Amodiaquine

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Amodiaquine
Amodiaquine.svg
Clinical data
Trade names Amdaquine, Amobin, Camoquin, others [1]
AHFS/Drugs.com International Drug Names
ATC code
Identifiers
  • 4-[(7-chloroquinolin-4-yl)amino]-2-[(diethylamino)methyl]phenol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.001.518 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C20H22ClN3O
Molar mass 355.87 g·mol−1
3D model (JSmol)
  • Clc1cc2nccc(c2cc1)Nc3cc(c(O)cc3)CN(CC)CC
  • InChI=1S/C20H22ClN3O/c1-3-24(4-2)13-14-11-16(6-8-20(14)25)23-18-9-10-22-19-12-15(21)5-7-17(18)19/h5-12,25H,3-4,13H2,1-2H3,(H,22,23) Yes check.svgY
  • Key:OVCDSSHSILBFBN-UHFFFAOYSA-N Yes check.svgY
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Amodiaquine (ADQ) is a medication used to treat malaria, including Plasmodium falciparum malaria when uncomplicated. [2] [3] It is recommended to be given with artesunate to reduce the risk of resistance. [2] Due to the risk of rare but serious side effects, it is not generally recommended to prevent malaria. [2] Though, the World Health Organization (WHO) in 2013 recommended use for seasonal preventive in children at high risk in combination with sulfadoxine and pyrimethamine. [4]

Contents

Amodiaquine is a 4-aminoquinoline compound related to chloroquine. [2] The side effects of amodiaquine are generally minor to moderate and are similar to those of chloroquine. [3] Rarely liver problems or low blood cell levels may occur. [2] When taken in excess headaches, trouble seeing, seizures, and cardiac arrest may occur. [2] The WHO recommends its use for pregnant women during the second and third trimester as well as during lactation, but reports that evidence for use in the first trimester is still insufficient. [5]

Amodiaquine was first made in 1948. [6] It is on the World Health Organization's List of Essential Medicines. [7] [8] While not available in the United States, [9] it is widely available in Africa. [2] [10]

Medical uses

Amodiaquine has become an important drug in the combination therapy for malaria treatment in Africa. [11] It is often used in combination with artesunate as a by mouth artemisinin-based combination therapy (ACT) for uncomplicated P. falciparum malaria. [12] Amodiaquine has also been found to work against chloroquine-resistant P. falciparum strains of malaria, though there is geographic variation in its activity against chloroquine-resistant strains. [13] [14]

It is also used in combination with sulfadoxine/pyrimethamine. [15] [16]

Interactions

There have been reports of increased liver toxicity in people with HIV/AIDS on zidovudine or efavirenz when treated with amodiaquine-containing ACT regimens, therefore it is recommended that these people avoid amodiaquine. [12]

Pharmacokinetics and pharmacogenetics

It is bioactivated hepatically to its primary metabolite, N-desethylamodiaquine, by the cytochrome p450 enzyme CYP2C8. Among amodiaquine users, several rare but serious side effects have been reported and linked to variants in the CYP2C8 alleles. CYP2C8*1 is characterized as the wild-type allele, which shows an acceptable safety profile, while CYP2C8*2, *3 and *4 all show a range of "poor metabolizer" phenotypes. People who are poor metabolizers of amodiaquine display lower treatment efficacy against malaria, as well as increased toxicity. [17] Several studies have been conducted to determine the prevalence of CYP2C8 alleles amongst malaria patients in East Africa, and have tentatively shown the variant alleles have significant prevalence in that population. [18] About 3.6% of the population studied showed high risk for a poor reaction to or reduced treatment outcomes when treated with amodiaquine. This information is useful in developing programs of pharmacovigilance in East Africa, and have important clinical considerations for prescribing antimalarial medications in regions with high CYP2C8 variant frequency.

See also

Related Research Articles

<span class="mw-page-title-main">Malaria</span> Mosquito-borne infectious disease

Malaria is a mosquito-borne infectious disease that affects humans and other vertebrates. Human malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria.

Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young children and pregnant women. As of 2018, modern treatments, including for severe malaria, continued to depend on therapies deriving historically from quinine and artesunate, both parenteral (injectable) drugs, expanding from there into the many classes of available modern drugs. Incidence and distribution of the disease is expected to remain high, globally, for many years to come; moreover, known antimalarial drugs have repeatedly been observed to elicit resistance in the malaria parasite—including for combination therapies featuring artemisinin, a drug of last resort, where resistance has now been observed in Southeast Asia. As such, the needs for new antimalarial agents and new strategies of treatment remain important priorities in tropical medicine. As well, despite very positive outcomes from many modern treatments, serious side effects can impact some individuals taking standard doses.

