Usage
Ibutilide fumarate is prescribed for the rapid conversion of recent-onset atrial fibrillation and atrial flutter to sinus rhythm. It is classified as a Class III antiarrhythmic agent. Ibutilide works by prolonging the action potential duration in cardiac cells, primarily by activating a slow inward sodium current (INa-s). This leads to increased refractoriness in both the atria and ventricles, helping to restore normal sinus rhythm.
Alternate Names
Ibutilide is often referred to as ibutilide fumarate, reflecting the salt form used in pharmaceutical preparations. A common brand name for ibutilide is Corvert®.
How It Works
Pharmacodynamics: Ibutilide primarily affects the heart’s electrical activity. By activating the slow inward sodium current (INa-s), it prolongs the action potential duration and the effective refractory period in atrial and ventricular myocardial cells. This delay in repolarization reduces the likelihood of re-entrant circuits, which are common triggers for atrial fibrillation and flutter.
Pharmacokinetics: Ibutilide is administered intravenously. Following administration, plasma concentrations decrease rapidly in a multiexponential manner. It has a high volume of distribution and is cleared rapidly, primarily through hepatic metabolism and renal excretion. The elimination half-life is approximately 6 hours (range 2-12 hours). No dose adjustments are typically necessary for renal or hepatic impairment.
Mode of Action: Ibutilide’s primary mechanism involves activation of the slow inward sodium current. It does not significantly affect other ionic currents like IKr or IKs.
Elimination Pathways: Ibutilide is eliminated through both hepatic metabolism and renal excretion, with the majority of the drug and its metabolites excreted in the urine.
Dosage
Standard Dosage
Adults:
- <60 kg: 0.01 mg/kg IV infusion over 10 minutes. A second dose of the same amount may be administered after 10 minutes if the arrhythmia persists.
- ≥60 kg: 1 mg IV infusion over 10 minutes. A second dose of 1 mg may be administered after 10 minutes if the arrhythmia persists.
Infusion should be discontinued immediately upon conversion to sinus rhythm, onset of sustained or non-sustained ventricular tachycardia, or marked QT/QTc prolongation.
Children:
The safety and efficacy of ibutilide in pediatric patients have not been established. It is not recommended for use in this population.
Special Cases:
- Elderly Patients: Initiate therapy at the lower end of the dosing range and monitor closely.
- Patients with Renal Impairment: Dose adjustment is not necessary.
- Patients with Hepatic Dysfunction: Dose adjustment is not necessary.
- Patients with Comorbid Conditions: Use with caution in patients with congestive heart failure, recent myocardial infarction, bradycardia, or electrolyte abnormalities. Correct any electrolyte imbalances (especially hypokalemia and hypomagnesemia) before and during treatment.
Clinical Use Cases
Ibutilide is specifically indicated for the pharmacological cardioversion of recent-onset atrial fibrillation or flutter. It is not typically used in the context of intubation, surgical procedures, mechanical ventilation, or general ICU use. Its use in emergency situations like cardiac arrest has not been established.
Dosage Adjustments
While no specific dosage adjustments are recommended for renal or hepatic impairment, careful monitoring is necessary. For other comorbid conditions, refer to the “Special Cases” section above.
Side Effects
Common Side Effects
Rare but Serious Side Effects
- Torsades de pointes (a type of polymorphic ventricular tachycardia)
- Prolonged QT interval
- Hypotension
- Bradycardia
- Heart block
Long-Term Effects
Long-term effects are not typically associated with ibutilide, as it is used for acute conversion of atrial fibrillation or flutter.
Adverse Drug Reactions (ADR)
The most significant ADRs are proarrhythmic effects, including torsades de pointes and other ventricular tachycardias, which can be life-threatening.
