ISOPRENALINE HYDROCHLORIDE MONICO Solution for injection
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
ISOPRENALINE HYDROCHLORIDE MONICO 0.2 mg/1 mL Solution for injection
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One ampoule contains:
Active ingredient: Isoprenaline Hydrochloride 0.2 mg
For the complete list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Solution for injection. The solution is clear and devoid of visible particles.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment of complete atrioventricular block (including Stokes-Adams syndrome) and cardiac arrest. Treatment of bronchial spasm during anaesthesia. In addition to treatment for cardiogenic shock.
4.2 Posology and method of administration
Treatment of complete atrioventricular block (including Stokes-Adams syndrome) and cardiac arrest. Intramuscular administration: 0.2 mg followed by 0.02-1.0 mg based on the response of the patient. Intravenous administration: 2 -10 mcg/min, to be adjusted based on the response of the patient. Subcutaneous administration: 0.2 mg followed by 0.15-0.20 mg based on the response of the patient.
Treatment of bronchial spasm during anaesthesia. Intravenous administration: initial dose of 0.01-0.02 mg, to be repeated, if necessary.
In addition to treatment for cardiogenic shock Intravenous administration: 0.5-5 mcg/min, based on the response of the patient. Higher doses (up to 20 mcg/minute) can at times be used in severe conditions of shock, depending on the clinical condition and on the response of the patient.
The use of Isoprenaline is not recommended in children due to the lack of safety and efficacy data.
Instructions for use For intravenous injection Dilute 1 mL of Isoprenaline Hydrochloride 0.2 mg/mL solution for injection with 10 mL of 0.9% sodium chloride or 5% glucose to obtain a solution with a concentration of 0.02 mg/mL. For intravenous infusion Dilute 10 mL of Isoprenaline Hydrochloride 0.2 mg/mL solution for injection with 500 mL of 0.9% sodium chloride or 5% glucose to obtain a solution with a concentration of 0.004 mg/mL.
Use a microdrip or a continuous infusion pump to prevent sudden flow of an excessive quantity of drug.
Hypersensitivity to the active ingredient or to any of the excipients.
Isoprenaline is contraindicated in the following conditions:
– cardiac arrest or tachycardia induced by digitalis compounds;
– Children younger than 12 years.
– Generally contraindicated during pregnancy and lactation (see section 4.6).
4.4 Special warnings and precautions for use
Extreme caution is recommended when administering the drug in the following conditions:
– convulsive disorders;
– coronary heart failure;
– diabetes mellitus;
– hyperresponsivity to sympathomimetic amines;
Attention The product contains sodium metabisulphite: in sensitive subjects, and particularly in asthmatics, this substance can cause allergic reactions and severe asthma attacks.
4.5 Interaction with other medicinal products and other forms of interaction
Isoprenaline must not be administered concomitantly with:
– cardioactive glycosides and general anaesthetics (halothane, cyclopropane): concomitant administration can cause arrhythmias;
– ergot alkaloids: concomitant administration can enhance peripheral vasoconstriction;
– phenelzine, selegiline, tranylcypromine: concomitant administration along with one of these drugs can enhance the hypertensive effect by reducing the sympathomimetic metabolism. Hence, the need to monitor patients for clinical effects typical of a rise in blood pressure (headache, arrhythmias, fever, vomiting). If the patient develops an episode of hypertension, immediately suspend administration of the drug and start therapy to reduce blood pressure;
– entacapone: concomitant use can increase the risk of tachycardia, hypertension and arrhythmias through inhibition of the COMT metabolism;
– nebivolol: concomitant administration with this drug can modify the beta-blocking effect and cause severe hypotension due to a mechanism of pharmacological antagonism subsequent to the vasodilatory effect of isoprenaline; hence the need to closely monitor patients under treatment with the two drugs specified below:
– theophylline: concomitant administration with this drug can reduce theophylline levels by increasing metabolism; hence the need to adjust the doses of theophylline;
– tolcapone: concomitant administration with this drug can inhibit Isoprenaline metabolism as tolcapone inhibits COMTs. Therefore, reducing the dose of Isoprenaline must be considered in patients taking tolcapone.
