DOPAMINE GRIFOLS 200 mg INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Dopamine Grifols 200 mg Solution for Injection

Dopamine

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet.

Contents of the Package Leaflet

1. What Dopamine Grifols 200 mg is and what it is used for
2. What you need to know before you use Dopamine Grifols 200 mg
3. How to use Dopamine Grifols 200 mg
4. Possible side effects

5 Storage of Dopamine Grifols 200 mg

1. Contents of the pack and other information

1. What Dopamine Grifols 200 mg is and what it is used for

Dopamine Grifols 200 mg belongs to the group of medicines called adrenergic and dopaminergic agents. This medicine is a cardiac stimulant that acts by increasing the force of contraction of the heart muscle, causing an increase in cardiac output (volume of blood expelled by the heart per minute).

Dopamine is indicated for the correction of hemodynamic imbalances (blood flow) that occur when there is a state of shock (acute decrease in blood flow) due to myocardial infarction, trauma, endotoxic septicemia (severe blood infection), open-heart surgery, renal failure, and decompensated congestive heart failure.

2. What you need to know before you use Dopamine Grifols 200 mg

Do not use Dopamine Grifols 200 mg:

• if you are allergic to dopamine or any of the other components of this medicine (listed in section 6)

• if you have pheochromocytoma (a tumor that usually develops in the medulla of the adrenal glands)
  • if you have tachyarrhythmias (fast or irregular heart rhythm) such as atrial fibrillation, ventricular tachycardia, or ventricular fibrillation.

Warnings and Precautions

Consult your doctor or nurse before starting to use Dopamine Grifols 200 mg.

• Before starting treatment with this medicine, if possible, your blood volume should be restored with whole blood or a plasma expander.

• Dopamine should always be diluted before administration.

• The rate of administration should be carefully controlled to avoid accidental administration of a bolus.

• Situations of hypoxia (decreased oxygen in the blood), hypercapnia (excessive increase in carbon dioxide in the blood), or acidosis (decrease in blood pH) should be corrected before or during administration of the medicine to avoid increasing side effects or reducing its efficacy.

• The use of dopamine should be assessed based on your clinical situation, and it should be administered with special care if you have a state of shock due to myocardial infarction, open-heart surgery, or acute heart failure, as well as if you have arrhythmias, ischemic heart disease, or hypertension (high blood pressure).

• If you have hyperthyroidism (increased activity of the thyroid gland), you may be at greater risk of cardiac effects or be more sensitive to the medicine.

• If you have or have had any disease that causes obstruction of the arteries (such as atherosclerosis, arterial embolism, Raynaud's disease, frostbite, diabetic endarteritis, or Buerger's disease), you should inform your doctor of any changes in skin color or temperature or if you experience pain in the extremities, who will assess the benefits of continuing treatment versus the risk of suffering a possible necrosis. This condition can be reversed by decreasing or interrupting the administration of the medicine.

• Since this medicine must be diluted in a perfusion solution before administration, it can cause fluid overload and/or dissolved substances, leading to dilution of electrolyte concentrations in the blood, hyperhydration, congestion, or pulmonary edema (fluid accumulation in the lungs). Similarly, excessive administration of potassium-free intravenous solutions can cause hypokalemia (low potassium levels in the blood). You should undergo clinical and laboratory tests to monitor fluid balance, electrolyte concentrations, and acid-base balance if intravenous treatment is prolonged or your health condition requires it.

• During administration of this medicine, it is necessary to monitor certain physiological parameters such as heart rate, diuresis, cardiac output, and blood pressure.

If tachyarrhythmia or an increase in ectopic beats (heart rhythm disorder) is observed, the dose of dopamine should be reduced if possible.

If at low perfusion rates, a decrease in blood pressure is observed, the rate should be increased until an adequate blood pressure is achieved. If blood pressure does not increase, treatment should be discontinued and a more potent vasoconstrictor such as norepinephrine should be administered.

