hemodynamics leads to a diuretic effect. Has a specific stimulating effect on postsynaptic dopamine receptors in smooth muscle vessels and kidneys.

At low doses (0.5-3 mcg/kg/min) acts predominantly on dopamine receptors, causing an expansion of the renal, mesenteric, coronary and cerebral vessels. It has a positive inotropic effect. Expansion of the vessels of the kidneys leads to an increase in renal blood flow, an increase in the glomerular filtration rate, an increase in diuresis and sodium excretion; there is also an expansion of the mesenteric vessels (this action of dopamine on the renal and mesenteric vessels differs from the action of other catecholamines).

In medium doses (2-10 mcg / kg / min) dopamine stimulates postsynaptic beta 1-adrenergic receptors, has a positive inotropic effect (due to increased contractile function of the myocardium) and increases cardiac output. Systolic blood pressure and pulse pressure may increase; while diastolic blood pressure does not change or slightly increases. Coronary blood flow and myocardial oxygen consumption tend to increase. Stimulation of beta 2 -adrenergic receptors is negligible or absent, so the total peripheral vascular resistance (TPVR) usually does not change. Peripheral blood flow may slightly decrease, mesenteric blood flow increases.

At high doses (10 mcg/kg/min or more) predominantly stimulates alpha 1-adrenergic receptors, causes an increase in peripheral vascular resistance, an increase in heart rate and narrowing of the renal vessels (the latter may reduce previously increased renal blood flow and diuresis). Due to the increase in minute volume of blood and peripheral vascular resistance, both systolic and diastolic blood pressure increase.

Start therapeutic effect- within 5 minutes against the background of intravenous administration. After cessation of administration, the effect persists for 10 minutes. Newborns and children younger age more sensitive to the vasoconstrictor action of dopamine than adults.

Dopamine is administered only intravenously. About 25% of the administered dose is captured by neurosecretory vesicles, where hydroxylation occurs and is formed. It is widely distributed in the body (volume of distribution in adults 0.89 l / kg), partially passes through the blood-brain barrier. Communication with blood plasma proteins - 50%.

Dopamine is rapidly metabolized in the liver, kidneys and blood plasma by monoamine oxidase and catechol-O-methyltransferase to inactive metabolites of homovanillic acid (HVA) and 3,4-dihydroxyphenylacetate.

The half-life of the drug (T 1/2) - adults: from blood plasma - 2 minutes; from the body - 9 min; the total clearance of dopamine is 4.4 l / kg / hour. Excreted with urine; 80% of the dose of dopamine is excreted within 24 hours in the form of metabolites, in small quantities - unchanged. In children under 2 years of age, dopamine clearance is doubled compared to adults. In newborns, there is a significant variability in dopamine clearance (5-11 minutes, on average 6.9 minutes). The apparent volume of distribution in neonates is 1.8 L/kg.

Shock of various origins: cardiogenic, postoperative, infectious toxic, anaphylactic, hypovolemic (after restoration of circulating blood volume);

Acute cardiovascular failure;

Syndrome of "low minute volume of blood circulation" in cardiac surgery patients;

Severe arterial hypotension.

Hypersensitivity to the components of the drug (including other sympathomimetics);

thyrotoxicosis;

Pheochromocytoma;

In combination with monoamine oxidase inhibitors, with cyclopropane and halogen-containing agents for general anesthesia;

With uncorrected supraventricular and ventricular tachyarrhythmias (including with tachysystolic atrial fibrillation) and with ventricular fibrillation;

Angle-closure glaucoma;

Age up to 18 years (efficacy and safety not established).

hypovolemia;

Pathological conditions leading to obstruction of the outflow tract of the left ventricle (hypertrophic obstructive cardiomyopathy, severe aortic stenosis);

Metabolic acidosis, hypercapnia, hypoxia, hypokalemia;

Peripheral arterial disease (including atherosclerosis, arterial thromboembolism, thromboangiitis obliterans, obliterating endarteritis, diabetic angiopathy, Raynaud's disease), frostbite of the extremities;

Acute myocardial infarction;

Heart rhythm disturbances;

Arterial hypotension in the pulmonary circulation;

Diabetes;

Bronchial asthma;

Pregnancy.

