1. What Dobutamine 12.5 mg/ml is and what it is used for

Transcription

1 Labelling and Package Leaflet page 1/ Package Leaflet PACKAGE LEAFLET: INFORMATION FOR THE USER, concentrate for solution for infusion Active substance: dobutamine Read all of this leaflet carefully before you start using this medicine. Keep this leaflet. You may need to read it again. If you have any further questions, ask your doctor. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor. In this leaflet: 1. What is and what it is used for 2. Before you use 3. How to use 4. Possible side effects 5. How to store 6. Further information 1. What is and what it is used for Dobutamine belongs to the group of medicines that strengthen the contraction of the heart. Dobutamine is used in patients who need a stronger heartbeat because of a decrease in their heart function, which is caused by a disease or a heart operation. By acting directly on the heart, dobutamine provides a more powerful contraction of the heart.

2 Labelling and Package Leaflet page 2/14 2. Before you use Do not use if you are allergic (hypersensitive) to dobutamine, substances related to dobutamine or any of the other ingredients of dobutamine. if your heart does not pump enough blood around (decompensation) due to a disease of the heart muscle through which the heart is enlarged (hypertrophic cardiomyopathy). if you are allergic (hypersensitive) to the antioxidant sulphite: especially asthmatic patients can react upon this with shortness of breath (bronchospasm) and an allergic shock (anaphylactic shock). if you suffer from a mechanical obstruction of blood flow to or from the heart, especially with the following heart diseases: obstructive cardiomyopathy, aortic stenosis or pericarditis obstruction. Take special care with if your blood pressure or heart beat increase strongly or the heart beat becomes irregular during usage. Your doctor should temporarily stop the treatment or decrease the dosage. if you have a specific type of irregular heart beat (atrial fibrillation with rapid ventricular response). Your doctor should give you medicines that increase the pumping power of the heart (digitalis glycosides) before starting therapy with dobutamine. if you are receiving a prolonged infusion (48-72 hours) of dobutamine. The effect of dobutamine can decrease so you may need a higher dosage. if you experience a cardiac shock with decreased blood volume before the start of dobutamine therapy. Your doctor needs to correct your blood volume before starting dobutamine therapy. if you experience symptoms like rash, pruritus of the scalp, fever and shortness of breath (bronchospasm). This may be a hypersensitivity reaction. if you are susceptible to sulphite. Dobutamine can cause allergic-type reactions varying from light asthmatic episodes to a, sometimes fatal, analphylactic shock. if you have a history of severe heart rhythm disorder. Your doctor should exercise caution when starting dobutamine therapy.

3 Labelling and Package Leaflet page 3/14 Use in children Great care should be taken when dobutamine is administered to children younger than one year of age. They may react different from adults on dobutamine. Using other medicines Other medicines may be affected by dobutamine. They, in turn, may affect how well dobutamine works. Dobutamine can interact with: certain medicines used for the treatment of high blood pressure (betablocking agents). These medicines decrease the effect of dobutamine certain medicines to control your blood pressure, to improve your blood flow or to control sudden pain in the chest (nitroprusside and glyceryl trinitrate). These medicines increase the effect of dobutamine. inhalation anaesthetics. These can increase the chance for heart rhythm disorders (ventricular arrhytmias). vitamin B 1 (thiamine). Dobutamine can decrease the vitamin B 1 levels in your body. Please tell your doctor if you are taking or have recently taken any of the medicines listed above or any other medicines, including medicines obtained without a prescription. Using with food and drink Food and drink do not influence the effect of dobutamine. Pregnancy and breast-feeding When you are pregnant you should not use dobutamine. Not enough information is available to evaluate the possible harmful effects of dobutamine when used during pregnancy. When you are breast-feeding you should stop for the duration of the treatment with dobutamine. Ask your doctor or pharmacist for advice before taking any medicine. Driving and using machines No information is available about the effects of this product on the ability to drive and use machines. An effect is not probable. Important information about some of the ingredients of Dobutamine 12.5 mg/ml

4 Labelling and Package Leaflet page 4/14 Dobutamine contains sodium metabisulphite. Sulphites may rarely cause severe hypersensitivity reactions and bronchospasm. 3. How to use Usually dobutamine is administered by a doctor or by medical personnel. The dosage (rate of infusion and duration of treatment) can be different for each patient and is specifically determined for you by your doctor. Dobutamine is added to an infusion bag using a sterile injection syringe with a solution of glucose or salt. The effect of dobutamine starts 1-2 minutes after administration. The colourless solution can become slightly pink during administration. This has no effect on the action of dobutamine. If you use more than you should The following symptoms can indicate you took more dobutamine than you should: high blood pressure (severe hypertension) fast heart beat (tachycardia) The effect of dobutamine is only of short duration. To alleviate the mentioned symptoms, pause the administration of dobutamine temporarily or decrease the infusion rate until stabilisation. If you have any further questions on the use of this product, ask your doctor. 4. Possible side effects Like all medicines, dobutamine can cause side effects, although not everybody gets them. These may include: fast or irregular heart beat (tachycardia or ventricular ectopic activity) increase in blood pressure nausea headache chest pain (anginal pain, non-specific chest pain) heart palpitations shortness of breath low levels of potassium in the blood (hypokalaemia)

