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Chloroquine


Chloroquine

Article Author:
Pranshul Goel
Article Editor:
Valerie Gerriets
Updated:
7/10/2020 1:36:39 AM
For CME on this topic:
Chloroquine CME
PubMed Link:
Chloroquine

Indications

Chloroquine is FDA-approved for the treatment and prophylaxis of uncomplicated malaria in countries where chloroquine-sensitive malaria (certain strains of P. falciparum, P. ovale, P. vivax, and P. malariae) is present. These countries include Mexico, areas of Central America to the west of the Panama Canal, the Caribbean, East Asia, as well as some Middle Eastern countries.[1] The FDA also recommends chloroquine for the treatment of extraintestinal amebiasis.[2] Non-FDA approved indications of chloroquine include the treatment of certain autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus.[3] Also, current research suggests that chloroquine may be helpful as an antitumor medication for the treatment of cancer in association with chemotherapy and radiation.[4]

Mechanism of Action

Chloroquine exerts its antimalarial effects by preventing the polymerization of heme into hemozoin (a food source for the malarial parasite). Chloroquine forms a drug-hemozoin complex, and this complex caps the polymerizing chain, thereby preventing additional polymerization. Along with the prevention of polymerization, the free heme accumulates in the food vacuole, exerting its toxic effects on the parasite.[5] Chloroquine also functions as an anti-autoimmune therapy. It exerts its effects by binding to transcriptional factors on T helper 17 cells and preventing differentiation. At the same time, chloroquine also activates the transcription factor Foxp3, driving the formation of regulatory T cells. Regulatory T cells have been shown to treat and prevent autoimmune diseases.[3] Specifically, for the treatment of rheumatoid arthritis, chloroquine prevents the presentation of autoantigens from MHC class II, therefore, preventing activation of CD4+ T cells.[6]

Administration

Chloroquine is currently administered orally when used as a prophylaxis for malaria, as well as for the treatment of chronic autoimmune diseases.[7]  For malaria prophylaxis, 500 mg is typically administered orally two weeks before, during, and up to 8 weeks after exposure to an endemic area, taken as a weekly dose. When used as a treatment for extraintestinal amoebas, chloroquine dosing 21 mg/kg for three weeks.[8] Under severe or emergent cases of malaria, chloroquine can be administered parenterally.[9] Some research has shown that parenteral administration is potentially toxic; therefore, subcutaneous administration has been shown to be a more effective method in circumstances of severe malaria.[10] 

Adverse Effects

Although chloroquine has relatively few side effects when taken as prescribed, higher doses of chloroquine have been shown to have severe adverse effects. The most severe adverse effects associated with high doses of chloroquine include retinal toxicity, long and subtle symptoms of reduced visual acuity, diplopia, and bilateral loss of vision.[11] High doses have also been shown to cause severe psychiatric issues, such as paranoia, hallucinations, and suicidal ideations.[12] 

  • Dermatological reactions include pruritus and photosensitivity.
  • Retinopathy will typically present with the inability to focus between near and far objects. 
  • Neuropathy can include seizures, paranoia, and hallucinations.

When administered intramuscularly, chloroquine has been shown to cause potentially lethal hypotension.[13] 

Contraindications

Chloroquine has been proven safe to use during pregnancy and in children. Chloroquine has few but serious contraindications. There are reports of cases with death in relating to chloroquine administered to patients with porphyria cutaneous tarda.[14] Chloroquine should not be used in patients with retinal or vision changes unless it is to treat acute malaria. Chloroquine is also contraindicated in patients who suffer from a known hydroxychloroquine-sensitivity. 

Monitoring

Ideally, chloroquine should be dosed depending on body weight and height. For use as malarial prophylaxis, the appropriate chloroquine dose is 5 mg/kg of body weight with a maximum of around 500 mg given on a once per week dosing regimen.[15] 

Toxicity

Chloroquine toxicity is rare but has been known to occur when unusually high doses of chloroquine are ingested or after chronic IV administration. Accidental ingestion has also occurred in children.[16] When toxicity is present, the most common symptom is retinal toxicity. Treatment of chloroquine toxicity includes mechanical ventilation and administration of diazepam and epinephrine, although these methods have not been a proven method of treatment in all cases.[17] 

Enhancing Healthcare Team Outcomes

Safely and effectively treating and preventing malaria requires an interprofessional team of healthcare professionals that include a primary care provider, infectious disease specialist, and pharmacist. Similarly, the treatment of autoimmune and inflammatory conditions requires an interprofessional team consisting of primary care providers, healthcare specialists, and pharmacists. Without proper consultation, patients are at risk of exposure to a very preventable disease. The recommended order of steps that should be taken by the team for the prevention and prophylaxis of malaria are as follows:

  1. The patient informs their primary care provider about plans to travel to a country with a prevalence of malaria. Similarly, a primary care provider may also ask the patient during a normal history and physical whether the patient has any intention of traveling outside of the country in which they reside.
  2. Once informed of out of country travel, the primary care provider will refer the patient to an infectious disease specialist.
  3. The infectious disease specialist can assess the risks of transmission and infection of the patient, depending on the country to which they will be traveling.
  4. Following the risk assessment, the infectious disease specialist can recommend chloroquine as prophylaxis to malaria, if the patient will be in a country where chloroquine-sensitive malaria is present.
  5. The pharmacist will provide weight-dependent dosing of chloroquine and also provide instructions that maximize the effectiveness of the prophylaxis, such as taking the medication before, during, and after the expected travel.
  6. Nursing staff can also counsel the patient regarding proper dosing and administration, as well as answer any question that the patient may have regarding the use and adverse events associated with chloroquine.

