Pacerone


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Related to Pacerone: metoprolol

amiodarone hydrochloride

Amyben (UK), Cordarone, Cordarone X (UK), Nexterone, Pacerone

Pharmacologic class: Benzofuran derivative

Therapeutic class: Antiarrhythmic (class III)

Pregnancy risk category D

FDA Box Warning

Oral products

• Because of substantial toxicity, drug is indicated only in patients with life-threatening arrhythmias.

• Drug may cause potentially fatal pulmonary toxicities, including hypersensitivity pneumonitis and interstitial/alveolar pneumonitis. Pulmonary toxicity is fatal about 10% of time.

• Hepatic injury is common but usually mild, manifesting only as abnormal liver enzyme levels. However, overt hepatic disease can occur and, in rare cases, is fatal.

• Drug may exacerbate arrhythmias by reducing tolerance for them or making them harder to reverse. Arrhythmias and significant heart block or sinus bradycardia occur in 2% to 5% of patients.

• Even in patients at high risk for arrhythmic death in whom toxicity is an acceptable risk, drug poses major management problems. Therefore, other agents should be tried first whenever possible.

• Difficulty of using drug effectively and safely poses significant risk. Patients with indicated arrhythmias must be hospitalized to receive loading dose; response generally takes at least 1 week, but usually 2 or more.

Action

Prolongs duration and refractory period of action potential. Slows electrical conduction, electrical impulse generation from sinoatrial node, and conduction through accessory pathways. Also dilates blood vessels.

Availability

Injection: 50 mg/ml in 3-ml ampules

Injection, premixed in dextrose: 1.5 mg/ml (150 mg/100 ml), 1.8 mg/ml (360 mg/200 ml) in single-use plastic containers

Tablets: 100 mg, 200 mg, 400 mg

Indications and dosages

Life-threatening ventricular arrhythmias

Adults: 150 mg in 100 ml of dextrose 5% in water (D5W) by rapid I.V. infusion over 10 minutes; then dilute 900 mg in 500 ml of D5W and administer 360 mg by slow I.V. infusion over next 6 hours; then 540-mg I.V. maintenance infusion over next 18 hours. Or 800 to 1,600 mg P.O. daily in one to two doses for 1 to 3 weeks; then 600 to 800 mg P.O. daily in one to two doses for 1 month; then 400-mg P.O. daily as maintenance dosage. All dosages are titrated to individual patient's clinical needs.

Frequently recurring ventricular fibrillation (VF), hemodynamically unstable ventricular tachycardia (VT)

Adults: Initially, 1,000 mg I.V. infusion over first 24 hours, by following infusion regimen: 150 mg/100 ml (1.5 mg/ml) rapid I.V. infusion over 10 minutes, followed by 360 mg (1 mg/minute) by slow I.V. infusion over 6 hours; then 540 mg (0.5 mg/minute) by slow I.V. infusion over remaining 18 hours as maintenance infusion. For breakthrough episodes of VF or hemodynamically unstable VT, repeat initial loading dose of 150 mg/100 ml I.V. infusion over 10 minutes as needed. After first 24 hours, continue maintenance infusion of 720 mg/24 hours (0.5 mg/minute) for up to 3 weeks. Increase maintenance infusion rate to achieve effective arrhythmia suppression as needed.

Off-label uses

• Atrioventricular (AV) nodal reentry tachycardia (with parenteral use)
• Conversion of atrial fibrillation to normal sinus rhythm

Contraindications

• Hypersensitivity to drug or its components, including iodine
• Cardiogenic shock
• Second- or third-degree AV block
• Marked sinus bradycardia
• Breastfeeding
• Neonates

Precautions

Use cautiously in:
• electrolyte imbalances, severe pulmonary or hepatic disease, thyroid disorders
• history of heart failure
• elderly patients
• pregnant patients
• children.

Administration

Know that I.V. amiodarone is a high-alert drug.

Give loading dose only in hospital setting with continuous ECG monitoring.
• Administer oral loading dose in two equal doses with meals. Give maintenance dose daily or in two divided doses to minimize GI upset.
• Don't give I.V. unless patient is on continuous ECG monitoring.
• Dilute I.V. drug (except premixed drug) with dextrose 5% in water and use an in-line filter. Drug isn't compatible with normal saline solution.
• Don't combine premixed drug with any other product in the same I.V. line or premixed container.

