Bretylium is a medication that was historically used for the treatment of certain cardiac arrhythmias, particularly ventricular fibrillation (VF) and ventricular tachycardia (VT). It works by blocking the release of catecholamines from nerve endings, which helps to stabilize the heart's rhythm.

Bretylium is a class III anti-arrhythmic drug that prolongs the duration of action potential and the effective refractory period of ventricular tissues and Purkinje fibres. It is used in the treatment of life-threatening ventricular arrhythmias, primarily ventricular fibrillation and ventricular tachycardia, that are resistant to conventional anti-arrhythmic drugs. It has not been marketed since 2000 because of the lack of efficacy and unavailability of raw materials. It is currently on the FDA list of discontinued drugs.

Bretylium Dose in Adults

Note: Bretylium is a medicine used to treat certain heart rhythm problems, but it doesn't work right away, so it's not for emergencies. It's only meant for short-term use, usually for 3 to 5 days.

Bretylium Dose in the treatment of life-threatening Ventricular arrhythmia as in ventricular fibrillation:

• The initial dose of bretylium is 5 mg/kg given rapidly through an IV injection, which can be increased to 10 mg/kg and repeated every 15 to 30 minutes if needed, up to a maximum of 30 mg/kg.

Other ventricular arrhythmias:

• The initial dose ranges from 5 to 10 mg/kg given either intravenously over more than 8 minutes or intramuscularly.
• This dose can be repeated if necessary after 1 to 2 hours.

Maintenance dosing:

• Maintenance dosing can be given intermittently through IV infusion every 6 hours or continuously at a rate of 1 to 2 mg per minute, but this should be done while closely monitoring the heart's electrical activity.
• It's important to gradually reduce and stop the dosage within 3 to 5 days, and switch to other suitable antiarrhythmic medications if needed.

Bretylium Dose in Children

Efficacy and safety not established. 

Pregnancy Risk Factor: C

• There haven't been specific studies on bretylium's effects on human reproduction.
• However, the manufacturer suggests that if a pregnant woman needs bretylium, it should be given if the benefits to the mother outweigh any potential risks to the fetus.

Use during breastfeeding:

• It has not yet been tested in lactating mothers.  

Bretylium Dose in Renal Disease:

• While the manufacturer's labeling doesn't provide specific dosage adjustments for individuals with renal impairment, it's generally recommended to reduce the dosage in these cases.
• This adjustment helps to account for potential changes in drug metabolism and elimination in individuals with impaired kidney function.

Bretylium Dose in Liver Disease:

• The manufacturer hasn't suggested any changes to the dosage for people with liver disease.

Side Effects of Bretylium

Nausea, vomiting, dizziness, light-headedness, and local reaction at the injection site.

Contraindications to Bretylium Includes:

• Bretylium isn't typically used to prevent arrhythmias in patients who've recently had a heart attack.

Warnings and Precautions

Hypertension:

• At first, bretylium might cause a temporary increase in blood pressure or more frequent premature ventricular contractions or other heart rhythm irregularities, especially if someone is also using other medications that affect the heart's contractions, like inotropic catecholamines.

Hypotension

• Bretylium can lead to low blood pressure, even at lower doses, and may cause a drop in blood pressure when standing up, known as orthostatic hypotension.
• Patients should remain lying down until their body gets used to this effect.
• If necessary, doctors may use medications like vasopressors such as dopamine or norepinephrine to raise blood pressure and closely monitor the patient.

Cardiovascular disease

• Bretylium should be avoided in patients with conditions where the heart's output is fixed, like severe aortic stenosis or severe pulmonary hypertension, as it can cause a sudden drop in blood pressure without increasing the heart's output, leading to severe hypotension.
• If bretylium is necessary, doctors should be ready to use vasopressors promptly to treat severe drops in blood pressure.
• Additionally, caution is needed when using bretylium in patients with bradycardia, as it might worsen this condition.

Renal impairment

• Bretylium should be used cautiously in individuals with kidney problems, as dose adjustment might be needed.

Bretylium (United States: Not available): Drug Interaction

Monitor:

• Electrocardiogram (ECG) and Blood Pressure: Regular monitoring of heart rhythm and blood pressure is important during bretylium treatment to ensure safety and effectiveness.
• Renal Function: Keep an eye on kidney function, especially in individuals with existing kidney issues. Adjustments to the dosage might be necessary in such cases.
• Consult Institutional Policies and Procedures: Follow the specific guidelines and protocols set by the institution or healthcare facility regarding the use and monitoring of bretylium.

How to administer Bretylium?

Intramuscular Administration

• Undiluted Injection: Administer bretylium directly into the muscle without dilution.
• Rotate Injection Sites: Alternate the injection sites to prevent discomfort and tissue damage.
• Injection Volume Limit: Limit each injection site to a maximum of 5 mL to avoid complications.
• Avoid Nerves: Ensure injections are not made into or near major nerves to prevent nerve damage.

Intravenous Administration

• Undiluted Rapid Injection: In cases of immediately life-threatening ventricular arrhythmia like ventricular fibrillation, administer bretylium quickly without dilution.
• Intermittent Bolus Infusion: For non-emergency situations, dilute bretylium and administer it over more than 8 minutes in intermittent bolus infusions.
• Continuous Infusion: In certain cases, bretylium can be given as a continuous infusion.
• Rapid Administration Caution: Avoid rapid administration unless absolutely necessary (e.g., for ventricular fibrillation) to prevent severe nausea and vomiting.

Mechanism of action of Bretylium:

• Bretylium belongs to the Class III category of antiarrhythmic drugs, which means it works by prolonging the action potential duration and effective refractory period in certain heart tissues like the Purkinje fibers and ventricular tissue.
• It also accumulates in sympathetic ganglia and their postganglionic adrenergic neurons.
• Initially, it can cause the release of norepinephrine, which mimics the effects of the sympathetic nervous system.
• However, bretylium then inhibits the further release of norepinephrine by reducing the excitability of the nerve terminals, leading to its antiarrhythmic effects.

Onset of Action:

• Bretylium's effects may take some time to kick in, with a delayed onset ranging from 20 minutes to up to 6 hours.

Distribution:

• The volume of distribution of bretylium is between 3 to 7 liters per kilogram of body weight. It has minimal distribution into the central nervous system.

Protein Binding:

• Bretylium has a low level of protein binding, with less than 5% of the drug binding to proteins in the bloodstream.

Half-life Elimination:

• The half-life of elimination for bretylium ranges from 5 to 10 hours, indicating how long it takes for half of the drug to be removed from the body.

Excretion:

• Bretylium is primarily eliminated from the body through urine, with 80% to 90% of it excreted unchanged in the urine.

International Brands of Bretylium:

• Bretylate
• Bretylol

Bretylium Brands in Pakistan:

No brands available in Pakistan