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“Q.I.D.”… QUALITY INFORMATION on DRUGS
September 2004
Dunedin Medicines Information Service, Pharmacy Department, Dunedin Hospital
Telephone: 8876 (Internal), (03) 474 7658 (Direct), Facsimile: (03) 474 7638
Amiodarone
Amiodarone is a difficult drug to use due to its long half-life, interactions, adverse effects and
incompatibilities with solutions and containers. This bulletin aims to answer some of the
frequent questions that arise regarding its use.
Amiodarone is used to treat tachyarrhythmias including Wolff-Parkinson-White syndrome,
supraventricular, nodal and ventricular tachycardias as well as atrial fibrillation and atrial flutter.
Dosing
Cardiologists recommend various dosing regimens but the following is one that is commonly used in
Dunedin Hospital.
Route
IV
Use
Management of acute
arrhythmias
(Short term only)
Loading dose
Oral
Maintenance dose
Dose
Starting dose 5mg/kg in 5% Dextrose 250ml over 60 minutes.
Repeat infusions up to 1200mg in 24 hours
(administered via a pump with cardiac monitoring).
200mg three times daily for one week then reduce to
200mg twice daily for one week then reduce to
100 - 200mg daily
Notes on loading amiodarone:
ƒ IV amiodarone has a limited role in loading, it is used in clinical situations where a rapid
response is required. Oral loading is still required.
ƒ A shortened oral loading regimen can be given after IV dosing at the clinicians discretion for
less serious arrhythmia such as AF.
ƒ The full oral loading regimen should be used in life-threatening arrhythmias such as VF or VT.
Kinetics
Amiodarone has a very long half-life, reported to be between 14 and 110 days with chronic dosing.
ƒ Maximal antiarrhythmic effects of oral amiodarone may take up to 10 weeks, even with loading.
ƒ Amiodarone accumulates in many different tissues with a range of serious side effects
e.g. hypo/hyperthyroidism, corneal microdeposits, pulmonary toxicity, hepatotoxicity, peripheral
neuropathy, skin discolouration. These effects should be monitored during long-term therapy.
ƒ Amiodarone may cause photosensitivity so patients should protect themselves from the sun.
ƒ The effects of the drug can remain for months after it has been discontinued.
ƒ The effect of a missed dose or change in brand will be minor, and may not be measurable until
weeks afterwards.
Infusions
Amiodarone infusions must be administered carefully for two reasons. The drug itself can be
absorbed into PVC infusion bags and administration sets, and plasticisers from some administration
sets can leach out into the amiodarone solution.
ƒ For initial, rapid infusions (60mins), any type of bag can be used as absorption is minimal.
ƒ For slow infusions use glass or rigid PVC bottles and ‘LoSorb IV’ or ‘vented nitro-glycerine’
giving sets.
ƒ Hang infusion solution immediately after preparation and discard if not used within 12 hours.
Frequently Asked Questions
Do you increase the maintenance dose if there is poor control?
No, increasing the oral maintenance dose above 200mg is not recommended. Another antiarrhythmic medication can be added as the next step to achieve sinus rhythm. Occasionally, after
cardiologist consultation, amiodarone levels can be measured and the dose increased if necessary.
What if the patient is nil by mouth?
The bioavailability of amiodarone is approximately 50% so if a patient is switched from oral to iv, give
approximately half the oral dose. e.g. instead of 200mg tds po give 150mg bd iv.
Do you need to reduce the dose in renal impairment?
No, very small amounts are excreted in the urine.
Do the oral and IV formulations exert different effects?
There is some evidence that chronic oral dosing has different effects on conduction pathways than IV
dosing. IV amiodarone exerted additional benefits to long-term oral amiodarone therapy in one trial. It
is unclear whether cumulative effects, active metabolites or both are responsible for the differences.
Can the brands of oral amiodarone be switched safely?
Amiodarone is not on the interchangeable medicine list, so it is preferable that a patient remains on
the same brand if possible. There have been reports of increases and decreases in amiodarone
levels following a change in formulation. If the brand was switched temporarily during a hospital stay,
the effect is likely to be minor due to the long half-life. If the brand is switched permanently, patient
monitoring is recommended followed by a drug level after a few weeks if the clinician is particularly
concerned.
Drug Interactions
Due to amiodarone’s long half-life, interactions may take several weeks to fully develop and may
persist for months after the drug is discontinued. The following drugs should be monitored when
amiodarone is added to a stabilised regimen.
Interacting Drugs
Warfarin
Digoxin
CYP3A4 substrates
eg. diltiazem, cyclosporin
simvastatin
Drugs that slow AV
conduction
e.g. beta-blockers, calcium
channel blockers
Drugs that prolong the
QT interval
e.g. erythromycin, cisapride
antidepressants,
antipsychotics,
Management
Monitor INR closely as the effect of warfarin is likely to be increased.
Expect to reduce the warfarin dose by approximately 50% (variable).
The interaction can take at least two weeks to fully develop.
Amiodarone reduces the excretion of digoxin. The dose of digoxin
should be reduced by 1/3 to 1/2 when amiodarone is added to the
regimen. Monitor patient for signs of toxicity, digoxin levels can be
taken after a few days if toxicity is suspected, otherwise after a week or
two to check if the steady state level is not above the therapeutic range.
Amiodarone is a CYP3A4 substrate and inhibitor. The levels of drugs
metabolised by this enzyme are likely to be increased by the addition of
amiodarone. Monitor patient for side effects and toxicity, dose
reduction of these drugs should be considered.
The pharmacodynamic effects of amiodarone may be additive. Monitor
patient for hypotension, bradycardia and ECG changes.
Avoid if possible due to the potential to cause ‘torsades de pointes’.
References available on request from Medicines Information Service (Ext 8876).