DRUGS & SUPPLEMENTS
INDICATIONS AND USAGE
Ibutilide Injection is indicated for the rapid conversion of atrial fibrillation or atrial flutter of recent onset to sinus rhythm. Patients with atrial arrhythmias of longer duration are less likely to respond to Ibutilide. The effectiveness of ibutilide has not been determined in patients with arrhythmias of more than 90 days in duration.
LIFE-THREATENING ARRHYTHMIAS-APPROPRIATE TREATMENT ENVIRONMENT
Ibutilide can cause potentially fatal arrhythmias, particularly sustained polymorphic ventricular tachycardia, usually in association with QT prolongation, but sometimes without documented QT prolongation. In registration studies, these arrhythmias, which require cardioversion, occurred in 1.7% of treated patients during, or within a number of hours of, use of Ibutilide. These arrhythmias can be reversed if treated promptly. It is essential that Ibutilide be administered in a setting of continuous ECG monitoring and by personnel trained in identification and treatment of acute ventricular arrhythmias, particularly polymorphic ventricular tachycardia. Patients with atrial fibrillation of more than 2 to 3 days' duration must be adequately anticoagulated, generally for at least 2 weeks.
CHOICE OF PATIENTS
Patients with chronic atrial fibrillation have a strong tendency to revert after conversion to sinus rhythm and treatments to maintain sinus rhythm carry risks. Patients to be treated with Ibutilide, therefore, should be carefully selected such that the expected benefits of maintaining sinus rhythm outweigh the immediate risks of Ibutilide, and the risks of maintenance therapy, and are likely to offer an advantage compared with alternative management.
Ibutilide Injection is contraindicated in patients who have previously demonstrated hypersensitivity to Ibutilide or any of the other product components.
Like other antiarrhythmic agents, Ibutilide Injection can induce or worsen ventricular arrhythmias in some patients. This may have potentially fatal consequences. Torsades de pointes, a polymorphic ventricular tachycardia that develops in the setting of a prolonged QT interval, may occur because of the effect Ibutilide has on cardiac repolarization, but Ibutilide can also cause polymorphic VT in the absence of excessive prolongation of the QT interval. In general, with drugs that prolong the QT interval, the risk of torsades de pointes is thought to increase progressively as the QT interval is prolonged and may be worsened with bradycardia, a varying heart rate, and hypokalemia. In clinical trials conducted in patients with atrial fibrillation and atrial flutter, those with QTc intervals >440 msec were not usually allowed to participate, and serum potassium had to be above 4.0 mEq/L. Although change in QTc was dose dependent for ibutilide, there was no clear relationship between risk of serious proarrhythmia and dose in clinical studies, possibly due to the small number of events. In clinical trials of intravenous ibutilide, patients with a history of congestive heart failure (CHF) or low left ventricular ejection fraction appeared to have a higher incidence of sustained polymorphic ventricular tachycardia (VT), than those without such underlying conditions; for sustained polymorphic VT the rate was 5.4% in patients with a history of CHF and 0.8% without it. There was also a suggestion that women had a higher risk of proarrhythmia, but the sex difference was not observed in all studies and was most prominent for nonsustained ventricular tachycardia. The incidence of sustained ventricular arrhythmias was similar in male (1.8%) and female (1.5%) patients, possibly due to the small number of events. Ibutilide is not recommended in patients who have previously demonstrated polymorphic ventricular tachycardia (eg, torsades de pointes).
During registration trials, 1.7% of patients with atrial flutter or atrial fibrillation treated with Ibutilide developed sustained polymorphic ventricular tachycardia requiring cardioversion. In these clinical trials, many initial episodes of polymorphic ventricular tachycardia occurred after the infusion of Ibutilide was stopped but generally not more than 40 minutes after the start of the first infusion. There were, however, instances of recurrent polymorphic VT that occurred about 3 hours after the initial infusion. In two cases, the VT degenerated into ventricular fibrillation, requiring immediate defibrillation. Other cases were managed with cardiac pacing and magnesium sulfate infusions. Nonsustained polymorphic ventricular tachycardia occurred in 2.7% of patients and nonsustained monomorphic ventricular tachycardias occurred in 4.9% of the patients.
Proarrhythmic events must be anticipated. Skilled personnel and proper equipment, including cardiac monitoring equipment, intracardiac pacing facilities, a cardioverter/defibrillator, and medication for treatment of sustained ventricular tachycardia, including polymorphic ventricular tachycardia, must be available during and after administration of Ibutilide. Before treatment with Ibutilide, hypokalemia and hypomagnesemia should be corrected to reduce the potential for proarrhythmia. Patients should be observed with continuous ECG monitoring for at least 4 hours following infusion or until QTc has returned to baseline. Longer monitoring is required if any arrhythmic activity is noted. Management of polymorphic ventricular tachycardia includes discontinuation of ibutilide, correction of electrolyte abnormalities, especially potassium and magnesium, and overdrive cardiac pacing, electrical cardioversion, or defibrillation. Pharmacologic therapies include magnesium sulfate infusions. Treatment with antiarrhythmics should generally be avoided.