Don't use plastic containers in series connections because of risk of air embolism.
• Use central venous catheter when giving repeated doses. If possible, use dedicated catheter for drug.

Adverse reactions

CNS: dizziness, fatigue, headache, insomnia, paresthesia, peripheral neuropathy, poor coordination, involuntary movements, tremor, sleep disturbances

CV: hypotension, heart failure, worsening arrhythmia, AV block, sinoatrial node dysfunction, bradycardia, asystole, cardiac arrest, cardiogenic shock, electromechanical dissociation, ventricular tachycardia

EENT: corneal microdeposits, corneal or macular degeneration, visual disturbances, dry eyes, eye discomfort, optic neuritis or neuropathy, scotoma, lens opacities, photophobia, visual halos, papilledema

GI: nausea, vomiting, constipation, abdominal pain, abnormal salivation, anorexia

GU: decreased libido

Hematologic: coagulation abnormalities, thrombocytopenia

Hepatic: nonspecific hepatic disorders, hepatic dysfunction

Metabolic: hypothyroidism, hyperthyroidism

Respiratory: cough, adult respiratory distress syndrome, pulmonary inflammation or fibrosis, pulmonary edema

Skin: flushing, photosensitivity, toxic epidermal necrolysis

Other: abnormal taste and smell, edema, fever, Stevens-Johnson syndrome

Interactions

Drug-drug.Anticoagulants: increased prothrombin time (PT)

Azole antifungals, fluoroquinolones, loratadine, macrolide antibiotics, trazodone: increased risk of life-threatening arrhythmias

Beta-adrenergic blockers: increased risk of bradycardia and hypotension

Calcium channel blockers: increased risk of AV block (with verapamil, diltiazem) or hypotension (with any calcium channel blocker)

Cholestyramine: decreased amiodarone blood level

Cimetidine, ritonavir: increased amiodarone blood level

Class I antiarrhythmics (disopyramide, flecainide, lidocaine, mexiletine, procainamide, quinidine): increased blood levels of these drugs, leading to toxicity

Cyclosporine: elevated cyclosporine and creatinine blood levels

Dextromethorphan: impaired dextromethorphan metabolism (with amiodarone therapy of 2 weeks or longer)

Digoxin: increased digoxin blood level, leading to toxicity

Fentanyl: increased bradycardia, hypotension

Methotrexate: impaired methotrexate metabolism, possibly causing toxicity (with amiodarone use longer than 2 weeks)

Phenytoin: decreased amiodarone blood level or increased phenytoin blood level (with amiodarone use longer than 2 weeks)

Protease inhibitors (atazanavir, indinavir, nelfinavir): possible increased amiodarone concentration

Rifampin: decreased amiodarone concentration

Theophylline: increased theophylline blood level (with amiodarone use longer than 1 week)

Drug-diagnostic tests.Kidney function tests: abnormal results

Drug-food.Grapefruit juice: increased drug concentration

Drug-herb.St. John's wort: decreased drug blood level

Patient monitoring

Monitor patient closely. Drug may cause serious or life-threatening adverse reactions.

Watch for slow onset of life-threatening arrhythmias, especially after giving loading dose.

Monitor ECG continuously during loading dose and when dosage is changed.
• Check patient's blood pressure, pulse, and heart rhythm regularly.
• Assess for signs and symptoms of lung inflammation.
• Monitor baseline and subsequent chest X-rays, as well as pulmonary, liver, and thyroid function test results.
• Closely monitor patient who's receiving other drugs concurrently because amiodarone can interact with many drugs. Check digoxin blood level if patient is receiving digoxin; monitor PT or International Normalized Ratio if patient is receiving anticoagulants.