5 Labelling and Package Leaflet page 5/14 In bronchial asthmatic patients hypersensitive to sulphites the following side effects can occur: vomiting diarrhoea coughing/wheezing/shortness of breath (bronchoconstriction) disturbed consciousness shock Usually these side effects disappear after the infusion is temporarily stopped or after the rate of infusion is reduced. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor. 5. How to store Keep out of the reach and sight of children. Do not use dobutamine after the expiry date which is stated on the packaging after EXP. The first two digits indicate the month and the last four digits indicate the year. The expiry date refers to the last day of that month. Prior to dilution Store in the original packaging at 2-30 C. Do not freeze. Diluted product If dilution takes place under strict aseptic conditions, the diluted solution is stable for 24 hours at C (room temperature). If dilution does not take place under strict aseptic conditions, the diluted solution is stable for a maximum of 24 hours at 2-8 C (in the refrigerator), or 12 hours at C (room temperature). Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6 6. Further information Labelling and Package Leaflet page 6/14 What contains The active substance is dobutamine, 12.5 mg/ml. Dobutamine is present as dobutamine hydrochloride (14 mg/ml), corresponding to 12.5 mg/ml of dobutamine. The other ingredients are sodium metabisulphite, hydrochloric acid, sodium hydroxide and water for injections. What looks like and contents of the pack Dobutamine is a clear, colourless concentrate for solution for infusion packaged in a clear, colourless glass ampoule with coloured point. A slightly pink colouration of the solution may occur that intensifies in time, without affecting the activity of the infusion solution Dobutamine is available in boxes of 1, 5 or 10 ampoules of 20 ml. Not all pack sizes may be marketed. Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder: [To be completed nationally] Manufacturer(s): Synthon BV Microweg CM Nijmegen This medicinal product is authorised in the Member States of the EEA under the following names: <{Name of the Member State}> <{Name of the medicinal product}> <{Name of the Member State}> <{Name of the medicinal product}> < > This leaflet was last approved in {MM/YYYY}. To be completed nationally

7 Labelling and Package Leaflet page 7/14 The following information is intended for medical or healthcare professionals only 1 Trade name of the medicinal product "", concentrate for solution for infusion. 2 Qualitative and quantitative composition Each ampoule with 20 ml of contains 280 mg dobutamine hydrochloride equivalent with 250 mg of dobutamine. 3 Pharmaceutical form Concentrate for solution for infusion. 4 Clinical particulars 4.1 Therapeutic indications Dobutamine is indicated for patients who require a positive inotropic support in the treatment of cardiac decompensation due to depressed contractility resulting either from organic heart disease or from cardiac surgical procedures, especially when a low cardiac output is associated with raised pulmonary capillary pressure. NOTE: In case of cardiogenic shock characterized by cardiac failure and severe hypotension and in case of septic shock dopamine is the drug of first choice after correction of possible hypovolemia. Dobutamine might be useful if added to dopamine in case of disturbed ventricular function, raised filling pressure of the ventricles and raised systemic resistance. 4.2 Posology and method of administration Just before administration Dobutamine should be diluted according to the table below with either 5 % glucose solution, 0.9 % sodium chloride solution, Ringer's lactated solution or sodium lactate solution. The concentration used depends on the dosage and fluid requirements of the patient.

8 Labelling and Package Leaflet page 8/14 The dilution should not be more concentrated than 5 mg/ml (5,000 µg/ml). Most patients will respond satisfactory to doses from 2.5 to 10 µg/kg/min. Occasionally, however, a dose as low as 0.5 µg/kg/min will be effective. Rarely, a dose as high as 40 µg /kg/min has been required. The table below is a directive for the rate of infusion. Drug Infusion Delivery Rate (ml/kg/min) Delivery Rate 250 µg/ml* 500 µg/ml** 1000 µg/ml*** 5000 µg/ml**** (µg/kg/min) * 250 mg of dobutamine (1 ampoule) added to 1 litre of diluent. ** 500 mg of dobutamine (2 ampoules) added to 1 litre of diluent or 250 mg (1 ampoule) added to 500 ml of diluent. ***1000 mg of dobutamine (4 ampoules) added to 1 litre of diluent or 250 mg (1 ampoule) added to 250 ml of diluent. ****250 mg of dobutamine (1 ampoule) added to 50 ml of diluent. This dilution can be used in patients with restricted fluid intake. The rate of administration and the duration of the therapy must be individualized to the patients requirements and response as determined by heart rate, blood pressure, urine flow, and, whenever possible, measurement of cardiac output. Because of the development of partial tolerance with continuous infusions of dobutamine for 72 hours or more, higher doses may be required to maintain the same effects. Rather than abruptly discontinuing the duration of therapy with dobutamine, it is often advisable to decrease the dosage gradually. 4.3 Contra-indications Dobutamine should not be used in the following cases: Hypersensitivity to dobutamine or one of its derivates Decompensation with hypertrophic cardiomyopathy

