Prescribing information
- Treatment by mouth
- 200 mg 3 times daily for 1 week reduced to 200 mg twice daily for a further week.
- Maintenance dose, usually 200 mg daily or the minimum required to control the arrhythmia.
- Treatment by intravenous infusion
- Via a central line, 5 mg/kg over 20-120 minutes with ECG monitoring; maximum 1.2 g in 24 hours.
- Emergency treatment during cardiopulmonary resuscitation
- VF or pulseless VT, 300 mg by intravenous injection over at least 3 minutes (pre-filled syringe).
Drugs with a long half-life. Onset and offset of action.
- Amiodarone is an example of a drug with a very long half-life (about 50 days). The half-life of a drug is the time taken for the plasma concentration of the drug to fall by half, and is a measure of how quickly a drug is eliminated from the body.
- When a second dose of a drug is taken, its pharmacokinetic profile is superimposed on that of the first dose, and so on for subsequent doses. For a given dose, the pattern of plasma concentrations that results will depend upon two factors: the dosage interval and the half-life of the drug. A consequence of first-order pharmacokinetics (essentially exponential decay) is that during repeated administration, drug accumulation occurs. This is because the higher the plasma concentration is, the faster it falls. Eventually, during a dosage interval, the plasma concentration falls as fast as it rises. At this point a steady state is reached, after about four half-lives of administration, provided that the dosage interval is not excessively long. Before such a steady state has been reached one cannot say that the drug has reached its maximum effect.
- The practical consequence of this is that the maximum effect of amiodarone is not reached until about 4 half-lives have elapsed, about 200 days, unless a loading dose is given.
- It is unwise to declare that a drug is not effective until a steady state has been reached. Prematurely increasing the dose may lead to excessive accumulation and toxicity.
- In the same way as it takes a very long time for amiodarone to have its maximum effect, it takes a very long time for amiodarone to be eliminated from the body once it has been stopped. Adverse effects and drug interactions can occur weeks after amiodarone has been stopped.
| Drugs with long half-lives | |||
| Years (in bone) 50 days 48 days 18 days 21 days 6 days 14 days 7 days 5 days Variable, up to 60 hours or more 48 hours 40 hours 24 hours | ||
Amiodarone has a complex mechanism of action that is incompletely understood, but is probably mediated through effects on cardiac potassium channels.
- Amiodarone prolongs the action potential and refractory period homogeneously throughout the heart.
- The principal ECG change is a prolongation of the QT interval.
- Amiodarone is a class III antiarrhythmic drug in the Vaughan-Williams classification.
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