Preclinical studies have shown that when administered intravenously at doses up to 6 mg / kg / day, it did not have a teratogenic and fetotoxic effect in rats and rabbits, but increased the mortality of pregnant female rats. Available clinical data are insufficient to assess the fetotoxic and teratogenic effects of dopamine when used during pregnancy.

In pregnant women, the drug should be used only if the expected benefit to the mother exceeds potential risk for the fetus and/or child.

Data on the penetration of dopamine through the placenta and on the excretion of the drug in breast milk missing. When using the drug Dopamine, breastfeeding should be discontinued.

Dopamine is administered intravenously as a continuous infusion using appropriate equipment (infusion pumps).

The dose of the drug and the rate of administration should be selected individually, depending on the severity of shock, the magnitude of blood pressure and the patient's response to treatment.

To increase diuresis and achieve a positive inotropic effect (increase contractile activity myocardial) Dopamine is administered at a rate of 100-250 mcg / min (1.5-3.5 mcg / kg / min - the area of ​​\u200b\u200blow doses).

In intensive surgical therapy Dopamine is administered at a rate of 300-700 µg/min (4-10 µg/kg/min is the medium dose range).

For septic shock Dopamine is administered at a rate of 750-1500 mcg / min (10.5-20 mcg / kg / min - area maximum doses).

Most patients will be able to maintain a satisfactory condition with doses of Dopamine less than 20 mcg/kg/min. In some cases, the dose in order to influence the blood pressure of Dopamine can be increased to 40-50 mcg / kg / min or more. If the effect of continuous infusion of Dopamine is insufficient, norepinephrine () may be additionally prescribed at a dose of 5 μg / min (with a patient's body weight of about 70 kg).

When violations occur or increase heart rate further increase in the dose of Dopamine is contraindicated.

The duration of dopamine administration depends on individual characteristics patient. Available positive experience Dopamine infusions for up to 28 days. After stabilization of the patient's condition, the drug is discontinued gradually.

Solution preparation rule: 0.9% sodium chloride solution, 5% dextrose (glucose) solution (including mixtures thereof), 5% dextrose (glucose) solution in Ringer's lactate solution, sodium lactate solution and Ringer's lactate are used for dilution.

In order to prepare a solution for intravenous infusion, 400 or 800 mg of dopamine must be added, respectively, to 250 ml or 500 ml of the above solvents. The resulting solution contains 1600 micrograms of dopamine per ml.

The preparation of the infusion solution should be made immediately before use (the stability of the solution is maintained for 24 hours, with the exception of a mixture with Ringer's lactate solution - a maximum of 6 hours). The dopamine solution should be clear and colorless.

Classification of the World Health Organization (WHO) of adverse drug reactions according to the frequency of development: very often (> 1/10 appointments); often (>1/100 and<1/10 назначений); нечасто (>1/1000 and<1/100 назначений); редко (>1/10000 and<1/1000 назначений); очень редко (<1 /10000), включая отдельные сообщения.

From the side of the cardiovascular system: often - extrasystole, tachycardia, anginal pain, lowering blood pressure, symptoms of vasoconstriction. Rarely - bradycardia, conduction disturbances, increased blood pressure, expansion of the QRS complex on the ECG; life-threatening ventricular arrhythmias.

From the side of the central nervous system: often - headache; rarely - anxiety, restlessness.

From the respiratory system: rarely - shortness of breath.

From the digestive system: often - nausea, vomiting.

From the urinary system: rarely - polyuria (when administered in low doses).

From the side of the organ of vision: rarely - mydriasis.

Reactions at the injection site: rarely - phlebitis, soreness at the injection site. If the drug gets under the skin - necrosis of the skin and subcutaneous tissue.

Laboratory indicators:rarely - azotemia.

Others : rarely - piloerection.

Allergic reactions: the drug contains sodium disulfite, the use of which may in rare cases cause or exacerbate hypersensitivity reactions and bronchospasm (especially in patients with bronchial asthma).

Pharmaceutical drug interactions

Dopamine is pharmaceutically incompatible with alkaline solutions (inactivate), acyclovir, alteplase, amikacin, amphotericin B, ampicillin, cephalothin, dacarbazine citrate, aminophylline (eufillin), calcium theophylline solution, furosemide, gentamicin, heparin, sodium nitroprusside, benzipenicillin, tobramycin, oxidizing agents, iron salts, thiamine (dopamine contributes to the destruction of vitamin B 1).