<span class="mw-page-title-main">Artemisinin</span> Group of drugs used against malaria

Artemisinin and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to Plasmodium falciparum. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for her discovery. Artemisinin-based combination therapies (ACTs) are now standard treatment worldwide for P. falciparum malaria as well as malaria due to other species of Plasmodium. Artemisinin is extracted from the plant Artemisia annua a herb employed in Chinese traditional medicine. A precursor compound can be produced using a genetically engineered yeast, which is much more efficient than using the plant.

<span class="mw-page-title-main">Artemether</span> Chemical compound

Artemether is a medication used for the treatment of malaria. The injectable form is specifically used for severe malaria rather than quinine. In adults, it may not be as effective as artesunate. It is given by injection in a muscle. It is also available by mouth in combination with lumefantrine, known as artemether/lumefantrine.

<span class="mw-page-title-main">Artesunate</span> Chemical compound

Artesunate (AS) is a medication used to treat malaria. The intravenous form is preferred to quinine for severe malaria. Often it is used as part of combination therapy, such as artesunate plus mefloquine. It is not used for the prevention of malaria. Artesunate can be given by injection into a vein, injection into a muscle, by mouth, and by rectum.

<span class="mw-page-title-main">Proguanil</span> Chemical compound

Proguanil, also known as chlorguanide and chloroguanide, is a medication used to treat and prevent malaria. It is often used together with chloroquine or atovaquone. When used with chloroquine the combination will treat mild chloroquine resistant malaria. It is taken by mouth.

Artesunate/amodiaquine, sold under the trade name Camoquin among others, is a medication used for the treatment of malaria. It is a fixed-dose combination of artesunate and amodiaquine. Specifically it recommended for acute uncomplicated Plasmodium falciparum malaria. It is taken by mouth.

<span class="mw-page-title-main">Mass drug administration</span>

The administration of drugs to whole populations irrespective of disease status is referred to as mass drug administration (MDA) or mass dispensing.

Intermittent preventive therapy or intermittent preventive treatment (IPT) is a public health intervention aimed at treating and preventing malaria episodes in infants (IPTi), children (IPTc), schoolchildren (IPTsc) and pregnant women (IPTp). The intervention builds on two tested malaria control strategies to clear existing parasites and to prevent new infections (prophylaxis).

<span class="mw-page-title-main">Chlorproguanil</span> Chemical compound

Chlorproguanil is an antimalarial drug. In the late 90s and early 2000s, it was studied under collaboration with the UNICEF/UNDP/World Bank Special Program for Research and Training on Tropical Diseases and GlaxoSmithKline. It was a potential alternative to the preexisting combination therapy of chloroquine and sulfadoxine/pyrimethamine, as malaria was showing drug resistance to this approach. It has been trialled in combination therapy with artesunate to treat haemolysis after malaria treatment, however its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency.

<span class="mw-page-title-main">Pyronaridine</span> Chemical compound

Pyronaridine is an antimalarial drug. It was first made in 1970 and has been in clinical use in China since the 1980s.

<span class="mw-page-title-main">Piperaquine</span> Chemical compound

Piperaquine is an antiparasitic drug used in combination with dihydroartemisinin to treat malaria. Piperaquine was developed under the Chinese National Malaria Elimination Programme in the 1960s and was adopted throughout China as a replacement for the structurally similar antimalarial drug chloroquine. Due to widespread parasite resistance to piperaquine, the drug fell out of use as a monotherapy, and is instead used as a partner drug for artemisinin combination therapy. Piperaquine kills parasites by disrupting the detoxification of host heme.

Pregnancy-associated malaria (PAM) or placental malaria is a presentation of the common illness that is particularly life-threatening to both mother and developing fetus. PAM is caused primarily by infection with Plasmodium falciparum, the most dangerous of the four species of malaria-causing parasites that infect humans. During pregnancy, a woman faces a much higher risk of contracting malaria and of associated complications. Prevention and treatment of malaria are essential components of prenatal care in areas where the parasite is endemic – tropical and subtropical geographic areas. Placental malaria has also been demonstrated to occur in animal models, including in rodent and non-human primate models.

Sulfadoxine/pyrimethamine, sold under the brand name Fansidar, is a combination medication used to treat malaria. It contains sulfadoxine and pyrimethamine. For the treatment of malaria it is typically used along with other antimalarial medication such as artesunate. In areas of Africa with moderate to high rates of malaria, three doses are recommended during the second and third trimester of pregnancy.

Artesunate/sulfadoxine/pyrimethamine is an artesunate-based oral medication used to treat malaria. It consists of artesunate and sulfadoxine/pyrimethamine.

Piperaquine/dihydroartemisinin (DHA/PPQ), sold under the brand name Eurartesim among others, is a fixed dose combination medication used in the treatment of malaria. It is a combination of piperaquine and dihydroartemisinin. Specifically it is used for malaria of the P. falciparum and P. vivax types. It is taken by mouth.

