disopyramide (Norpace)
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Introduction
Tradename: Norpace. Class Ia antiarrhythmic agent.
Indications
- atrial fibrillation
- chemical cardioversion
- preventing recurrence of atrial fibrillation
- paroxysmal supraventricular tachycardia (PSVT)
- ventricular tachycardia
- not 1st or 2nd line agent
- preventing inducible & spontaneous neurally-mediated syncope
* useful anti-arrhythmic in hypertrophic cardiomyopathy
Contraindications
(cautions)
- myasthenia gravis
- anticholinergic effect may precipitate myasthenic crisis
- avoid other agents which prolong the QT interval
- avoid in men with benign prostatic hypertrophy
- avoid in patients with LV systolic dysfunction
Dosage
100-300 mg PO TID/QID
Tabs: 100, 150 mg. Norpace CR: 200-300 mg PO BID. 100, 150 mg
Therapeutic range: 2-5 ug/mL. Dose adjustment for renal failure:
| Creatinine clearance | dose (maintenance) in divided doses |
|---|---|
| > 40 mL/min | 400-800 mg/day (max 1.6 g/day) |
| 30-40 mL/min | 300 mg/day |
| 15-30 mL/min | 200 mg/day |
| <15 mL/min | 100 mg/day |
Pharmacokinetics
- rapidly & nearly completely absorbed from the GI tract
- protein binding is concentration-dependent, 50-65%
- metabolized in the liver by cyt P450 3A4
- 50% of drug is excreted unchanged in the urine, 30% as metabolites
- 1/2life is 6.7 hours
- increased with renal insufficiency
- 8-18 hours when creatinine clearance is < 40 mL/min
elimination via kidney 90 %
elimination via liver 10 %
1/2life = 4.4-8.2 hours
protein binding = 68 % 0.4 ug/mL
protein binding = 28 % 4 ug/mL
elimination by hemodialysis = -
Adverse effects
- common (> 10%)
- less common (1-10%)
- uncomon (< 1%)
- weight gain, dyspnea, syncope,
- conduction disturbances
- AV block
- widening of QRS
- lengthening of QT interval
- fatigue, malaise, nervousness, acute psychosis, depression, dizziness, weakness, headache, generalized rash, hypoglycemia, constipation, nausea/vomiting, diarrhea, pain, gas, anorexia, hepatic cholestasis, elevated liver enzymes, increased cholesterol & triglycerides, dry noses, eyes & throat (anticholinergic effects)
- other
- depression of myocardial contractility
- may initiate contraction of pregnant uterus
- hyperkalemia may enhance toxicity
- masking symptoms of hypoglycemia
Drug interactions
- avoid other agents which prolong the QT interval
- barbiturates may increase metabolism
- any drug that inhibits cyt P450 3A4 may increase levels of disopyramide
- any drug that induces cyt P450 3A4 may diminish levels of disopyramide
Laboratory
Mechanism of action
More general terms
Additional terms
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (ed), Companion Handbook, McGraw Hill, NY, 1994
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 - not on National VA formulary
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com