Home Drugs A to Z Qu Quinidine Side Effects

Quinidine Side Effects

Brand Names: Quin-Release

Please note - some side effects for Quinidine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Quinidine - for the Consumer

Quinidine Sulfate

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Quinidine Sulfate:

Blurred vision; diarrhea; heartburn; nausea; stomach discomfort; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Quinidine Sulfate:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); dark urine; dizziness or lightheadedness; fainting; fast, slow, or irregular heartbeat; headache; hearing changes or loss of hearing; mood or mental changes; pale stools; ringing in ears; severe or persistent stomach pain; vision changes; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Quinidine Gluconate Controlled-Release Tablets

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Quinidine Gluconate Controlled-Release Tablets:

Blurred vision; diarrhea; heartburn; nausea; stomach discomfort; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Quinidine Gluconate Controlled-Release Tablets:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); dark urine; deafness; dizziness; fainting; fast or slow heartbeat; headache; hearing loss; irregular heartbeat; lightheadedness; liver toxicity; pale stools; psychotic reactions; ringing in ears; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Quinidine Sulfate Controlled-Release Tablets

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Quinidine Sulfate Controlled-Release Tablets:

Blurred vision; diarrhea; heartburn; nausea; stomach discomfort; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Quinidine Sulfate Controlled-Release Tablets:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); dark urine; dizziness or lightheadedness; fainting; fast, slow, or irregular heartbeat; headache; hearing changes or loss of hearing; mood or mental changes; pale stools; ringing in ears; severe or persistent stomach pain; vision changes; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Quinidine Side Effects - for the Professional

Quinidine

Quinidine preparations have been used for many years, but there are only sparse data from which to estimate the incidence of various adverse reactions. The adverse reactions most frequently reported have consistently been gastrointestinal, including diarrhea, nausea, vomiting, and heart–burn/esophagitis. In one study of 245 adult outpatients who received Quinidine to suppress premature ventricular contractions, the incidences of reported adverse experiences were as shown in the table below. The most serious Quinidine–associated adverse reactions are described above under Warnings.

Adverse Experiences in a 245–Patient PVC Trial

Incidence (%)

diarrhea

85 (35)

"upper gastrointestinal distress"

55 (22)

lightheadedness

37 (15)

headache

18 (7)

fatigue

17 (7)

palpitations

16 (7)

angina–like pain

14 (6)

weakness

13 (5)

rash

11 (5)

visual problems

8 (3)

change in sleep habits

7 (3)

tremor

6 (2)

nervousness

5 (2)

discoordination

3 (1)

Intramuscular injections of Quinidine gluconate are typically followed by moderate to severe local pain. Some patients will develop tender nodules at the site of injection that persist for several weeks.

Vomiting and diarrhea can occur as isolated reactions to therapeutic levels of Quinidine, but they may also be the first signs of cinchonism, a syndrome that may also include tinnitus, reversible high–frequency hearing loss, deafness, vertigo, blurred vision, diplopia, photophobia, headache, confusion, and delirium. Cinchonism is most often a sign of chronic Quinidine toxicity, but it may appear in sensitive patients after a single moderate dose.

A few cases of hepatotoxicity, including granulomatous hepatitis, have been reported in patients receiving Quinidine. All of these have appeared during the first few weeks of therapy, and most (not all) have remitted once Quinidine was withdrawn.

Autoimmune and inflammatory syndromes associated with Quinidine therapy have included fever, urticaria, flushing, exfoliative rash, bronchospasm, pneumonitis, psoriasiform rash, pruritus and lymphadenopathy, hemolytic anemia, vasculitis, thrombocytopenic purpura, uveitis, angioedema, agranulocytosis, the sicca syndrome, arthralgia, myalgia, elevation in serum levels of skeletal–muscle enzymes, and a disorder resembling systemic lupus erythematosus.

Convulsions, apprehension, and ataxia have been reported, but it was not clear that these were not simply the results of hypotension and consequent cerebral hypoperfusion. There are many reports of syncope. Acute psychotic reactions have been reported to follow the first dose of Quinidine, but these reactions appear to be extremely rare.

Other adverse reactions occasionally reported include depression, mydriasis, disturbed color perception, night blindness, scotomata, optic neuritis, visual field loss, photo–sensitivity, and abnormalities of pigmentation.

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Side Effects by Body System - for Healthcare Professionals

General

Cinchonism may be classified as mild, moderate, or severe depending on symptoms. Mild cinchonism includes symptoms of blurred vision, transient deafness, anorexia, nausea, weakness, vertigo, tinnitus, diarrhea, and headache. Mild cinchonism does not always occur with higher dosages, nor does it preclude further quinidine therapy. Moderate cinchonism includes vomiting, hypotension, a 25% to 50% increase in QRS duration, and rare premature ventricular contractions. Severe cinchonism is characterized by myocardial toxicity such as malignant arrhythmias, QRS duration greater than 50%, high degree AV heart block, or cardiac arrest.

Quinidine side effects have varied from vague neurological and gastrointestinal complaints to myocardial toxicity. The most frequently reported symptoms have been diarrhea, nausea, and vomiting. The risk of toxicity is greater when plasma quinidine concentrations exceed 4 mg/L.