9 Labelling and Package Leaflet page 9/14 Known hypersensitivity to sulphite: Especially asthmatic patients can react upon this with bronchospasms and anaphylactic shock Mechanical obstacle to the left ventricular filling or ejection, especially obstructive cardiomyopathy, aortic stenosis, pericarditis obstruction 4.4 Special warnings and special precautions for use Due to stimulation of cardiac β 1 -receptors by dobutamine an obvious increase in systolic blood pressure, or an undesirable increase in heart rate, or an arrhythmia usually accompanied by ventricular extrasystoles, may occur in certain cases after administration. Dose reduction or a temporary discontinuation of the administration has to be considered in case of one of the above effects. In patients who have an existing artrial fibrillation with rapid ventricular response, a digitalis preparation should be used prior to initiation of therapy with dobutamine. No special actions are needed in case of extravasation, because no vasoconstriction or ischemia has been observed in those cases. During prolonged infusion (48 to 72 hours) a decrease in the haemodynamic effect may occur, which indicates that an increase of dosage may be desirable. Caution is recommended in case of a cardiogenic shock with hypovolemia; prior to initiation of dobutamine therapy, possible hypovolemia should be corrected. Occasionally hypersensitivity reactions such as rash, pruritus of the scalp, fever, bronchospasm and eosinophilia are observed. Administration of dobutamine can induce a slight decrease of serum potassium concentrations, however a manifest hypokalaemia is very rare. Therefore, the monitoring of serum potassium concentrations should be considered. "" contains sulphite which may cause allergic-type reactions in susceptible individuals. These reactions can vary from light asthmatic episodes to a, sometimes fatal, anaphylactic shock. Caution is recommended in patients who have a history of severe ventricular arrhythmias. Geriatric use: No special problems are to be expected when dobutamine is used in this group of patients. Pediatric use: Great care should be taken when dobutamine is administered to children younger than one year of age. They may react qualitatively and quantitatively different from adults.

10 Labelling and Package Leaflet page 10/ Interaction with other medicaments and other forms of interaction Interaction is possible in the following cases: β blocking agents, especially cardiac selective ones. The positive inotropic effect of dobutamine by stimulation of the cardiac receptors may be decreased by these agents. However, dobutamine has the potential to abolish the β blockade in dosages that do not cause any serious undesirable effects. Especially in patients treated with β blocking agents now and then a slight vasoconstriction is observed. Inhalation anesthetics may increase the potential for ventricular arrhythmias due to sensitising the myocardium. Concurrent use of dobutamine with nitroprusside or dobutamine with glyceryl trinitrate may result in higher cardiac output and a lower pulmonary wedge pressure, which is more than for each drug when given separately. The antioxidant sodium metabisulphite present in the may react with thiamine which can lead to a thiamine decrease. 4.6 Pregnancy and lactation Insufficient data are available to evaluate possible harmful effects of dobutamine when used during pregnancy. So far, animal studies have revealed no indications of harmful effects. If treatment becomes necessary during lactation breastfeeding should be interrupted for the duration of exposure. 4.7 Effects on ability to drive and use machines No information is available about the effects of this product on the ability to drive and use machines. An effect is not probable. 4.8 Undesirable effects Undesirable effects that may occur after use of "" are: An increase in systolic blood pressure (10 to 20 mm Hg) is observed in most patients. In patients with existing hypertension sometimes an abnormal increase of the arterial blood pressure may occur (50 mm Hg). An increase in heart rate is possible (5 to 10 bpm). This increase is lower than the increase caused by an equipotent dose of isoprenaline. In a few patients an obvious tachycardia or ventricular ectopic activity are observed. In patients with already existing atrium fibrillation, dobutamine can increase the ventricular frequency. Usually these side-effects disappear if the infusion is temporarily discontinued or if the dose is reduced.

