Cardiovascular
Soladeno Adenosine Injection USP
Presentation
6 mg/2 ml
For the use of a Registered Medical Practitioner or a Hospital or a Institution only.
EFFECTIVE AT RESTORING THE NORMAL SINUS RHYTHM
Treatment of Paroxysmal Supraventricular Tachycardia
Diagnosis of Re-Entrant Atrial and Ventricular Tachycardias
Non-invasive Assessment of Coronary Artery Disease
DESCRIPTION:
Adenosine is an endogenous nucleoside occurring in all cells of the body. Chemically, Adenosine is 9-β-D-ribofuranosyladenine. The molecular formula is C10H13N5O4 and the molecular weight is 267.25.
STRUCTURAL FORMULA :
Its structural formula is :
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DESCRIPTION OF INJECTION:
COMPOSITION :
Each ml contains :
Adenosine USP 3 mg
Sodium Chloride I.P. 9 mg
Water for Injections I.P. q.s.
Contains no preservative.
ACTIONS :
Adenosine administered by rapid intravenous injection slows conduction through the AV node. This action can interrupt re-entry circuits involving the AV node and restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardias. Once the circuit has been interrupted, the tachycardia stops and normal sinus rhythm is re-established. One acute interruption of the circuit is usually sufficient to arrest the tachycardia. Since atrial fibrillation and atrial flutter do not involve the AV node as part of a re-entry circuit, adenosine will not terminate these arrhythmias. By transiently slowing AV conduction, atrial activity is easier to evaluate from ECG recordings and therefore the use of adenosine can aid the diagnosis of broad or narrow complex tachycardias. Adenosine may be useful during electrophysiological studies to determine the site of AV block or to determine in some cases of pre-excitation, whether conduction is occurring by an accessory pathway or via the AV node.
PHARMACOKINETICS :
Intravenously administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system that is reversible, nonconcentrative and bidirectionally symmetrical. Intracellular adenosine is rapidly metabolized either via phosphorylation to adenosine monophosphate by adenosine kinase or via deamination to inosine by adenosine deaminase in the cytosol. Since adenosine kinase has a lower Km and Vmax than adenosine deaminase, deamination plays a significant role only when cytosolic adenosine saturates the phosphorylation pathway. Inosine formed by deamination of adenosine can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid. Adenosine monophosphate formed by phosphorylation of adenosine is incorporated into the high-energy phosphate pool. While extracellular adenosine is primarily cleared by cellular uptake with a half-life of less than 10 seconds in whole blood, excessive amounts may be deaminated by an ecto-form of adenosine deaminase. As adenosine requires no hepatic or renal function for its activation or inactivation, hepatic and renal failure would not be expected to alter its effectiveness or tolerability.
INDICATIONS :
1. Treatment of paroxysmal supraventricular tachycardia (PSVT).
2. Diagnosis of re-entrant atrial and ventricular tachycardias.
3. Non-invasive assessment of coronary artery disease (CAD) using techniques like pharmacological stress testing, single photon emission computed tomography (SPECT), thallium-201 scintigraphy and positron emission tomography.
CONTRAINDICATIONS :
Soladeno is contraindicated in :
1. Second-or third-degree AV block (except in patients with a functioning artificial pacemaker).
2. Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker).
3. Known hypersensitivity to adenosine.
4. Asthama.
DOSAGE AND ADMINISTRATION:
Administration :
For rapid bolus intravenous use only.
SOLADENO should be given as a rapid bolus by the peripheral intravenous route. To be certain the solution reaches the systemic circulation, it should be administered either directly into a vein or, if given into an IV line, it should be given as close to the patient as possible and followed by a rapid saline flush.
INSTRUCTION FOR USE OF AMPOULE :
The ampoule used in this product is equipped with O.P.C (One Point Cut) opening system. No ampoule file is needed to open the ampoule. The neck of the ampoule is prescored at the point of constriction. A coloured dot on the ampoule head helps to orientate the ampoule. Take the ampoule and face the coloured dot. Let the solution at the head of the ampoule to flow down by shaking or a gentle stroke. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards as shown.
Dosage :
Adenosine is intended for hospital use only with monitoring and cardiorespiratory resuscitation equipment available for immediate use. It should be administered by rapid IV bolus injection according to the ascending dosage schedule below. To be certain the solution reaches the systemic circulation administer either directly into a vein or into an IV line. If given into an IV line it should be injected as proximally as possible, and followed by a rapid saline flush.Adenosine should only be used when facilities exist for cardiac monitoring. Patients who develop high-level AV block at a particular dose should not be given further dosage increments.
Therapeutic dose :
Adult :
Initial dose : 3 mg given as a rapid intravenous bolus (over 2 seconds).
Second dose : If the first dose does not result in elimination of the supraventricular tachycardia within 1 to 2 minutes, 6 mg should be given also as a rapid intravenous bolus.
Third dose : If the second dose does not result in elimination of the supraventricular tachycardia within 1 to 2 minutes. 12 mg should be given also as a rapid intravenous bolus. Additional or higher doses are not recommended.
Children : No controlled paediatric study has been undertaken. Published uncontrolled studies show similar effects of adenosine in adults and children : effective doses for children were between 0.0375 and 0.25 mg/kg.
Elderly : See dosage recommendations for adults.
Diagnostic dose : The above ascending dosage schedule should be employed until sufficient diagnostic information has been obtained.
