Amodiaquine

Amodiaquine
Clinical data
Trade names Amdaquine, Amobin, others[1]
AHFS/Drugs.com International Drug Names
ATC code P01BA06 (WHO)
Identifiers
CAS Number 86-42-0 YesY
PubChem (CID) 2165
DrugBank DB00613 YesY
ChemSpider 2080 YesY
UNII 220236ED28 YesY
KEGG D02922 YesY
ChEBI CHEBI:2674 YesY
ChEMBL CHEMBL682 YesY
Chemical and physical data
Formula C20H22ClN3O
Molar mass 355.861 g/mol
3D model (Jmol) Interactive image
  (verify)

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. Due to the risk of rare but serious side effects, it is not generally recommended to prevent malaria.[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. When taken in excess headaches, trouble seeing, seizures, and cardiac arrest may occur.[2] While not extensively studied as of 2007, it appeared to be safe in pregnancy.[4] Amodiaquine is a 4-aminoquinoline compound related to chloroquine.[2]

Amodiaquine was first made in 1948.[5] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[6] The wholesale cost is about 0.01 USD per dose as of 2014.[7] While not avaliable in the United States,[8] it is widely available in Africa.[2][9]

Medical uses

Amodiaquine has become an important drug in the combination therapy for malaria treatment in Africa.[10] It is often used in combination with artensunate as a by mouth artemisinin-based combination therapy (ACT) for uncomplicated P. falciparum malaria.[11] Amodiaquine has also been found to work against chloroquine-resistant P. falciparum strains of malaria.[12]

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.[13]

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.[14] 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.[15] 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.

References

  1. ↑ "Amodiaquine". drugs.com. Retrieved 27 November 2016.
  2. 1 2 3 4 5 Nair, A; Abrahamsson, B; Barends, DM; Groot, DW; Kopp, S; Polli, JE; Shah, VP; Dressman, JB (December 2012). "Biowaiver monographs for immediate release solid oral dosage forms: amodiaquine hydrochloride.". Journal of pharmaceutical sciences. 101 (12): 4390–401. PMID 22949374.
  3. 1 2 Olliaro, P; Mussano, P (2003). "Amodiaquine for treating malaria.". The Cochrane database of systematic reviews (2): CD000016. PMID 12804382.
  4. ↑ Tagbor, HK; Chandramohan, D; Greenwood, B (November 2007). "The safety of amodiaquine use in pregnant women.". Expert opinion on drug safety. 6 (6): 631–5. PMID 17967151.
  5. ↑ Profiles of Drug Substances, Excipients and Related Methodology. Academic Press. 1992. p. 45. ISBN 9780080861166.
  6. ↑ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
  7. ↑ "Amodiaquine". International Drug Price Indicator Guide. Retrieved 4 December 2015.
  8. ↑ "Amodiaquine". Livertox. Retrieved 27 November 2016.
  9. ↑ Centers for Disease Control, (CDC). (12 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.
  10. ↑ Kerb, Reinhold; Fux; Morike; Kremsner; Gil; Gleiter; Schwab (2009). "Pharmacogenetics of antimalarial drugs: effect on metabolism and transport". Lancet Infectious Disease. 9 (12): 760–774. doi:10.1016/S1473-3099(09)70320-2.
  11. ↑ Guidelines for the Treatment of Malaria - 2nd Edition. World Health Organization. 2010. p. 33. ISBN 9789241547925.
  12. ↑ Pubchem. "amodiaquine | C20H22ClN3O - PubChem". pubchem.ncbi.nlm.nih.gov. Retrieved 2016-10-28.
  13. ↑ Guidelines for the Treatment of Malaria - 2nd Edition. World Health Organization. 2010. p. 33. ISBN 9789241547925.
  14. ↑ Elyazar, Iqbal; Hay, Baird (April 2011). "Malaria Distribution, Prevalence, Drug Resistance, and control in Indonesia". Advanced Parasitology. Advances in Parasitology. 74 (74): 41–175. doi:10.1016/B978-0-12-385897-9.00002-1. ISBN 9780123858979.
  15. ↑ Roederer, Mary; Mcleod, Juliano (2011). "Can pharmacogenetics improve malaria". Bulletin of World Health Organization. 89 (11): 838–845. doi:10.2471/BLT.11.087320.
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