Procainamide

Observational studies

In a prospective study of 488 in-patients there were adverse reactions in 45 cases (9.2%); they were thought to have been life-threatening in 7 (1.4%) but there were no deaths; all seven had cardiovascular effects [ ]. Common adverse reactions included gastrointestinal upsets (19 cases) and fever (8 cases). Reactions were more common at daily doses of 3 g and more.

Comparative studies

Adverse reactions to intravenous procainamide (400 mg up to three times infused over 10 minutes) have been reported in 60 adults with atrial flutter or fibrillation in a comparison with ibutilide [ ]. The adverse reactions were headache in 11%, hypotension in 11%, flushing in 3.1%, dizziness in 3.1%, and hypesthesia in 3.1%. The mean fall in systolic blood pressure was about 20 mmHg and occurred at 30–35 minutes after infusion; the corresponding fall in diastolic blood pressure was 10 mmHg. However, in seven patients there was severe hypotension, with a fall in diastolic blood pressure of up to 67 mmHg; in three cases withdrawal of the infusion was required and these patients were treated with intravenous fluids, dopamine, or both. In the severe cases the hypotension occurred during or immediately after the infusion of procainamide.

A comparison between procainamide and propafenone in 62 patients, who had undergone coronary artery bypass grafting or valvular surgery within 3 weeks and developed sustained atrial fibrillation, showed that both drugs converted the dysrhythmia to sinus rhythm in up to 76% of cases, but that propafenone did it more quickly [ ]. Symptomatic arterial hypotension occurred more frequently with procainamide (nine of 33 patients) than with propafenone (two of 29 patients). Other adverse effects of procainamide were nausea (n = 2) and junctional escape rhythm (n = 2).

Cardiovascular

Procainamide has a negative inotropic effect and can cause hypotension after both intravenous and oral administration [ , ]. When given intravenously it should therefore be infused slowly, at no more than 20 mg/minute. In patients with poor cardiac function procainamide can worsen heart failure, and it may reduce survival after myocardial infarction [ ].

Procainamide prolongs the QT interval [ ] and can cause dysrhythmias. It can also impair cardiac conduction and can cause bradycardia and heart block [ ]. In the sick sinus syndrome it can alter sinus node recovery time [ ], although the clinical significance of this is not clear.

Pericarditis and tamponade have been reported as rare complications of procainamide-induced lupus-like syndrome [ ].

Respiratory

Procainamide can cause lung damage in the context of a lupus-like syndrome [ , ].

Nervous system

Procainamide rarely causes nervous system reactions. Acute confusion [ ], cerebellar ataxia [ ], tremor [ ], and muscle weakness [ ] have all been occasionally reported. In high dosages procainamide has anticholinergic effects [ ].

Procainamide has been reported to cause a chronic inflammatory demyelinating polyradiculoneuropathy [ ].

• A 68-year-old man took procainamide 500 mg qds for 3 years and developed distal paresthesia and dysesthesia in the legs, followed by progressive muscle weakness, mainly affecting the legs. His gait became unsteady and was wide-based. He had antinuclear antibodies directed against histones in a titer of 1:320, but no antibodies to double-stranded DNA. He had a circulating lupus anticoagulant. The serum procainamide concentration was 3.3 μg/ml (target range 4–8). Nerve conduction studies showed a reduction in sensory nerve action potential amplitudes, a mild reduction in sensory nerve conduction velocity, prolongation of distal motor latencies, and reduced conduction velocities, but no conduction block or temporal dispersions. Electromyography was normal. A left sural nerve biopsy showed perivascular inflammation around a single vessel, without evidence of vasculitis. Myelinated nerve fibers were reduced, and scattered nerve fibers showed thin myelin sheaths. About 30% of the fibers showed randomly distributed demyelinated or remyelinated segments. Procainamide was withdrawn and prednisone was given in combination with six plasma exchanges over 2 weeks; after 1 month there was clinical improvement.

This case of polyneuropathy was attributed to a lupus-like effect of procainamide.

Sensory systems

Scleritis has been reported as part of a procainamide-induced, lupus-like syndrome [ ].

Psychiatric

Acute psychosis has been attributed to procainamide [ ].

• A 45-year-old woman developed an acute psychosis within 72 hours of starting to take procainamide 75 mg intravenously, followed by a continuous infusion of 2 mg/minute for atrial fibrillation. The plasma procainamide concentration was 8.2 μg/ml and the plasma concentration of the main acetylated metabolite, acecainide, was 4.6 μg/ml. She was then given oral procainamide 500 mg qds, and 2 days later her trough concentrations of procainamide and acecainide were 4.5 and 4.9 μg/ml respectively. The following day she had visual hallucinations and was later found wandering the hospital asking about the babies under her bed. She had no previous history of psychiatric illness and she recovered completely 24 hours after withdrawal of procainamide.

There have been a few previous reports of similar adverse reactions to procainamide in therapeutic dosages, and in most cases the plasma concentrations of procainamide and acecainide have been within the usual target ranges, as in this case.