Patient teaching

Inform patient that drug may cause serious adverse reactions. Instruct him to report these immediately.
• Tell patient to take oral doses with meals. Advise him to divide daily dose into two doses if drug causes GI upset.
• Tell patient that adverse reactions are most common with high doses and may become more frequent after 6 months of therapy.
• Inform patient that he'll undergo regular blood testing, eye examinations, chest X-rays, and pulmonary function tests during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

amiodarone

(am-ee-oh-da-rone) ,

Cordarone

(trade name),

Nexterone

(trade name),

Pacerone

(trade name)

Classification

Therapeutic: antiarrhythmics
Pregnancy Category: D

Indications

Life-threatening ventricular arrhythmias unresponsive to less toxic agents. Oral: Management of supraventricular tachyarrhythmias. Intravenous: As part of the Advanced Cardiac Life Support (ACLS) and Pediatric Advanced Life Support (PALS) guidelines for the management of ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT) after cardiopulmonary resuscitation and defibrillation have failed; also for other life-threatening tachyarrhythmias.

Action

Prolongs action potential and refractory period.
Inhibits adrenergic stimulation.
Slows the sinus rate, increases PR and QT intervals, and decreases peripheral vascular resistance (vasodilation).

Therapeutic effects

Suppression of arrhythmias.

Pharmacokinetics

Absorption: Slowly and variably absorbed from the GI tract (35–65%). IV administration results in complete bioavailability.
Distribution: Distributed to and accumulates slowly in body tissues. Reaches high levels in fat, muscle, liver, lungs, and spleen. Crosses the placenta and enters breast milk.
Protein Binding: 96% bound to plasma proteins.
Metabolism and Excretion: Metabolized by the liver, excreted into bile. Minimal renal excretion. One metabolite has antiarrhythmic activity.
Half-life: 13–107 days.

Time/action profile (suppression of ventricular arrhythmias)

ROUTEONSETPEAKDURATION
PO2–3 days (up to 2–3 mo)3–7 hrwk–mos
IV2 hr3–7 hrunknown

Contraindications/Precautions

Contraindicated in: Patients with cardiogenic shock;Severe sinus node dysfunction;2nd- and 3rd-degree AV block;Bradycardia (has caused syncope unless a pacemaker is in place);Hypersensitivity to amiodarone or iodine; Obstetric: Can cause fetal hypo- or hyperthyroidism; Lactation: Enters breast milk and can cause harm to the neonate; use an alternative to breast milk; Pediatric: Safety not established; products containing benzyl alcohol should not be used in neonates.
Use Cautiously in: History of HF;Thyroid disorders;Corneal refractive laser surgery;Severe pulmonary or liver disease; Geriatric: Initiate therapy at the low end of the dosing range due to ↓ hepatic, renal, or cardiac function; comorbid disease; or other drug therapy.

Adverse Reactions/Side Effects

Central nervous system

  • confusional states
  • disorientation
  • hallucinations
  • dizziness (most frequent)
  • fatigue (most frequent)
  • malaise (most frequent)
  • headache
  • insomnia

Ear, Eye, Nose, Throat

  • corneal microdeposits (most frequent)
  • abnormal sense of smell
  • dry eyes
  • optic neuritis
  • optic neuropathy
  • photophobia

Respiratory

  • adult respiratory distress syndrome (ards) (life-threatening)
  • pulmonary fibrosis (life-threatening)
  • pulmonary toxicity (life-threatening)

Cardiovascular

  • chf (life-threatening)
  • worsening of arrhythmias (life-threatening)
  • bradycardia (most frequent)
  • hypotension (most frequent)

Gastrointestinal

  • anorexia (most frequent)
  • constipation (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • abdominal pain
  • abnormal sense of taste
  • ↑ liver enzymes

Genitourinary

  • ↓ libido
  • epididymitis

Dermatologic

  • toxic epidermal necrolysis (rare) (life-threatening)
  • photosensitivity (most frequent)
  • blue discoloration

Endocrinologic

  • hypothyroidism (most frequent)
  • hyperthyroidism

Neurologic

  • ataxia (most frequent)
  • involuntary movement (most frequent)
  • paresthesia (most frequent)
  • peripheral neuropathy (most frequent)
  • poor coordination (most frequent)
  • tremor (most frequent)

