Skip to main content

Pronestyl Side Effects

Generic name: procainamide

Medically reviewed by Drugs.com. Last updated on Jun 14, 2023.

Note: This document contains side effect information about procainamide. Some dosage forms listed on this page may not apply to the brand name Pronestyl.

Applies to procainamide: intravenous solution.

Warning

Intravenous route (Solution)

WarningThe prolonged administration of procainamide often leads to the development of a positive anti-nuclear antibody (ANA) test, with or without symptoms of a lupus erythematosus-like syndrome. If a positive ANA titer develops, the benefit versus risks of continued procainamide therapy should be assessed.MortalityIn the National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term, muliticentered, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a myocardial infarction more than six days but less than two years previously, an excessive mortality or non-fatal cardiac arrest rate (7.7%) was seen in patients treated with encainide or flecainide compared with that seen in patients assigned to carefully matched placebo-treated groups (3.0%). The average duration of treatment with encainide or flecainide in this study was 10 months.The applicability of the CAST results to other populations (eg, those without recent myocardial infarction) is uncertain. Considering the known proarrhythmic properties of procainamide and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of procainamide hydrochloride as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.Blood DyscrasiasAgranulocytosis, bone marrow depression, neutropenia, hypoplastic anemia and thrombocytopenia in patients receiving procainamide hydrochloride have been reported at a rate of approximately 0.5%. Most of these patients received procainamide hydrochloride within the recommended dosage range. Fatalities have occurred (with approximately 20% to 25 % mortality in reported cases of agranulocytosis). Since most of these events have been noted during the first 12 weeks of therapy, it is recommended that complete blood counts including white cell, differential and platelet counts be performed at weekly intervals for the first three months of therapy, and periodically thereafter. Complete blood counts should be performed promptly if the patient develops any signs of infection (such as fever, chills, sore throat, or stomatitis), bruising or bleeding. If any of these hematologic disorders are identified, procainamide therapy should be discontinued. Blood counts usually return to normal within one month of discontinuation. Caution should be used in patients with pre-existing marrow failure or cytopenia of any type.

Serious side effects of Pronestyl

Along with its needed effects, procainamide (the active ingredient contained in Pronestyl) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking procainamide:

Less common

Rare

Get emergency help immediately if any of the following symptoms of overdose occur while taking procainamide:

Symptoms of overdose

Other side effects of Pronestyl

Some side effects of procainamide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Less common

For Healthcare Professionals

Applies to procainamide: compounding powder, injectable solution, oral capsule, oral tablet, oral tablet extended release.

General

Some side effects of procainamide (the active ingredient contained in Pronestyl) are related to serum levels of the parent compound and its metabolite, N-acetylprocainamide (NAPA). Side effects are uncommon at levels less than 4 mg per liter, more common at 7 to 8 mg per liter, and expected at 16 mg per liter. Side effects may be more likely and more severe in patients with renal insufficiency.[Ref]

Cardiovascular

Cardiovascular side effects may be acute and serious, such as hypotension, polymorphous ventricular tachycardia, or asystole. Administration of intravenous procainamide (the active ingredient contained in Pronestyl) in dosages that do not exceed 20 mg/min minimizes the risk of hypotension, and should be considered in patients with low blood pressure and/or cardiac dysfunction. Procainamide may induce QT interval lengthening and torsades de pointes, although less commonly than with quinidine. The possible negative inotropic side effects of procainamide, especially with high serum levels, may be deleterious to some patients with compromised cardiac function.[Ref]

Procainamide may induce the formation of a circulating immunoglobulin directed against some coagulation factors, which has been associated with deep venous thrombosis. This may induce an elevation in the partial thromboplastin time.

A case of myocarditis without pericarditis and several cases of pericarditis associated with procainamide is reported in association with a lupus-like syndrome.[Ref]

Hematologic

Many of the cases of procainamide-induced agranulocytosis presented with complaints of sore throat, malaise, or fever. Prompt evaluation of the complete blood count and differential cell count is recommended since rare cases of serious infection, and even death, associated with this problem have been reported.

