QUININE SULFATE
Clinical safety rating
avoidOther drugs that prolong the QT interval increase risk of torsades de pointes Can cause cinchonism and blackwater fever.
Quinine sulfate is a blood schizonticide effective against the asexual erythrocytic forms of Plasmodium spp. It interferes with the parasite's ability to digest hemoglobin, leading to accumulation of toxic heme and parasite death. Quinine also has mild analgesic and antipyretic effects, and may depress cardiac conduction and contractility.
| Metabolism | Primarily metabolized by hepatic CYP3A4, with minor contributions from CYP2C19, CYP2C9, and CYP2D6. Major metabolites include 3-hydroxyquinine (active) and other hydroxylated derivatives. |
| Excretion | Renal: 20% unchanged; hepatic metabolism (CYP3A4, CYP2C9) accounts for 80% with metabolites (primarily 3-hydroxyquinine) excreted renally and fecally. Biliary excretion is minor (<5%). |
| Half-life | Terminal elimination half-life: 18 hours (range 16-21 hours) in healthy adults; prolonged in renal impairment (up to 25-30 hours) and severe hepatic impairment. |
| Protein binding | 70-95% bound primarily to alpha-1-acid glycoprotein (AAG) and, to a lesser extent, albumin. Binding is concentration-dependent and saturable. |
| Volume of Distribution | 1.5-2.5 L/kg, indicating extensive tissue distribution. Higher in severe malaria due to increased AAG levels (Vd up to 3.5 L/kg). |
| Bioavailability | Oral: 76-88% (mean 80%) with peak plasma concentration at 1-3 hours. Rectal bioavailability is ~40-60% (variable). |
| Onset of Action | Oral: 1-3 hours (antimalarial effect peaks at 6-12 hours after dose). Intravenous: 30 minutes (for severe malaria). Intramuscular: 1-2 hours. |
| Duration of Action | Antimalarial effect: 8-12 hours after single dose; for nocturnal leg cramps: up to 8 hours. Clinical duration varies with dosing interval (typically 8-hourly). |
| Molecular Weight | 324.42 |
324 mg orally every 8 hours for 7 days (for treatment of chloroquine-resistant falciparum malaria, in combination with other antimalarials).
| Dosage form | CAPSULE |
| Renal impairment | No adjustment required for mild to moderate renal impairment (CrCl >10 mL/min). For severe renal impairment (CrCl <10 mL/min), reduce dose by 33% and monitor closely. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Avoid use or use with extreme caution. |
| Pediatric use | 8.3 mg base/kg (10 mg sulfate salt/kg) orally every 8 hours for 7 days (for chloroquine-resistant falciparum malaria). |
| Geriatric use | Start at lower end of dosing range (e.g., 324 mg every 12 hours) due to potential renal and hepatic age-related decline; monitor for QT prolongation and cinchonism. |
| 1st trimester | Avoid. Quinine is associated with congenital malformations (e.g., auditory nerve hypoplasia, limb defects) if used in high doses. Use only for malaria when no alternative. |
| 2nd trimester | Avoid unless essential. Potential for ototoxicity and hypoglycemia in fetus. Use only for chloroquine-resistant malaria. |
| 3rd trimester | Avoid near term. May cause neonatal hypoglycemia, thrombocytopenia, and hemolysis (G6PD deficiency). Use only for severe malaria. |
Clinical note
Other drugs that prolong the QT interval increase risk of torsades de pointes Can cause cinchonism and blackwater fever.
| FDA category | Positive |
| Placental transfer | Quinine readily crosses the placenta, achieving fetal concentrations similar to maternal. Associated with fetal hypoglycemia and ototoxicity. |
| Breastfeeding | Quinine is excreted into breast milk in small amounts (approximately 2-3% of maternal dose). Risk of infant hemolysis if G6PD deficient. Use with caution; avoid in G6PD-deficient infants or mothers. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Quinine sulfate is classified as FDA Pregnancy Category D. First trimester: Associated with congenital malformations (cranial, limb, cardiac) and increased risk of spontaneous abortion. Second and third trimesters: Risk of hypoglycemia, thrombocytopenia, and neonatal hemolytic anemia. Use only for malaria when benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal ECG for QT prolongation, blood glucose (risk of hypoglycemia), platelet count (thrombocytopenia), and visual/auditory toxicity. Fetal monitoring includes ultrasound for growth restriction and assessment for hydrops due to hemolytic anemia. Check neonatal G6PD status if indicated. |
| Fertility Effects | Quinine may impair male fertility via spermatogenic suppression and hormonal alterations. Female fertility is not significantly affected, but caution is advised in pregnancy due to teratogenicity. |
■ FDA Black Box Warning
WARNING: QUININE SULFATE IS NOT APPROVED FOR THE TREATMENT OR PREVENTION OF NOCTURNAL LEG CRAMPS. ITS USE FOR THIS INDICATION MAY CAUSE SERIOUS AND LIFE-THREATENING ADVERSE REACTIONS, INCLUDING CARDIAC ARRHYTHMIAS, THROMBOCYTOPENIA, HEMOLYTIC UREMIC SYNDROME, AND DEATH.
| Common Effects | Cinchonism (tinnitus |
| Serious Effects |
G6PD deficiencyPregnancy (for non-essential use)Myasthenia gravisProlonged QT intervalHistory of quinine-induced thrombocytopeniaHypersensitivity to quinine
| Precautions | Cardiotoxicity: QT prolongation, ventricular arrhythmias, hypotension. Hematologic: Thrombocytopenia, hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. Hypersensitivity: Severe cutaneous reactions, angioedema. Neurologic: Cinchonism (tinnitus, headache, nausea, visual disturbances), neurotoxicity. Metabolic: Hypoglycemia, especially in pregnancy. Pancreatitis. Renal impairment: Dose adjustment required. Hepatic impairment: Caution. Drug interactions: Potent CYP3A4 inhibitors/inducers, antiarrhythmics, anticoagulants, antacids. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase quinine levels and risk of toxicity. Take with or after meals to minimize nausea. |
| Clinical Pearls | Quinine sulfate is used for chloroquine-resistant Plasmodium falciparum malaria, not for leg cramps. Monitor for cinchonism (tinnitus, headache, nausea), hypoglycemia, and prolonged QT interval. Do not use in pregnancy except for malaria due to risk of fetal harm. Avoid concurrent use with CYP3A4 inhibitors or QT-prolonging drugs. |
| Patient Advice | Take with food to reduce gastrointestinal upset. · Complete the full course even if you feel better. · Report ringing in ears, vision changes, confusion, or irregular heartbeat immediately. · Avoid driving or operating machinery if you experience dizziness or blurred vision. · Inform your doctor if you are pregnant or breastfeeding. |
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