The treatment and prevention of malaria do not stop here. The patient must abide by the recommended regimen. If the patient fails to follow the regimen, they put themselves at a higher risk of infection.

Similarly, prescribing chloroquine in the context of inflammatory diseases have a similar recommended course of action:

  1. The patient will come to the primary care provider complaining of symptoms related to autoimmune and/or inflammatory disorders.
  2. The primary care provider will perform a history and physical and provide proper referrals for the patient's treatment.
  3. Referrals may be necessary for specialists, such as orthopedics and/or genetic counselors. 
  4. The specialists can provide the right course of treatment or management of the inflammatory condition, most likely a chronic regimen of medications, including chloroquine. 
  5. The pharmacist will adjust the dose depending on the weight and condition of the patient.
  6. As above, nursing staff can offer patient counseling and directions on dosing and administration, as well as adverse events for which the patient may need to be aware.

The above exemplified the interprofessional healthcare team approach that makes chloroquine therapy more effective and with fewer adverse events, enhancing patient care. [Level 5]


References

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[2] Sulfonamides 2012;     [PubMed PMID: 31643703]
[3] Park TY,Jang Y,Kim W,Shin J,Toh HT,Kim CH,Yoon HS,Leblanc P,Kim KS, Chloroquine modulates inflammatory autoimmune responses through Nurr1 in autoimmune diseases. Scientific reports. 2019 Oct 29;     [PubMed PMID: 31664129]
[4] Plantone D,Koudriavtseva T, Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neoplastic, and Neurological Diseases: A Mini-Review. Clinical drug investigation. 2018 Aug;     [PubMed PMID: 29737455]
[5] Sullivan DJ Jr,Gluzman IY,Russell DG,Goldberg DE, On the molecular mechanism of chloroquine's antimalarial action. Proceedings of the National Academy of Sciences of the United States of America. 1996 Oct 15;     [PubMed PMID: 8876229]
[6] Fox RI, Mechanism of action of hydroxychloroquine as an antirheumatic drug. Seminars in arthritis and rheumatism. 1993 Oct;     [PubMed PMID: 8278823]
[7] Lewis MD,Pfeil J,Mueller AK, Continuous oral chloroquine as a novel route for Plasmodium prophylaxis and cure in experimental murine models. BMC research notes. 2011 Jul 28;     [PubMed PMID: 21798062]
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[9] White NJ,Watt G,Bergqvist Y,Njelesani EK, Parenteral chloroquine for treating falciparum malaria. The Journal of infectious diseases. 1987 Feb;     [PubMed PMID: 3543146]
[10] White NJ,Miller KD,Churchill FC,Berry C,Brown J,Williams SB,Greenwood BM, Chloroquine treatment of severe malaria in children. Pharmacokinetics, toxicity, and new dosage recommendations. The New England journal of medicine. 1988 Dec 8;     [PubMed PMID: 3054558]
[11] Braga CB,Martins AC,Cayotopa AD,Klein WW,Schlosser AR,da Silva AF,de Souza MN,Andrade BW,Filgueira-Júnior JA,Pinto Wde J,da Silva-Nunes M, Side Effects of Chloroquine and Primaquine and Symptom Reduction in Malaria Endemic Area (Mâncio Lima, Acre, Brazil). Interdisciplinary perspectives on infectious diseases. 2015;     [PubMed PMID: 26357512]
[12] Lysack JT,Lysack CL,Kvern BL, A severe adverse reaction to mefloquine and chloroquine prophylaxis. Australian family physician. 1998 Dec;     [PubMed PMID: 9919736]
[13] Prakongpan S,Sirimai S,Edwards G,McGrath CS,White NJ, An improved formulation of chloroquine for intramuscular administration: absorption kinetics in rabbits. The Journal of pharmacy and pharmacology. 1989 Oct;     [PubMed PMID: 2575156]
[14] Drasch G,Eisenmenger W, [Death following administration of 1,250 mg chloroquine in porphyria cutanea tarda]. Zeitschrift fur Rechtsmedizin. Journal of legal medicine. 1986;     [PubMed PMID: 3577436]
[15] Dresser CK, Chloroquine dose for malaria prevention. Canadian family physician Medecin de famille canadien. 1986 Feb;     [PubMed PMID: 21267237]
[16] Wittes R, Adverse reactions to chloroquine and amodiaquine as used for malaria prophylaxis: a review of the literature. Canadian family physician Medecin de famille canadien. 1987 Nov;     [PubMed PMID: 21264010]
[17] Clemessy JL,Taboulet P,Hoffman JR,Hantson P,Barriot P,Bismuth C,Baud FJ, Treatment of acute chloroquine poisoning: a 5-year experience. Critical care medicine. 1996 Jul;     [PubMed PMID: 8674334]