Chloroquine is a drug used in several unrelated diseases: malaria, amoebiasis, rheumatoid arthritis, and lupus erythematosus. Chloroquine was synthesized in 1934 and after numerous studies entered clinical practice in 1947. The history of its discovery is connected with the cinchona tree, which grows in the highlands of Latin America. Its bark contains quinine, an antipyretic agent especially useful in treating malaria. In recent years, new possible effects of chloroquine have been investigated. In 2019, several scientific papers were published on the use of chloroquine in oncology. A new surge of interest in chloroquine and hydroxychloroquine (a related drug) occurred in 2020 when new studies implied that the drugs are effective against the coronavirus.

Chloroquine in the treatment of Covid-19

There is no consensus in the scientific community regarding the effectiveness of chloroquine and hydroxychloroquine in the treatment of Covid-19. Major public health agencies such as the WHO and FDA do not recommend their use for this purpose because no proof of effectiveness and possible side effects. In the early months of the pandemic, a study was published showing that a combination of hydroxychloroquine and azithromycin (an antibacterial drug) helped reduce mortality among elderly Covid-19 patients. Although the study was small and not reliable enough to draw strong conclusions, the news was encouraging and interest in chloroquine and hydroxychloroquine skyrocketed. Later, a larger study was conducted, which did not support the previous data. However, serious claims arose against this study too. Patients with severe cardiac pathology, chronic heart failure, significant cardiac arrhythmias, etc., should be aware that the cardiac toxicity of chloroquine is well known and can cause life-threatening side effects. Taking chloroquine and azithromycin for Covid-19 can be potentially dangerous, although further study is needed.

Chloroquine prices for sale

Prices for chloroquine vary greatly and depend on the manufacturer. The brand-name chloroquine (Aralen) has been discontinued in the US but generic equivalents are widely available. Generic chloroquine remains an expensive drug in the US, prices ranging from $1.6 to $8 per tablet. In foreign pharmacies, the drug can cost as low as $0.6.

Indications

• Malaria (prevention and treatment of all chloroquine-sensitive species). So far, malaria has been a huge problem for humanity. This is due to the growing resistance to traditional treatment and the emergence of malaria cases in new areas. Since the middle of the last century, chloroquine has been the drug of choice in the treatment of all forms of malaria, except the resistant forms caused by Plasmodium falciparum.
• Lupus erythematosus (systemic and subacute form). Chloroquine and hydroxychloroquine have been used to treat this condition for over 50 years. Chloroquine (preferably hydroxychloroquine) is indicated for most patients immediately after diagnosis.
• Rheumatoid arthritis
• Scleroderma
• Lichen planus (if other methods are ineffective)
• Photodermatosis
• Extraintestinal amoebiasis, amoebic liver abscess

Mechanism of action

Chloroquine has a variety of mechanisms of action; it is difficult to single out one responsible for reducing symptoms and improving the course of the disease. Chloroquine easily penetrates through cell membranes and can accumulate in the cell in high concentrations. As a result, intracellular pH rises, which leads to important physiological consequences. This explains the anti-inflammatory, analgesic, antimicrobial, and hypoglycemic effects of chloroquine. The photoprotective effect on skin lesions in systemic lupus erythematosus is also known. This effect may be related to the antioxidant effect of the drug. The features of the antirheumatic effect include a delayed clinical result that occurs 4–12 weeks after the start of administration. Patients taking chloroquine are less likely to experience opportunistic infections, including viral and fungal.

Contraindications of Chloroquine

• hypersensitivity to 4-aminoquinoline derivatives and quinine
• liver or kidney failure
• suppression of bone marrow hematopoiesis
• severe heart failure
• neutropenia
• retinopathy
• psoriatic arthritis

Administration with caution

• deficiency of glucose-6-phosphate dehydrogenase
• epilepsy
• myasthenia gravis
• severe diseases of the gastrointestinal tract
• psoriasis (risk of exacerbation)
• severe neurological diseases

Side effects

Over the past decades, many scientific studies have been published on adverse events that have developed against the background of taking chloroquine. Although chloroquine is considered a relatively safe drug, the incidence of side effects is significantly higher than that of hydroxychloroquine.

