Antimalarial (4-aminoquinoline)
Chloroquine is an antimalarial medicine, used to treat and prevent malaria in areas where the parasite is still sensitive. It is also used in some rheumatic diseases and lupus. Long-term treatment requires eye monitoring.
Also known as: Cloroquina fosfato
Two QT-prolonging antimalarials combined — higher arrhythmic risk with no therapeutic benefit.
Both chloroquine and mefloquine prolong the QT interval and can cause ventricular arrhythmias; the chloroquine label warns about the increased risk during concomitant administration with QT-prolonging drugs, and the mefloquine label has a dedicated section on QTc prolongation and interactions (advising against, for example, halofantrine and ketoconazole because of the risk of potentially fatal prolongation). The chloroquine+mefloquine combination should be avoided (they are not used together in antimalarial practice); if unavoidable, monitor the ECG and electrolytes and correct hypokalaemia/hypomagnesaemia.
Chloroquine + mefloquine: additive risk of QT prolongation. Avoid the combination; monitor the ECG if unavoidable.
Additive QT prolongation; additive CNS effects.
ECG and neurological surveillance.
Palpitations, seizures, behavioural changes.
Avoid; use a single antimalarial regimen.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd
High risk of QT prolongation and ventricular arrhythmias; the association should be avoided in most patients.
Chloroquine blocks cardiac potassium and sodium channels and prolongs the QT interval; with amiodarone the effect is additive and the risk of ventricular arrhythmias increases, especially with hypokalaemia, bradycardia or heart disease. In patients on chronic amiodarone (e.g. AF), prefer another antimalarial for acute malaria. If the combination is unavoidable, monitor the ECG and electrolytes and correct hypokalaemia/hypomagnesaemia.
Chloroquine + amiodarone: additive QT prolongation with risk of torsades de pointes. Avoid the combination or monitor the ECG.
Additive effect on cardiac repolarisation (both Chloroquine and Amiodarone prolong QT via potassium channel blockade).
ECG (QTc), potassium and magnesium.
Syncope, palpitations, seizures.
Avoid the association; if unavoidable, ECG and electrolytes before and during, with maximum caution.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Additive QT prolongation with risk of ventricular arrhythmias.
Both chloroquine and clarithromycin prolong the QT interval (hERG blockade); the effect is additive and the torsades de pointes risk increases, especially with hypokalaemia, bradycardia, renal impairment or heart disease. In patients receiving chloroquine (malaria, lupus), prefer an antibiotic without QT effects; if the combination is unavoidable, monitor the ECG and electrolytes and correct hypokalaemia/hypomagnesaemia.
Chloroquine + clarithromycin: additive QT prolongation with risk of torsades de pointes. Avoid the combination or monitor the ECG.
Both block cardiac potassium channels; additive effect on repolarisation.
ECG (QTc) and electrolytes.
Palpitations, syncope, dizziness.
Use with caution; monitor the ECG; consider an alternative antibiotic.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Antacids reduce Chloroquine absorption, which may lower its efficacy.
Antacids containing kaolin, magnesium or aluminium adsorb chloroquine in the gastrointestinal lumen and reduce its absorption, potentially lowering plasma concentrations and compromising antimalarial treatment or prophylaxis. The chloroquine label recommends separating administration by at least 4 hours when an antacid is needed. This precaution is especially relevant in patients on malaria prophylaxis or treatment of autoimmune diseases (lupus, rheumatoid arthritis), where adherence and efficacy are critical.
Antacids + chloroquine: antacids (kaolin, magnesium, aluminium) reduce chloroquine absorption. Separate administration by at least 4 hours.
Chelation and changes in gastric pH reduce Chloroquine solubility and absorption.
Clinical response; reassess if therapeutic failure.
Lack of response to treatment.
Separate doses by 2–4 hours (antacids after Chloroquine).
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Antacids label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c72f0736-ee20-45b4-baf0-b80f1e3fa9cb
Fluconazole plus Chloroquine carries a risk of QT prolongation.
Chloroquine prolongs the QT interval (torsade de pointes and ventricular arrhythmias reported, with a higher risk at high doses and with concomitant QT-prolonging drugs — the chloroquine label explicitly warns about this risk), and fluconazole can also prolong the QT (the label contraindicates fluconazole with QT-prolonging CYP3A4-metabolised drugs). The combination adds up the risk of ventricular arrhythmias, especially in patients with long QT, hypokalaemia, hypomagnesaemia, bradycardia or cardiac disease. Whenever possible, avoid or choose an alternative antifungal; if unavoidable, monitor the ECG and electrolytes and correct hypokalaemia/hypomagnesaemia.
