amodiaquine

Action and Spectrum

Actions and Spectrum: 

amodiaquine is an anti-malarial medication primarily used to treat and prevent malaria infections. Its mechanism of action involves interfering with the metabolism of the malaria parasite within the red blood cells.  

• Heme Polymerization Inhibition: Malaria parasites digest hemoglobin in the red blood cells, releasing heme as a byproduct. Heme is toxic to the parasite and must be converted into non-toxic hemozoin. amodiaquine interferes with this process by binding to heme, preventing its polymerization into hemozoin. This accumulation of toxic heme damages the parasite’s digestive and detoxification systems, leading to its death. 
• Interference with Electron Transport: amodiaquine also interferes with the electron transport chain of the parasite, disrupting its energy production and further contributing to its demise. 

amodiaquine is primarily effective against the blood stages of Plasmodium falciparum, the deadliest malaria parasite prevalent in sub-Saharan Africa. It is less effective against other Plasmodium parasites, such as Plasmodium vivax and Plasmodium ovale. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Vomiting 

Stomach upset  

Loss of vision 

Skin rash 

Muscle pain 

Nausea 

Itching 

Headache 

Loss hearing 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: amodiaquine should not be used in individuals with known hypersensitivity or allergic reactions to the drug or its components. 
• Severe Liver Disease: amodiaquine is metabolized by the liver, and individuals with severe liver disease may not be able to metabolize the drug properly. It can lead to increased levels of the drug in the body, potentially causing adverse effects. 
• Severe Kidney Disease: amodiaquine is primarily excreted by the kidneys, and individuals with severe kidney dysfunction may not be able to eliminate the drug, leading to potential toxicity effectively. 
• Pre-existing Heart Conditions: amodiaquine can cause changes in heart rhythm (prolongation of the QT interval), which could be problematic for individuals with pre-existing heart conditions or those taking medications that also affect heart rhythm. 

Cautions: 

• G6PD Deficiency: Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk of hemolysis (destruction of red blood cells) when taking amodiaquine. G6PD deficiency is more common in specific populations, and testing may be recommended before prescribing the medication. 
• Allergic Reactions: If you experience an allergic reaction to amodiaquine, such as rash, itching, swelling, severe dizziness, or difficulty breathing, seek medical attention immediately. 
• Liver and Kidney Function: amodiaquine is metabolized by the liver and excreted by the kidneys.

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

<b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

amodiaquine’s anti-malarial activity is believed to be primarily due to its interference with heme metabolism within the malaria parasite, Plasmodium falciparum. Heme is a toxic byproduct of hemoglobin digestion by the parasite. amodiaquine prevents the polymerization of heme into hemozoin, a process necessary for the parasite to detoxify heme. This leads to the accumulation of toxic heme within the parasite, resulting in its death. Additionally, amodiaquine may disrupt the parasite’s metabolism and energy production, contributing to its anti-malarial effects. 

Pharmacokinetics: 

Absorption 

amodiaquine is well absorbed from the gastrointestinal tract after oral administration. Its absorption can be influenced by food intake and drug formulations. 

Distribution 

amodiaquine is widely distributed throughout the body, including to tissues such as the liver, spleen, and adipose tissue. It can cross the blood-brain barrier, contributing to its anti-malarial effects against cerebral malaria. 

Metabolism 

amodiaquine undergoes extensive metabolism in the liver. It is metabolized primarily by cytochrome P450 enzymes, particularly CYP2C8, and to a lesser extent by CYP3A4. These enzymes convert amodiaquine into its active metabolite, desethylamodiaquine (DEAQ), contributing to the drug’s anti-malarial effects. 

Elimination and Excretion 

Both amodiaquine and its active metabolite, DEAQ, are primarily excreted in the urine, with a small proportion eliminated in the feces. The elimination half-life of amodiaquine varies, but it’s generally in the range of 9 to 24 hours. 

Adminstartion

Administration: 

Oral administration 

amodiaquine is available in various dosage forms, including tablets and oral suspension. The dosage form may vary based on the patient’s age and ability to swallow tablets. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: amodiaquine 

Why do we use amodiaquine? 

amodiaquine is primarily used to treat and prevent malaria, a mosquito-borne infectious disease caused by Plasmodium parasites. Here are the primary uses of amodiaquine: 

• Treatment of Malaria: amodiaquine is used to treat uncomplicated malaria infections caused by Plasmodium falciparum, especially in areas where the parasite is sensitive to the drug. It can be used as a monotherapy or in combination with other anti-malarial drugs, such as artemisinin derivatives, to enhance effectiveness and reduce the risk of drug resistance. 
• Malaria Prophylaxis: amodiaquine can also be used for prophylactic purposes to prevent malaria infection in individuals traveling to regions with a high risk of malaria transmission.