Quinine is an antimalarial medicine used to treat uncomplicated Plasmodium falciparum malaria, usually in combination. At low doses it is used for nocturnal leg cramps, a use that has been restricted because of its risks.
Also known as: Sulfato de quinina, Quinino
High risk of QT prolongation and torsades de pointes.
Quinine prolongs the QT interval and inhibits CYP3A4, the main pathway of amiodarone metabolism, potentially raising its levels; the QT effect is additive and the torsades de pointes risk increases markedly. In patients on chronic amiodarone, prefer another antimalarial (atovaquone+proguanil, doxycycline). If the combination is unavoidable, monitor the ECG and electrolytes and reduce the amiodarone dose if needed.
Quinine + amiodarone: additive QT prolongation and CYP3A4 inhibition by quinine (amiodarone levels ↑). Avoid the combination.
Additive effect on cardiac potassium channel blockade.
ECG (QTc) and electrolytes.
Syncope, seizures, palpitations.
Avoid the association; if unavoidable, strict cardiac monitoring.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0 ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Clarithromycin inhibits Quinine metabolism and prolongs QT — risk of toxicity and arrhythmias.
Quinine is metabolised by CYP3A4 and prolongs the QT interval; clarithromycin inhibits CYP3A4, potentially raising quinine concentrations (with risk of cinchonism and cardiac toxicity), and also prolongs the QT — the torsades de pointes risk is additive. During quinine malaria treatment, prefer a non-interacting antibiotic; if the combination is unavoidable, monitor the ECG, quinine levels and toxicity signs.
Quinine + clarithromycin: clarithromycin raises quinine levels (CYP3A4 inhibition) and both prolong the QT. Avoid the combination.
CYP3A4 inhibition (raises Quinine) + additive QT prolongation.
ECG, signs of cinchonism and arrhythmia.
Tinnitus, visual changes, palpitations.
Avoid; if needed, reduce Quinine and monitor.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Risk of additive QT prolongation; not combined in clinical practice.
Piperaquine (the dihydroartemisinin-piperaquine component, Eurartesim) prolongs the QT interval in a dose-dependent way and the EMA EPAR contraindicates co-administration with other QT-prolonging drugs, including quinine, chloroquine and amodiaquine; the quinine label, in turn, documents consistent, dose-dependent QT prolongation with potentially fatal ventricular arrhythmias (torsade de pointes, ventricular fibrillation), recommending avoiding other QT-prolonging drugs. The combination is not used in antimalarial practice (quinine is an alternative to the artemisinin derivatives), but overlap can occur in patients with therapeutic failure or severe malaria, especially with hypokalaemia, hypomagnesaemia, bradycardia or cardiac disease. Avoid; if unavoidable, monitor the ECG and electrolytes before and during therapy and correct hypokalaemia/hypomagnesaemia.
Quinine + dihydroartemisinin-piperaquine: additive QT (piperaquine prolongs the QT). Avoid the combination; ECG if unavoidable.
Additive effect on cardiac repolarisation.
ECG (QTc) and signs of toxicity.
Palpitations, tinnitus, syncope.
Avoid; choose a single regimen.
EMA — EPAR Eurartesim (dihydroartemisinin + piperaquine): https://www.ema.europa.eu/en/medicines/human/EPAR/eurartesim ; DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0
Fluconazole plus Quinine carries a risk of QT prolongation and ventricular arrhythmias.
Quinine prolongs the QT interval consistently and in a dose-dependent way, with a risk of potentially fatal ventricular arrhythmias (torsade de pointes, ventricular fibrillation), and the label contraindicates its use in patients with QT prolongation and recommends avoiding other QT-prolonging drugs. Quinine is predominantly metabolised by CYP3A4, and inhibitors of this enzyme raise its concentrations — the label documents ketoconazole increasing quinine AUC by 45% and links CYP3A4 inhibition to a fatal torsade de pointes case (erythromycin+quinine). Fluconazole combines both risks: it prolongs the QT (torsade de pointes in post-marketing experience) and inhibits CYP3A4, potentiating quinine toxicity (cinchonism, cardiotoxicity, hypoglycaemia). Whenever possible, avoid the combination; if unavoidable, monitor the ECG, electrolytes (correct hypokalaemia/hypomagnesaemia) and signs of quinine toxicity.
Fluconazole + quinine: additive QT and increased quinine levels (CYP3A4 inhibition). Avoid; if unavoidable, ECG and monitoring.
Additive effect on cardiac repolarization; fluconazole may also raise quinine levels.
ECG (QT interval), electrolytes (K+, Mg2+), signs of arrhythmia.
