AMIODARONE 150 mg/3 ml PHARMC

Indications

• Ventricular tachycardia
• Atrial fibrillation
• Atrial flutter
• Supraventricular tachycardia
• Life-threatening ventricular arrhythmias

Dosage

Adults: The typical loading dose is 800 mg to 1,600 mg daily for 1 to 3 weeks, followed by a maintenance dose of 100 mg to 400 mg daily, adjusted

Mechanism of action

Amiodarone blocks potassium currents responsible for cardiac repolarization during the third phase of the cardiac action potential, increasing action potential duration and effective refractory period in myocytes. Additionally, it interferes with beta-adrenergic receptors and sodium and calcium channels, which can lead to effects such as hypotension and bradycardia. It also has an effect on thyroid receptors due to its iodine content, potentially causing thyroid dysfunction.

Pharmacodynamics

Amiodarone relaxes vascular smooth muscles, decreases peripheral vascular resistance, and has a minimal effect on the cardiac index when administered intravenously. It prolongs the QRS duration and QT interval, decreases sinoatrial node automaticity, and inhibits ectopic pacemaker automaticity. While it is effective in treating arrhythmias, its oral form does not significantly alter left ventricular ejection fraction, and clinical trials have not consistently shown an increase in survival with oral administration.

Pharmacokinetics

Amiodarone is highly lipophilic, leading to extensive tissue distribution and a long half-life, which can exceed several weeks. It is metabolized predominantly by the liver, and its elimination is prolonged in cases of hepatic impairment. The drug has a complex pharmacokinetic profile with significant variability in bioavailability due to factors such as food intake and individual patient metabolism.

Contra-indications

• Severe bradycardia
• Sick sinus syndrome
• Second or third-degree heart block (without a functioning pacemaker)
• Severe hepatic impairment
• Hypersensitivity to amiodarone or any of its components

Adverse effects

• Hypotension
• Bradycardia
• Thyroid dysfunction (hypothyroidism or thyrotoxicosis)
• Pulmonary toxicity (including pulmonary fibrosis)
• Hepatic toxicity
• Corneal deposits
• Skin discoloration (blue-gray skin)
• Photosensitivity
• Gastrointestinal disturbances

Interactions

• agalsidase alfa: Severe (decreases effects)
• agalsidase beta: Severe (decreases effects)
• calcium channel blockers: Severe (increases risk of cardiodepression)
• diltiazem: Severe (increases risk of cardiodepression)
• verapamil: Severe (increases risk of cardiodepression)
• grapefruit juice: Severe (increases exposure)
• ribociclib: Severe (increases exposure)
• thyroid hormones: Severe (increases risk of thyroid dysfunction)
• ciclosporin: Moderate (increases concentration)
• opioids: Moderate (increases concentration)

Precautions

• Monitor thyroid function tests regularly during treatment
• Caution in patients with pre-existing lung disease
• Monitor liver function tests periodically
• Use with caution in patients with bradycardia or AV block
• Consider drug interactions when prescribing

Pregnancy

Amiodarone should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus. It crosses the placenta and may lead to fetal thyroid dysfunction.

Breast-feeding

Amiodarone is excreted in breast milk. Caution is advised when administering to nursing mothers due to the potential for serious adverse effects in the infant.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Oral tablets
• Intravenous injection

Indications

• Supraventricular arrhythmias
• Ventricular arrhythmias
• Ventricular fibrillation
• Pulseless ventricular tachycardia

Dosage

Children: Neonate: Initially 5–10 mg/kg twice daily for 7–10 days, then reduced to 5–10 mg/kg daily. Child 1 month–11 years: Initially 5–10 mg/kg twice daily for 7–10 days, then reduced to 5–10 mg/kg once daily; maximum 200 mg per day. Child 12–17 years: 200 mg 3 times a day for 1 week, then 200 mg twice daily for 1 week, then adjusted according to response.