Interactions

Drug-Drug interaction

↑ risk of QT prolongation with fluoroquinolones, macrolides, and azole antifungals (undertake concurrent use with caution).↑ levels of digoxin (↓ dose of digoxin by 50%).↑ levels of class I antiarrhythmics (quinidine, mexiletine, lidocaine, or flecainide —↓ doses of other drugs by 30–50%).↑ levels of cyclosporine, dextromethorphan, methotrexate, phenytoin, carvedilol, and theophylline.Phenytoin ↓ amiodarone levels.↑ activity of warfarin (↓ dose of warfarin by 33–50%).↑ risk of bradyarrhythmias, sinus arrest, or AV heart block with beta blockers or calcium channel blockers.Cholestyramine may ↓ amiodarone levels.Cimetidine and ritonavir ↑ amiodarone levels.Risk of myocardial depression is ↑ by volatile anesthetics.↑ risk of myopathy with lovastatin and simvastatin (do not exceed 40 mg/day of lovastatin or 20 mg/day of simvastatin).St. John's wort induces enzymes that metabolize amiodarone; may ↓ levels and effectiveness. Avoid concurrent use.Grapefruit juice inhibits enzymes in the GI tract that metabolize amiodarone resulting in ↑ levels and risk of toxicity; avoid concurrent use.

Route/Dosage

Ventricular Arrhythmias

Oral (Adults) 800–1600 mg/day in 1–2 doses for 1–3 wk, then 600–800 mg/day in 1–2 doses for 1 mo, then 400 mg/day maintenance dose.
Oral (Children) 10 mg/kg/day (800 mg/1.72 m2/day) for 10 days or until response or adverse reaction occurs, then 5 mg/kg/day (400 mg/1.72 m2/day) for several weeks, then ↓ to 2.5 mg/kg/day (200 mg/1.72 m2/day) or lowest effective maintenance dose.
Intravenous (Adults) 150 mg over 10 min, followed by 360 mg over the next 6 hr and then 540 mg over the next 18 hr. Continue infusion at 0.5 mg/min until oral therapy is initiated. If arrhythmia recurs, a small loading infusion of 150 mg over 10 min should be given; in addition, the rate of the maintenance infusion may be ↑. Conversion to initial oral therapy—If duration of IV infusion was <1 wk, oral dose should be 800–1600 mg/day; if IV infusion was 1–3 wk, oral dose should be 600–800 mg/day; if IV infusion was >3 wk, oral dose should be 400 mg/day. ACLS guidelines for pulseless VF/VT—300 mg IV push, may repeat once after 3–5 min with 150 mg IV push (maximum cumulative dose 2.2 g/24 hr; unlabeled).
Intravenous Intraosseous: (Children and infants) PALS guidelines for pulseless VF/VT—5 mg/kg as a bolus; Perfusion tachycardia—5 mg/kg loading dose over 20–60 min (maximum of 15 mg/kg/day; unlabeled).

Supraventricular Tachycardia

Oral (Adults) 600–800 mg/day for 1 wk or until desired response occurs or side effects develop, then ↓ to 400 mg/day for 3 wk, then maintenance dose of 200–400 mg/day.
Oral (Children) 10 mg/kg/day (800 mg/1.72 m2/day) for 10 days or until response or side effects occur, then 5 mg/kg/day (400 mg/1.72 m2/day) for several weeks, then ↓ to 2.5 mg/kg/day (200 mg/1.72 m2/day) or lowest effective maintenance dose.

Availability (generic available)

Tablets: 100 mg, 200 mg, 400 mg
Injection: 50 mg/mL
Premixed infusion (Nexterone): 150 mg/100 mL D5W (does not contain polysorbate 80 or benzyl alcohol), 360 mg/200 mL D5W (does not contain polysorbate 80 or benzyl alcohol)