Pharmacodynamic drug interactions

With simultaneous use with adrenomimetics, monoamine oxidase inhibitors (including moclobemide, selegiline, furazolidone, procarbazine) and guanethidine, the sympathomimetic effect of dopamine is enhanced (an increase in the duration and an increase in cardiostimulatory and pressor effects).

With the simultaneous use of dopamine with diuretics, the diuretic effect of the latter is enhanced.

Inhalation drugs for general anesthesia - derivatives of hydrocarbons (cyclopropane, enflurane, methoxyflurane, chloroform) - increase the cardiotoxic effect of dopamine (increased risk of severe supraventricular or ventricular tachyarrhythmias).

With the simultaneous use of dopamine with tricyclic antidepressants (including), selective serotonin and epinephrine (adrenaline) reuptake inhibitors (, ) and cocaine, the pressor effect of dopamine increases, the risk of developing heart rhythm disturbances, severe arterial hypertension or hyperpyrexia increases.

With simultaneous use with beta-blockers (,), the pharmacological effects of dopamine are reduced.

Derivatives of butyrophenone () and phenothiazine reduce dilatation of the mesenteric and renal arteries caused by low doses of dopamine.

With the simultaneous use of dopamine with guanethidine and preparations containing rauwolfia alkaloids (, raunatin), severe arterial hypertension may develop. If combined use of these drugs is necessary, the lowest possible dose of dopamine should be used.

With the simultaneous use of dopamine with levodopa, the risk of developing cardiac arrhythmias increases.

With the simultaneous use of dopamine with thyroid hormones, it is possible to increase the pharmacological action of both dopamine and thyroid hormones.

Ergot alkaloid derivatives (, ergotamine, etc.) and enhance the vasoconstrictor effect of dopamine and increase the risk of ischemia and gangrene, as well as severe arterial hypertension.

Phenytoin, when used simultaneously with dopamine, can contribute to the development of arterial hypotension and bradycardia (the effect depends on the dose of drugs and the rate of administration).

With the simultaneous use of dopamine with cardiac glycosides, the inotropic effect increases and the risk of developing cardiac arrhythmias increases (continuous ECG monitoring is required).

Dopamine reduces the antianginal effect of nitrates, which, in turn, can reduce the pressor effect of dopamine and increase the risk of arterial hypotension.

The drug Dopamine is intended only for intravenous infusions and can only be used in a diluted form!

Hypovolemia (through the administration of blood plasma and other blood-substituting fluids), acidosis, hypoxia, and hypokalemia should be corrected in patients in shock before Dopamine is administered.

Dopamine infusion should be carried out under the control of diuresis, heart rate, minute volume of blood, blood pressure and ECG. An increase in blood pressure indicates the need to reduce the dose of Dopamine.

Dopamine improves atrioventricular conduction and may increase ventricular rate in patients with atrial fibrillation and flutter. Dopamine increases myocardial excitability and can lead to the appearance or increase in ventricular extrasystoles; the occurrence of ventricular tachycardia and ventricular fibrillation is rare. In patients with a history of such arrhythmias, continuous ECG monitoring should be performed.

Monoamine oxidase inhibitors increase the pressor effect of sympathomimetics and may contribute to the development of a hypertensive crisis and / or cardiac arrhythmias.

Do not use the drug in critically ill patients in order to correct or prevent acute renal failure.

Strictly controlled studies of the use of the drug in patients under the age of 18 years have not been conducted. There are separate reports of the occurrence in this group of patients of arrhythmias and gangrene associated with extravasation of the drug when administered intravenously.

To reduce the risk of extravasation in patients of any age, dopamine should be administered into large veins whenever possible. To prevent tissue necrosis in case of extravasal ingestion of the drug, an abundant infiltration of the affected area with 10-15 ml of 0.9% sodium chloride solution containing 5-10 mg of phentolamine should be immediately carried out. The solution is injected with a syringe through a thin hypodermic needle. Sympathetic blockade with phentolamine leads to immediate development of local hyperemia within the first 12 hours after exposure to Dopamine, so infiltration should be performed as soon as possible after detection of Dopamine extravasation.

