PACERONE
Clinical safety rating
cautionComprehensive clinical and safety monograph for PACERONE (PACERONE).
Class III antiarrhythmic agent; prolongs action potential duration and refractory period by blocking potassium channels, and also exhibits class I, II, and IV effects.
| Metabolism | Primarily hepatic via CYP3A4 and CYP2C8; active metabolite desethylamiodarone; substrate of P-glycoprotein. |
| Excretion | Primarily hepatic metabolism (CYP3A4, CYP2C8) to desethylamiodarone (active). Renal elimination of drug and metabolites: <1% of unchanged drug; ~40% of dose as metabolites. Fecal elimination: ~70% of dose as metabolites, with some parent drug. |
| Half-life | Biphasic: initial 3-10 days; terminal elimination half-life 40-58 days (mean ~53 days) due to extensive tissue distribution and slow release from fat. Clinical context: steady-state achieved in 2-4 months without loading dose. |
| Protein binding | 96% bound, primarily to albumin and beta-lipoproteins. |
| Volume of Distribution | 66 L/kg (range 10-200 L/kg) indicating extensive tissue distribution, especially in adipose tissue, liver, and lungs. |
| Bioavailability | Oral: 30-80% (mean ~50%), increased by food; erratic absorption due to high lipophilicity. IV: 100%. |
| Onset of Action | IV: within 2-3 hours for antiarrhythmic effect. Oral: 2-7 days; full effect may take weeks due to slow accumulation. |
| Duration of Action | Long; persists for weeks to months after discontinuation due to long half-life. Antiarrhythmic effect may last 30-45 days post-cessation. |
| Molecular Weight | 645.31 |
Loading dose: 800-1600 mg/day PO in divided doses for 1-3 weeks, then 600-800 mg/day PO for 1 month; maintenance: 200-400 mg/day PO once daily. IV: 150 mg over 10 min, then 1 mg/min for 6 hours, then 0.5 mg/min.
| Dosage form | TABLET |
| Renal impairment | No specific GFR-based dose adjustment required; caution in severe renal impairment due to possible accumulation of active metabolite desethylamiodarone. Monitor serum levels and QT interval. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). In moderate impairment (Child-Pugh class B), reduce maintenance dose by 50% and monitor liver function. Mild impairment (Child-Pugh A): no adjustment, but monitor. |
| Pediatric use | Loading: 10-20 mg/kg/day PO in divided doses for 7-10 days; maintenance: 5-10 mg/kg/day PO once daily. IV loading: 5 mg/kg over 30 min, then 5-15 mg/kg/day continuous infusion. |
| Geriatric use | Lower maintenance doses (100-200 mg/day PO) due to increased risk of bradycardia, QT prolongation, and thyroid dysfunction. Monitor renal function and electrolytes closely. |
| 1st trimester | Risk of fetal bradycardia and hypoglycemia; avoid unless maternal condition requires. |
| 2nd trimester | Monitor fetal thyroid function; may cause hypothyroidism or goiter. |
| 3rd trimester | Potential for neonatal bradycardia, QT prolongation, and hypoglycemia. |
Clinical note
Comprehensive clinical and safety monograph for PACERONE (PACERONE).
| Placental transfer | Amiodarone crosses the placenta (fetal serum levels ~10-25% maternal levels). Accumulates in fetal tissues, especially thyroid. |
| Breastfeeding | Amiodarone and its active metabolite are excreted in breast milk in significant amounts; risk of neonatal hypothyroidism and bradycardia. Avoid breastfeeding or use with caution. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | Pacerone (amiodarone) is FDA Pregnancy Category D. First trimester: risk of congenital anomalies including hypothyroidism, goiter, and neurodevelopmental delays due to iodine content. Second and third trimesters: continued risk of fetal hypothyroidism and bradycardia; neonatal monitoring for thyroid function and ECG is recommended. |
| Fetal Monitoring | Monitor maternal thyroid function (TSH, free T4), liver function tests, pulmonary function, and ECG. Fetal monitoring: serial ultrasound for growth and anatomy, fetal heart rate monitoring, and postnatal thyroid function tests and ECG in the newborn. |
| Fertility Effects | Amiodarone may cause menstrual irregularities and amenorrhea in women; effects on male fertility are not well documented but thyroid dysfunction may impact spermatogenesis. Overall, fertility effects are likely reversible upon discontinuation. |
■ FDA Black Box Warning
Only for patients with life-threatening arrhythmias due to risk of pulmonary toxicity, hepatotoxicity, and proarrhythmia; requires baseline and periodic monitoring of pulmonary function, liver enzymes, thyroid function, and ECG.
| Serious Effects |
Severe sinus node dysfunctionSecond- or third-degree AV block (unless pacemaker),Marked bradycardia (unless pacemaker),Cardiogenic shockKnown hypersensitivity to amiodarone or iodine
| Precautions | Pulmonary toxicity (interstitial pneumonitis, pulmonary fibrosis), hepatotoxicity (elevated liver enzymes, hepatic failure), proarrhythmia (worsening arrhythmias, torsades de pointes), thyroid dysfunction (hypo- or hyperthyroidism), optic neuropathy/neuritis, skin discoloration, photosensitivity, bradycardia, and drug interactions (CYP450 and P-gp mediated). |
| Food/Dietary | Avoid grapefruit juice as it inhibits CYP3A4 and can increase amiodarone levels. St. John's wort may decrease amiodarone efficacy by inducing metabolism. Take with food to reduce gastrointestinal irritation. |
| Clinical Pearls | Amiodarone has an extremely long half-life (up to 107 days) causing delayed onset and prolonged effects. Monitor for thyroid dysfunction, pulmonary fibrosis, liver toxicity, and corneal deposits. Avoid coadministration with drugs prolonging QT interval. Use lowest effective dose due to cumulative toxicity. |
| Patient Advice | Take exactly as prescribed; do not skip doses or stop without consulting your doctor. · Report any new or worsening shortness of breath, cough, chest pain, or palpitations. · Inform your doctor if you experience vision changes, thyroid symptoms (weight change, heat/cold intolerance), or skin discoloration. · Avoid grapefruit juice and St. John's wort as they may affect drug levels. · Use sun protection; amiodarone increases sun sensitivity. · Do not breastfeed while taking this medication. · Keep all follow-up appointments for blood tests, eye exams, and lung function tests. · This medication can cause birth defects; use effective contraception. |
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