Dose-related cinchonism may be the first sign of quinidine toxicity. Cinchonism refers to a syndrome caused by any of the cinchona alkaloids, including quinidine. It most often is a sign of chronic toxicity, but may occur after a single moderate dose in sensitive patients.

Cardiovascular

Cardiovascular side effects have included hypotension, syncope, increased QRS duration (500 to 600 msec), and myocardial toxicity. Tachyarrhythmia has occurred in approximately 2% of patients. Quinidine-induced long QT syndrome has resulted in rare cases of torsades de pointes.

Myocardial toxicity may present as malignant arrhythmias, increased QRS duration of greater than 50%, high degree AV heart block, or cardiac arrest. Quinidine may significantly decrease stroke volume and cardiac output.

Routine use following myocardial infarction is not recommended in view of the Cardiac Arrhythmia Suppression Trial (CAST) data.

The use of quinidine to prevent atrial fibrillation in patients with chronic atrial fibrillation is somewhat controversial. A large, randomized, controlled study comparing quinidine to placebo has shown no difference in efficacy and no demonstrable reduction in overall mortality in treated patients. The crude mortality rate was greater in patients treated with quinidine relative to patients treated with placebo.

Gastrointestinal

A 76-year-old man developed progressive dysphagia to solids during quinidine therapy. Upper endoscopy revealed a proximal narrowing, but no findings of cancer or infection. Quinidine pill esophagitis was suspected and the drug was discontinued. The lesion resolved one month later and did not recur.

Gastrointestinal side effects have been the most frequently reported adverse effects. Anorexia, nausea, vomiting, and diarrhea occurred in up to 30% of patients. Quinidine pill esophagitis has been reported. Nausea, vomiting, and diarrhea may be part of the cinchonism syndrome resulting from dose-related quinidine toxicity.

Nervous system

Nervous system side effects have included dizziness, headache, tremor, nervousness and coordination difficulties. Such symptoms may be part of the cinchonism syndrome and signs of quinidine toxicity. The anticholinergic activity of quinidine may exacerbate myasthenia gravis. Convulsions have been reported, but the association with quinidine has not been clearly defined.

Hepatic

An 85-year-old man with atrial flutter developed drowsiness, emesis, and icterus associated with elevated liver function tests and marked centrilobular cholestasis with mild bile duct inflammation per liver biopsy within ten days after beginning quinidine therapy. There was no evidence of biliary obstruction per ultrasound. The signs and symptoms of hepatitis resolved after discontinuation of quinidine.

A 58-year-old man with paroxysmal atrial fibrillation developed fever, lethargy, nausea, and abdominal pain associated with elevated liver function tests and no serological evidence of a viral etiology within ten days after beginning quinidine therapy. No liver biopsy was performed. The signs and symptoms of hepatitis began to resolve within three days after discontinuation of quinidine.

Rare cases of reversible granulomatous hepatitis, presenting as fever, urticarial rash, elevated liver function tests, and mild thrombocytopenia have been associated with quinidine. In a long-term study of 15 patients with a history of quinidine-associated hepatitis, no persistent liver function abnormalities were observed.

Hepatic toxicity associated with quinidine is believed primarily due to hypersensitivity to quinidine. Hypersensitivity-induced hepatitis has occurred in approximately 2% of patients, usually within the first two weeks of therapy. Jaundice occurred rarely. Resolution was complete in most cases within 4 to 8 weeks following discontinuation. Not all cases have resolved. Granulomatous hepatitis has been reported.

Ocular

A 66-year-old man with coronary artery disease developed photophobia and blurred vision while taking quinidine, metoprolol, furosemide, isosorbide, and digoxin. Slit-lamp examination revealed superficial granular deposits within the corneal epithelium; the epithelial surface was smooth and did not contain fluorescein upon staining. The corneal deposits disappeared within two months after discontinuing quinidine.

Ocular side effects have included mydriasis, color perception changes, night blindness, scotomata, optic neuritis, and visual field loss. Blurred vision, diplopia, and photophobia may be part of the dose-related cinchonism syndrome. Quinidine keratopathy, an extremely rare ocular side effect, has been reported.

Hematologic

Hematologic abnormalities including leukopenia, thrombocytopenia, and rare cases of leukocytosis have occurred.

Cases of an IgG antibody requiring the presence of quinidine, with activity against leukocytes and platelets have been reported. In some cases, significant infection or hemorrhage resulted.

A 60-year-old man developed malaise, weakness, chills, and oral ulcerations within three days of beginning quinidine and digoxin for atrial fibrillation. Laboratory examination revealed a profoundly low leukocyte count and bone marrow aspiration revealed a hypocellular myeloid line. The neutrophil count returned to baseline within three days after discontinuation of quinidine and continuation of digoxin. The authors found eight other such cases in a review of medical literature.