Syncope, palpitations, torsades de pointes.
Use with caution; monitor ECG (QT) and electrolytes; prefer an alternative antimalarial regimen when possible.
DailyMed/FDA (NIH/NLM) — approved Fluconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7961c029-746c-48c3-888b-8f8344102873 ; approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0
Voriconazole plus Quinine carries a risk of QT prolongation and arrhythmias.
Voriconazole is an azole antifungal associated with QT prolongation (the label states that "some azoles, including voriconazole, have been associated with prolongation of the QT interval on the ECG" and recommends correcting potassium, magnesium and calcium before use) and is a CYP3A4 inhibitor; quinine is predominantly metabolised by CYP3A4 and its label warns that "CYP3A4 inhibitors alter plasma quinine concentration — monitor for lack of efficacy or increased adverse events of quinine" (the class is documented: ketoconazole increased quinine AUC by 45%). The combination adds up the two risks: additive QT (potentially fatal ventricular arrhythmias) and increased quinine levels (cinchonism, cardiotoxicity, hypoglycaemia). Avoid whenever possible; if unavoidable, monitor the ECG, electrolytes and signs of quinine toxicity.
Quinine + voriconazole: additive QT and increased quinine levels (CYP3A4 inhibition). Avoid; if unavoidable, ECG and monitoring.
Additive effect on cardiac repolarization.
ECG (QT interval), electrolytes (K+, Mg2+).
Syncope, palpitations, torsades de pointes.
Use with caution; monitor ECG (QT) and electrolytes.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0
Additive QT prolongation — risk of ventricular arrhythmias.
Quinine, used in severe malaria and cramps, prolongs the QT interval and can cause torsade de pointes, especially at high doses or with hypokalaemia; ciprofloxacin adds the fluoroquinolone class effect. The combination adds up the risk of ventricular arrhythmias, particularly in patients with long QT, cardiac disease or taking other QT-prolonging drugs. Whenever possible, avoid the combination or choose an alternative antibiotic; if unavoidable, monitor the ECG and electrolytes.
Ciprofloxacin + quinine: additive risk of QT prolongation. Avoid or monitor the ECG in at-risk patients.
Additive effect on cardiac repolarisation.
ECG (QTc) and electrolytes.
Palpitations, syncope.
Caution; ECG in at-risk patients.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0 ; approved Ciprofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14c3bc33-201d-492e-9aee-a4d84c813a3d
Quinine may increase the effect of Warfarin — bleeding risk.
Quinine inhibits warfarin metabolism (CYP2C9 and CYP3A4) and, through its high plasma protein binding, can displace the active free fraction. The result is a marked INR elevation with bleeding risk — a well-documented interaction, with reports of severe bleeding in patients using quinine (or quinine-containing tonic water in large amounts) with warfarin. The INR should be monitored frequently during treatment and after discontinuation, the warfarin dose reduced if needed, and the patient alerted to bleeding signs.
Quinine inhibits CYP2C9/CYP3A4 and is highly protein-bound, potentially raising the INR markedly. Monitor the INR closely and consider a warfarin dose reduction.
Inhibition of Warfarin metabolism (CYP2C9) and possible protein displacement.
Frequent INR and signs of bleeding.
Bleeding, bruising, dark stools.
Monitor the INR and adjust the dose.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057
Quinine markedly raises Digoxin levels — high risk of digoxin toxicity.
Quinine is a potent P-glycoprotein inhibitor: it reduces renal and intestinal digoxin excretion and can raise its concentrations by 50–100%, with a significant risk of digitalis toxicity. Studies at therapeutic quinine doses show substantial increases in digoxin levels. Monitor digoxin levels when quinine is started (reducing the digoxin dose by about 30–50%), watch the ECG and toxicity symptoms (nausea, arrhythmias, visual disturbances) during and after antimalarial treatment.
Quinine inhibits P-gp and can markedly raise digoxin levels. Monitor digoxin levels and reduce the digoxin dose.
P-glycoprotein inhibition and reduced Digoxin volume of distribution.
Digoxin level, ECG and renal function.
Nausea, vomiting, visual disturbances, bradycardia, arrhythmias.
Monitor digoxin levels and the ECG; reduce the Digoxin dose if needed.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4
Risk of QT prolongation and additive cinchonism-like toxicity (tinnitus, dizziness, visual changes).
