Miozac

Package leaflet: Information for the user

MIOZAC 250 mg/20 ml infusion solution for intravenous use

dobutamine hydrochloride
Generic medicine
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 questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What MIOZAC is and what it is used for
2. What you need to know before using MIOZAC
3. How to use MIOZAC
4. Possible side effects
5. How to store MIOZAC
6. Contents of the pack and other information

1. What MIOZAC is and what it is used for

MIOZAC contains the active substance dobutamine hydrochloride, which belongs to a group of medicines called
catecholamines that act by stimulating heart activity, improving blood flow throughout the body.
MIOZAC is used in emergency situations to improve heart function when this is impaired (heart failure),
following organ damage (organic heart disease) or after surgical procedures.
In patients with an abnormal heart rate (atrial fibrillation), a digitalis medicine must be administered to treat
arrhythmias prior to administration of dobutamine hydrochloride.

2. What you need to know before using MIOZAC

Do not use MIOZAC

• if you are allergic to dobutamine hydrochloride, to other similar substances, or to any of the other ingredients of this medicine (listed in section 6);
• if you suffer from obstructive heart or blood vessel disorders (idiopathic hypertrophic subaortic stenosis);

Warnings and precautions
Please consult your doctor or nurse before MIOZAC is administered to you.
This medicine must be administered with great care and under strict medical supervision in the following cases:

• if you have heart disorders;
• if you are dehydrated (hypovolemia);
• if you are being treated with beta-blockers, medicines used to lower blood pressure;
• if you have low potassium levels in the blood, as these may decrease further.

The use of this medicine following a heart attack must be carried out with extreme caution, as it could worsen heart damage.
During administration of MIOZAC, heart parameters must be continuously monitored (heart rate and rhythm, infusion rate, ECG, blood pressure, pulmonary capillary pressure, and cardiac output).
For athletes: using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.

Other medicines and MIOZAC
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are taking the following medicines:

• medicines used for heart problems such as sodium nitroprusside;

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or nurse before this medicine is administered to you.
This medicine must not be administered during pregnancy unless strictly necessary.

Driving and using machines
There are no data available to determine the effect of this medicine on the ability to drive vehicles or operate machinery.

MIOZAC contains sodium metabisulfite and sodium
This medicine contains sodium metabisulfite, which may rarely cause severe hypersensitivity reactions and bronchospasm.
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e., essentially ‘sodium-free’.

3. How to use MIOZAC

This medicine will be administered to you in hospital by specialized healthcare personnel. If you have any doubts, consult your doctor or nurse.
This medicine is given as an intravenous infusion (into a vein) after appropriate dilution.
The initial dose is 2.5–10 micrograms per kg of body weight per minute, administered as a continuous intravenous infusion. The infusion rate and dosage will be adjusted according to your response to therapy.
If you use more MIOZAC than you should
Since this medicine will be administered by specialized personnel, it is unlikely that you will receive an excessive dose.
Symptoms of overdose may include loss of appetite (anorexia), nausea, vomiting, tremor, anxiety, headache (cephalalgia), difficulty in breathing (dyspnoea), and heart and circulatory problems (palpitations, anginal or non-specific chest pain, increased blood pressure, changes in heart rhythm, myocardial ischemia).
If you experience any of these symptoms or think you have been given too much of this medicine, contact your doctor or nurse immediately.
If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur:

• increased blood pressure (hypertension) and increased heart rate (heart rate);
• changes in heart rhythm (ventricular arrhythmias);
• decreased blood pressure (hypotension);
• nausea;
• headache;
• difficulty breathing (dyspnea);
• non-specific chest pain or chest pain due to heart problems (angina), palpitations;
• inflammation of the veins at the injection site (phlebitis) and tissue damage at the injection site if the medicine leaks out of the veins (extravasation) during infusion;
• reduction in potassium levels in the blood (hypokalaemia);

Problems affecting the heart muscle (stress cardiomyopathy, also known as Takotsubo syndrome), presenting with chest pain, shortness of breath, dizziness, fainting, irregular heartbeat, when dobutamine is used for stress echocardiography (frequency not known: frequency cannot be estimated based on available data).
Side effects observed with prolonged treatment (up to 72 hours) were not different from those seen with short-term treatment.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store MIOZAC

Medical and nursing staff are aware of the proper storage methods for this medicine.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp".
The expiry date refers to the last day of that month.
Store below 25°C and protect from light.
After dilution, the solutions prepared from the vial must be used within 24 hours.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What MIOZAC contains

• The active substance is dobutamine. Each vial contains 280.28 mg of dobutamine hydrochloride, equivalent to 250 mg of dobutamine.
• The other components (excipients) are: sodium metabisulfite, water for injections.