When prescribing Dopamine to patients with peripheral vascular disease and / or disseminated intravascular coagulation syndrome (DIC), a history of abrupt and pronounced vasoconstriction may occur, leading to skin necrosis and gangrene of the limb. Careful monitoring of the patient's condition and blood circulation in the limbs should be carried out. If signs of peripheral ischemia are detected, the administration of the drug should be stopped immediately.

The effect on the ability to drive vehicles or other mechanisms has not been studied.

5 ml in neutral glass ampoules.

5 ampoules in a blister pack made of PVC film.

1 or 2 blister packs together with instructions for use and an ampoule knife or an ampoule scarifier in a cardboard box.

5 or 10 ampoules, together with instructions for use and an ampoule knife or an ampoule scarifier, in a cardboard box for consumer packaging with a corrugated liner.

When using ampoules with a break point or ring, an ampoule knife or an ampoule scarifier is not inserted.

Packaging for hospitals

50, 100 blister packs with ampoules, together with an equal number of instructions for use, are placed in a corrugated cardboard box.

In a place protected from light, at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Do not use after the expiry date stated on the packaging.

C.01.C.A.03 Norepinephrine

Norepinephrine is a biogenic amine, a neurotransmitter.

It has a powerful stimulating effect on α-adrenergic receptors and a moderately stimulating effect on β 1 -adrenergic receptors.

Getting into the blood even at low concentrations, it causes generalized vasoconstriction, with the exception of the coronary vessels, which expand due to indirect action (due to an increase in oxygen consumption), which leads to an increase in the strength and (in the absence of vagotonia) the frequency of myocardial contraction, increasing the stroke and minute volume hearts.

It causes an increase in blood pressure (BP), both systolic and diastolic, increases total peripheral vascular resistance (OPSS) and central venous pressure. The cardiotropic effect of norepinephrine is associated with its stimulating effect on the β 1 -adrenergic receptors of the heart.

Suction

After intravenous administration, the effects of norepinephrine develop rapidly. has a short duration of action. The half-life is approximately 1-2 minutes.

Distribution

Norepinephrine is rapidly cleared from plasma by reuptake and metabolism.

Poorly penetrates the blood-brain barrier.

Metabolism

Metabolized in the liver and other tissues by methylation with catechol-o-methyltransferase and deamination with monoamine oxidase. The final metabolite is 4-hydroxy-3-methoxymandelic acid. Intermediate metabolites: normetanephrine and 3,4-dihydroxymandelic acid.

breeding

Norepinephrine metabolites are predominantly excreted in the urine as sulfate conjugates and to a lesser extent as glucuronides.

The drug Norepinephrine Kabi is indicated as an emergency remedy for restoring blood pressure in case of its acute decrease.

Norepinephrine Kabi is contraindicated:

Patients with arterial hypotension caused by hypovolemia (except when used to maintain cerebral and coronary blood flow until the end of therapy aimed at replenishing the volume of circulating blood);

In case of hypersensitivity to the drug or to any of the excipients;

With thrombosis of mesenteric (mesenteric) and peripheral vessels due to the risk of ischemic events and an increase in the infarct zone;

When conducting anesthesia with cyclopropane or halothane due to the risk of developing cardiac arrhythmias;

With severe hypoxia and hypercapnia.

Severe left ventricular failure;

Acute heart failure;

Recent myocardial infarction;

Prinzmetal's angina;

Thrombosis of the coronary, mesenteric or peripheral vessels (risk of aggravation of ischemia and an increase in the infarct zone), insufficient blood circulation;

Violation of the heart rhythm during the infusion of the drug (correction measures are described in the "Special Instructions" section);

Hyperthyroidism or diabetes mellitus;

Elderly patients.

Norepinephrine can interfere with placental circulation and cause fetal bradycardia. Also, the drug can cause uterine contractions, which can lead to fetal asphyxia in the later months of pregnancy.

The drug norepinephrine during breastfeeding should be used with caution, as there is no data on its ability to penetrate into breast milk.

Therefore, before deciding to start norepinephrine infusion, it should be determined whether the expected benefit to the mother outweighs the potential risk to the fetus.

Enter only intravenously.

The individual dose of norepinephrine is determined by the physician depending on the clinical condition of the patient.

Norepinephrine must be administered through central venous access devices in order to reduce the risk of extravasation and subsequent tissue necrosis (see section "Special Instructions").

