Clinical safety rating
cautionPositive evidence of fetus risks but benefits may outweigh risks in some cases
Quinine is a cinchona alkaloid that acts as a blood schizonticide against Plasmodium falciparum. It inhibits heme polymerase, leading to accumulation of toxic heme, and disrupts parasite membrane integrity. It also has mild analgesic and antipyretic properties.
| Metabolism | Primarily metabolized by hepatic CYP3A4 and CYP2C19; also metabolized by CYP2C9. Major metabolites include 3-hydroxyquinine and 2'-quinidinone. |
| Excretion | Renal: ~20% unchanged; Hepatic metabolism (CYP3A4) to inactive metabolites, excreted in urine and feces. Total renal elimination of parent and metabolites ~80%. |
| Half-life | Terminal elimination half-life: 18 hours (range 8–21 h) in healthy adults; prolonged to 26–44 h in severe malaria or hepatic impairment. |
| Protein binding | Approximately 70–90% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 1.5–2.5 L/kg, indicating extensive tissue distribution; concentrates in erythrocytes (5x plasma) and tissues. |
| Bioavailability | Oral: 76–88% (fasting); reduced with food (delayed absorption ~2h). |
| Onset of Action | Oral: 1–3 h for antimalarial effect; IV: within 30–60 min for parasitemia reduction. |
| Duration of Action | Duration of antimalarial effect: ~6–8 h after single oral dose; requires multiple doses for radical cure. Prolonged with severe malaria. |
| Molecular Weight | 324.417 |
Adults: 648 mg (2 capsules) orally every 8 hours for 7 days for uncomplicated chloroquine-resistant malaria, typically used in combination with other antimalarials.
| Renal impairment | No specific dose adjustment for quinine in renal impairment; however, caution is advised in severe renal impairment (GFR <10 mL/min) as quinine clearance may be reduced, and monitoring for toxicity is recommended. |
| Liver impairment | No specific dose adjustment provided for hepatic impairment; however, quinine is extensively metabolized in the liver, and caution is advised in severe hepatic impairment (Child-Pugh class C) with dose reduction or increased monitoring. |
| Pediatric use | Children: 25 mg/kg/day divided into 3 doses (every 8 hours) for 7 days; maximum adult dose per day should not be exceeded. Safety and efficacy not established for children <1 year in malaria treatment. |
| Geriatric use | Elderly: Start at lower end of dosing range due to potential age-related renal and hepatic function decline; monitor for QT prolongation, hypoglycemia, and cinchonism. |
| 1st trimester | Contraindicated due to teratogenicity (risk of congenital malformations, particularly deafness). Avoid use unless no safer alternatives exist for malaria treatment. |
| 2nd trimester | Use only if clearly needed; potential for ototoxicity and hypoglycemia in fetus. Monitor for maternal hypoglycemia. |
| 3rd trimester | Use may increase risk of preterm labor and fetal distress; avoid near term. Risk of neonatal hypoglycemia and thrombocytopenia. |
Clinical note
Historical first-line antimalarial now reserved primarily for severe malaria (IV quinine or artesunate) or T1 uncomplicated malaria when ACTs are not preferred. At high doses or therapeutic doses, quinine can cause cinchonism (tinnitus, headache) and, in overdose, uterine stimulation. Hypoglycemia is a significant maternal risk with IV quinine — monitor blood glucose closely. For severe malaria in pregnancy, IV artesunate is now preferred by WHO over IV quinine.
| Placental transfer | Rapidly crosses placenta; achieves fetal serum concentrations similar to maternal levels. |
| Breastfeeding | Small amounts excreted into breast milk; considered compatible with breastfeeding in usual doses for malaria treatment, but monitor infant for irritability, rash, and hypoglycemia. Avoid in G6PD-deficient infants. |
| Lactation Rating | L2 – Safer (limited data, no increased risk) |
| Teratogenic Risk | Quinine is teratogenic in the first trimester, associated with congenital malformations including deafness, optic nerve hypoplasia, and limb defects. In the second and third trimesters, it may cause hypoglycemia and hemolytic anemia in the fetus. Use is contraindicated in pregnancy except for severe malaria when no alternatives exist. |
| Fetal Monitoring | Monitor maternal blood glucose (risk of hypoglycemia), cardiac status (QT prolongation), and renal function. Fetal monitoring for bradycardia and signs of hemolysis (anemia, jaundice). |
| Fertility Effects | No adverse effects on fertility reported in humans. Animal studies suggest no significant reproductive impact. |
■ FDA Black Box Warning
Quinine may cause serious and life-threatening adverse reactions including cardiac arrhythmias (e.g., QT prolongation, torsades de pointes), severe hypersensitivity reactions, and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. It should not be used for the treatment or prevention of nocturnal leg cramps due to risk of serious adverse events.
| Serious Effects |
History of hypersensitivity to quinine or cinchona alkaloidsG6PD deficiency (risk of hemolytic anemia)Tinnitus or optic neuritis (pre-existing auditory or visual disturbances)Myasthenia gravis (may exacerbate weakness)Prolonged QT interval or concurrent QT-prolonging drugsThrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS) associated with prior quinine use
| Precautions | Monitor for cardiac effects (QT prolongation, especially with electrolyte disturbances or concomitant QT-prolonging drugs). Hematologic effects: thrombocytopenia, hemolytic anemia, agranulocytosis. Hypersensitivity reactions. Use with caution in atrial fibrillation, heart block, and myasthenia gravis. Cinchonism (nausea, tinnitus, headache) occurs at therapeutic doses. Avoid IV administration in patients with previous adverse reactions to quinine or quinidine. |
| Food/Dietary | Grapefruit and grapefruit juice may increase quinine levels (CYP3A4 inhibition). Avoid excessive caffeine as quinine may increase its effects. Take with food to reduce gastrointestinal irritation. |
| Clinical Pearls | Quinine is indicated only for treatment of chloroquine-resistant Plasmodium falciparum malaria, not for leg cramps due to risk of thrombocytopenia. Monitor for hypoglycemia, hypotension, and cardiac arrhythmias (QT prolongation). Administer with significant food to reduce GI upset. |
| Patient Advice | Take with food to minimize nausea. · Complete full course even if symptoms improve. · Report any signs of bleeding, bruising, or rash immediately. · Avoid use for leg cramps due to serious side effects. · Do not drive or operate machinery if dizziness or blurred vision occurs. |
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