Dose	Infusion rate
10 mg/hr	10 mL/hr
15 mg/hr	15 mL/hr
20 mg/hr	20 mL/hr
25 mg/hr	25 mL/hr
30 mg/hr	30 mL/hr
35 mg/hr	35 mL/hr
40 mg/hr	40 mL/hr
45 mg/hr	45 mL/hr
50 mg/hr	50 mL/hr
55 mg/hr	55 mL/hr
60 mg/hr	60 mL/hr
65 mg/hr	65 mL/hr
70 mg/hr	70 mL/hr
75 mg/hr	75 mL/hr

Amiodarone (Cordarone)

USES

1. Initiation of treatment and prophylaxis of recurring ventricular fibrillation and unstable ventricular tachycardia in patients refractory to other therapy.

2. In patients for whom oral amiodarone is indicated but who are NPO.

SOLUTION PREPARATION

Loading dose: Amiodarone is added to D5W bag (150 mg in 100 mL). Maintenance dose: 900 mg amiodarone is added to 500 mL D5W in a glass bottle.

Dose

1. Infuse 150 mg over 10 minutes (15 mg/min). Prepare solution with 150 mg amiodarone in 100-mL D5W bag. The initial infusion rate is not greater than 30 mg/min.

2. Follow with a slow infusion of 360 mg over the next 6 hours (1 mg/min). Prepare solution with 900 mg amiodarone in 500 mL D5W glass bottle.

3. Follow with a maintenance infusion of 540 mg over the remaining 18 hours (0.5 mg/min).

4. After the first 24 hours: 0.5 mg/min continuous infusion. If IV concentration is greater than 2 mg/mL, it should be administered through a central venous catheter with in-line filter. (For greater than 2 mg/mL, administer via central venous catheter only.)

5. If breakthrough episodes of ventricular fibrillation or tachycardia should occur, an additional infusion of 150 mg over 10 minutes may be administered (150 mg in 100 mL D5W).

6. When switching from IV to PO, use the following as a guide:

a. less than 1 week IV → 800-1600 mg/day

b. 1-3 weeks IV → 600-800 mg/day

c. greater than 3 weeks IV → 400 mg/day

7. During cardiac arrest, 300 mg (2 ampules 150 mg each) may be given IV push. May repeat 150-mg IV push in 3-5 minutes, up to a maximum cumulative dose of 2.2 g IV in 24 hours.

WARNINGS

1. Although IV amiodarone has been used safely in some patients with acute myocardial infarction (AMI), it is clearly a negative inotrope. Use cautiously in patients with left ventricular dysfunction.

2. Hypotension is the main complication of IV therapy; therefore use with caution in hypotensive patients.

3. Marked cardiomegaly, particularly resulting from myocardiopathy, is a relative contraindication to IV use of amiodarone.

4. Use cautiously in patients with thyroid dysfunction. Amiodarone has been reported to produce hypothyroidism or hyperthyroidism.

5. Because of extensive tissue distribution and prolonged elimination period, the time at which a life-threatening arrhythmia will recur following discontinued therapy or an interaction with subsequent treatment may be unpredictable. Patients must be observed carefully when other antiarrhythmic agents are substituted after amiodarone is stopped.

ADVERSE REACTIONS

The incidence of side effects increases over time; many adverse drug reactions (ADRs) may be related to the total dose administered over time (i.e., accumulation).

1. Cardiovascular: Sinus bradycardia, hypotension, heart block, proarrhythmic effects.

2. Pulmonary: Within the first few weeks, may present with acute onset of nonspecific symptoms (e.g., fever, shortness of breath, and cough). These are probably symptoms of a hypersensitivity reaction associated with an eosinophilic lung infiltrate (e.g., pulmonary fibrosis, interstitial pneumonitis).

3. Thyroid: Interferes with T₄ → T₃ conversion (hypothyroidism occurs more often than hyperthyroidism).

4. GI: Nausea/vomiting, anorexia, abdominal pain, and constipation.

5. Hepatic: Abnormal liver function tests, especially elevated aminotransferase and alkaline phosphatase levels, ≈25% of patients. Increased prothrombin time (PT)/international normalized ratio (INR).

6. Dermatologic: Allergic rash, photosensitivity, and unusual blue-gray skin discoloration.

7. Neurologic: Tremor, ataxia, peripheral neuropathy, fatigue, and weakness.

8. Ophthalmologic: High occurrence of corneal microdeposits caused by the secretion of amiodarone by the lacrimal gland with accumulation on corneal surface. This does not seem to affect vision and is reversible once the drug is discontinued.