Adults: Initially 150 mg by slow intravenous injection over 10 minutes, followed by an infusion of 1 mg/min for 6 hours, then 0.5 mg/min. The oral maintenance dose is typically 200 mg to 400 mg daily, adjusted according to response.

Mechanism of action

Amiodarone works by prolonging the action potential and refractory period in myocardial tissue, thereby inhibiting adrenergic stimulation. It also exhibits some calcium channel blocking effects and sodium channel blocking properties, which contribute to its antiarrhythmic effects.

Pharmacodynamics

Amiodarone decreases the heart rate and increases the refractory period of cardiac tissues, which helps in restoring normal rhythm in arrhythmias. It also has vasodilatory properties, which can help in reducing cardiac workload.

Pharmacokinetics

Amiodarone is well-absorbed after oral administration. It is highly lipid-soluble and has a long half-life, leading to accumulation in tissues. It is extensively metabolized in the liver, primarily by cytochrome P450 enzymes. The elimination half-life can vary significantly, often ranging from 15 to 100 days, depending on individual patient factors.

Contra-indications

• Severe bradycardia
• Severe hepatic impairment
• Severe respiratory failure
• Cardiogenic shock
• Circulatory collapse
• Hypotension
• Acute porphyrias

Adverse effects

• Arrhythmias
• Hepatic disorders
• Hyperthyroidism
• Nausea
• Respiratory disorders
• Skin reactions
• Constipation
• Corneal deposits
• Hypothyroidism
• Movement disorders
• Photosensitivity
• Headache
• Delirium
• Pancreatitis
• Severe cutaneous adverse reactions (SCARs)
• Alopecia
• Aplastic anemia
• Epididymo-orchitis
• Erectile dysfunction
• Hemolytic anemia
• Thrombocytopenia
• Pulmonary hemorrhage
• Vertigo

Precautions

• Monitor thyroid function regularly
• Use with caution in patients with severe respiratory failure
• Adjust dose in patients with hepatic impairment

Pregnancy

Use only if the benefits outweigh the risks. Amiodarone crosses the placenta.

Breast-feeding

Not recommended due to potential adverse effects on the infant.

Storage

Store in a cool, dry place away from light.

Formulations

• Oral tablet
• Intravenous injection
• Intravenous infusion

Mechanism of action

Amiodarone is considered a class III anti-arrhythmic drug. It blocks potassium currents that cause repolarization of the heart muscle during the third phase of the cardiac action potential. As a result amiodarone increases the duration of the action potential as well as the effective refractory period for cardiac cells (myocytes). Therefore, cardiac muscle cell excitability is reduced, preventing and treating abnormal heart rhythms. Unique from other members of the class III anti-arrhythmic drug class, amiodarone also interferes with the functioning of beta-adrenergic receptors, sodium channels, and calcium channels channels. These actions, at times, can lead to undesirable effects, such as hypotension, bradycardia, and Torsades de pointes (TdP). In addition to the above, amiodarone may increase activity of peroxisome proliferator-activated receptors, leading to steatogenic changes in the liver or other organs. Finally, amiodarone has been found to bind to the thyroid receptor due to its iodine content, potentially leading to amiodarone induced hypothyroidism or thyrotoxicosis.

Pharmacodynamics

After intravenous administration, amiodarone acts to relax smooth muscles that line vascular walls, decreases peripheral vascular resistance (afterload), and increases the cardiac index by a small amount. Administration by this route also decreases cardiac conduction, preventing and treating arrhythmias. When it is given orally, however, amiodarone does not lead to significant changes in the left ventricular ejection fraction. Similar to other anti-arrhythmic agents, controlled clinical trials do not confirm that oral amiodarone increases survival. Amiodarone prolongs the QRS duration and QT interval. In addition, a decreased SA (sinoatrial) node automaticity occurs with a decrease in AV node conduction velocity. Ectopic pacemaker automaticity is also inhibited. Thyrotoxicosis or hypothyroidism may also result from the administration of amiodarone, which contains high levels of iodine, and interferes with normal thyroid function.