QUINIDINE GLUCONATE
Clinical safety rating: safe
Inhibits CYP2D6 and CYP3A4 increasing levels of many drugs Can cause cinchonism and thrombocytopenia.
Class Ia antiarrhythmic agent; blocks sodium channels (Nav1.5) and potassium channels (IKr, IKs), prolongs action potential duration and effective refractory period; also has anticholinergic and alpha-adrenergic blocking effects.
| Metabolism | Hepatic via CYP3A4 to active metabolites (3-hydroxyquinidine, quinidine-N-oxide); also CYP2C9 and CYP2E1 contribute. |
| Excretion | Renal: 50-70% unchanged; Biliary/fecal: 20-30%; Hepatic metabolism accounts for 10-30%. |
| Half-life | Terminal elimination half-life: 6-8 hours (range 4-12 hours) in healthy adults; prolonged in HF, renal impairment, or elderly. |
| Protein binding | 80-90% bound to albumin and alpha-1 acid glycoprotein; reduced binding in hypoalbuminemia or uremia. |
| Volume of Distribution | Vd: 2.0-3.5 L/kg; extensive tissue distribution (heart, liver, kidneys). |
| Bioavailability | Oral: 70-85% (first-pass metabolism reduces bioavailability); IM: nearly 100%; IV: 100%. |
| Onset of Action | Oral: 1-3 hours (immediate release); IM: 30-90 minutes; IV: 5-15 minutes. |
| Duration of Action | Oral: 6-8 hours (immediate release); sustained-release: 8-12 hours; IV: 4-6 hours. |
324-648 mg orally every 8-12 hours; maximum 3.24 g/day. Also administered IV as quinidine gluconate 200-400 mg (diluted) at a rate ≤1 mL/min.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 10-50 mL/min: administer 75-100% of usual dose; GFR <10 mL/min: administer 50-75% of usual dose with monitoring. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: administer 50-75% of usual dose; Child-Pugh C: avoid use or administer 25-50% of usual dose with close monitoring. |
| Pediatric use | 30-60 mg/kg/day orally in 4-5 divided doses; maximum single dose 15 mg/kg. IV: 5-10 mg/kg over 30 minutes, then 15-40 mcg/kg/min continuous infusion. |
| Geriatric use | Initiate at lower doses (50-75% of adult dose), titrate slowly due to increased risk of toxicity from reduced renal function and altered distribution. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Inhibits CYP2D6 and CYP3A4 increasing levels of many drugs Can cause cinchonism and thrombocytopenia.
| FDA category | Animal |
| Breastfeeding | Quinidine is excreted into breast milk with a milk-to-plasma (M/P) ratio of approximately 0.7–1.0. Estimated infant dose is 1–3% of maternal weight-adjusted dose. Risk of cumulative toxicity in neonates is low but caution is warranted; monitor infant for arrhythmias, cinchonism, or gastrointestinal effects. American Academy of Pediatrics considers compatible with breastfeeding, but use lowest effective dose. |
| Teratogenic Risk |
■ FDA Black Box Warning
May cause potentially fatal arrhythmias such as torsade de pointes; reserve for life-threatening arrhythmias when less toxic agents are ineffective; monitor ECG and serum electrolytes.
| Common Effects | GI upset |
| Serious Effects |
Known hypersensitivity to quinidine; history of drug-induced torsade de pointes; complete AV block without pacemaker; myasthenia gravis; thrombocytopenia; prolonged QT interval; concurrent use with agents that prolong QT (except under special circumstances).
| Precautions | Proarrhythmic effects (worsening arrhythmias or new VT/VF); monitor QT interval; risk of digoxin toxicity (decreases digoxin clearance); thrombocytopenia; cinchonism; hepatotoxicity; hypotension; caution in heart failure, renal impairment, myasthenia gravis. |
Loading safety data…
| Quinidine gluconate is classified as FDA Pregnancy Category C. First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses, but fetal toxicity at high doses. Second and third trimesters: Potential for fetal arrhythmias (quinidine crosses placenta) and oxytocic effects stimulating uterine contractions; use only if benefit outweighs risk. There is no documented association with major malformations, but fetal monitoring is advised. |
| Fetal Monitoring | Maternal: ECG monitoring for QT prolongation, arrhythmias, and cinchonism (tinnitus, blurred vision, dizziness). Serum quinidine levels (therapeutic range 2–6 mcg/mL; avoid >8 mcg/mL). Electrolytes (K+, Mg2+). Fetal: Ultrasound for fetal heart rate and rhythm; nonstress test and biophysical profile as clinically indicated. Neonatal: QT interval assessment and serum glucose. |
| Fertility Effects | Quinidine has no established direct effect on human fertility. Animal studies show no impairment of fertility at therapeutic doses. However, arrhythmia control in patients with underlying cardiac disease may improve pregnancy outcomes indirectly. No evidence of mutagenesis or impairment of spermatogenesis or oogenesis. |