The introduction of the drug

Recommended initial dose and rate of administration of the drug- from 0.1 to 0.3 mcg / kg / min norepinephrine hydrotartrate. The rate of infusion is progressively increased by titration in steps of 0.05-0.1 µg/kg/min, according to the observed pressor effect, until the desired normotension is achieved.

There are individual differences in the dose required to achieve and maintain normotension. The goal is to achieve the lower limit of normal systolic pressure (100-120 mmHg) or achieve a sufficient level of the average value (above 65-80 mmHg, depending on the patient's condition). The individual dose, due to the high variability of the clinical response with the introduction of the drug, is set depending on the patient's condition.

Before or during therapy, correction of hypovolemia, hypoxia, acidosis, hypercapnia is necessary.

Norepinephrine should be used concomitantly with adequate volume replacement.

It is necessary to beware of the introduction of a solution of norepinephrine under the skin and into the muscles because of the risk of developing necrosis.

Concentrate dilution

The concentrate should be diluted in 5% dextrose solution. Do not mix with other drugs.

For administration using a syringe infusion pump, 23 ml of a 5% dextrose solution is added to 2 ml of a concentrate for preparing a solution for intravenous administration of the drug Norepinephrine Kabi, 1 mg / ml.

For administration using a dropper, 230 ml of a dextrose solution are added to 20 ml of a concentrate for preparing a solution for intravenous administration of the drug Noradrenaline Kabi, 1 mg / ml.

With both dilution options, the final concentration of the resulting solution for intravenous administration is 0.08 mg/ml norepinephrine hydrogen tartrate, which corresponds to 0.04 mg/ml norepinephrine base. After diluting the concentrate, the solution must be used within 12 hours.

Volume of injected liquid: the level of dilution depends on the condition of the patient. If a large volume of liquid is required, the drug should be diluted with a large amount of dextrose and, therefore, a drug with a lower concentration should be used for administration. If it is undesirable to introduce a large volume of liquid, the concentrate is diluted with a smaller volume of dextrose, obtaining a more concentrated solution.

To determine the infusion rate of a solution of the drug Noradrenaline Kabi with a concentration of 0.08 mg / ml and the corresponding amount of norepinephrine hydrotartrate, you can use the data from the table:

Table. Calculation of the infusion rate (ml / h) of a solution of the drug Noradrenaline Kabi with a concentration of 0.08 mg / ml *

*When using a different dilution of the concentrate, you should replace the value of the concentration of the solution in the formula used:

Infusion rate (ml/h) = dosage (mcg/kg/min) x patient weight (kg) x 60 (min) x 0.001 / 0.08 mg/ml

Arterial pressure:

The duration, rate of administration and dosing of the norepinephrine solution are determined by the data of cardiac activity monitoring with mandatory medical monitoring of blood pressure (every 2 minutes until normotonia is reached, after every 5 minutes during the entire infusion) in order to avoid the occurrence of arterial hypertension.

P termination of therapy:

Norepinephrine therapy should be reduced in stages, as abrupt withdrawal may lead to acute hypotension.

The course of treatment can last from several hours to 6 days.

With the introduction of norepinephrine, the following side effects may occur:

From the side of the cardiovascular system : arterial hypertension and tissue hypoxia; ischemic disorders (caused by severe vasoconstriction, which can lead to pallor and coldness of the extremities and face); tachycardia, bradycardia (probably reflex as a result of increased blood pressure), arrhythmias, palpitations, increased contractility of the heart muscle as a result of a β-adrenergic effect on the heart (inotropic and chronotropic), acute heart failure.

With rapid administration, there is: headache, chills, cooling of the extremities, tachycardia.

From the side of the central nervous system :anxiety, insomnia, headache, mental states, weakness, tremor, confusion, decreased attention, nausea, vomiting, anorexia.

From the respiratory system : shortness of breath, pain in the sternum and mediastinum, difficulty breathing, respiratory failure.

From the urinary system : urinary retention.

From the organs of vision : acute glaucoma (in patients with an anatomical predisposition - with the closure of the angle of the anterior chamber of the eyeball).

From the side of the immune system : in case of hypersensitivity to one of the ingredients of the drug, allergic reactions and difficulty breathing are possible.

Local reactions : irritation at the injection site or the development of necrosis (see section "Special Instructions").