Discontinuation of administration will be done by gradually decreasing the dose of dopamine while increasing blood volume with intravenous solutions. Sudden discontinuation of treatment could cause a significant decrease in blood pressure.

If an disproportionate increase in diastolic pressure (minimum blood pressure value) is detected, the perfusion rate should be decreased. The doctor should monitor your condition, and in some cases, it may be necessary to administer a short-acting alpha-adrenergic blocker such as phentolamine.

• Extravasation of the solution during administration can cause necrosis in the infusion area, so the area should be continuously monitored.

• If you have received monoamine oxidase inhibitors (MAOIs) such as tranylcypromine and moclobemide before starting treatment with this medicine, you should receive reduced doses of dopamine.

Using Dopamine Grifols 200 mg with other medicines

Tell your doctor if you are using, have recently used, or might use any other medicines.

It is important to inform your doctor if you are using any of the following medicines:

• diuretic medicines (such as furosemide): their combined administration with a low dose of dopamine can increase diuretic effects.

• tricyclic antidepressants: they can potentiate the cardiovascular effects of dopamine.

• vasopressor or vasoconstrictor medicines such as ergot alkaloids (e.g., ergometrine) or other oxytocic medicines: their combined administration with dopamine can cause a significant increase in blood pressure.

• beta-adrenergic blockers (such as propranolol or metoprolol): they have an opposite effect to dopamine on the heart.

• alpha-adrenergic blockers (such as tolazoline): the combined administration of dopamine and tolazoline could lead to a severe decrease in blood pressure, as they have an opposite effect to peripheral vasoconstriction caused by high doses of dopamine.

• butyrophenones (such as haloperidol) and phenothiazines: these substances can suppress the mesenteric and renal vasodilation caused by the administration of dopamine at low doses.

• phenytoin: its combined administration with dopamine can cause a decrease in blood pressure and heart rate.

• monoamine oxidase inhibitors (MAOIs) (such as tranylcypromine and moclobemide): these medicines prolong and potentiate the action of dopamine, so if you have used them before administration of dopamine, you will require a substantially lower dose. It is estimated that if you have used these medicines 2-3 weeks before administration of dopamine, you should receive an initial dose of dopamine of no more than one-tenth of the normal dose.

• guanethidine: dopamine decreases the effect of this medicine.

• methyldopa and entacapone: these medicines increase the effect of dopamine.

Dopamine should be used with extreme caution in patients anesthetized by inhalation of cyclopropane or halogenated hydrocarbons, as their simultaneous administration can cause arrhythmias and increased blood pressure.

It has also been described that the combined administration of dopamine and the anesthetic propofol causes a decrease in the concentration of the anesthetic.

Pregnancy and Breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Adequate and well-controlled studies have not been conducted in pregnant women, and it is unknown if dopamine crosses the placenta. Dopamine Grifols 200 mg should not be used during pregnancy unless, in the doctor's judgment, it is clearly necessary.

In case dopamine needs to be administered to a pregnant woman for advanced life support (ALS) during cardiopulmonary resuscitation, the doctor should consider that blood flow to the uterus may decrease. Also, if dopamine is used during labor along with oxytocic medicines, it should be taken into account that the simultaneous use of both medicines can lead to a severe increase in blood pressure.

It is unknown if dopamine is excreted in breast milk. The doctor will assess the possible risk to the infant and inform you if the administration of dopamine during breastfeeding is advisable.

Dopamine Grifols 200 mg contains sodium metabisulfite

This medicine can cause severe allergic reactions and bronchospasm (sudden feeling of suffocation) because it contains sodium metabisulfite.

This medicine contains less than 23 mg (1 mmol) of sodium per 5 ml ampoule, so it is considered essentially "sodium-free".

3. How to use Dopamine Grifols 200 mg

Dopamine Grifols 200 mg must be diluted before administration.

Once diluted, dopamine will be administered intravenously by perfusion, preferably through a large-caliber vein, through a suitable catheter or needle.

This medicine will be used in a hospital by the corresponding healthcare personnel.

