Quinidine information from DrugsUpdate  

Pharmacodynamics

Pharmacokinetics

Quinidine is a class Ia antiarrhythmic. Its actions include depression of phase 0 action potential, decrease of myocardial excitability, conduction, velocity, sodium influx during depolarisation and potassium efflux in repolarisation. Quinidine prevents calcium from diffusing across cell membrane. It reduces rate of depolarisation phase of cardiac action potential, slows depolarisation and prolongs refractory period. Exerts vagal blockade, controls atrial fibrillation, ventricular and supraventricular tachycardias.

Absorption
Rapidly absorbed from the GI tract.

Distribution
Crosses the placenta and enters breast milk. Protein-binding: 80-90%.

Metabolism
Hepatic: mainly by cytochrome CYP450 isoenzymes.

Excretion
Plasma half-life: 6-8 hours.

Quinidine Indications / Quinidine Uses

Information Not Available

Quinidine Adverse Reactions / Quinidine Side Effects

Muscle weakness, nausea, vomiting, diarrhoea; cinchonism symptoms including impaired hearing, headache, blurred vision, dizziness and vomiting; urticaria and skin reactions.

Potentially Fatal: Asystole, syncope, ventricular fibrillation. Thrombocytopenia, exfoliative dermatitis, granulomatous hepatitis (hypersensitivity); CHF; heart block, ventricular arrhythmias, tachycardia, seizure, coma.

Precautions

Heart block
In patients without implanted pacemakers who are at high risk of complete atrioventricular block (eg, those with digitalis intoxication, second–degree atrioventricular block, or severe intraventricular conduction defects), Quinidine should be used only with caution.

Overdosage
May result in ventricular arrhythmias and hypotension. Other symptoms include nausea, vomiting, tinnitus, blurred vision, confusion and delirium.

Special Precautions

Test dose is recommended. Atrial flutter; widening QRS complex; incomplete AV block; uncompensated heart failure, myasthenia gravis, acute infections, fever, digitalised patients; hypokalaemia; acute MI; obstructive GI tract changes; renal or hepatic impairment; elderly. Prolonged QT interval, history of torsade de pointes, myocarditis, severe myocardial damage. Rapid infusion may result in hypotension and vascular collapse. Pregnancy and lactation.

Other Drug Interactions

May enhance effects of antihypertensives, vasodilators, myocardiac depressants, oral anticoagulants and non-depolarizing muscle relaxants. Reduced clearance when used with drugs that alkalinise the urine eg. thiazides. Increased plasma levels when used with cimetidine or amiodarone. Increased metabolism when used with enzyme inducers eg. phenobarbital, phenytoin and rifampicin. Decreased metabolism when used with verapamil. Increased serum levels of procainamide and haloperidol.

Potentially Fatal: Increases plasma digitalis concentration.

Other Interactions

Information Not Available

Dosage

Oral
Atrial and ventricular premature contractions
Adult: As sulfate: 200-300 mg 3-4 times daily.
CrCl (ml/min)    Dosage Recommendation
<10                  Use 75% of normal dose.
Hepatic impairment: Dose reduction may be needed.

Oral
Uncomplicated falciparum malaria
Adult: As sulfate: 300-600 mg or 10 mg/kg every 8 hr for 5-7 days.
Child: As sulfate: 300-600 mg or 10 mg/kg every 8 hr for 5-7 days.
CrCl (ml/min)    Dosage Recommendation
<10                  Use 75% of normal dose.
Hepatic impairment: Dose reduction may be needed.

Oral
Paroxysmal supraventricular tachycardia
Adult: 400-600 mg every 2-3 hr until paroxysm is terminated.
CrCl (ml/min)    Dosage Recommendation
<10                  Use 75% of normal dose.
Hepatic impairment: Dose reduction may be needed.

Oral
Conversion of atrial fibrillation
Adult: 200 mg every 2-3 hr for 5-8 doses. Subsequent doses may be increased on a daily basis until normal sinus rhythm is achieved or toxicity occurs. Max: 3-4 g/day. Maintenance: 200-300 mg 3-4 times daily.
CrCl (ml/min)    Dosage Recommendation
<10                  Use 75% of normal dose.
Hepatic impairment: Dose reduction may be needed.

Intravenous
Cardiac arrhythmias
Adult: As gluconate: IV admin: 800 mg diluted in 40 ml of 5% dextrose inj and infused at a rate of 0.25 mg/kg/min. Monitor ECG and BP continuously during infusion. To discontinue treatment if conversion to sinus rhythm has not occurred after reaching the max dose. Max dose: total IV dosage: 10 mg/kg.
CrCl (ml/min)    Dosage Recommendation
<10                  Use 75% of normal dose.
Hepatic impairment: Dose reduction may be needed.

Intravenous
Malaria
Adult: Loading dose: Infuse 15 mg/kg (diluted in 250 mL normal saline) over 4 hr. Maintenance: To start 24 hr after the start of loading dose, infuse 7.5 mg/kg over 4 hr, every 8 hr for 7 days or until oral therapy can be used. Alternatively, infuse 10 mg/kg (diluted in 250 mL normal saline) over 1-2 hr. Maintenance: Infuse 0.02 mg/kg/min for up to 72 hr or until parasitemia is reduced to <1% or oral therapy can be used.
Child: Can be given via continuous infusion or intermittent inj. Continuous infusion: initial loading dose of 6.25 mg/kg of quinidine base, diluted in 5 ml/kg of normal saline, given by IV infusion over 1–2 hr, followed by a continuous maintenance infusion of 12.5 mcg/kg of base per min, given for at least 24 hr and until parasitemia is reduced to <1% and oral quinine sulfate can be substituted. Intermittent inj: initial loading dose of 15 mg/kg of quinidine base, diluted in 250 ml of normal saline and infused over 4 hr, followed 4 hr later by maintenance doses of 7.5 mg/kg of base, given by IV infusion over 4 hr at 8-hr intervals until 3 maintenance doses have been admin and parasitemia is reduced to <1% and oral quinine sulfate can be substituted.
CrCl (ml/min)    Dosage Recommendation
<10                  Use 75% of normal dose.
Hepatic impairment: Dose reduction may be needed.

Food(before/after)

Should be taken with food. (Best taken at meal times.)

Quinidine and Pregnancy

Caution when used during pregnancy.

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Quinidine and Lactation

Caution when used during lactation

Quinidine and Children

Safety and efficacy not established

Quinidine and Geriatic

Safety and efficacy of Quinidine in elderly patients has not been systematically studied. Clinical studies of Quinidine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. The reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy.

Quinidine and Other Contraindications

Hypersensitivity, complete heart block, history of thrombocytopenia during treatment with quinine or quinidine, digitalis intoxication.

Storage

Intravenous
Store at 20-25°C.

Oral
Store at 20-25°C.

Lab interference

Intravenous
Store at 20-25°C.

Oral
Store at 20-25°C.