Contraindications
- Hypersensitivity to ibutilide
- Congenital long QT syndrome
- History of polymorphic ventricular tachycardia (torsades de pointes)
- Concurrent use with other QT-prolonging drugs
Drug Interactions
Ibutilide interacts with numerous medications, most notably those that also prolong the QT interval. Concomitant use with Class Ia and Class III antiarrhythmics (e.g., amiodarone, sotalol, disopyramide, quinidine) is contraindicated. Other drugs that can prolong the QT interval, such as certain antipsychotics, antidepressants, and antibiotics, should be used with extreme caution or avoided. Consult a comprehensive drug interaction resource for a full list of interacting medications.
Pregnancy and Breastfeeding
Ibutilide has been shown to be teratogenic in animal studies. It should not be used during pregnancy unless the potential benefit outweighs the risk to the fetus. The excretion of ibutilide in breast milk is unknown; therefore, breastfeeding is not recommended during treatment.
Drug Profile Summary
- Mechanism of Action: Prolongs cardiac action potential duration and refractoriness via activation of INa-s.
- Side Effects: Headache, nausea, torsades de pointes, QT prolongation, hypotension, bradycardia, heart block.
- Contraindications: Hypersensitivity, congenital long QT syndrome, history of torsades de pointes, concurrent use with QT-prolonging drugs.
- Drug Interactions: Numerous drug interactions, particularly with other QT-prolonging agents.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy unless benefits outweigh risks; breastfeeding not recommended.
- Dosage: <60 kg: 0.01 mg/kg IV over 10 min (repeat if necessary); ≥60 kg: 1 mg IV over 10 min (repeat if necessary).
- Monitoring Parameters: Continuous ECG monitoring, including QT interval, heart rate, and rhythm. Serum electrolyte monitoring (potassium, magnesium).
Popular Combinations
Ibutilide is typically used as a single agent for cardioversion. Combining it with other antiarrhythmic drugs, especially those that prolong the QT interval, is contraindicated due to the increased risk of proarrhythmia.
Precautions
- Administer only in settings with continuous ECG monitoring and personnel trained in managing cardiac arrhythmias.
- Correct electrolyte imbalances before and during therapy.
- Patients with a history of atrial fibrillation lasting more than 2-3 days should be adequately anticoagulated prior to ibutilide administration.
- Use with caution in patients with bradycardia, congestive heart failure, recent myocardial infarction, or prolonged baseline QT interval.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ibutilide?
A: For patients <60 kg: 0.01 mg/kg IV over 10 minutes. For patients ≥60 kg: 1 mg IV over 10 minutes. A second dose may be given after 10 minutes if needed.
Q2: What are the most serious side effects of Ibutilide?
A: Torsades de pointes, other ventricular arrhythmias, and QT prolongation.
Q3: Is Ibutilide safe to use in patients with heart failure?
A: No, ibutilide is contraindicated in patients with heart failure due to the increased risk of serious ventricular arrhythmias.
Q4: Can Ibutilide be used in pregnant or breastfeeding women?
A: Ibutilide is generally contraindicated in pregnancy and breastfeeding. It should only be used if the potential benefit clearly outweighs the risk.
Q5: What medications should be avoided when taking Ibutilide?
A: Avoid concomitant use with other QT-prolonging medications, including Class Ia and Class III antiarrhythmics. Consult a drug interaction resource for a comprehensive list.
Q6: How should Ibutilide be administered?
A: Ibutilide should be administered as an intravenous infusion over 10 minutes in a setting with continuous ECG monitoring.
Q7: What is the mechanism of action of Ibutilide?
A: Ibutilide prolongs the cardiac action potential and refractoriness, primarily by activating the slow inward sodium current.
Q8: What should be monitored during Ibutilide administration?
A: Continuous ECG monitoring (heart rate, rhythm, QT interval), and serum electrolytes (potassium and magnesium).
Q9: When should the Ibutilide infusion be stopped?
A: The infusion should be stopped immediately upon successful conversion to sinus rhythm, onset of sustained or non-sustained ventricular tachycardia, or marked QT/QTc prolongation.