Chloroquine + fluconazole: additive risk of QT prolongation. Avoid or monitor the ECG in at-risk patients.
Additive effect on cardiac repolarization (both prolong the QT).
ECG (QT interval), electrolytes (K+, Mg2+).
Syncope, palpitations.
Use with caution; monitor ECG (QT) and electrolytes.
DailyMed/FDA (NIH/NLM) — approved Fluconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7961c029-746c-48c3-888b-8f8344102873 ; approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570
Combining Moxifloxacin with Chloroquine may prolong the QT interval and increase the risk of ventricular arrhythmias (torsades de pointes).
Chloroquine prolongs the QT interval (torsade de pointes and ventricular arrhythmias reported, with a higher risk with concomitant QT-prolonging drugs — chloroquine label), and moxifloxacin also prolongs the QT, with cases of torsade de pointes; the moxifloxacin label recommends avoiding use in patients with known prolongation, proarrhythmic conditions (clinically significant bradycardia, acute myocardial ischaemia), hypokalaemia, hypomagnesaemia and with drugs that prolong the QT. The combination should be avoided whenever possible; if unavoidable, monitor the ECG and electrolytes and use the shortest antibiotic course possible.
Chloroquine + moxifloxacin: additive risk of QT prolongation. Avoid or monitor the ECG in at-risk patients.
Moxifloxacin prolongs the QT interval and Chloroquine also affects cardiac repolarization; the additive effect increases the risk of serious ventricular arrhythmias.
Monitor the ECG (QT), potassium/magnesium and cardiac symptoms; caution in patients with long QT or heart disease.
Palpitations, syncope or a very prolonged QT require urgent intervention.
Avoid the combination when possible; monitor the ECG and correct electrolyte disturbances in at-risk patients.
DailyMed/FDA (NIH/NLM) — approved Moxifloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1ed191f5-7df5-488c-bb72-91ac0b618d9a ; approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Additive QT prolongation; low-to-moderate risk, higher in patients with risk factors.
Chloroquine, an antimalarial and immunomodulator, prolongs the QT interval and can cause torsade de pointes; ciprofloxacin belongs to the fluoroquinolone class, also associated with QT prolongation. The combination adds up the risk, especially in patients with long QT, hypokalaemia, 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 and use the shortest treatment duration possible.
Ciprofloxacin + chloroquine: additive risk of QT prolongation. Avoid or monitor the ECG in at-risk patients.
Ciprofloxacin and Chloroquine both slightly prolong QT — additive effect on repolarisation.
ECG if risk factors or symptoms.
Palpitations, syncope.
Caution in at-risk patients (long QT, hypokalaemia, elderly); monitor if symptomatic.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Ciprofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14c3bc33-201d-492e-9aee-a4d84c813a3d
Omeprazole may reduce Chloroquine absorption by raising gastric pH.
Chloroquine is a weak base whose gastrointestinal absorption can be reduced when gastric pH is raised, as happens with proton pump inhibitors. Although the clinical impact is variable, reduced absorption can compromise malaria prophylaxis or treatment or use in autoimmune diseases. Separate administration (for example, omeprazole on an empty stomach and chloroquine at a distant time), ensure adherence and monitor the clinical response; in patients with unexplained therapeutic failure, reassess the combination.
Omeprazole + chloroquine: raised pH can reduce chloroquine absorption. Monitor response and separate administration.
Lower Chloroquine solubility at higher pH.
Response to treatment.
Malaria treatment failure.
Consider an alternative and monitor the clinical response.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1
Chloroquine can enhance the effect of Warfarin, raising the INR and the bleeding risk.
Chloroquine and its analogues can inhibit warfarin metabolism and raise the INR, although the exact mechanism is not fully established (possible CYP2C9 inhibition and an effect on gut flora). Reports exist of INR elevation and bleeding when chloroquine is added to warfarin. The INR should be monitored at the start and end of antimalarial treatment and the warfarin dose adjusted; watch for bleeding signs, especially in prolonged treatment (e.g. systemic lupus erythematosus, rheumatoid arthritis).
Chloroquine can increase the effect of warfarin (metabolism inhibition). Monitor the INR when starting and stopping the antimalarial.
Mechanism not fully established; possible reduction of Warfarin clearance.
INR (more often in the first weeks) and signs of bleeding.