Prolonged administration of a vasopressor to maintain blood pressure in the absence of recovery of circulating blood volume can cause the following side effects:

Severe peripheral and visceral angiospasm;

Decreased renal blood flow;

tissue hypoxia;

An increase in the level of lactate in the blood serum;

Decreased urine production.

In case of hypersensitivity to the action of the drug (for example, with hyperthyroidism ):

when using high or usual doses of the drug, a pronounced increase in blood pressure is observed (accompanied by headache, photophobia, stabbing retrosternal pain, pallor of the skin, increased sweating and vomiting); dyspepsia.

When using norepinephrine simultaneously with cardiac glycosides, quinidine, tricyclic antidepressants, the risk of developing arrhythmias increases.

Alpha-blockers (, labetalol, phenoxybenzamine, phentolamine, talazosin) and other drugs with alpha-blocking activity (, loxapine, phenothiazines, thioxanthenes) counteract the vasoconstrictor effect.

Means for inhalation general anesthesia (chloroform, enflurane, cyclopropane, and methoxyflurane) - the risk of developing ventricular arrhythmias.

Tricyclic antidepressants and - possibly increased cardiovascular effects, pressor action, tachycardia and arrhythmias.

Antihypertensive drugs and diuretics - a decrease in the effect of the action of norepinephrine.

β-blockers - mutual weakening of the action.

Cocaine, doxapram - mutual enhancement of hypertensive action.

MAO inhibitors, and - it is possible to lengthen and enhance the pressor effect.

Nitrates - weakening of antianginal action.

Ergot alkaloids or may enhance vasopressor and vasoconstriction effects.

Thyroid hormones - the risk of coronary insufficiency against the background of angina pectoris.

Norepinephrine should only be used if adequate circulating blood volume is being replenished. Before the introduction of a diluted solution of norepinephrine, a mandatory visual control is necessary for the presence of a precipitate, turbidity or discoloration of the solution. If there are any changes, the introduction of the solution is prohibited. The solution should be colorless and transparent.

During infusion, blood pressure and infusion rate should be checked frequently (every 2 minutes) to avoid arterial hypertension.

With prolonged use of the drug, a decrease in plasma volume may be observed (correction is necessary to avoid recurrent arterial hypotension when the drug is discontinued).

Elderly patients may be particularly sensitive to the effects of norepinephrine.

If a heart rhythm disturbance occurs during infusion, the dose should be reduced.

When using norepinephrine in patients with hyperthyroidism and diabetes mellitus, care must also be taken.

Particular caution should be observed in patients with coronary, mesenteric or peripheral vascular thrombosis, as it can lead to increased ischemia and an increase in the area of ​​infarction.

For patients with arterial hypotension after myocardial infarction and patients with Prinzmetal's angina, caution is also necessary.

Risk of extravasation :

In order to reduce the risk of extravasation and subsequent tissue necrosis, it is necessary to constantly monitor the position of the needle in the vein during the introduction of norepinephrine.

The infusion site should be checked frequently for free flow (infiltration). Care must be taken to avoid leakage of the drug from the vessel (extravasation). Due to vasoconstriction of a vein with increased vascular wall permeability, leakage of norepinephrine into the tissues surrounding the vein may occur, in which case the infusion site should be shifted to reduce the effect of local vasoconstriction.

Treatment of ischemia caused by extravasation:

When norepinephrine leaks from a vessel or if injected past a vein, blanching and subsequent tissue necrosis may occur as a result of the vasoconstrictive effect of the drug on the vessels.

If the drug gets past the venous blood flow, 5-10 ml of phentolamine in 10-15 ml of saline is injected into the injection site.

When taking the drug, it is forbidden to drive vehicles and engage in other activities that require increased concentration of attention and speed of psychomotor reactions.

1 ml, 5 ml or 10 ml in dark glass ampoules.

5 ampoules are in a plastic tray with cells.

Ampoules of 1 ml, 5 ml and 10 ml are packed:

2 plastic pallets with cells (10 ampoules) together with instructions for use in a cardboard pack.

Ampoules of 1 ml can be packed:

10 plastic pallets with cells (50 ampoules) together with instructions for use in a cardboard box.

Store at a temperature not exceeding 25 ° C, protected from light.

Do not freeze.

Keep out of the reach of children.

Do not use the drug after the expiration date indicated on the package.