Hypersensitivity

A 52-year-old man developed malaise, an extensive maculopapular rash, palpable purpura, mental status changes, rigors, nausea, and night sweats during therapy with quinidine and digoxin. Laboratory findings included proteinuria, elevated liver function tests, eosinophilia, an elevated antinuclear antibody titer, and renal biopsy findings consistent with allergic granulomatous angiitis. The syndrome worsened following quinidine discontinuation, but resolved gradually with steroid therapy. Because allergic reactions to digoxin are rare, the authors implicated quinidine. Rechallenge was not performed.

A 54-year-old man with a history of atrial fibrillation, treated with digoxin and quinidine sulfate, developed fever and malaise associated with nodular infiltrates on chest X-ray. His condition worsened despite treatment with an oral cephalosporin. A diagnostic evaluation ruled out heart failure; tests for typical and atypical infections were negative. Pulmonary function testing revealed mild restriction. Two days after stopping quinidine the signs and symptoms of pneumonitis resolved. Bronchoalveolar lavage and transbronchial biopsy revealed changes consistent with allergic pneumonitis. Rechallenge with quinidine resulted in recurrent signs and symptoms of allergic pneumonitis.

Hypersensitivity-induced hepatitis has occurred in approximately 2% of patients, usually within the first two weeks of therapy. Hypersensitivity reactions including of uveitis, allergic vasculitis, lymphadenopathy, hemolytic anemia, thrombocytopenia, agranulocytosis, bronchospasm, pneumonitis and photosensitive dermatitis psoriaform rash, angioedema, sicca syndrome, arthralgia, myalgia, and elevated levels of skeletal muscle enzymes have been reported.

Dermatologic

Dermatologic side effects including photosensitive rashes, psoriasis, abnormal pigmentation, and actinic dermatitis have been reported. Quinidine has been identified as a possible cause of lichen planus in susceptible patients.

A 57-year-old man with premature ventricular depolarizations developed a papular rash on his back and chest. Resolution was complete within four weeks of discontinuation of therapy. The patient was on no other oral medications.

An 83-year-old man developed a bluish-grey discoloration involving his skin, oral mucosa, and nailbeds which resolved over four months following discontinuation of quinidine. Other medications were continued.

A 64-year-old man with a history of convalescent psoriasis vulgaris experienced an exacerbation of psoriasis within 72 hours after initiating quinidine therapy. The psoriasis was refractory to aggressive PUVA therapy and resolved only when quinidine was discontinued.

Immunologic

Immunologic side effects including systemic lupus erythematosus have been rarely associated with quinidine therapy. Rare cases of quinidine-induced polyarthropathy without development of antinuclear antibodies have been reported.

Approximately 30 cases of quinidine-induced systemic lupus erythematosus have been reported. The majority of patients were Caucasian and elderly, without gender difference. The most frequent complaint was polyarthralgias (87%).

Renal

Renal side effects have been limited to rare reports of quinidine-induced nephrotic syndromes.

A 64-year-old woman developed edema, proteinuria (3 grams per 24 hours), hypercholesterolemia, elevated complement levels, and elevated antinuclear antibody titers within three months after beginning digoxin and quinidine. Signs of the nephrotic syndrome resolved within seven days after discontinuation of quinidine, but continuation of digoxin. Rechallenge with quinidine resulted in fatigue, myalgias, arthralgias, anorexia, and weakness. The author believed this case represented quinidine-induced nephrotic syndrome or a quinidine-induced lupus erythematosus-like illness complicated by renal disease.

A 63-year-old man receiving allopurinol for gout developed progressive uremia, proteinuria, edema, and purpura after beginning quinidine therapy. The patient required hemodialysis secondary to biopsy-proven, rapidly progressive glomerulonephritis. A macrophage migration-inhibition test was negative in the presence of both quinidine and allopurinol. Such tests may be falsely negative in the presence of uremia. The authors believed quinidine caused Henoch-Schonlein purpura in this patient based on a chronologic association and lack of allopurinol-associated problems following chronic therapy.

Psychiatric

A 73-year-old man with supraventricular tachycardia developed visual hallucinations, delusions, and psychomotor agitation within 90 minutes of the initial dose of quinidine. A serum quinidine level at the time was 0.8 mg/L (therapeutic 3 to 6 mg/L). The patient's mental status returned to baseline after discontinuation of quinidine.

A 67-year-old man with a supraventricular arrhythmia and hypertension developed psychosis and psychomotor hyperactivity within two hours after starting quinidine. A serum quinidine level at the time was 1 mg/L (therapeutic 3 to 6 mg/L). The patient's mental status returned to baseline after discontinuation of quinidine.

Psychiatric side effects of depression have been associated with quinidine. Rare cases of acute psychosis and psychomotor agitation have been reported with subtherapeutic quinidine levels in elderly patients.

Musculoskeletal

A 68-year-old woman with paroxysmal atrial fibrillation developed progressive proximal limb muscle weakness within two weeks after starting quinidine. Symptoms resolved upon discontinuation of therapy. Rechallenge was associated with recurrent weakness and a diffuse, pruritic rash. A diagnostic evaluation failed to reveal evidence of myasthenia gravis.

Musculoskeletal effects including a case of profound musculoskeletal weakness has been reported.

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