Amodiaquine (ADQ) is a medication used to treat

malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...

, including ''Plasmodium falciparum'' malaria when uncomplicated. 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. Though, the

World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...

(WHO) in 2013 recommended use for seasonal preventive in children at high risk in combination with sulfadoxine and pyrimethamine. Amodiaquine is a 4-aminoquinoline compound related to

chloroquine Chloroquine is an antiparasitic medication that treats malaria. It works by increasing the levels of heme in the blood, a substance toxic to the malarial parasite. This kills the parasite and stops the infection from spreading. Certain types ...

. The side effects of amodiaquine are generally minor to moderate and are similar to those of chloroquine. Rarely

liver problems Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground gla ...

or low blood cell levels may occur. When taken in excess headaches, trouble seeing,

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

, and

cardiac arrest Cardiac arrest (also known as sudden cardiac arrest CA is when the heart suddenly and unexpectedly stops beating. When the heart stops beating, blood cannot properly Circulatory system, circulate around the body and the blood flow to the ...

may occur. 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. Amodiaquine was first made in 1948. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. While not available in the United States, it is widely available in

Africa Africa is the world's second-largest and second-most populous continent after Asia. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 20% of Earth's land area and 6% of its total surfac ...

Medical uses

Amodiaquine has become an important drug in the

combination therapy In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are ...

for malaria treatment in Africa. It is often used in combination with artesunate as a by mouth artemisinin-based combination therapy (ACT) for uncomplicated '' P. falciparum'' malaria. 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. It is also used in combination with sulfadoxine/pyrimethamine.

Interactions

There have been reports of increased liver toxicity in people with

HIV/AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

zidovudine Zidovudine (ZDV), also known as azidothymidine (AZT), was the first antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mothe ...

efavirenz Efavirenz (EFV), sold under the brand names Sustiva among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlesti ...

when treated with amodiaquine-containing ACT regimens, therefore it is recommended that these people avoid amodiaquine.

Pharmacokinetics and pharmacogenetics

It is bioactivated hepatically to its primary metabolite, N-desethylamodiaquine, by the

cytochrome p450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzyme

CYP2C8 Cytochrome P4502C8 (CYP2C8) is a member of the cytochrome P450 mixed-function oxidase system involved in the metabolism of xenobiotics in the body. Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-chain polyunsat ...

. 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 The wild type (WT) is the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, " ...

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. 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. 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 Pharmacovigilance (PV, or PhV), also known as drug safety, is the pharmaceutical science relating to the "collection, detection, assessment, monitoring, and prevention" of adverse effects with pharmaceutical products. The etymological roots ...

in East Africa, and have important clinical considerations for prescribing antimalarial medications in regions with high CYP2C8 variant frequency.

References

External links

* {{portal bar, Medicine Antimalarial agents Quinolines Phenols Chloroarenes Drugs developed by Pfizer World Health Organization essential medicines Wikipedia medicine articles ready to translate Diethylamino compounds

Medical uses

Interactions

Pharmacokinetics and pharmacogenetics

See also

References

External links