Nursing implications

Nursing assessment

  • Monitor ECG continuously during IV therapy or initiation of oral therapy. Monitor heart rate and rhythm throughout therapy; PR prolongation, slight QRS widening, T-wave amplitude reduction with T-wave widening and bifurcation, and U waves may occur. QT prolongation may be associated with worsening of arrhythmias and should be monitored closely during IV therapy. Report bradycardia or increase in arrhythmias promptly; patients receiving IV therapy may require slowing rate, discontinuing infusion, or inserting a temporary pacemaker.
    • Assess pacing and defibrillation threshold in patients with pacemakers and implanted defibrillators at beginning and periodically during therapy.
    • Assess for signs of pulmonary toxicity (rales/crackles, decreased breath sounds, pleuritic friction rub, fatigue, dyspnea, cough, wheezing, pleuritic pain, fever, hemoptysis, hypoxia). Chest x-ray and pulmonary function tests are recommended before therapy. Monitor chest x-ray every 3–6 mo during therapy to detect diffuse interstitial changes or alveolar infiltrates. Bronchoscopy or gallium radionuclide scan may also be used for diagnosis. Usually reversible after withdrawal, but fatalities have occurred.
  • Intravenous: Assess for signs and symptoms of ARDS throughout therapy. Report dyspnea, tachypnea, or rales/crackles promptly. Bilateral, diffuse pulmonary infiltrates are seen on chest x-ray.
    • Monitor BP frequently. Hypotension usually occurs during first several hours of therapy and is related to rate of infusion. If hypotension occurs, slow rate.
  • Oral: Assess for neurotoxicity (ataxia, proximal muscle weakness, tingling or numbness in fingers or toes, uncontrolled movements, tremors); common during initial therapy, but may occur within 1 wk to several mo of initiation of therapy and may persist for more than 1 yr after withdrawal. Dose reduction is recommended. Assist patient during ambulation to prevent falls.
  • Ophthalmic exams should be performed before and regularly during therapy and whenever visual changes (photophobia, halos around lights, decreased acuity) occur. May cause permanent loss of vision.
  • Assess for signs of thyroid dysfunction, especially during initial therapy. Lethargy; weight gain; edema of the hands, feet, and periorbital region; and cool, pale skin suggest hypothyroidism and may require decrease in dose or discontinuation of therapy and thyroid supplementation. Tachycardia; weight loss; nervousness; sensitivity to heat; insomnia; and warm, flushed, moist skin suggest hyperthyroidism and may require discontinuation of therapy and treatment with antithyroid agents.
  • Lab Test Considerations: Monitor liver and thyroid functions before and every 6 mo during therapy. Drug effects persist long after discontinuation. Thyroid function abnormalities are common, but clinical thyroid dysfunction is uncommon.
    • Monitor AST, ALT, and alkaline phosphatase at regular intervals during therapy, especially in patients receiving high maintenance dose. If liver function studies are 3 times normal or double in patients with elevated baseline levels or if hepatomegaly occurs, dose should be reduced.
    • May cause asymptomatic ↑ in ANA titer concentrations.

Potential Nursing Diagnoses

Decreased cardiac output (Indications)
Impaired gas exchange (Side Effects)