WARNINGS:
Heart Block :
Adenosine exerts its effect by decreasing conduction through the AV node and may produce a short lasting first, second or third-degree heart block. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adenosine should not be given additional doses. Because of the very short half-life of adenosine, these effects are generally self-limiting. Transient or prolonged episodes of asystole have been reported with fatal outcomes in some cases. Rarely, ventricular fibrillation has been reported following adenosine administration, including both resuscitated and fatal events. In most instances, these cases were associated with the concomitant use of digoxin and, less frequently with digoxin and verapamil. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving digoxin or digoxin and verapamil in combination. Appropriate resuscitative measures should be available.
Arrhythmias at Time of Conversion :
At the time of conversion to normal sinus rhythm, a variety of new rhythms may appear on the electrocardiogram. They generally last only a few seconds without intervention, and may take the form of premature ventricular contractions, atrial premature contractions, sinus bradycardia, sinus tachycardia, skipped beats, and varying degrees of AV nodal block. Such findings were seen in 55 % of patients.
Bronchoconstriction :
Adenosine is a respiratory stimulant (probably through activation of carotid body chemoreceptors) and intravenous administration in man has been shown to increase minute ventilation (Ve) and reduce arterial PCO2 causing respiratory alkalosis. Adenosine administered by inhalation has been reported to cause bronchoconstriction in asthmatic patients presumably due to mast cell degranulation and histamine release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with asthma and mild to moderate exacerbation of their symptoms has been reported. Respiratory compromise has occurred during adenosine infusion in patients with obstructive pulmonary disease. Adenosine should be used with caution in patients with obstructive lung disease not associated with bronchoconstriction (e.g., emphysema, bronchitis, etc.) and should be avoided in patients with bronchoconstriction or bronchospasm (e.g., asthma). Adenosine should be discontinued in any patient who develops severe respiratory difficulties.
PREGNANCY AND LACTATION:
Pregnancy : Teratogenic Effects : Pregnancy Category C
Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no foetal effects would be anticipated. However, since it is not known whether adenosine can cause foetal harm when administered to pregnant women, adenosine should be used during pregnancy only if clearly needed.
Paediatric Use :
No controlled studies have been conducted in paediatric patients to establish the safety and efficacy of adenosine for the conversion of paroxysmal supraventricular tachycardia (PSVT). However, intravenous adenosine has been used for the treatment of PSVT in neonates, infants, children and adolescents.
Geriatric Use :
Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in geriatric patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter haemodynamic function and produce severe bradycardia or AV block.
LACTATION :
In the absence of clinical experience use of adenosine during lactation should be considered only if essential.
DRUG INTERACTION:
Intravenous adenosine has been effectively administered in the presence of other cardioactive drugs, such as quinidine, beta-adrenergic blocking agents, calcium channel blocking agents, and angiotensin converting enzyme inhibitors, without any change in the adverse reaction profile. Digoxin and verapamil use may be rarely associated with ventricular fibrillation when combined with adenosine. Because of the potential for additive or synergistic depressant effects on the SA and AV nodes, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving digitalis may be rarely associated with ventricular fibrillation.
The effects of adenosine are antagonized by methylxanthines such as caffeine and theophylline. In the presence of these methylxanthines, larger doses of adenosine may be required or adenosine may not be effective. Adenosine effects are potentiated by dipyridamole. Thus, smaller doses of adenosine may be effective in the presence of dipyridamole. Carbamazepine has been reported to increase the degree of heart block produced by other agents. As the primary effect of adenosine is to decrease conduction through the AV node, higher degrees of heart block may be produced in the presence of carbamazepine.
SIDE EFFECTS :
Facial flush dyspnoea, nausea, and light-headedness occurs commonly. More rarely observed side effects have been : feeling of discomfort; sweating; palpitations; hyperventilation; blurred vision; burning sensation; bradycardia; headache; heaviness in arms. Almost all the side effects were mild, of short duration (usually less than 1 minute and never more than 2 minutes in any case) and therefore adenosine is generally very well tolerated by patients. Severe bradycardia has been reported and some patients have required temporary pacing. The effect of adenosine are blocked by Atropine.
At the time of conversion to normal sinus rhythm, the ECG may show premature ventricular contractions, premature atrial contractions, sinus bradycardia, sinus tachycardia, skipped beats, sinus pause and/or artioventricular block. The induced bradycardia predisposes to ventricular excitability disorders, including ventricular fibrillation, which
justify the recommendation made under "Dosage and administration."
OVERDOSAGE :
The half-life of adenosine is less than 10 seconds. Thus, adverse effects are generally rapidly self-limiting.
TREATMENT OF OVERDOSAGE :
Treatment of any prolonged adverse effects should be individualized and be directed toward the specific effect. Methylxanthines, such as caffeine and theophylline, are competitive antagonists of adenosine.
PHARMACEUTICAL PRECAUTIONS :
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
STORAGE :
Store at controlled room temperature between 15°C to 30°C (59°F to 86°F).
DO NOT REFRIGERATE as crystallization may occur. If crystallization has occurred, dissolve crystals by warming to room temperature. The solution must be clear at the time of use.
Discard unused portion.
SHELF LIFE :
24 months from the date of manufacture.
PRESENTATION :
SOLADENO is supplied as 6 mg adenosine in 2 ml aqueous solution. Such one ampoule of 2 ml is packed in a Box.
Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.