Artesunate/mefloquine is a medication used to treat malaria. It is a fixed dose combination of artesunate and mefloquine. Specifically it is recommended to treat uncomplicated falciparum malaria. It is taken by mouth.

Artesunate/pyronaridine, sold under the brand name Pyramax, is a fixed-dose combination medication for the treatment of malaria. It can be used for malaria of both the P. falciparum and P. vivax types. It combines artesunate and pyronaridine. It is taken by mouth.

References

  1. ↑ "Amodiaquine". drugs.com. Archived from the original on 27 November 2016. Retrieved 27 November 2016.
  2. 1 2 3 4 5 6 7 Nair A, Abrahamsson B, Barends DM, Groot DW, Kopp S, Polli JE, et al. (December 2012). "Biowaiver monographs for immediate release solid oral dosage forms: amodiaquine hydrochloride". Journal of Pharmaceutical Sciences. 101 (12): 4390–4401. doi:10.1002/jps.23312. PMID   22949374.
  3. 1 2 Olliaro P, Mussano P (2003). "Amodiaquine for treating malaria". The Cochrane Database of Systematic Reviews (2): CD000016. doi:10.1002/14651858.CD000016. PMC   6532704 . PMID   12804382.
  4. ↑ Seasonal malaria chemoprevention with sulfadoxine–pyrimethamine plus amodiaquine in children: a field guide (PDF). Geneva: The World Health Organization. August 2013. ISBN   978-92-4-150473-7.
  5. ↑ "WHO Guidelines for malaria". www.who.int. Retrieved 2024-01-22.
  6. ↑ Ahmad I, Ahmad T, Usmanghani K (1992). "Amodiaquine hydrochloride". Profiles of Drug Substances, Excipients and Related Methodology. Analytical Profiles of Drug Substances and Excipients. Vol. 21. Academic Press. p. 45. doi:10.1016/S0099-5428(08)60388-3. ISBN   978-0-08-086116-6. Archived from the original on 2017-09-08.
  7. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  8. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  9. ↑ "Amodiaquine". Livertox. Archived from the original on 27 November 2016. Retrieved 27 November 2016.
  10. ↑ Centers for Disease Control (CDC) (April 1985). "Revised recommendations for preventing malaria in travelers to areas with chloroquine-resistant Plasmodium falciparum". MMWR. Morbidity and Mortality Weekly Report. 34 (14): 185–90, 195. PMID   3156271.
  11. ↑ Kerb R, Fux R, Mörike K, Kremsner PG, Gil JP, Gleiter CH, Schwab M (December 2009). "Pharmacogenetics of antimalarial drugs: effect on metabolism and transport". The Lancet. Infectious Diseases. 9 (12): 760–774. doi:10.1016/S1473-3099(09)70320-2. PMID   19926036.
  12. 1 2 World Health Organization (2015). Guidelines for the treatment of malaria (3rd ed.). World Health Organization. hdl: 10665/162441 . ISBN   978-92-4-154912-7.
  13. ↑ "Amodiaquine". PubChem. U.S. National Library of Medicine. Archived from the original on 2016-10-29. Retrieved 2016-10-28.
  14. ↑ Bennett, John Eugene; Dolin, Raphael; Blaser, Martin J., eds. (2020). "41 - Antimalarial Drugs". Mandell, Douglas, and Bennett's principles and practice of infectious diseases (Ninth ed.). Philadelphia, PA: Elsevier. pp. 519–534. ISBN   978-0-323-48255-4.
  15. ↑ Staedke SG, Kamya MR, Dorsey G, Gasasira A, Ndeezi G, Charlebois ED, Rosenthal PJ (August 2001). "Amodiaquine, sulfadoxine/pyrimethamine, and combination therapy for treatment of uncomplicated falciparum malaria in Kampala, Uganda: a randomised trial". Lancet. 358 (9279): 368–374. doi:10.1016/S0140-6736(01)05557-X. PMID   11502317. S2CID   42745422.
  16. ↑ World Health Organization (2013). Seasonal malaria chemoprevention with sulfadoxine–pyrimethamine plus amodiaquine in children: a field guide. World Health Organization. hdl: 10665/85726 . ISBN   978-92-4-150473-7.
  17. ↑ Elyazar IR, Hay SI, Baird JK (April 2011). "Malaria distribution, prevalence, drug resistance and control in Indonesia". Advances in Parasitology. 74 (74): 41–175. doi:10.1016/B978-0-12-385897-9.00002-1. ISBN   978-0-12-385897-9. PMC   3075886 . PMID   21295677.
  18. ↑ Roederer MW, McLeod H, Juliano JJ (November 2011). "Can pharmacogenomics improve malaria drug policy?". Bulletin of the World Health Organization. 89 (11): 838–845. doi:10.2471/BLT.11.087320. PMC   3209725 . PMID   22084530.
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