The most common and mild side effects are gastrointestinal, including nausea, abdominal pain, and diarrhea (7–12%). Skin itching and rashes are also possible (4–12%). Undesirable effects associated with the brain are usually minor and short-lived, manifested by headache (12%) and dizziness. Tinnitus (ringing in the ears), insomnia, and irritability occur rarely.

The most serious complication is retinopathy. According to the study, in patients treated with chloroquine for more than 10 years, retinopathy is observed in 2.5% (0.1% in those taking hydroxychloroquine). For early detection of possible complications, it is recommended not to exceed a dose of 4 mg/kg and undergo a preventive examination by an ophthalmologist at least 1 time in 6 months. One of the most difficult and late-diagnosed side effects is myopathy, a neuromuscular disease characterized by muscle damage. One of the rare but serious adverse events is cardiotoxicity, which is manifested by the development of chronic heart failure.

The use of chloroquine is accompanied by rare and moderate adverse events. Serious side effects causing hospitalization are uncommon. The use of hydroxychloroquine is preferable due to the much lower number of undesirable effects.

Use during pregnancy and lactation

The use of drugs during pregnancy always requires considering their toxic effects on the fetus. Chloroquine can cross the placenta and has the potential to cause birth defects. The doctor must carefully weigh the need for drug use during pregnancy and lactation. Current data support the safety of chloroquine use during pregnancy and breastfeeding, however, data are limited and further research is required.

Drug interactions of Chloroquine

• Antacids disrupt the absorption of chloroquine (the interval between their administration should be at least 4 hours). Cimetidine increases its concentration in the blood plasma.
• Combination with other antimalarials may cause an antagonistic effect.
• Incompatible with gold compounds, penicillamine, phenylbutazone, cytostatics, levamisole (neurotoxicity and the likelihood of skin reactions increase).
• In combination with glucocorticoids increase the risk of developing myopathy and cardiomyopathy; with MAO inhibitors increase the risk of toxicity; with ethanol, hepatotoxicity; with cardiac glycosides, glycoside intoxication.
• Chloroquine reduces the effectiveness of the rabies vaccine.

Dosage and administration:

The tablets are taken orally during or immediately after a meal.

• Malaria prevention: 500 mg 2 times a week, then 500 mg 1 time on the same day of the week.
• Malaria treatment: the first day, 1 g once, after 6–8 hours, 500 mg, on the 2nd and 3rd day, 750 mg at a time.
• Amoebiasis treatment: 500 mg 3 times a day for a week, then 250 mg 3 times a day for the second week, after that,750 mg 2 times a week for 2–6 months.
• Systemic lupus erythematosus: 250–500 mg chloroquine daily. Duration: within a few weeks or months depending on the patient’s response. It is possible to use maintenance therapy at half the daily dose.
• Cutaneous lupus erythematosus, scleroderma, LP: 250 mg chloroquine 2 times a day. Duration: 10 days courses with a break of 5 days; 20 days courses with a break of 10 days. The number of courses depends on the response. Prophylactic use in the spring-summer period is possible.
• Photodermatoses and tardive cutaneous porphyria: 250 mg chloroquine daily for a week, then 500–750 mg weekly.

Overdose

Symptoms: headache, impaired consciousness, vomiting, visual disturbances, rhythm disturbance up to cardiac arrest, convulsions, and collapse.

Treatment: gastric lavage; activated charcoal (at a dose 5 times the expected dose of chloroquine). It is possible to use emetics, peritoneal dialysis, and plasmapheresis. Parenteral administration of diazepam is advisable (to decrease cardiotoxicity of chloroquine).

Chloroquine has proven effective in treating malaria, lupus erythematosus, and rheumatoid arthritis, however, its use in Covid remains questionable. Considering the possible side effects, chloroquine should be taken responsibly and only after consulting a physician.