Class Ia antiarrhythmic drugs, such as disopyramide, quinidine, and procainamide, and other class III drugs, such as amiodarone and sotalol, should not be given concomitantly with Ibutilide Injection or within 4 hours postinfusion because of their potential to prolong refractoriness. In the clinical trials, class I or other class III antiarrhythmic agents were withheld for at least 5 half-lives prior to ibutilide infusion and for 4 hours after dosing, but thereafter were allowed at the physician's discretion.
Other drugs that prolong the QT interval
The potential for proarrhythmia may increase with the administration of Ibutilide Injection to patients who are being treated with drugs that prolong the QT interval, such as phenothiazines, tricyclic antidepressants, tetracyclic antidepressants, and certain antihistamine drugs (H1 receptor antagonists).
Of the nine ibutilide-treated patients with reports of reversible heart block, five had first degree, three had second degree, and one had complete heart block.
Laboratory Test Interactions
No specific pharmacokinetic or other formal drug interaction studies were conducted.
Supraventricular arrhythmias may mask the cardiotoxicity associated with excessive digoxin levels. Therefore, it is advisable to be particularly cautious in patients whose plasma digoxin levels are above or suspected to be above the usual therapeutic range. Coadministration of digoxin did not have effects on either the safety or efficacy of ibutilide in the clinical trials.
Calcium channel blocking agents
Coadministration of calcium channel blockers did not have any effect on either the safety or efficacy of ibutilide in the clinical trials.
Beta-adrenergic blocking agents
Coadministration of beta-adrenergic blocking agents did not have any effect on either the safety or efficacy of ibutilide in the clinical trials.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No animal studies have been conducted to determine the carcinogenic potential of Ibutilide; however, it was not genotoxic in a battery of assays,. Similarly, no drug-related effects on fertility or mating were noted in a reproductive study in rats in which ibutilide was administered orally to both sexes up to doses of 20 mg/kg/day. On a mg/m2 basis, corrected for 3% bioavailability, the highest dose tested was approximately four times the maximum recommended human dose (MRHD).
Ibutilide administered orally was teratogenic (abnormalities included adactyly, interventricular septal defects, and scoliosis) and embryocidal in reproduction studies in rats. On a mg/m2 basis, corrected for the 3% oral bioavailability, the "no adverse effect dose" (5 mg/kg/day given orally) was approximately the same as the maximum recommended human dose (MRHD); the teratogenic dose (20 mg/kg/day given orally) was about four times the MRHD on a mg/m2 basis, or 16 times the MRHD on a mg/kg basis. Ibutilide should not be administered to a pregnant woman unless clinical benefit outweighs potential risk to the fetus.
The excretion of ibutilide into breast milk has not been studied; accordingly, breastfeeding should be discouraged during therapy with Ibutilide.
Clinical trials with Ibutilide in patients with atrial fibrillation and atrial flutter did not include anyone under the age of 18. Safety and effectiveness of ibutilide in pediatric patients has not been established.
Clinical studies of Ibutilide did not include sufficient numbers of subjects less than age 65 (45%) to determine whether they respond differently from older subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Use in Patients With Hepatic or Renal Dysfunction
The safety, effectiveness, and pharmacokinetics of Ibutilide have not been established in patients with hepatic or renal dysfunction. However, it is unlikely that dosing adjustments would be necessary in patients with compromised renal or hepatic function based on the following considerations: (1) Ibutilide is indicated for rapid intravenous therapy (duration ≤ 30 minutes) and is dosed to a known, well-defined pharmacologic action (termination of arrhythmia) or to a maximum of two 10-minute infusions; (2) less than 10% of the dose of Ibutilide is excreted unchanged in the urine; and (3) drug distribution appears to be one of the primary mechanisms responsible for termination of the pharmacologic effect. Nonetheless, patients with abnormal liver function should be monitored by telemetry for more than the 4-hour period generally recommended.
In 285 patients with atrial fibrillation or atrial flutter who were treated with Ibutilide, the clearance of ibutilide was independent of renal function, as assessed by creatinine clearance (range 21 to 140 mL/min).
Ibutilide Injection was generally well tolerated in clinical trials. Of the 586 patients with atrial fibrillation or atrial flutter who received Ibutilide in phase II/III studies, 149 (25%) reported medical events related to the cardiovascular system, including sustained polymorphic ventricular tachycardia (1.7%) and nonsustained polymorphic ventricular tachycardia (2.7%).
Other clinically important adverse events with an uncertain relationship to Ibutilide include the following (0.2% represents one patient): sustained monomorphic ventricular tachycardia (0.2%), nonsustained monomorphic ventricular tachycardia (4.9%), AV block (1.5%), bundle branch block (1.9%), ventricular extrasystoles (5.1%), supraventricular extrasystoles (0.9%), hypotension/postural hypotension (2.0%), bradycardia/sinus bradycardia (1.2%), nodal arrhythmia (0.7%), congestive heart failure (0.5%), tachycardia/sinus tachycardia/supraventricular tachycardia (2.7%), idioventricular rhythm (0.2%), syncope (0.3%), and renal failure (0.3%). The incidence of these events, except for syncope, was greater in the group treated with Ibutilide than in the placebo group.