A case of pure red cell aplasia associated with procainamide (the active ingredient contained in Pronestyl) and confirmed by rechallenge, has been reported.[Ref]

Hematologic side effects are rare, but may be severe. The overall incidence of blood dyscrasias (1980 to 1992) was 0.0022% (90% of affected patients were receiving Procan SR). "Blood dyscrasia" was defined as any diagnosis of agranulocytosis, granulocytopenia, neutropenia, leukopenia, thrombocytopenia, pancytopenia, bone marrow suppression, or aplastic anemia--regardless of severity. These reversible dyscrasias do not appear to be related to drug levels. Periodic monitoring of the complete blood count and careful attention to even minor signs of infection during procainamide therapy is recommended. In addition, lupus anticoagulants, which are evident in 25% to 35% of patients with systemic lupus erythematosus, have been reported in patients treated with procainamide in the absence of other lupus-like symptoms. The presence of such immunoglobulins can lead to thromboembolic complications.[Ref]

Hypersensitivity

Hypersensitivity reactions include reports of angioedema, urticarial rash, and pruritus. Such reactions may be more likely in patients with a sulfite sensitivity. Though not proven, procainamide-induced hepatitis is believed to be hypersensitivity-mediated.[Ref]

Immunologic

Immunologic side effects include a lupus-like syndrome. Chronic use of procainamide (the active ingredient contained in Pronestyl) may induce production of an antinuclear antibody (ANA) in up to 70% of asymptomatic patients after 6 weeks of therapy. This antibody may be associated with a reversible lupus-like syndrome (myalgias, arthralgias, arthritis, and pulmonary or pericardial serositis) in rare cases. Symptoms appear in only approximately 30% of affected patients. Checking the ANA titer every other month or quarterly is recommended, although many clinicians opt to continue the drug in some patients with a positive ANA titer, taking into account the need for procainamide therapy.[Ref]

The lupus-like syndrome may manifest as arthralgias (most common), fever, chills, myalgias, pericarditis, pleuritis, pleural effusion, hepatomegaly, and hemorrhagic cardiac tamponade. Nephritis and cerebritis are not reported. If periodic monitoring reveals a high antinuclear antibody (ANA) titer, or if the patient develops lupus-like symptoms, reevaluation of the use of procainamide and consideration of aspirin and/or corticosteroid therapy is recommended.

The lupus-like syndrome associated with procainamide shows no predilection for females, is reversible upon discontinuation of procainamide, and is more common among slow acetylators.[Ref]

Gastrointestinal

Gastrointestinal side effects are usually minor, and include nausea, vomiting, anorexia, and diarrhea.[Ref]

Nervous system

Nervous system side effects are uncommon, and include case reports of dizziness and tremors.[Ref]

Rare cases of reversible peripheral neuropathy have been associated with a procainamide-induced lupus-like syndrome.[Ref]

Musculoskeletal

Musculoskeletal weakness is unusual, but may be more likely in patients with underlying myasthenia gravis (MG). At least one case of respiratory failure due to necrotizing myopathy with diaphragmatic involvement in an elderly patient without evidence of MG has been reported.[Ref]

A 74-year-old man with post-coronary artery bypass grafting supraventricular arrhythmias developed upper body symmetrical muscle weakness and tenderness two weeks after beginning procainamide. Associated findings included a sterile, exudative pleural effusion, elevated creatinine kinase levels, and positive anti-double stranded DNA and anti-histone antibodies. Renal function and antinuclear antibodies were normal. Procainamide was withdrawn. The patient's weakness progressed over the next seven days. He developed diaphragmatic weakness, respiratory acidosis, and the need for mechanical ventilation. An extensive neuromuscular work-up revealed a necrotizing myopathy and no evidence of impaired neuromuscular junction transmission. The muscle biopsy showed no inflammatory infiltrates and antinuclear antibodies were not present. The patient recovered over the next month.[Ref]

Psychiatric

A case of reversible mania has been reported in a patient with nontoxic serum procainamide (the active ingredient contained in Pronestyl) levels.