Description of the appearance of MIOZAC and contents of the pack
Pack containing 1 vial of 20 ml solution for intravenous infusion.
Marketing Authorization Holder and Manufacturer
FISIOPHARMA SRL,
Nucleo Industriale - 84020 PALOMONTE (SA) - Italy

Package leaflet: information for the physician

MIOZAC 250 mg/20 ml solution for intravenous infusion

dobutamine hydrochloride
Equivalent medicinal product
The following information is intended exclusively for physicians or healthcare professionals
CLINICAL INFORMATION
Dosage and method of administration
The infusion rate required to increase cardiac output generally ranges from 2.5 to 10 mcg/kg/min.
Rarely, the rate required to achieve the desired effect may rise up to 40 mcg/kg/min (see table). Below is the infusion rate schedule (ml/kg/min) for concentrations of 250, 500, and 1000 mcg/ml.

Administration dosage Infusion rate
250 mcg/ml 500 mcg/ml 1000 mcg/ml
(mcg/kg/min) (ml/kg/min) (ml/kg/min) (ml/kg/min)
2.5 0.01 0.005 0.0025
5.0 0.02 0.010 0.0050
7.5 0.03 0.015 0.0075
10.0 0.04 0.020 0.0100
12.5 0.05 0.025 0.0125
15.0 0.06 0.030 0.0150

The rate of administration and duration of therapy must be adjusted according to the patient's response, as determined by heart rate, presence of ectopic activity, arterial pressure, urinary flow, and, whenever possible, pulmonary capillary wedge pressure and cardiac output measurements.

Concentrations up to 5000 mcg/ml (250 mg/50 ml) have been administered in humans.

The total volume of fluids to be administered should be determined based on the patient's fluid and electrolyte requirements.

Reconstitution of the medicinal product
At the time of administration, MIOZAC must be further diluted in an intravenous container to a final volume of at least 50 ml with one of the following intravenous solutions:
5% Dextrose Lactated Ringer's
5% Dextrose and 0.45% Sodium Chloride 5% Dextrose in Lactated Ringer's
5% Dextrose and 0.9% Sodium Chloride Osmitrol® 20% in water
10% Dextrose Sodium Chloride 0.9%
Lactated Sodium Normosol®-M in D5-W
Isolyte®M with 5% Dextrose

Prepared solutions must be used within 24 hours. Solutions containing MIOZAC may develop a pink coloration, which may intensify over time.
This color change is due to slight oxidation of the drug, but within the recommended administration period, there is no significant loss of potency.

Warnings
MIOZAC may cause a marked increase in heart rate or arterial pressure.
In clinical studies, approximately 10% of patients experienced heart rate increases of 30 beats/min or more, and about 7.5% had systolic blood pressure increases of 50 mmHg or more.
Generally, reducing the dose reduces or eliminates these effects.

Precautions for use
1 - During administration of MIOZAC solution, as with any other adrenergic agent, continuous ECG and arterial pressure monitoring should be performed.
Additionally, whenever possible, pulmonary capillary wedge pressure and cardiac output should be monitored to ensure safe and effective infusion of MIOZAC solution.
2 - Hypovolemia should be adequately corrected prior to initiating treatment with MIOZAC solution.
3 - Animal studies indicate that MIOZAC solution may be ineffective if beta-blocking agents have been recently administered.
In such cases, peripheral vascular resistance may increase.
4 - No improvement may be observed in the presence of significant mechanical obstruction, such as in severe aortic valve stenosis.
5 - Dobutamine, like other β-agonists, may cause a mild reduction in serum potassium, rarely reaching levels indicative of hypokalemia. Therefore, monitoring of serum potassium levels is recommended during therapy with MIOZAC solution.

Use after acute myocardial infarction
Clinical experience with MIOZAC solution after acute myocardial infarction is insufficient to establish the safety of the drug for this use.
It is known that any pharmacological agent capable of increasing myocardial contractility and heart rate may increase the size of the infarcted area, but it is not known whether this may also occur with dobutamine.

Overdose
Cases of dobutamine overdose have been rarely reported.
Initial management consists of discontinuing dobutamine administration, ensuring airway patency, and providing oxygenation and ventilation. Prompt resuscitation measures should be instituted.
Severe ventricular tachyarrhythmias may be successfully treated with propranolol or lidocaine. Hypertension generally responds to dose reduction or discontinuation of therapy.
If necessary, carefully monitor and maintain within acceptable limits vital signs, blood gases, serum electrolytes, etc. Gastrointestinal absorption of drugs may be reduced using activated charcoal, which is often more effective than induction of emesis or gastric lavage. Consider administering activated charcoal in addition to or instead of gastric lavage. Repeated administration of activated charcoal may accelerate the elimination of previously ingested drugs.
When performing gastric emptying or administering activated charcoal, ensure airway integrity.
Forced diuresis, peritoneal dialysis, hemodialysis, and charcoal hemoperfusion have not been shown to provide benefit in cases of dobutamine overdose.

Incompatibilities
Do not dilute MIOZAC with 5% sodium bicarbonate or other strongly alkaline solutions. MIOZAC should not be used in combination with other substances containing sodium metabisulfite and ethanol.

For further information, consult the Summary of Product Characteristics.