Implementation

  • high alert: IV vasoactive medications are inherently dangerous; fatalities have occurred from medication errors involving amiodarone. Before administering, have second practitioner check original order, dose calculations, and infusion pump settings. Patients should be hospitalized and monitored closely during IV therapy and initiation of oral therapy. IV therapy should be administered only by physicians experienced in treating life-threatening arrhythmias.
  • Do not confuse amiodarone with amantadine.
  • Hypokalemia and hypomagnesemia may decrease effectiveness or cause additional arrhythmias; correct before therapy.
    • Monitor closely when converting from IV to oral therapy, especially in geriatric patients.
  • Oral: May be administered with meals and in divided doses if GI intolerance occurs or if daily dose exceeds 1000 mg.
  • Intravenous Administration
  • pH: 4.1.
  • Intravenous: Administer via volumetric pump; drop size may be reduced, causing altered dosing with drop counter infusion sets.
    • Administer through an in-line filter.
    • Infusions exceeding 2 hr must be administered in glass or polyolefin bottles to prevent adsorption. However, polyvinyl chloride (PVC) tubing must be used during administration because concentrations and infusion rate recommendations have been based on PVC tubing.
  • Diluent: Administer undiluted. May also be diluted in 20–30 mL of D5W or 0.9% NaCl.Concentration: 50 mg/mL.
  • Rate: Administer IV push.
  • Intermittent Infusion: Diluent: Dilute 150 mg of amiodarone in 100 mL of D5W. Infusion stable for 2 hr in PVC bag, or use pre-mixed bags.Concentration: 1.5 mg/mL.
  • Rate: Infuse over 10 min. Do not administer IV push.
  • Continuous Infusion: Diluent: Dilute 900 mg (18 mL) of amiodarone in 500 mL of D5W. Infusion stable for 24 hr in glass or polyolefin bottle.Concentration: 1.8 mg/mL. Concentration may range from 1–6 mg/mL (concentrations >2 mg/mL must be administered via central venous catheter).
  • Rate: Infuse at a rate of 1 mg/min for the first 6 hr, then decrease infusion rate to 0.5 mg/min and continue until oral therapy initiated.
  • Y-Site Compatibility: alemtuzumab, amikacin, amphotericin B colloidal, amphotericin B lipid complex, anidulafungin, atracurium, atropine, bleomycin, bumetanide, calcium chloride, calcium gluconate, carboplatin, caspofungin, ceftaroline, ceftriaxone, cefuroxime, ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, dactinomycin, daptomycin, dexmedetomidine, diltiazem, dobutamine, docetaxel, doripenem, dopamine, doripenem, doxacurium, doxycycline, epinephrine, erythromycin lactobionate, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, gemcitabine, gentamicin, granisetron, haloperidol, idarubicin, ifosfamide, irinotecan, isoproterenol, ketamine, labetalol, lidocaine, linezolid, lorazepam, meperidine, metaraminol, methylprednisolone, metoprolol, metronidazole, midazolam, milrinone, mitoxantrone, morphine, mycophenolate, nesiritide, nitroglycerin, norepinephrine, octreotide, oxaliplatin, palonosetron, pemetrexed, penicillin G potassium, phentolamine, phenylephrine, potassium chloride, procainamide, quinupristin/dalfopristin, rifampin, rocuronium, tacrolimus, teniposide, tirofiban, tobramycin, vancomycin, vasopressin, vecuronium, vincristine, vinorelbine, voriconazole, zoledronic acid
  • Y-Site Incompatibility: aminocaproic acid, aminophylline, ampicillin/sulbactam, bivalirudin, ceftazidime, cytarabine, digoxin, doxorubicin hydrochloride, ertapenem, fludarabine, fluorouracil, heparin, imipenem-cilastatin, levofloxacin, mechlorethamine, methotrexate, micafungin, paclitaxel, piperacillin/tazobactam, potassium acetate, potassium phosphates, sodium acetate, sodium bicarbonate, sodium phosphates, yhiopental, thiotepa, tigecycline

Patient/Family Teaching

  • Instruct patient to take amiodarone as directed. Advise patient to read the Medication Guide prior to first dose and with each Rx refill. If a dose is missed, do not take at all. Consult health care professional if more than two doses are missed.
  • Advise patient to avoid drinking grapefruit juice during therapy.
  • Inform patient that side effects may not appear until several days, weeks, or yr after initiation of therapy and may persist for several mo after withdrawal.
  • Teach patients to monitor pulse daily and report abnormalities.
  • Advise patients that photosensitivity reactions may occur through window glass, thin clothing, and sunscreens. Protective clothing and sunblock are recommended during and for 4 mo after therapy. If photosensitivity occurs, dosage reduction may be useful.
  • Inform patients that bluish discoloration of the face, neck, and arms is a possible side effect of this drug after prolonged use. This is usually reversible and will fade over several mo. Notify health care professional if this occurs.
  • Instruct male patients to notify health care professional if signs of epididymitis (pain and swelling in scrotum) occur. May require reduction in dose.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
  • Instruct patient to notify health care professional of medication regimen before treatment or surgery.
  • Advise patient to notify health care professional if signs and symptoms of thyroid dysfunction occur.
  • Caution female patients to avoid breast feeding during therapy.
  • Emphasize the importance of follow-up exams, including chest x-ray and pulmonary function tests every 3–6 mo and ophthalmic exams after 6 mo of therapy, and then annually.

Evaluation/Desired Outcomes

  • Cessation of life-threatening ventricular arrhythmias. Adverse effects may take up to 4 mo to resolve.

Pacerone®

Amiodarone Cardiology An antiarrhythmic similar to Cordarone®. See Antiarrhythmic.