Chloroquine is one of the oldest and most important antimalarial medicines in clinical use. First synthesised in 1934 and introduced into widespread medical practice after World War II, chloroquine remained the drug of first choice for uncomplicated malaria for decades. Despite growing resistance in Plasmodium falciparum chloroquine remains effective against Plasmodium vivax malaria which accounts for a significant proportion of malaria cases in India.

Drug Class: Antimalarial - What That Means

Chloroquine belongs to the 4-aminoquinoline class of antimalarial drugs. Antimalarials are medicines that either kill the malaria parasite (Plasmodium) at various stages of its life cycle or prevent the parasite from establishing infection in the human body. Within the antimalarial drug class, chloroquine is grouped alongside hydroxychloroquine, amodiaquine and primaquine. It also has anti-inflammatory properties, which is why it was historically used for rheumatoid arthritis and lupus, though hydroxychloroquine has largely replaced it for these indications.

Medical Uses: Malaria Prevention and Treatment, Amoeba Infections

Doctors prescribe chloroquine for:

• Treatment of uncomplicated Plasmodium vivax malaria: Chloroquine remains the first-line treatment for P. vivax malaria in India, as recommended by the NVBDCP; always combined with primaquine to eliminate the liver stage (hypnozoites)

• Treatment of uncomplicated Plasmodium malariae malaria: Chloroquine is effective against P. malariae, a less common but chronic form of malaria found in India

• Malaria prophylaxis (prevention): Chloroquine 300 mg base weekly, starting 1 week before travel and continued for 4 weeks after leaving a malaria-endemic area; only recommended for areas where chloroquine-sensitive P. vivax predominates

• Extraintestinal amoebiasis: Chloroquine is used as a second-line treatment for amoebic liver abscess when metronidazole has failed or is contraindicated; it reaches high concentrations in the liver and kills amoebic trophozoites.

How Chloroquine Works Against the Malaria Parasite

The malaria parasite digests haemoglobin (the oxygen-carrying protein in red blood cells) as its primary food source inside red blood cells. This digestion releases haem (a toxic iron-containing compound) which the parasite normally converts into a non-toxic crystalline form called haemozoin (malaria pigment). Chloroquine accumulates in the parasite's digestive vacuole and prevents this conversion. Toxic haem accumulates and kills the parasite. Chloroquine is active against the erythrocytic (blood) stage of the parasite but not against liver stages.

Available Forms and Strengths of Chloroquine

Chloroquine is typically available as oral tablets in strengths of 250 mg or 500 mg, formulated as chloroquine phosphate. Some regions also offer syrup formulations particularly useful for children or patients who have difficulty swallowing tablets. The exact strength and form prescribed usually depends on the condition being treated whether that's malaria prevention, an active malarial infection or certain autoimmune conditions (like lupus or rheumatoid arthritis). 

How to Take Chloroquine Correctly

Chloroquine is generally taken orally, ideally with food or a glass of milk as this helps reduce stomach upset. Tablets should be swallowed whole with water rather than crushed or chewed (unless a doctor specifically advises otherwise for patients who struggle with swallowing). Consistency matters considerably with this medication therefore it should be taken at the same time each day or week, depending on the prescribed schedule. Missing doses or taking it irregularly can reduce its effectiveness particularly when it's being used for malaria prevention rather than active treatment.

Dosage and Duration – How Much Chloroquine to Take

Dosage varies considerably depending on what's being treated. For malaria prevention adults typically take 500 mg once weekly starting one to two weeks before travel and continuing for four weeks after returning. Active malaria treatment usually follows a higher initial dose followed by smaller doses over the next two days. For chronic conditions like lupus, doses tend to be lower but sustained over months or years. Because requirements differ so much by indication, age and weight dosage should always be determined by a doctor rather than estimated independently.

Common and Serious Side Effects

Common side effects are:

• Gastrointestinal side effects: Nausea, vomiting, abdominal discomfort and diarrhoea are the most common side effects; reduced by taking chloroquine with food or milk

• Headache and dizziness: Common at the start of treatment; usually mild and transient

• Skin reactions: Rashes, photosensitivity, and bleaching of hair and skin can occur with prolonged use; patients should use sunscreen in India's sunny climate

Serious side effects are: 

• QT interval prolongation (life-threatening ventricular arrhythmias)

• Retinopathy (permanent eye damage with long-term use)

• Rare blood dyscrasias (agranulocytosis, aplastic anaemia)

• Eeizures at high doses

• Severe hypoglycaemia, particularly in children

Precautions: Who Should Use Chloroquine with Caution?

Certain groups need to be especially careful with chloroquine. They are:

• Patients with pre-existing retinal disease or visual field defects: Long term chloroquine use accelerates retinal damage

• Patients with psoriasis: Chloroquine can precipitate severe and potentially fatal exacerbation of psoriasis

• Patients with epilepsy: Chloroquine can lower the seizure threshold and may trigger seizures

• Patients with G6PD deficiency: Chloroquine can cause haemolysis; G6PD deficiency is common in malaria-endemic regions of India including Odisha, Jharkhand, Chhattisgarh, and tribal areas of Maharashtra

• Patients with known QT prolongation or those taking QT-prolonging drugs: Chloroquine prolongs the QT interval and concurrent use with other QT-prolonging drugs can cause fatal arrhythmias

• Pregnant or breastfeeding women: They should use it only under close medical supervision, weighing the benefits against potential risks case by case.

Drug Interactions 

Key interactions are:

• Antacids containing magnesium or aluminium 

• Ampicillin

• Cimetidine

• Digoxin

• Kaolin

• Mefloquine

• Methotrexate

• QT-prolonging drugs like antipsychotics, fluoroquinolones, erythromycin and azithromycin

• Rifampicin.