Your doctor will indicate the duration of your treatment.

Administration rate:

Adults

Intravenous perfusion of dopamine is usually started at a dose between 2 and 5 micrograms/kg/min, increasing by 1-4 micrograms/kg/min every 10-30 minutes until the desired therapeutic effects are achieved. The maintenance dose ranges from 5 to 20 micrograms/kg/min, depending on the severity of the condition. When blood pressure, diuresis, and general circulatory status improve, continue infusion with the dose that has proven to be effective.

The maximum recommended dose is 20 micrograms/kg/min, although in severe situations, doses of up to 50 micrograms/kg/min or even higher have been administered, and urine excretion should be frequently checked. The effects of dopamine depend on the administered dose.

Elderly

No dose adjustment is required in these patients, although it is recommended to start treatment with low doses and closely monitor blood pressure, urine flow, and peripheral perfusion.

Use in Children

The safety and efficacy of this medicine have not been established, so it is not recommended for use in these patients.

If you are given more Dopamine Grifols 200 mg than you should

Overdose with dopamine causes excessive elevation of blood pressure and vasoconstriction (narrowing of a blood vessel) due to the alpha-adrenergic action of dopamine, especially in patients with a history of vascular occlusive disease. In this case, the administration rate of the medicine should be reduced or its administration temporarily discontinued until your condition stabilizes.

If these measures do not stabilize your condition, the doctor should consider administering a short-acting alpha-adrenergic blocker such as phentolamine.

In case of overdose or accidental ingestion, consult the Toxicology Information Service. Phone: 915 620 420.

If you have any other questions about the use of this product, ask your doctor or nurse.

4. Possible Side Effects

Like all medicines, Dopamine Grifols 200 mg can cause side effects, although not everybody gets them.

The most frequently observed side effects are: extrasystoles (heart rhythm disorder), nausea, vomiting, tachycardia, angina pectoris, palpitations, dyspnea (breathing difficulties), headache, hypotension, and vasoconstriction.

At very high doses of dopamine, ventricular arrhythmias can also occur.

Administration of dopamine at high doses for prolonged periods or at low doses in patients with a history of vascular occlusive disease can cause gangrene of the extremities.

If the solution extravasates in the injection area during administration, necrosis and eschar (scab) can occur in the surrounding tissue.

Other less frequent side effects are: cardiac conduction disorders, bradycardia (decreased heart rate), piloerection (hair standing on end), azotemia (excessive nitrogen compounds in the blood), hypertension, prolonged QRS complex on the electrocardiogram, and anxiety. Dopamine has also caused some cases of peripheral cyanosis (bluish discoloration of the skin and mucous membranes of the extremities). It can also cause an increase in blood glucose levels, although these usually do not exceed normal values.

A case of choreoathetosis (involuntary movements) has been described after administration of dopamine.

Dopamine has been shown to inhibit the release of hormones such as prolactin, somatotropin, thyrotropin, and thyroid hormones. There is a possibility that these changes may affect immune function.

Given the short duration of action of the medicine, most side effects disappear after discontinuation of treatment or reduction of the administration rate.

Since this medicine contains sodium metabisulfite, severe allergic reactions and bronchospasm can occur.

If you experience side effects, consult your doctor or nurse, even if they are not listed in this leaflet.

5. Storage of Dopamine Grifols 200 mg

Keep in the original packaging to protect from light.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date stated on the packaging.

Do not use this medicine if the solution is not transparent or contains precipitates.

Once the packaging is opened, the solution should be used immediately.

6. Container Content and Additional Information

Composition of Dopamine Grifols 200 mg

The active ingredient is dopamine hydrochloride. Each 5 ml ampoule of solution contains 200 mg of dopamine hydrochloride (40 mg/ml).

The other components (excipients) are: sodium metabisulfite (E-223) and water for injectable preparations.

Appearance of the Product and Container Content

Dopamine Grifols 200 mg is a clear and colorless or very pale yellow injectable solution, presented in 5 ml ampoules (box of 6 ampoules).