9. Hematologic: Thrombocytopenia ≈ less than 1%.

INCOMPATIBILITY

COMPATIBILITY

Drug	Interaction effect
Warfarin	Increased anticoagulation effect
Beta-blockers	Beta-blocker effects are enhanced
Calcium channel blockers	Additive effects of both drugs are enhanced, resulting in reduced cardiac sinus and AV nodal conduction, and contractility
Digoxin	Increased digoxin concentrations, thus increasing toxic potential
Flecainide	Increased flecainide concentrations
Phenytoin	Increased phenytoin concentrations
Procainamide	Increased procainamide concentrations
Quinidine	Increased quinidine concentrations, which can cause fatal cardiac arrhythmias

NURSING CONSIDERATIONS

1. Consult the Amiodarone Drip Rate Calculation Chart to determine the drip rate.

2. Muscle weakness may present a great hazard for ambulation.

3. Give PO dosage with food.

4. Monitor ECG and rhythm throughout therapy.

5. Assess patient for signs of lethargy, edema of the hands and feet, weight loss, and pulmonary toxicity (e.g., shortness of breath, cough, rales, fever, pulmonary function tests).

Amiodarone (Cordarone)

Amiodarone Drip Rate Calculation Chart

Dose	Concentration	Infusion rate
15 mg/min	150 mg amiodarone /100 mL D5W = 1.5 mg/1 mL D5W	600 mL/hr
1 mg/min	900 mg/500 mL D5W = 1.8 mg/1 mL D5W	33 mL/hr × 6 hr
0.5 mg/min	900 mg/500 mL D5W = 1.8 mg/1 mL D5W	17 mL/hr × 18 hr
After the first 24 hr 0.5 mg/min	600 mg/500 mL = 1.2 mg/mL	25 mL/hr

Argatroban (Acova)

USES

1. Anticoagulation for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT).

2. Anticoagulant therapy in patients who have or are at risk for HIT undergoing percutaneous coronary intervention (PCI).

SOLUTION PREPARATION

Argatroban is available in 250-mg (2.5-mL) single use vials and should be added to 250-mL NS, D5W, or LR, to a final concentration of 1 mg/mL. Alternatively, 500 mg (5 mL) may be added to 500 mL of diluent. The final solution must be mixed by repeated inversion of the diluent bag for 1 minute. Upon preparation, the solution may show slight but brief haziness because of the formation of microprecipitates that rapidly dissolve upon mixing.

DOSES

Dosage adjustment: After the initial dose, the dose of argatroban can be adjusted as clinically indicated (not to exceed 10 mcg/kg/min), until the steady-state aPTT is 1.5 to 3 times the initial baseline value, usually about 55-80 seconds (not to exceed 100 seconds).

WARNINGS

1. Heparin must be discontinued before administration of argatroban.

2. A baseline aPTT should be obtained before initiating therapy.

3. Patients with hepatic impairment require a dosage adjustment.

4. Doses greater than 10 mcg/kg/min should not be administered.

5. Contraindicated in overt bleeding.

6. Hemorrhage can occur at any site in the body; an unexplained fall in hematocrit or blood pressure should be evaluated for bleeding.

7. Use extreme caution in the following instances: Severe hypertension; immediately following lumbar puncture; spinal anesthesia; major surgery, especially involving the brain, spinal cord or eye; hematologic conditions associated with increased bleeding tendencies such as congenital or acquired bleeding disorders and GI lesions such as ulcerations.

ADVERSE REACTIONS

1. Bleeding (5.3%) is the most common serious reaction.

2. Hypotension (7.2%), fever (6.9%), diarrhea (6.2%), nausea (4.8%), and vomiting (4.2%) have been reported.

INCOMPATIBILITIES

No compatibility studies have been done with argatroban. Argatroban should be infused in alone and not mixed with other agents.

NURSING CONSIDERATIONS

1. Monitor therapy using the aPTT. The aPTT typically reaches steady-state effect levels within 1 to 3 hours after initiation.

2. Dose adjustment may be required to attain the target aPTT. Check the aPTT 2 hours after initiation of therapy or dosage adjustment to confirm that the patient has attained the desired therapeutic range (1.5 to 3 times control, usually about 55-80 seconds).

3. For conversion to oral therapy with warfarin, maintain argatroban infusion until INR is greater than 4. Combination therapy with argatroban and warfarin does produce a combined effect on laboratory measurement of INR. Once INR is greater than 4, then stop the infusion, repeat INR 4-6 hours later; if INR is between 2 and 3, maintain warfarin monotherapy.

Argatroban Dosing Charts
Usual Dose 2 mcg/kg/min Mix 250 mg in 250 mL NS Final Concentration: 1 mg/ml

Argatroban Dosing Adjustments

HIT patients	HIT patients with renal impairment	HIT patients with hepatic impairment
Initiate at 2 mcg/kg/min	No dosage adjustment required	Initiate at 0.5 mcg/kg/min
Titrate until steady-state aPTT is 1.5 to 3 times baseline value		Titrate until steady-state aPTT is 1.5 to 3 times baseline value