Chloroquine Phosphate vs Hydroxychloroquine - How Are They Different?

Main differences are:

• Chemical structure: Hydroxychloroquine (HCQ) is a hydroxylated derivative of chloroquine; a hydroxyl group (-OH) added to the side chain makes HCQ slightly less lipophilic

• Potency and toxicity: Chloroquine is approximately 1.5 to 2 times more potent than hydroxychloroquine as an antimalarial; hydroxychloroquine has a more favourable toxicity profile for the eyes and heart and is preferred for long-term use in rheumatoid arthritis and lupus

• Current medical uses in India: Chloroquine is used primarily for malaria treatment and prophylaxis; hydroxychloroquine is used for rheumatoid arthritis and systemic lupus erythematosus (SLE); both drugs gained widespread public attention during the COVID-19 pandemic though neither has proven clinical efficacy for COVID-19.

FAQs

1. What is chloroquine used for?

   Chloroquine is used primarily to treat and prevent malaria. In India, it is the first-line treatment for Plasmodium vivax malaria (always combined with primaquine) and is used for malaria prophylaxis in areas where chloroquine-sensitive strains predominate. It is also used as a second-line treatment for amoebic liver abscess.

2. Is chloroquine the same as hydroxychloroquine?

   No chloroquine and hydroxychloroquine are closely related but distinct drugs. Hydroxychloroquine has a hydroxyl group (-OH) added to its side chain, making it slightly less potent as an antimalarial but also less toxic to the eyes and heart. In current practice, chloroquine is used mainly for malaria, while hydroxychloroquine is used mainly for rheumatoid arthritis and lupus.

3. Can chloroquine damage the eyes with long-term use?

   Yes chloroquine retinopathy is a serious, potentially irreversible side effect that occurs with prolonged use. Chloroquine accumulates in the pigmented cells of the retina, causing progressive damage to the macula and eventually irreversible central vision loss. All long-term users should have a baseline eye examination before starting and annual eye examinations thereafter.

4. Is chloroquine still effective against malaria?

   Chloroquine is effective against Plasmodium vivax malaria and remains the first-line treatment. However it is no longer effective against Plasmodium falciparum malaria because chloroquine-resistant P. falciparum has become widespread; artemisinin-based combination therapies (ACTs) are now the first-line treatment for P. falciparum.

5. Why is chloroquine resistance a problem in some regions?

   Chloroquine resistance in Plasmodium falciparum is caused by mutations in the pfcrt gene, which allow the parasite to pump chloroquine out of its digestive vacuole before it can act. 

6. Can chloroquine be taken for malaria prevention before travelling?

   Yes chloroquine 300 mg base once weekly is used for malaria prophylaxis before travel to areas where chloroquine-sensitive Plasmodium vivax predominates, starting 1 week before travel and continuing for 4 weeks after leaving. Chloroquine is not appropriate for travel to areas with chloroquine-resistant Plasmodium falciparum; atovaquone-proguanil or doxycycline are recommended for those areas instead.

7. What are the early warning signs of chloroquine toxicity?

   Early retinal toxicity signs are often subtle including difficulty reading fine print, reduced contrast sensitivity and mild visual field defects and are best detected on formal eye testing. Early cardiac toxicity may present as palpitations, dizziness or fainting. Any visual disturbance in a patient on long-term chloroquine should prompt immediate ophthalmological assessment.

8. Is chloroquine safe during pregnancy for malaria?

   Yes chloroquine is considered safe for use during pregnancy and is the treatment of choice for Plasmodium vivax malaria in pregnant women. However, primaquine normally given alongside chloroquine for P. vivax to eliminate the liver stage is contraindicated in pregnancy because it can cause haemolysis in the foetus. Pregnant women with P. vivax malaria are therefore treated with chloroquine alone, with primaquine deferred until after delivery.

9. Can chloroquine affect heart rhythm?

   Yes chloroquine can cause QT interval prolongation, predisposing to a dangerous ventricular arrhythmia called torsades de pointes. This risk is highest at high doses, in patients with pre-existing heart disease and when chloroquine is combined with other QT-prolonging drugs. A baseline ECG is recommended before long-term use. Patients who develop palpitations, dizziness or fainting should seek urgent medical attention.

10. What is the difference between chloroquine phosphate and chloroquine sulphate?

    Chloroquine phosphate and chloroquine sulphate are two salt forms of the same active drug - chloroquine base. Chloroquine phosphate 250 mg contains approximately 150 mg of chloroquine base; chloroquine sulphate 200 mg contains approximately 150 mg of chloroquine base. In India, chloroquine phosphate is the standard formulation; doses should always be specified in terms of chloroquine base to avoid confusion.

References

1. World Health Organization. WHO guidelines for malaria. WHO. 2023. https://www.who.int/publications/i/item/guidelines-for-malaria

2. Wellems TE, Plowe CV. Chloroquine-resistant malaria. J Infect Dis. 2001;184(6):770–6. https://doi.org/10.1086/322858

3. Marmor MF, Kellner U, Lai TY, et al. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016;123(6):1386–94. https://doi.org/10.1016/j.ophtha.2016.01.058

4. National Vector Borne Disease Control Programme. National Drug Policy on Malaria (2013). Ministry of Health and Family Welfare, Government of India. 2013. https://nvbdcp.gov.in/Doc/national-drug-policy-2013.pdf

5. Baird JK. Resistance to chloroquine unhinges vivax malaria therapeutics. Antimicrob Agents Chemother. 2011;55(5):1827–30. https://doi.org/10.1128/AAC.01296-10