Another adverse reaction that may be associated with the administration of Ibutilide was nausea, which occurred with a frequency greater than 1% more in ibutilide-treated patients than those treated with placebo.
The medical events reported for more than 1% of the placebo- and ibutilide-treated patients are shown in the following Table.
In the post-cardiac surgery study, similar types of medical events were reported. In the 1 mg Ibutilide treatment group (N=70), 2 patients (2.9%) developed sustained polymorphic ventricular tachycardia and 2 other patients (2.9%) developed nonsustained polymorphic ventricular tachycardia. Polymorphic ventricular tachycardia was not reported in the 73 patients in the 0.5 mg dose group or in the 75 patients in the 0.25 mg dose group.
Acute Experience in Animals
Acute overdose in animals results in CNS toxicity; notably, CNS depression, rapid gasping breathing, and convulsions. The intravenous median lethal dose in the rat was more than 50 mg/kg which is, on a mg/m2 basis, at least 250 times the maximum recommended human dose.
In the registration trials with Ibutilide Injection, four patients were unintentionally overdosed. The largest dose was 3.4 mg administered over 15 minutes. One patient (0.025 mg/kg) developed increased ventricular ectopy and monomorphic ventricular tachycardia, another patient (0.032 mg/kg) developed AV block-3rd degree and nonsustained polymorphic VT, and two patients (0.038 and 0.020 mg/kg) had no medical event reports. Based on known pharmacology, the clinical effects of an overdosage with ibutilide could exaggerate the expected prolongation of repolarization seen at usual clinical doses. Medical events (eg, proarrhythmia, AV block) that occur after the overdosage should be treated with measures appropriate for that condition.
DOSAGE AND ADMINISTRATION
The recommended dose based on controlled trials is outlined in the Table below. Ibutilide infusion should be stopped as soon as the presenting arrhythmia is terminated or in the event of sustained or nonsustained ventricular tachycardia, or marked prolongation of QT or QTc.
In a trial comparing ibutilide and sotalol, 2 mg Ibutilide administered as a single infusion to patients weighing more than 60 kg was also effective in terminating atrial fibrillation or atrial flutter.
In the post-cardiac surgery study, one or two intravenous infusions of 0.5 mg (0.005 mg/kg per dose for patients weighing less than 60 kg) was effective in terminating atrial fibrillation or atrial flutter.
Patients should be observed with continuous ECG monitoring for at least 4 hours following infusion or until QTc has returned to baseline. Longer monitoring is required if any arrhythmic activity is noted. Skilled personnel and proper equipment, such as a cardioverter/defibrillator, and medication for treatment of sustained ventricular tachycardia, including polymorphic ventricular tachycardia, must be available during administration of Ibutilide and subsequent monitoring of the patient.
Ibutilide Injection may be administered undiluted or diluted in 50 mL of diluent. Ibutilide may be added to 0.9% Sodium Chloride Injection or 5% Dextrose Injection before infusion. The contents of one 10 mL vial (0.1 mg/mL) may be added to a 50 mL infusion bag to form an admixture of approximately 0.017 mg/mL Ibutilide. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Compatibility and Stability
The following diluents are compatible with Ibutilide Injection (0.1 mg/mL):
The following intravenous solution containers are compatible with admixtures of Ibutilide Injection (0.1 mg/mL):
Admixtures of the product, with approved diluents, are chemically and physically stable for 24 hours at room temperature (15° to 30° C or 59° to 86° F) and for 48 hours at refrigerated temperatures (2° to 8°C or 36° to 46°F). Strict adherence to the use of aseptic technique during the preparation of the admixture is recommended in order to maintain sterility.
Ibutilide Injection (ibutilide fumarate injection) is supplied as an acetate-buffered isotonic solution at a concentration of 0.1 mg/mL that has been adjusted to approximately pH 4.6 in 10 mL clear glass, single-dose, flip-top vials.
Single-dose 10 mL vial, 1 mg /10 mL (0.1 mg/mL) NDC 0009-3794-01
Store at controlled room temperature 20° to 25°C (68° to 77°F). Store vial in carton until used.
10 mL Single-Dose Vial
(ibutilide fumarate injection)
1 mg/10 mL
For IV use only
Ibutilide pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Ibutilide available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Ibutilide destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Ibutilide Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Ibutilide pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Ibutilide?
Depending on the reaction of the Ibutilide after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Ibutilide not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Ibutilide addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Reviewsdrugs.com conducted a study on Ibutilide, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Ibutilide consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
Visitor reported usefulNo survey data has been collected yet
Visitor reported side effectsNo survey data has been collected yet
Visitor reported price estimatesNo survey data has been collected yet
Visitor reported frequency of useNo survey data has been collected yet
Visitor reported dosesNo survey data has been collected yet
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The information was verified by Dr. Arunabha Ray, MD Pharmacology