Marketing Authorization Holder and Manufacturer

LABORATORIOS GRIFOLS, S.A.

Can Guasch, 2

08150 Parets del Vallès, Barcelona (SPAIN)

Date of the Last Revision of this Leaflet: December 2012

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

The effects of dopamine depend on the dose administered, although the patient's actual response will largely depend on their clinical condition:

• at low doses (up to 2 micrograms/kg/min) it causes vasodilation at the renal, mesenteric, coronary, and intracerebral levels (probably due to a specific agonist action on dopaminergic receptors) and diuresis. Hypotension may sometimes occur.
• at moderate doses (2-10 micrograms/kg/min) it stimulates the ß1-adrenergic receptors in the myocardium, increasing the contractile force of the cardiac muscle and impulse conduction. Peripheral blood flow may decrease while mesenteric flow increases due to increased cardiac output. Systolic and pulse pressure usually increase.
• at higher doses (10-20 micrograms/kg/min) it produces α-adrenergic stimulation, increasing the vasoconstrictor effect and blood pressure.
• at high doses (>20 micrograms/kg/min) α-adrenergic stimulation predominates, resulting in strong peripheral vasoconstriction that can cancel out the dopaminergic effects of the medication.

Dopamine Grifols 200 mg must be diluted before administration.

• Instructions for correct dilution of the medication:

Use an aseptic technique.

Dilute the contents of an ampoule in 250 or 500 ml bottles of one of the following sterile intravenous solutions:

1. Sodium chloride 0.9% solution (isotonic saline solution)
2. 5% glucose solution
3. 5% glucose and 0.9% sodium chloride solution
4. 5% glucose and 0.45% sodium chloride solution
5. 5% glucose and lactated Ringer's solution
6. 1/6M sodium lactate solution
7. Lactated Ringer's solution

These dilutions will result in the following final concentrations for administration:

• 250 ml of dilution contain 800 micrograms/ml of dopamine.
• 500 ml of dilution contain 400 micrograms/ml of dopamine.

If a higher concentration of dopamine is required, more than one ampoule can be diluted in the mentioned sterile intravenous solutions.

Dopamine is stable at room temperature for at least 24 hours after dilution in any of the aforementioned sterile intravenous solutions. However, as with all intravenous mixtures, the dilution should be made extemporaneously.

Do not dilute dopamine injectable with solutions containing sodium bicarbonate or any other alkaline solution, as dopamine is inactivated by alkalis.

Dopamine is degraded by oxygen, so contact with oxidants and iron salts should be avoided.

Do not administer dopamine mixtures that show coloration, as this is indicative of dopamine alteration.

• Incompatibilities:

Dopamine is inactivated in alkaline solution and is incompatible with alkaline substances such as sodium bicarbonate, furosemide, and thiopental sodium. It is also incompatible with oxidizing agents and iron salts.

Similarly, signs of incompatibility of dopamine with insulin, ampicillin, amphotericin B, gentamicin sulfate, sodium cefalotin, sodium oxacillin, sodium acyclovir, alteplase, potassium penicillin G, aldesleukin, cefepime hydrochloride, indomethacin sodium trihydrate, and with some parenteral nutrition mixtures have been described.

In the absence of compatibility studies, this medication should not be mixed with others.

Dopamine should be perfused, whenever possible, in a large-caliber vein to avoid the possibility of infiltration into the perivascular tissue adjacent to the infusion site, as extravasation can cause necrosis and scarring of the surrounding tissue. The veins of the antecubital fossa are preferable to the veins of the back of the hand or ankle. Less suitable infusion sites should only be used if the patient's condition requires immediate attention or if large-caliber veins cannot be used, and as soon as possible, infusion should be administered in more appropriate locations. Free circulation in the infusion area should be continuously monitored.

In case of extravasation, a β-adrenergic blocker such as phentolamine (e.g., 5-10 mg in 10-15 ml of saline solution) should be administered quickly by infiltrating the affected area.