4.6 Pregnancy and lactation
Pregnancy Studies conducted on animals are inadequate to indicate the effects on pregnancy and/or on embryo/foetal development (see section 5.3). The potential risk for humans is not known. Isoprenaline must not be administered during pregnancy, unless it is absolutely necessary. Since Isoprenaline is used as a life-saving drug in cardiac emergencies, the risk-benefit ratio is not questioned. Isoprenaline easily crosses the placenta and can inhibit uterine contractions and delay preterm delivery. Lactation It is not known whether Isoprenaline is excreted in breast milk, and neither are potential adverse effects for the neonate following exposure to the drug known. It is not known whether Isoprenaline influences the quantity or composition of breast milk. Until further data is available, caution is recommended when administering Isoprenaline to breast-feeding women.
4.7 Effects on the ability to drive and use machinery
4.8 Undesirable effects
The undesirable effects of Isoprenaline, organised according to the MedDRA’s organic systemic classification, are given below. The data available is inadequate to establish the incidence of the single effects listed below.
Cardiac diseases: palpitations, tachycardia, variation in blood pressure, ventricular arrhythmias and Stokes- Adams syndrome in patients with transient atrioventricular block, cardiac arrest.
Gastrointestinal diseases: nausea, gastrointestinal distress.
Haemolymphopoietic system disorders: thrombocytopenia, eosinopenia (studies conducted on healthy volunteers).
Nervous system disorders: tremors, dizziness, agitation, drowsiness, headache and insomnia.
Ophthalmological disorders: blurred vision.
Renal and urinary disorders: urinary hesitancy.
Respiratory, thoracic and mediastinal diseases: cough, throat irritation, bronchitis, increased sputum production, pulmonary oedema.
Endocrine diseases: swollen parathyroid gland following prolonged use, discoloured saliva. Skin and subcutaneous tissue diseases: perspiration and skin reddening.
Overdose of Isoprenaline can cause tremors, palpitations, angina, arrhythmias, tachycardia, an increase or drop in blood pressure, seizures, agitation, headache, xerostomia, nausea, dizziness, fatigue, malaise and insomnia.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: adrenergic and dopaminergic agents: ATC Code: C01CA02.
Isoprenaline causes bronchodilation by relaxing bronchial muscles through stimulation of beta-2 receptors. It increases heart rate and myocardial contractility by stimulating beta-1 receptors, also increasing cardiac flow.
5.2 Pharmacokinetic properties
Absorption It is rapidly absorbed by intramuscular or subcutaneous injection.
Metabolism 25-35% of the Isoprenaline administered is metabolised, in the liver and in other tissues, by COMTs into 3-O- methyl isoprenaline, an inactive metabolite that is excreted in urine, either unmodified or as conjugated sulphate. In children, 77-87% of the dose of Isoprenaline is converted after one hour into its conjugated metabolite, which is then eliminated by urinary excretion after 2 hours.
Excretion Following intravenous administration, about 50% of the dose is excreted unchanged in urine. In children a high percentage of unmodified drug is present in urine after 5 minutes. More than 80% of the conjugated metabolite is eliminated after 2 hours, especially as 3-O-methyl-isoprenaline.
5.3 Preclinical safety data
Preclinical data are scarcely important in the clinical framework in the light of the extensive experience acquired through human use of the medicine.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium metabisulphite 0.2 mg, water for injectable preparations q.s. to 1 mL.
Isoprenaline must not be mixed with medicinal solutions that have an alkaline pH (e.g. sodium bicarbonate, aminophylline, alkaline buffer antibiotics) because oxidation velocity increases considerably in conditions presenting pH levels higher than 6. Data is divergent about the incompatibility of Isoprenaline administered concomitantly with doxycycline and secobarbital. In any case, the Isoprenaline solution must be administered soon after its preparation.
6.3 Shelf life
2 years for a correctly stored package that is intact.
6.4 Special precautions for storage
Store under 25°C in the original container to protect the product from light. If it is exposed to air, light or a temperature rise, the solution can develop a colour ranging from pink to brownish pink. The solution must not be used if it is coloured or presents a precipitate.
KEEP OUT OF THE REACH AND SIGHT OF CHILDREN.
6.5 Nature and contents of container
Amber coloured type 1 glass ampoule, 1 mL.
6.6 Special precautions for disposal and handling
All unused medicine or waste resulting from such medicine must be disposed of in compliance with local regulations.
7 MARKETING AUTHORISATION HOLDER
MONICO S.p.A. – Ponte di Pietra, 7 – VENICE/MESTRE.
8 MARKETING AUTHORISATION NUMBER
Isoprenaline Hydrochloride MONICO 0.2 mg/1 mL, 5 ampoules MA No.: 030794 010
9 DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION
11 November 1993/14 January 2016
10 DATE OF REVISION OF THE TEXT
3 September 2016.