A 45-year-old female undergoing a mitral valve replacement and tricuspid valve repair began experiencing visual hallucinations and other symptoms suggestive of psychosis four days after beginning procainamide. Within 24 hours of discontinuing procainamide, the patient returned to normal sensorium.[Ref]

Psychiatric side effects include euphoria, hallucinations, psychosis, and mental depression.[Ref]

Hepatic

Only approximately five cases of procainamide-induced granulomatous hepatitis or intrahepatic cholestasis have been reported. Of the five reported cases, all experienced fever, two had vomiting, one pruritus, and none had lymphadenopathy. The onset of signs and symptoms of liver dysfunction began 1 to 17 days after drug administration, and normalized as soon as one day to as long as several months after drug withdrawal. While the mechanism of injury is not known, most believe procainamide-induced hepatitis to be hypersensitivity-mediated.[Ref]

Hepatic side effects are rare. Rare cases of reversible cholestatic jaundice associated with procainamide have been reported. These cases were thought to be due to hypersensitivity reactions. Frequent monitoring of liver function tests is recommended in patients with hepatic insufficiency.[Ref]

References

1. Multum Information Services, Inc. Expert Review Panel

2. Gold MR, Ogara PT, Buckley MJ, Desanctis RW. Efficacy and safety of procainamide in preventing arrhythmias after coronary artery bypass surgery. Am J Cardiol. 1996;78:975-9.

3. Koch-Weser J, Klein S, Foo-Canto L, et al. Antiarrhythmic prophylaxis with procainamide in acute myocardial infarction. N Engl J Med. 1969;281:1253-60.

4. Koch-Weser J, Klein S. Procainamide dosage schedules, plasma concentrations, and clinical effects. JAMA. 1971;215:1454-61.

5. Giardina E, Fenster P, Bigger J, et al. Efficacy, plasma concentrations and adverse effects of a new sustained release procainamide preparation. Am J Cardiol. 1980;46:855-62.

6. Strasberg B, Sclarovsky S, Erdberg A, et al. Procainamide-induced polymorphous ventricular tachycardia. Am J Cardiol. 1981;47:1309-14.

7. Boccardo D, Pitchon R, Wiener I. Adverse Reactions and Efficacy of High-Dose Procainamide Therapy in Resistant Tachyarrhythmias. Am Heart J. 1981;102:797-8.

8. Schwartz A, Klausner S, Yee S, Turchyn M. Cerebellar ataxia due to procainamide toxicity. Arch Intern Med. 1984;144:2260-1.

9. Stratmann H, Walter K, Kennedy H. Torsade de pointes associated with elevated N-acetylprocainamide levels. Am Heart J. 1985;109:375-6.

10. Li G, Greenberg C, Currie M. Procainamide-induced lupus anticoagulants and thrombosis. South Med J. 1988;81:262-4.

11. Lawson D, Jick H. Adverse reactions to procainamide. Br J Clin Pharmacol. 1977;4:507-11.

12. Yang BB, Abel RB, Uprichard ACG, Smithers JA, Forgue ST. Pharmacokinetic and pharmacodynamic comparisons of twice daily and four times daily formulations of procainamide in patients with frequent ventricular premature depolarization. J Clin Pharmacol. 1996;36:623-33.

13. Scifman R, Garewal H, Shillinton D. Reticulocytopenic, Coombs' positive anemia induced by procainamide. Am J Clin Pathol. 1983;80:66-8.

14. Berger B, Hauser D. Agranulocytosis due to new sustained-release procainamide. Am Heart J. 1983;105:1035-6.

15. Reidy T, Upshaw J. Procainamide-induced agranulocytosis. South Med J. 1984;77:1582-4.

16. Ellrodt A, Murata G, Riedinger M, et al. Severe neutropenia associated with sustained-release procainamide. Ann Intern Med. 1984;100:197-201.

17. Christensen D, Palma L, Phelps K. Agranulocytosis, thrombocytopenia, and procainamide. Ann Intern Med. 1984;100:918.

18. Rubinstein A, Cabili S. Tremor induced by procainamide. Am J Cardiol. 1986;57:340-1.

19. Hoyt R. Severe neutropenia due to sustained-release procainamide. South Med J. 1987;80:1196-7.

20. Heyman MR, Flores RH, Edelman BB, Carliner NH. Procainamide-induced lupus anticoagulant. South Med J. 1988;81:934-6.

21. Meisner DJ, Carlson RJ, Gottlieb AJ. Thrombocytopenia following sustained-release procainamide. Arch Intern Med. 1985;145:700-2.

