Dosing and uses of Norpace, Norpace CR (disopyramide)
Adult dosage forms and strengths
capsule
- 100mg
- 150mg
capsule, controlled-release
- 100mg
- 150mg
Ventricular Arrythmias
>50 kg
- Immediate-release: 150 mg PO q6hr
- Controlled-release: 300 mg q12hr
- Range: 400-800 mg/day
<50 kg
- Immediate-release: 100 mg PO q6hr
- Controlled-release: 200 mg PO q12hr
Rapid Control of Ventricular Arrythmias
>50 kg
- Immediate-release: 300 mg PO initially, THEN 150-300 mg q6hr
- If no response within 6 hours, give 200 mg PO q6hr, may increase to 250-300 mg q6hr if no response in 48 hours
<50 kg
- Immediate-release: 200 mg PO initially, THEN 150-300 mg q6hr
- CR should not be used initially for rapid control
Renal Impairment
Immediate-release
- CrCl >40 mL/min: 100 mg PO q6hr
- CrCl 30-40 mL/min: 100 mg PO q8hr
- CrCl 15-30 mL/min: 100 mg PO q12hr
- CrCl <15 mL/min: 100 mg PO qDay
Controlled-release
- CrCl >40 mL/min: 200 mg q12hr
- CrCl ≤40 mL/min: CR not recommended
Hepatic Impairment
Immediate-release: 100 mg PO q6hr Or
Controlled-release: 200 mg q12hr
Monitoring
Therapeutic range 2-4 mcg/mL, toxic range >9 mcg/mL
Pediatric dosage forms and strengths
capsule
- 100mg
- 150mg
capsule, extended-release
- 100mg
- 150mg
Ventricular Arrhythmias (Off-label)
<1 year old: 10-30 mg/kg/day divided q6hr PO
1-4 years old: 10-20 mg/kg/day divided q6hr PO
4-12 years old: 10-15 mg/kg/day divided q6hr PO
12-18 years old: 6-15 mg/kg/day divided q6hr PO
Geriatric dosage forms and strengths
Avoid; potent negative inotrope that may induce heart failure in older adults; nonanticholinergic antiarrhythmic drugs preferred (Beers criteria)
Dose selection in the elderly should be cautious, usually starting at the low end of the dosing range
CNS anticholinergic effects such as confusion, agitation and hallucinations can be intolerable and may lead to discontinuation
Norpace, Norpace CR (disopyramide) adverse (side) effects
>10%
Xerostomia (32%)
Urinary hesitancy (23%)
Constipation (11%)
1-10%
Impotence
Urinary urgency
Urinary retention
Dry throat
Weight gain
Abdominal distension
Flatulence
Anorexia
Vomiting
Nausea
Dermatoses
Pruritus
Generalized rash
Increased triglycerides and cholesteroL
Hypokalemia
Muscle weakness
Muscular pain
Dyspnea
Blurred vision
Dry eyes
Fatigue
Malaise
Headache
Dizziness
Nervousness
Syncope
Hypotension
Chest pain
Edema
<1%
AV block
Hypoglycemia (rare)
Agranulocytosis
Respiratory distress
Creatinine increased
Psychotic reaction
Paresthesia
Lupus (rare)
Peripheral neuropathy
Insomnia
Warnings
Black box warnings
National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST): Excessive mortality or nonfatal cardiac arrest (7.7%) shown with encainide or flecainide compared with placebo (3%)
CAST was a long-term, multicenter, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction (MI) >6 days but <2 yr previously
Average duration of treatment with encainide or flecainide in CAST was 10 months
Applicability of CAST results to other populations (eg, patients without recent MI) is uncertain
Reserve use of Class IC antiarrhythmics for life-threatening ventricular arrhythmias: Considering the known proarrhythmic properties of disopyramide & lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, disopyramide use, as well as other antiarrhythmic agents, should be reserved for patients with life-threatening ventricular arrhythmias
Contraindications
Hypersensitivity
Cardiogenic shock, preexisting second or third degree heart block, congenital QT syndrome, sick sinus syndrome
Cautions
CHF, ECG abnormalities, electrolyte abnormalities (hypo/hyper K), glaucoma, hypoglycemia, myasthenia gravis, sick sinus syndrome, BPH/urinary retention, need normal potassium prior to use, hypotension, cardiac myopathies, heart failure, prostatic enlargement, Wolff-Parkinson-White syndrome, bundle branch block, hepatic/renal impairment
Hypotension may occur
May cause QTc prolongation and subsequent torsade de pointes
Can both precipitate and exacerbate HF due to marked myocardial depressant effects in HF
Pregnancy and lactation
Pregnancy category: C
Lactation: crosses into breast milk, discontinue drug or do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Norpace, Norpace CR (disopyramide)
Mechanism of action
Direct membrane depressant that decreases conduction velocity, prolongs refractoriness, decreases automaticity and reduces repolarization abnormalities
Absorption
Bioavailability: 60-83%
Peak Plasma Time: 1-2.5 hr (immediate-release); 4-7 hr (controlled-release)
Onset: 30 min-3.5 hr
Duration: 1.5-8.5 hr
Distribution
Protein Bound: 20-60%
Vd: 0.8-2 L/kg
Metabolism
Metabolised by CYP3A4 in liver (45%) and intestinal wall (16%)
Metabolites: N-monodealkylated metabolite (active met w/ less antiarrhythmic activity, but greater anticholinergic activity)
Elimination
Half-Life: 4-10 hr (parent drug); 12.9 hr (metabolite: N-monodealkylated metabolite)
Total Body Clearance: 1-2 mL/min/kg
Renal Clearance: 107 mL/min
Excretion: urine (40-80%); feces (10-15%)
Dialyzable: Yes, maintenance dose after dialysis is recommended