Both chloroquine and quinine prolong the QT interval and can cause torsade de pointes and ventricular arrhythmias; the quinine label contraindicates its use in patients with QT prolongation and describes a fatal ventricular arrhythmia case in a patient with prolonged QT, and the chloroquine label warns about the increased risk with concomitant QT-prolonging drugs. The chloroquine+quinine combination should be avoided (they are antimalarial alternatives, not complementary); if unavoidable, monitor the ECG and electrolytes, correct hypokalaemia/hypomagnesaemia and watch for signs of cardiotoxicity.
Chloroquine + quinine: additive risk of QT prolongation. Avoid the combination; monitor the ECG if unavoidable.
Additive effects on cardiac repolarisation and on the nervous system.
ECG, hearing and vision, signs of toxicity.
Tinnitus, hearing loss, severe dizziness, seizures.
Avoid the combination; not used together in current clinical practice.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0
Additive QT prolongation; the association is usually avoided as it adds no benefit and increases arrhythmic risk.
Both drugs are antimalarials that prolong the QT interval: the artemether-lumefantrine label states that "some antimalarials (e.g. quinine, quinidine), including artemether-lumefantrine, have been associated with prolongation of the QT interval on the ECG" and that "QT prolonging drugs, including quinine and quinidine, should be used cautiously following artemether-lumefantrine"; the quinine label documents consistent, dose-dependent QT prolongation with potentially fatal ventricular arrhythmias, and recommends avoiding other QT-prolonging drugs. In practice, these antimalarial combinations are not used together (quinine is an alternative to artemether-lumefantrine for malaria treatment), but they can overlap in patients with therapeutic failure or severe malaria. If the combination is needed, monitor the ECG, electrolytes (correct hypokalaemia/hypomagnesaemia) and signs of arrhythmia.
Quinine + artemether-lumefantrine: additive QT (both antimalarials prolong the QT). Use cautiously and monitor the ECG if combined.
Both prolong cardiac repolarisation via potassium channel blockade.
ECG (QTc), electrolytes and clinical surveillance for arrhythmia.
Palpitations, syncope, dizziness.
Avoid the combination; preferably use a single regimen (ACT or Quinine, not both).
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf ; approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0
Alcohol may potentiate the CNS-depressant effects of quinine and the risk of hypoglycaemia; limit intake.
Limit alcohol intake during treatment.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0
Quinine can be taken with food to reduce gastrointestinal discomfort; absorption is not relevantly affected.
Take with food if nausea or gastric discomfort occurs.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0
Quinine stimulates insulin release and can cause hypoglycaemia, especially in diabetic, malnourished or renally impaired patients.
Monitor blood glucose in at-risk patients; treat hypoglycaemia promptly.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0
Quinine prolongs the QT interval and can cause ventricular arrhythmias; the risk increases in QT prolongation or with QT-prolonging drugs.
Avoid in known QT prolongation; monitor ECG and electrolytes.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0
Quinine is used in pregnancy for chloroquine-resistant P. falciparum malaria; at high doses it has a historical abortifacient effect, so dosing must be strict.
Use at the indicated therapeutic doses, under supervision; monitor blood glucose.
Excreted into breast milk in small amounts; compatible with breastfeeding under supervision.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Alkaloid antimalarial. Oral bioavailability of 76 to 88%; higher exposure in malaria patients than in healthy subjects. Moderately bound to plasma proteins (69 to 92%, increasing to 78 to 95% during malaria, due to an increase in α1-acid glycoprotein). Prolongs the QTc interval (maximum ΔQTcI of 27.7 ms) and the PR and QRS intervals.
It inhibits nucleic acid synthesis, protein synthesis and glycolysis in Plasmodium falciparum and can bind to haemozoin in parasitised erythrocytes; it acts mainly on the blood schizont forms, is not gametocidal and has little effect on pre-erythrocytic forms.
Oral bioavailability of 76 to 88%; Tmax of about 2.8 hours in healthy subjects and 5.9 hours in patients with uncomplicated malaria, with higher Cmax and AUC in malaria. A high-fat meal delays Tmax to about 4 hours without changing Cmax and AUC; the capsules may be taken with or without food.
Metabolised almost exclusively via hepatic oxidative cytochrome P450 pathways, mainly CYP3A4, with four primary metabolites; the main one, 3-hydroxyquinine, is less active than the parent compound. About 20% is excreted unchanged in urine; renal excretion is twice as fast with acidic urine (reabsorption increases with alkaline urine).
Plasma elimination half-life of 9.7 to 12.5 hours in healthy subjects (after 600 mg); prolonged in severe chronic renal failure (26 hours) and in the elderly (18.4 hours); slower clearance in the acute phase of malaria. Multiple-dose activated charcoal shortens the half-life in poisoning.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
