Procainamide dosing

About 30% of the patients on chronic procainamide dosing develop a systemic lupusfike syndrome consisting of arthralgia, myalgia, skin rash, and fever. Patients who are slow acetylator phenotypes may be prone to this condition. Some may exhibit pleuropneumonic involvement and hepatomegaly... 

FIGURE 16.11 Simplified scheme of procainamide metabolism. In individuals with normal kidney function, renal excretion of unchanged drug accounts for more than half the elimination of a procainamide dose, wdiereas acetylation by NAX2 accounts for only 24% and 17% of elimination in rapid and slowr acetylators, respectively. A small amount is of procainamide is metabolized to a hydroxylamine, wdiich is in equilibrium with a postulated chemically unstable and reactive nitroso compound that is capable of haptenic binding to histone proteins. 

Procainamide has an active metabolite, AAacetylprocainamide (NAPA) with therapeutic procainamide dosing, NAPA levels can range from 15 to 25 mg/L. 

A man with sustained ventricular tachycardia taking high-dose intravenous procainamide 2 g every 8 hours had a 70% increase in his steady-state plasma procainamide levels, from 9.1 to 15.4 nanograms/mL, when he also took quinidine gluconate 324 mg every 8 hours. The procainamide half-life increased from 3.7 to 7.2 hours and its clearance fell from 27 to 16 L/hour. His QTc interval increased from 648 to 678 milliseconds. In another study in patients with ventricular arrhythmias, quinidine was combined with procainamide. The doses were adjusted based in part on the QT interval. The QTc interval was longer with the combination (499 milliseconds) than each drug alone (quinidine 470 milliseconds, procainamide 460 milliseconds) despite using reduced doses in the combination (mean quinidine dose reduced by 28% mean procainamide dose reduced by 32%) ... 

Procainamide may be adininistered by iv, intramuscular (im), or po routes. After po dosing, 75—90% of the dmg is absorbed from the GI tract. About 25% of the amount absorbed undergoes first-pass metaboHsm in the fiver. The primary metabolite is A/-acetylprocainamide (NAPA) which has almost the same antiarrhythmic activity as procainamide. This is significant because the plasma concentration of NAPA relative to that of procainamide is 0.5—2.5. In terms of dmg metabolism there are two groups of patients those that rapidly acetylate and those that slowly acetylate procainamide. About 15—20% of the dmg is bound to plasma proteins. Peak plasma concentrations are achieved in 60—90 min. Therapeutic plasma concentrations are 4—10 lg/mL. Plasma half-lives of procainamide and NAPA, which are excreted mainly by the kidneys, are 2.5—4.5 and 6 h, respectively. About 50—60% is excreted as unchanged procainamide (1,2). 

ADM INI STERI NG DISOPYRAMID E Disopyramide is administered to tiie patient with a full glass of water either 1 hour before or 2 hours after meals. If patients are receiving procainamide or quinidine tiie manufacturer suggests that disopyramide therapy not be started for 6 to 12 hours after tiie last dose of quinidine and 3 to 6 hours after tiie last dose of procainamide When tiie patient is to switch from taking tiie regular capsules to taking extended-release capsules, 6 hours should lapse after tiie last capsule before therapy is begun with tiie extended-release capsules. 

Autoantibodies to red blood cells and autoimmune hemolytic anemia have been observed in patients treated with numerous drugs, including procainamide, chlor-propaminde, captopril, cefalexin, penicillin, and methyldopa (Logue et al., 1970 Kleinman et al., 1984). Hydralazine- and procainamide-induced autoantibodies may also result in SLE. Approximately 20% of patients administered methyldopa for several weeks for the treatment of essential hypertension developed a dose-related titer and incidence of autoantibodies to erythrocytes, 1% of which presented with hemolytic anemia. Methlydopa does not appear to act as a hapten but appears to act by modifying erythrocyte surface antigens. IgG autoantibodies then develop against the modified erythrocytes. 

For the treatment of hemodynamically stable ventricular tachycardia in children, procainamide (loading dose of 15 mg/kg IV infused over 30 to 60 minutes) may be considered as an alternative agent to amiodarone. 

IM administration - IM administration may be used as an alternative to the oral route for patients with less threatening arrhythmias but who are nauseated or vomiting, who are ordered to receive nothing by mouth preoperatively, or who may have malabsorptive problems. An initial daily dose of 50 mg/kg may be estimated. Divide this amount into fractional doses of 1/8 to % to be injected IM every 3 to 6 hours until oral therapy is possible. If more than 3 injections are given, assess patient factors such as age and renal function, clinical response and, if available, blood levels of procainamide and NAPA in adjusting further doses for that individual. For treatment of arrhythmias associated with... 

Terminate IV therapy if persistent conduction disturbances or hypotension develop. As soon as the patient s basic cardiac rhythm appears to be stabilized, oral antiarrhythmic maintenance therapy is preferable (if indicated and possible). A period of approximately 3 to 4 hours (one half-life for renal elimination, ordinarily) should elapse after the last IV dose before administering the first dose of oral procainamide. 

Renai insufficiency Renal insufficiency may lead to accumulation of high plasma levels from conventional oral doses of procainamide, with effects similar to those of overdosage unless dosage is adjusted for the individual patient. 

Transfer to disopyramide Use the regular maintenance schedule, without a loading dose, 6 to 12 hours after the last dose of quinidine or 3 to 6 hours after the last dose of procainamide. Where withdrawal of quinidine or procainamide is likely to produce life-threatening arrhythmias, consider hospitalization. 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

Uses Rapid conversion of AF/artmal fluto Action Class III antiarrhythmic Dose Adults >60 kg. 0.01 mg/kg (max 1 mg) IV inf over 10 min may repeat x 1 <60 kg Use 0.01 mg/kg (ECC 2005 D/C cardioversion preferred) Caution [C, -] Contra w/ class I/III antiarrhythmics (Table VI-7) QTc >440 ms Disp Inj SE Arrhythmias, HA Interactions t Refractory effects W7 amiodarone, disopyra-mide, procainamide, quinidine, sotalol t QT int val W7 antihistamines, antidepressants, erythromycin, phenothiazines, TCAs EMS Use antihistamines w/ caution, may T QT interval OD May cause increased repolarization leading to arrhythmias, bradycardia, hypotension leading to cardiac arrest symptomatic and supportive... 

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