DIQTA 1.0: Drug-Induced QT Prolongation Atlas

PROCAINAMIDE HYDROCHLORIDE

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Most-DIQT concern

Severity Score:4.0

Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF

PRECAUTIONS
General
After achieving and maintaining therapeutic plasma concentrations and satisfactory electrocardiographic and clinical responses, continued frequent periodic monitoring of vital signs and electrocardiograms is advised. If evidence of QRS widening of more than 25 percent or marked prolongation of the Q-T interval occurs, concern for overdosage is appropriate, and interruption of the PA infusion is advisable if a 50 percent increase occurs. Elevated serum creatinine or urea nitrogen, reduced creatinine clearance or history of renal insufficiency, as well as use in older patients (over age 50), provide grounds to anticipate that less than the usual dosage or infusion rate may suffice, since the urinary elimination of PA and NAPA may be reduced, leading to gradual accumulation beyond normally-predicted amounts. If facilities are available for measurement of plasma PA and NAPA, or acetylation capability, individual dose adjustment for optimal therapeutic levels may be easier, but close observation of clinical effectiveness is the most important criterion.
CONTRAINDICATIONS
Torsades de Pointes: In the unusual ventricular arrhythmia called "les torsades de pointes" (twistings of the points), characterized by alternation of one or more ventricular premature beats in the directions of the QRS complexes on ECG in persons with prolonged Q-T and often enhanced U waves, Group 1A antiarrhythmic drugs are contraindicated. Administration of PA in such cases may aggravate this special type of ventricular extrasystole or tachycardia instead of suppressing it.
OVERDOSAGE
Progressive widening of the QRS complex, prolonged Q-T and P-R intervals, lowering of the R and T waves, as well as increasing A-V block, may be seen with doses which are excessive for a given patient. Increased ventricular extrasystoles, or even ventricular tachycardia or fibrillation may occur. After intravenous administration but seldom after oral therapy, transient high plasma levels of PA may induce hypotension, affecting systolic more than diastolic pressures, especially in hypertensive patients. Such high levels may also produce central nervous depression, tremor, and even respiratory depression.
CLINICAL PHARMACOLOGY
The electrocardiogram may reflect these effects by showing slight sinus tachycardia (due to the anticholinergic action) and widened QRS complexes and, less regularly, prolonged Q-T and P-R intervals (due to longer systole and slower conduction), as well as some decrease in QRS and T wave amplitude. These direct effects of PA on electrical activity, conduction, responsiveness, excitability and automaticity are characteristic of a Group 1A antiarrhythmic agent, the prototype for which is quinidine; PA effects are very similar. However, PA has weaker vagal blocking action than does quinidine, does not induce alpha-adrenergic blockade, and is less depressing to cardiac contractility.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24087

Other ADRs

134

38381453

Odds Ratio = 59.458

Drug Property Information

ATC Code(s):

C01BA02 - procainamide hydrochloride

C01BA - "Antiarrhythmics, class Ia"
C01B - "ANTIARRHYTHMICS, CLASS I AND III"
C01 - CARDIAC THERAPY
C - CARDIOVASCULAR SYSTEM

Active Ingredient:PROCAINAMIDE HYDROCHLORIDE

Active Ingredient UNII:SI4064O0LX

Drugbank ID:DB01035

PubChem Compound:4913

CTD ID:D011342

PharmGKB:PA451108

CAS Number:51-06-9

Dosage Form(s):injection, solution

Route(s) Of Administrator:intramuscular; intravenous

Daily Dose:

300.0 mg/day C01BA02

Chemical Structure:

SMILE Code:
CCN(CC)CCNC(=O)C1=CC=C(N)C=C1

Reference

1: Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs.

[Makkar R R,Fromm B S,Steinman R T,Meissner M D,Lehmann M H]
JAMA,1993 Dec 1;270(21):2590-7. PMID: 8230644

2: Drug-induced torsade de pointes.

[Raehl C L,Patel A K,LeRoy M]
Clin Pharm,Nov-Dec 1985;4(6):675-90. PMID: 2416504

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