QUINIDINE SULFATE

QUINIDINE SULFATE (kwin'i-deen sul-fate) Apo-Quinidine , Novoquinidin  QUINIDINE GLUCONATE Quinaglute Duratabs Classifications: antiarrhythmic class ia; Therapeutic: antiarrhythmic class ia Prototype: Procainamide Pregnancy Category: C

Availability

Quinidine sulfate: 200 mg, 300 mg tablets; 300 mg sustained release tablets;

Quinidine gluconate: 324 mg sustained release tablets; 80 mg/mL injection

Action

Class IA antiarrhythmic that depresses myocardial excitability, contractility, automaticity, and conduction velocity, and prolongs effective refractory period. Anticholinergic action blocks vagal stimulation of AV node, thus tending to increase ventricular rate, particularly in larger doses.

Therapeutic Effect

Depresses myocardial excitability, conduction velocity, and irregularity of nerve impulse conduction.

Uses

Premature atrial, AV junctional, and ventricular contraction; paroxysmal atrial tachycardia, chronic ventricular tachycardia (when not associated with complete heart block); maintenance therapy after electrical conversion of atrial fibrillation or flutter; life-threatening malaria.

Contraindications

Hypersensitivity or idiosyncrasy to quinine or quinidine. Thrombocytopenic purpura resulting from prior use of quinidine; intraventricular conduction defects, complete AV block, ectopic impulses and rhythms due to escape mechanisms; thyrotoxicosis; acute rheumatic fever; subacute bacterial endocarditis, extensive myocardial damage, frank CHF, hypotensive states; digitalis intoxication; pregnancy (category C).

Cautious Use

Incomplete heart block; impaired kidney or liver function; bronchial asthma or other respiratory disorders; myasthenia gravis; potassium imbalance.

Route & Dosage

(Dose of Quinidine Base) Ventricular Arrhythmias Sulfate Adult: PO 166 mg q6h until arrhythmia terminates, then 200–300 mg 3–4 times/d Gluconate Adult: PO 202 mg q8–12 h until sinus rhythm restored or toxicity occurs (max: 3–4 g) Atrial Fibrillation or Flutter Sulfate Adult: PO 332 mg q6h until sinus rhythm restored or toxicity occurs (max: 3–4 g) Gluconate Adult: PO 403 mg q8h x 3–4 doses OR 202 mg q8h x 2 d, then 403 mg q12h x 2 d, then 403 mg q8h up to 4 d IV 0.25 mg/kg/min; not more than 5–10 mg/kg until converted Malaria Adult: IV 15 mg/kg loading dose over 4 h, then 7.5 mg/kg q8h for a total of 7 d OR 6.25 mg/kg loading dose, then 12.5 mcg/kg/min for 72 h Renal Impairment Clcr <10 mL/min: give 75% of dose Hemodialysis: 200 mg supplement dose post-dialysis

Administration

Note: Sulfate contains 83% anhydrous quinidine base; polygalacturonate, 80%; and gluconate, 62%. Examine parenteral solution before preparation; use only if clear and colorless.

Oral

• Note: Test dose is used by some physicians to determine idiosyncrasy before establishing full dosage schedule.
• Take with a full glass of water on an empty stomach for optimum absorption (i.e., 1 h before or 2 h after meals). Administer drug with food if GI symptoms occur (nausea, vomiting, diarrhea are most common).
• Reserve sustained release tablets for maintenance and prophylactic therapy.
• Adjust dosage to maintain plasma concentration between 2–5 mcg/mL. Levels of 8 mcg/mL or more are associated with myocardial toxicity.
• Store in tight, light-resistant containers away from excessive heat.

Intramuscular

• Aspirate carefully before injection to avoid inadvertent entry into blood vessel.

Intravenous PREPARE: IV Infusion: Dilute 800 mg (10 mL) in at least 40 mL D5W to yield a maximum concentration of 16 mg/mL.   ADMINISTER: IV Infusion: Give via infusion pump at a rate not to exceed 16 mg (1 mL)/min.   INCOMPATIBILITIES Solution/additive: Amiodarone, atracurium, furosemide. Y-site: Furosemide, heparin in dextrose. Use supine position during drug administration; severe hypotension is most likely to occur in patients receiving drug via IV. Protect IV solutions from light and heat to prevent brownish discoloration and possibly precipitation.

