Pacerone

What Is Pacerone?

Pacerone (amiodarone HCl) is an antiarrhythmic drug indicated for treatment of recurrent ventricular fibrillation and recurrent hemodynamically unstable ventricular tachycardia only when these conditions have not responded to documented adequate doses of other available antiarrhythmics or when alternative agents could not be tolerated.

What Are Side Effects of Pacerone?

Common side effects of Pacerone include:

• general feeling of being unwell (malaise)
• fatigue
• tremor and involuntary movements
• poor coordination and gait
• numbness and tingling of extremities
• nausea
• vomiting
• constipation
• loss of appetite
• eye problems, and sensitivity of eyes and skin to sunlight

Side effects of Pacerone can be serious and may include:

• pulmonary toxicity
• exacerbation of arrhythmia
• rare serious liver injury
• congestive heart failure, and
• slow heartbeat

Other side effects of amiodarone include:

• Postmarketing side effects of amiodarone reported include:
• Corneal microdeposits
• Demyelinating polyneuropathy
• Hypersensitivity: Anaphylactic/anaphylactoid reaction (including shock), skin swelling, hives
• Pulmonary: Eosinophilic pneumonia, acute respiratory distress syndrome/ARDS (in postoperative setting), bronchospasm, possibly fatal respiratory disorders (including distress, failure, arrest, and ARDS), bronchiolitis obliterans organizing pneumonia (possibly fatal), fever, shortness of breath, cough, coughing up blood, wheezing, hypoxia, pulmonary infiltrates and/or mass, pulmonary alveolar hemorrhage, pleural effusion, pleuritis
• Gastrointestinal: Hepatitis, cholestatic hepatitis, cirrhosis, pancreatitis, dry mouth
• Nephrology: Renal impairment, renal insufficiency, acute renal failure
• Neurology: Pseudotumor cerebri, parkinsonian symptoms, such as restlessness and slow movement (sometimes reversible with discontinuation of therapy)
• Endocrine: syndrome of inappropriate antidiuretic hormone (SIADH), thyroid nodules/thyroid cancer
• Dermatology: Toxic epidermal necrolysis (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, drug rash with eosinophilia and systemic symptoms (DRESS), eczema, skin cancer, vasculitis, itching, bullous dermatitis
• Hematology: Hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, agranulocytosis, granuloma
• Musculoskeletal: Muscle disease, muscle weakness, muscle wasting, demyelinating polyneuropathy
• Psychiatric: Hallucination, confusion, disorientation, delirium
• Genitourinary: Epididymitis, impotence

Dosage for Pacerone

Because of the serious nature of the arrhythmia and the lack of predictable time course of effect, a loading dose of Pacerone should be performed in a hospital setting. Loading doses of 800 to 1,600 mg/day are required for 1 to 3 weeks (occasionally longer) until initial therapeutic response occurs.

What Drugs, Substances, or Supplements Interact with Pacerone?

Pacerone may interact with other antiarrhythmics, lithium, phenothiazines, tricyclic antidepressants, fluoroquinolone and macrolide antibiotics, IV pentamidine, azole antifungals, digoxin, beta blockers, verapamil, diltiazem, clonidine, protease inhibitors, loratadine, cimetidine, trazodone, rifampin, St. John's wort, grapefruit juice, cyclosporine, “statin” drugs, lidocaine, anticoagulants, clopidogrel, dabigatran, fentanyl, phenytoin, and dextromethorphan. Tell your doctor all medications and supplements you use.

Pacerone During Pregnancy or Breastfeeding

During pregnancy, Pacerone should be used only if prescribed. It may harm a fetus. Pacerone passes into breast milk. Breastfeeding while using Pacerone is not recommended.

Additional Information

Our Pacerone (Amiodarone HCl) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Pacerone Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Amiodarone takes a long time to completely clear from your body. You may continue to have side effects from amiodarone after you stop using it.

Call your doctor at once if you have any of these side effects, even if they occur up to several months after you stop using amiodarone:

• wheezing, cough, chest pain, cough with bloody mucus, fever;
• a new or a worsening irregular heartbeat pattern (fast, slow, or pounding heartbeats);
• a light-headed feeling, like you might pass out;
• blurred vision, seeing halos around lights (your eyes may be more sensitive to light);
• liver problems--nausea, vomiting, stomach pain (upper right side), tiredness, dark urine, jaundice (yellowing of the skin or eyes);
• nerve problems--loss of coordination, muscle weakness, uncontrolled muscle movement, or a prickly feeling in your hands or lower legs;
• signs of overactive thyroid--weight loss, thinning hair, feeling hot, increased sweating, tremors, feeling nervous or irritable, irregular menstrual periods, swelling in your neck (goiter); or
• signs of underactive thyroid--weight gain, tiredness, depression, trouble concentrating, feeling cold.

Common side effects may include:

• nausea, vomiting, loss of appetite; or
• constipation.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Pacerone (Amiodarone HCl Tablets)

 

Pacerone Professional Information

SIDE EFFECTS

The following serious adverse reactions are described in more detail in other sections of the prescribing information:

• Pulmonary Toxicity [see WARNINGS AND PRECAUTIONS]
• Hepatic Injury [see WARNINGS AND PRECAUTIONS]
• Worsened Arrhythmia [see WARNINGS AND PRECAUTIONS]
• Visual Impairment and Loss of Vision [see WARNINGS AND PRECAUTIONS]
• Thyroid Abnormalities [see WARNINGS AND PRECAUTIONS]
• Bradycardia [see WARNINGS AND PRECAUTIONS]
• Peripheral Neuropathy [see WARNINGS AND PRECAUTIONS]
• Photosensitivity and Skin Discoloration [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

At the usual maintenance dose (400 mg/day) and above, Pacerone® causes adverse reactions in about threefourths of all patients, resulting in discontinuation in 7 to 18%.

In surveys of almost 5,000 patients treated in open U.S. studies and in published reports of treatment with Pacerone®, the adverse reactions most frequently requiring discontinuation of Pacerone®  included pulmonary infiltrates or fibrosis, paroxysmal ventricular tachycardia, congestive heart failure, and elevation of liver enzymes. Other symptoms causing discontinuations less often included visual disturbances, photosensitivity, blue skin discoloration, hyperthyroidism, and hypothyroidism.

The following side-effect rates are based on a retrospective study of 241 patients treated for 2 to 1,515 days (mean 441.3 days):

Thyroid

Common

Hypothyroidism, hyperthyroidism.

Cardiovascular

Common

Congestive heart failure, cardiac arrhythmias, SA node dysfunction.

Gastrointestinal

Very common

Nausea, vomiting.

Common

Constipation, anorexia, abdominal pain.

Dermatologic

Common

Solar dermatitis/photosensitivity.

Neurologic

Common

Malaise and fatigue, tremor/abnormal involuntary movements, lack of coordination, abnormal gait/ataxia, dizziness, paresthesias, decreased libido, insomnia, headache, sleep disturbances.

Ophthalmic

Common

Visual disturbances.

Hepatic

Common

Abnormal liver-function tests, nonspecific hepatic disorders.

Respiratory

Common

Pulmonary inflammation or fibrosis.

Other

Common

Flushing, abnormal taste and smell, edema, abnormal salivation, coagulation abnormalities.

Uncommon

Blue skin discoloration, rash, spontaneous ecchymosis, alopecia, hypotension, and cardiac conduction abnormalities.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Pacerone®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hematologic

Hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, agranulocytosis, granuloma.

Immune

Anaphylactic/anaphylactoid reaction (including shock), angioedema.

Neurologic

Pseudotumor cerebri, parkinsonian symptoms such as akinesia and bradykinesia (sometimes reversible with discontinuation of therapy), demyelinating polyneuropathy.

Psychiatric

Hallucination, confusional state, disorientation, delirium.

Cardiac

Hypotension (sometimes fatal), sinus arrest.

Respiratory

Eosinophilic pneumonia, acute respiratory distress syndrome in the post-operative setting, bronchospasm, bronchiolitis obliterans organizing pneumonia, pulmonary alveolar hemorrhage, pleural effusion, pleuritis.

Gastrointestinal

Pancreatitis, acute pancreatitis.