11 Labelling and Package Leaflet page 11/14 In 1-3 % of the cases the following side-effects have been reported: nausea, headache, anginal pain, non-specific chest pain, palpitations and shortness of breath. As with all other catecholamines with β 2 -adrenergic activity, administration of dobutamine may lead to a slight decrease of the serum potassium concentrations, however a manifest hypokalaemia is very rare. Dose related undesirable effects are rarely observed with a dose smaller than 10 µg/kg/min; sometimes even doses of 40 µg/kg/min were administered without significant undesirable effects. Bronchial astmatic patients hypersensitive to sulphites may experience the following undesirable effects: vomitting, diarrhea, bronchoconstriction, disturbed consciousness, and shock. 4.9 Overdose The following symptoms can indicate a possible overdose of dobutamine: Severe hypertension Tachycardia Treatment of an overdose: Because of the short duration of action of dobutamine, temporarily discontinuation of the administration of dobutamine or decreasing the infusion rate until the patient's condition has stabilized will be sufficient. 5 Pharmacological properties 5.1 Pharmacodynamic properties Dobutamine hydrochloride is a synthetic direct-acting positive inotropic catecholamine. Unlike dopamine, dobutamine does not stimulate the heart indirectly by causing increased release of endogenous norepinephrine, but instead it acts almost exclusively on cardiac β 1 -adrenergic receptors, with little effect on β 2 and α- receptors. Its primary action is to increase the contractile force of the heart muscle. In patients with a diminished cardiac function, the cardiac output will be improved mainly by an increase of the cardiac stroke volume, which can increase

12 Labelling and Package Leaflet page 12/14 the pulse pressure. Each dose of dobutamine will decrease the peripheral resistance. An increase in heart rate can occur at higher doses. Dobutamine will only have a small influence on the mean arterial pressure in patients with normal blood pressure. However, in patients with hypotension caused by a low cardiac stroke volume, the mean arterial pressure will increase mainly by an increase in cardiac stroke volume. Dobutamine reduces elevated ventricular filling pressure (preload reduction) and improves atrioventricular (AV) node conduction. Coronary blood flow and myocardial oxygen consumption are usually increased because of increased myocardial contractility and by stimulation of β 2 -adrenergic receptors in the coronary circulation. 5.2 Pharmacokinetic properties The onset of action of dobutamine starts within 1 to 2 minutes after administration, however, sometimes 10 minutes may be required to obtain maximum action. The plasma half-life is 2 minutes. Hepatic inactivation of dobutamine mainly occurs by formation of dobutamine conjugates and 3-Omethyl dobutamine. Metabolites are excreted mainly renally. A small fraction is excreted in the faeces. 5.3 Preclinical safety data Dobutamine did not produce teratogenic effects in rats and rabbits nor did it affect fertility. There are no studies in humans regarding the use during pregnancy and lactation. 6 Pharmaceutical particulars 6.1 List of excipients Sodium metabisulphite, hydrochloric acid or sodium hydroxide for ph adjustment and Water for Injections. The is protected by nitrogen. 6.2 Incompatibilities Dobutamine is incompatible with 5% sodium bicarbonate solution or other alkaline reacting solutions (potassium phosphate, furosemide or phenytoine sodium).

13 Labelling and Package Leaflet page 13/14 Dobutamine hydrochloride should not be mixed with diluents containing both sodium bisulfite and ethanol. Mixing with or simultaneous administration of dobutamine through the same intravenous line as heparin, hydrocortisone sodium succinate, cefazolin sodium, cefamandol naftate, cephalothin sodium, penicillines, sodium ethacrynate, aciclovir, aminophylline, bretyllium, calcium chloride, calcium gluconate, diazepam, digoxin, insulin, potassium chloride, magnesium sulphate, streptokinase and verapamil is not recommended. 6.3 Shelf-life The shelf life of the product is 5 years. The expiry date ("exp") is printed on the packaging and the ampoule. If dilution takes place under strict aseptic conditions, the diluted solution is stable for 24 hours at C (room temperature). If dilution does not take place under strict aseptic conditions, the diluted solution is stable for a maximum of 24 hours in the refrigerator (2-8 C), or 12 hours at C (room temperature), seen from a microbiological point of view. Due to slight oxidation a slightly pink colouration of the solution may occur that intensifies in time, without affecting the activity of the infusion solution. 6.4 Special precautions for storage Prior to dilution the ampoules should be stored in the original packaging at a temperature between 2 and 30 C. Do not freeze. 6.5 Nature and contents of container 1, 5 or 10 ampoules with 20 ml equivalent with 250 mg of dobutamine and 0.2 mg/ml sodium metabisulphite. 6.6 Special instructions for disposal and other handling Prior to administration, Dobutamine should be diluted to the desired concentration with either 5% glucose solution, 0.9% sodium chloride solution, Ringer's lactated solution or sodium lactate solution (see table). Discard any unused infusion solution. 7 Marketing authorization holder Name or style and permanent address or registered place of business of the holder of the marketing authorization

14 Labelling and Package Leaflet page 14/14 <to be completed nationally> 8 Marketing authorization number <to be completed nationally> 9 Date of first authorization/renewal of authorization <to be completed nationally> 10 Date of (partial) revision of the text April 2007