22. Fleet S. Agranulocytosis, procainamide, and phenytoin. Ann Intern Med. 1984;100:616-7.

23. Gabrielson RM, Leininger NR. Procainamide and neutropenia. Ann Intern Med. 1984;100:766-7.

24. Landrum EM, Siegert EA, Hanlon JT, Currie MS. Prolonged thrombocytopenia associated with procainamide in an elderly patient. Ann Pharmacother. 1994;28:1172-6.

25. Danielly J, Dejong R, Radkemitchell LC, Uprichard ACG. Procainamide-associated blood dyscrasias. Am J Cardiol. 1994;74:1179-80.

26. Starkebaum G, Kenyon CM, Simrell CR, Creamer JI, Rubin RL. Procainamide-induced agranulocytosis differs serologically and clinically from procainamide-induced lupus. Clin Immunol Immunopathol. 1996;78:112-9.

27. Metzdorff MT, Hanses KS, Wright GL, Fried SJ. Interference with anticoagulation monitoring by procainamide-induced lupus anticoagulant. Ann Thorac Surg. 1996;61:994-5.

28. Ahn C, Tow D. Intrahepatic cholestasis due to hypersensitivity reaction to procainamide. Arch Intern Med. 1990;150:2589-90.

29. Worman HJ, Ip JH, Winters SL, et al. Hypersensitivity reaction associated with acute hepatic dysfunction following a single intravenous dose of procainamide. J Intern Med. 1992;232:361-3.

30. Chuang LC, Tunier AP, Akhtar N, Levine SM. Possible case of procainamide-induced intrahepatic cholestatic jaundice. Ann Pharmacother. 1993;27:434-7.

31. Eisner E, Shahidi N. Immune thrombocytopenia due to a drug metabolite. N Engl J Med. 1972;287:376-81.

32. Ahmad S. Procainamide and peripheral neuropathy. South Med J. 1981;74:509-10.

33. Myers DF, O'Connell JB, Subramanian R. Myocarditis resolving after discontinuation of procainamide. Int J Cardiol. 1983;4:322-4.

34. Amadio P, Cummings D, Dashow L. Procainamide, quinidine, and lupus erythematosus. Ann Intern Med. 1985;102:419-20.

35. Zech P, Colon S, Labeeuw M, et al. Nephrotic syndrome in procainamide induced lupus nephritis. Clin Nephrol. 1979;11:218-21.

36. Woosley R, Drayer D, Reidenberg M, et al. Effect of acetylator phenotype on the rate at which procainamide induces antinuclear antibodies and the lupus syndrome. N Engl J Med. 1978;298:1157-9.

37. Rubin RL, Nusinow SR, Johnson AD, et al. Serologic changes during induction of lupus-like disease by procainamide. Am J Med. 1986;80:999-1002.

38. Venkayya RV, Poole RM, Pentz WH. Respiratory failure from procainamide-induced myopathy. Ann Intern Med. 1993;119:345-6.

39. McDonald E, Marino C. Procainamide-induced lupus in the elderly. Hosp Pract (Off Ed). 1993;28:95-8.

40. Miller CD, Oleshansky MA, Gibson KF, Cantilena LR. Procainamide-induced myasthenia-like weakness and dysphagia. Ther Drug Monit. 1993;15:251-4.

41. Sheikh S, Seggiv J. Procainamide-induced pleural fibrosis. Am J Med. 1991;91:313-5.

42. Katsutani N, Shionoya H. Popliteal lymph node enlargement induced by procainamide. Int J Immunopharmacol. 1992;14:681-6.

43. Gold MR, O'Gara PT, Buckley MJ, DeSanctis RW. Efficacy and safety of procainamide in preventing arrhythmias after coronary artery bypass surgery. Am J Cardiol. 1996;78:975-9.

44. Niakan E, Bertorini T, Acchirardo S, Werner M. Procainamide-induced myasthenia-like weakness in a patient with periperal neuropathy. Arch Neurol. 1981;38:378-9.

45. Lewis C, Boheimer N, Rose P, Jackson G. Myopathy after short term administration of procainamide. Br Med J. 1986;292:593-4.

46. Rice H, Haltzman S, Tucek C. Mania associated with procainamide. Am J Psychiatry. 1988;145:129-30.

47. Bizjak ED, Nolan PE, Brody EA, Galloway JM. Procainamide-induced psychosis: A case report and review of the literature. Ann Pharmacother. 1999;33:948-51.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.