Hepatic

Hepatitis, cholestatic hepatitis, cirrhosis.

Skin And Subcutaneous Tissue Disorders

Urticaria, toxic epidermal necrolysis (sometimes fatal), erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, bullous dermatitis, drug rash with eosinophilia and systemic symptoms (DRESS), eczema, pruritus, skin cancer, lupus-like syndrome.

Musculoskeletal

Myopathy, muscle weakness, rhabdomyolysis.

Renal

Renal impairment, renal insufficiency, acute renal failure.

Reproductive

Epididymitis, impotence.

Body As A Whole

Fever, dry mouth.

Endocrine And Metabolic

Thyroid nodules/ thyroid cancer, syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Vascular

Vasculitis.

DRUG INTERACTIONS

Because of amiodarone's long half-life, expect drug interactions to persist for weeks to months after discontinuation of amiodarone.

Drug interactions with amiodarone are described in Table 1 below.

Table 1: Amiodarone Drug Interactions

Concomitant Drug Class/Name	Examples	Clinical Comment
Pharmacodynamic Interactions
QT Prolonging Drugs	class I and III antiarrhythmics, lithium, certain phenothiazines, tricyclic antidepressants, certain fluoroquinolone and macrolide antibiotics, azole antifungals, halogenated inhalation anesthetic agents	Increased risk of Torsade de Pointes. Avoid concomitant use.
Negative Chronotropes	digoxin, beta blockers, verapamil, diltiazem, clonidine, ivabradine	Potentiates the electrophysiologic and hemodynamic effects of amiodarone, resulting in bradycardia, sinus arrest, and AV block. Monitor heart rate.
Pharmacokinetic Interactions
CYP450 Inhibitors	grapefruit juice, certain fluoroquinolone and macrolide antibiotics, azole antifungals, cimetidine, certain protease inhibitors	Increased exposure of amiodarone. Avoid concomitant use.
CYP450 Inducers	St. John’s Wort	Reduced amiodarone serum levels.
Cyclosporine		Increased plasma levels of cyclosporine have been reported resulting in elevated creatinine, despite reduction of cyclosporine dose. Monitor cyclosporine drug levels and renal function with concomitant use.
Cholestyramine		Reduced amiodarone serum levels.
Antiarrhythmics	quinidine, procainamide, flecainide	Reserve concomitant use for patients who are unresponsive to a single agent. Antiarrhythmic metabolism inhibited by amiodarone. Initiate antiarrhythmic at a lower than usual dose and monitor patient carefully. Reduce dose levels of previously administered antiarrhythmic by 30 to 50% for several days after transitioning to oral amiodarone. Evaluate continued need for antiarrhythmic.
Digoxin		Increased digoxin concentration. Reduce digoxin by half or discontinue. If continued, monitor for evidence of toxicity.
HMG-CoA Reductase Inhibitors	simvastatin, lovastatin, atorvastatin	Increased plasma concentration of HMGCoA reductase inhibitor. Limit the dose of lovastatin to 40 mg. Limit the coadministered dose of simvastatin to 20 mg. Lower starting dose of other CYP3A4 substrates may be required.
Warfarin		Potentiates anticoagulant response and can result in serious or fatal bleeding. Coadministration increases prothrombin time by 100% after 3 to 4 days. Reduce warfarin dose by one-third to one-half and monitor prothrombin times.
Phenytoin		Increased steady-state levels of phenytoin. Monitor phenytoin levels.
Hepatitis C Direct Acting Antiviral	sofosbuvir	Cases of symptomatic bradyarrhythmia requiring pacemaker insertion have been reported in patients on oral maintenance amiodarone who initiated therapy with sofosbuvir.
CYP3A Substrate	lidocaine	Sinus bradycardia has been reported with oral amiodarone in combination with lidocaine given for local anesthesia. Monitor heart rate. A lower starting dose of lidocaine may be required.
CYP3A Substrate	fentanyl	Fentanyl in combination with amiodarone may cause hypotension, bradycardia, and decreased cardiac output.

Read the entire FDA prescribing information for Pacerone (Amiodarone HCl Tablets)