Bleeding, easy bruising, dark stools.
Monitor the INR after starting/stopping Chloroquine and adjust the Warfarin dose.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057
Chloroquine can raise Digoxin levels, with a risk of digoxin toxicity.
Chloroquine inhibits P-glycoprotein and can reduce digoxin elimination, raising its plasma concentrations and the risk of digitalis toxicity. Reports exist of increased digoxin levels with concomitant chloroquine. Monitor digoxin levels and the ECG when chloroquine is started (especially in prolonged treatment, such as lupus or rheumatoid arthritis) and watch for digitalis toxicity signs, adjusting the digoxin dose if needed.
Chloroquine can inhibit P-glycoprotein and raise digoxin levels. Monitor digoxin levels during antimalarial treatment.
Inhibition of renal P-glycoprotein, reducing Digoxin excretion.
Digoxin level, ECG and renal function.
Nausea, vomiting, visual disturbances, bradycardia, arrhythmias.
Monitor digoxin levels and signs of toxicity; reduce the dose if needed.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4
Two drugs of the same family (4-aminoquinolines) — no benefit from combining, with additive risk of ocular, QT and cardiac toxicity.
Chloroquine and hydroxychloroquine are antimalarials of the same class (4-aminoquinolines), both associated with QT prolongation, ventricular arrhythmias and, with prolonged use, cardiomyopathy (the hydroxychloroquine label describes fatal or potentially fatal cardiomyopathy and ventricular arrhythmias; the chloroquine label, QT prolongation, torsade de pointes and a higher risk with other QT-prolonging drugs). The combination adds no benefit and adds cardiac and retinopathy risk. Avoid; if for any reason they are co-administered (not recommended), monitor the ECG, electrolytes and signs of cardiotoxicity.
Chloroquine + hydroxychloroquine: additive QT and cumulative cardiotoxicity. Avoid the combination (same class).
Overlapping mechanisms: potassium channel blockade, tissue accumulation and additive retinal risk.
Not applicable if not combined; with prolonged use of either: ophthalmological screening.
Visual changes, palpitations, myopathy.
Do not combine; choose a single antimalarial drug.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Hydroxychloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=34496b43-05a2-45fb-a769-52b12e099341
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
Taking with food reduces chloroquine-related nausea without significantly affecting absorption.
Take with food or milk to improve GI tolerance.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570
Grapefruit may alter chloroquine metabolism (CYP2C8/CYP3A4), with a variable effect on concentrations.
Limit grapefruit juice during treatment.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570
Chloroquine can cause haemolysis in G6PD-deficient patients, especially at high doses.
Use with caution in G6PD deficiency; monitor for haemolysis signs.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570
Chloroquine accumulates in the retina and can cause irreversible retinopathy, especially with prolonged treatment.
Baseline and periodic ophthalmological monitoring in treatment > 5 years or high cumulative dose.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570
Chloroquine crosses the placenta; it is not teratogenic at antimalarial doses, but data are limited.
May be used for malaria prophylaxis and treatment in pregnancy, under supervision.
Excreted into breast milk; compatible with breastfeeding.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
4-aminoquinoline antimalarial. Rapid and almost complete absorption from the gastrointestinal tract; about 55% of the drug in plasma is bound to non-diffusible constituents. It is deposited in tissues in considerable amounts (200 to 700 times the plasma concentration in liver, spleen, kidney and lung; 10 to 30 times in brain). Prolongs the QTc interval in a dose-dependent manner, with greater risk at high doses.
It acts against the erythrocytic forms of susceptible Plasmodium species by concentrating in the acid vesicles of the parasite and inhibiting heme polymerisation; it can also inhibit certain enzymes by interaction with DNA. It is not active against gametocytes or exoerythrocytic forms (hypnozoites of P. vivax and P. ovale).
Rapid and almost complete gastrointestinal absorption; only a small proportion appears in the faeces. Excretion is slow and increased by urine acidification. Antacids and kaolin reduce absorption — an interval of at least 4 hours is advised; cimetidine inhibits its metabolism, increasing plasma levels.
It undergoes appreciable degradation in the body; the main metabolite is desethylchloroquine (about one quarter of the urinary material, with antimalarial activity); bisdesethylchloroquine, a carboxylic acid derivative, and other products appear in small amounts. Slightly more than half of the urinary products is unchanged chloroquine.
Slow excretion with important tissue deposition; the long half-life reflects the extensive tissue distribution (urinary excretion is increased by urine acidification and reduced by alkalinisation).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