Adverse Effects (≥1%)

CNS: Headache, fever, tremors, apprehension, delirium, syncope with sudden loss of consciousness, seizures. CV: Hypotension, CHF, widened QRS complex, bradycardia, heart block, atrial flutter, ventricular flutter, fibrillation or tachycardia; quinidine syncope, torsades de pointes. Special Senses: Mydriasis, blurred vision, disturbed color perception, reduced visual field, photophobia, diplopia, night blindness, scotomas, optic neuritis, disturbed hearing (tinnitus, auditory acuity). GI: Nausea, vomiting, diarrhea, abdominal pain, hepatic dysfunction. Hematologic: Acute hemolytic anemia (especially in patients with G6PD deficiency), hypoprothrombinemia, leukopenia. Thrombocytopenia, agranulocytosis (both rare). Body as a Whole: Cinchonism (nausea, vomiting, headache, dizziness, fever, tremors, vertigo, tinnitus, visual disturbances), angioedema, acute asthma, respiratory depression, vascular collapse. Skin: Rash, urticaria, cutaneous flushing with intense pruritus, photosensitivity. Metabolic: SLE, hypokalemia.

Interactions

Drug: May increase digoxin levels by 50%; amiodarone may increase quinidine levels, increasing its risk of heart block; other antiarrhythmics, phenothiazines, reserpine add to cardiac depressant effects; anticholinergic agents add to vagolytic effects; cholinergic agents may antagonize cardiac effects; anticonvulsants, barbiturates, rifampin increase the metabolism of quinidine, thus decreasing its efficacy; carbonic anhydrase inhibitors, sodium bicarbonate, chronic antacids decrease renal elimination of quinidine, thus increasing its toxicity; verapamil causes significant hypotension; may increase hypoprothrombinemic effects of warfarin. Diltiazem may increase levels and decrease elimination of quinidine. Food: Grapefruit juice (>1 qt/d) may decrease absorption.

Pharmacokinetics

Absorption: Almost completely from GI tract. Onset: 1–3 h. Peak: 0.5–1 h. Duration: 6–8 h. Distribution: Widely distributed to most body tissues except the brain; crosses placenta; distributed into breast milk. Metabolism: In liver (CYP3A4). Elimination: >95% in urine, <5% in feces. Half-Life: 6–8 h.

Nursing Implications

Assessment & Drug Effects

• Observe cardiac monitor and report immediately the following indications for stopping quinidine: (1) sinus rhythm, (2) widening QRS complex in excess of 25% (i.e., >0.12 sec), (3) changes in QT interval or refractory period, (4) disappearance of P waves, (5) sudden onset of or increase in ectopic ventricular beats (extrasystoles, PVCs), (6) decrease in heart rate to 120 bpm. Also report immediately any worsening of minor side effects.
• Continuous monitoring of ECG and BP is required. Observe patient closely (check sensorium and be alert for any sign of toxicity); determine plasma quinidine concentrations frequently when large doses (more than 2 g/d) are used or when quinidine is given parenterally (i.e., quinidine gluconate).
• Observe patient closely following each parenteral dose. Amount of subsequent dose is gauged by response to preceding dose.
• Monitor vital signs q1–2h or more often as needed during acute treatment. Count apical pulse for a full minute. Report any change in pulse rate, rhythm, or quality or any fall in BP.
• Severe hypotension is most likely to occur in patients receiving high oral doses or parenteral quinidine (i.e., quinidine gluconate).
• Be aware: Reversion to sinus rhythm in long-standing fibrillation or when fibrillation is complicated by CHF involves some risk of embolization from dislodgment of atrial mural emboli.
• Quinidine can cause unpredictable rhythm abnormalities in the digitalized heart. Patients with atrial flutter or fibrillation may be pretreated with digitalis (until ventricular rate is 100 bpm) to increase AV nodal block and thus reduce possibility of paradoxic tachycardia.
• Lab tests: Periodic blood counts, serum electrolyte determinations, and kidney and liver function during long-term therapy.
• Monitor I&O. Diarrhea occurs commonly during early therapy; most patients become tolerant to this side effect. Evaluate serum electrolytes, acid-base, and fluid balance when symptoms become severe; dosage adjustment may be required.

Patient & Family Education

• Report feeling of faintness to physician. "Quinidine syncope" is caused by quinidine-induced changes in ventricular rhythm resulting in decreased cardiac output and syncope.
• Note: Hypersensitivity reactions usually appear 3–20 d after drug is started. Fever occurs commonly and may or may not be accompanied by other symptoms. Inform physician if these S&S occur.
• Eat a balanced diet with no excesses in fruit or fruit juices, milk, or a vegetarian diet. A diet high in alkaline ash foods (vegetables, citrus fruit, milk) may prolong half-life of quinidine by decreasing its excretion and increasing danger of toxicity.
• Do not self-medicate with OTC drugs without advice from physician.
• Do not increase, decrease, skip, or discontinue doses without consulting physician.
• Notify physician immediately of disturbances in vision, ringing in ears, sense of breathlessness, onset of palpitations, and unpleasant sensation in chest. Be sure to note the time of occurrence and duration of chest symptoms.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug