artesunate, sulphadoxine and pyrimethamine

Action and Spectrum

Actions and spectrum: 

artesunate: 

• Action: artesunate is an artemisinin derivative, which is highly effective against Plasmodium falciparum, the parasite responsible for the most severe form of malaria. It acts by producing free radicals that damage the parasite’s cell membranes. 
• Spectrum: artesunate is primarily effective against P. falciparum, including drug-resistant strains. It is particularly valuable in treating severe malaria. 

sulphadoxine and pyrimethamine: 

• Action: sulphadoxine and pyrimethamine are both antifolate drugs. They inhibit the synthesis of folic acid in the malaria parasite, which is essential for its growth and reproduction. 
• Spectrum: This combination, often referred to as SP, is effective against a broader spectrum of malaria parasites, including Plasmodium vivax and some drug-resistant strains of P. falciparum. However, its efficacy has declined in some regions due to the development of resistance. 

The combination of artesunate, sulphadoxine, and pyrimethamine is used as a first-line therapy for uncomplicated malaria in some regions, particularly in areas where chloroquine and other antimalarials have lost effectiveness due to resistance.

Drug Interaction

Adverse Reaction

Frequency not defined 

Dizziness 

Vomiting 

Flatulence 

Bodyache 

Tinnitus 

Convulsions 

Pruritis 

Itching 

Abdominal pain 

Headache 

Diarrhoea 

Alopecia 

Neutropenia 

Skin rash 

Loss of appetite 

Nausea 

Hives 

Anorexia 

Thrombocytopenia 

Glossitis 

Megaloblastic anaemia 

Black Box Warning

Black Box Warning: 

There is no specific Black Box Warning for artesunate, sulphadoxine, and pyrimethamine. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: Patients who have a known hypersensitivity or allergy to any of the active ingredients or other components of the medication should not use this combination. 
• G6PD Deficiency: Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a hereditary enzyme disorder, may be at risk of hemolytic anemia when taking sulphadoxine and pyrimethamine. Therefore, caution is advised, and G6PD status should be assessed before prescribing this combination. 
• Pregnancy and Lactation: While this combination can be used to treat malaria during pregnancy, it should be done under the supervision of a healthcare professional. The safety profile may vary, and the potential risks and benefits should be carefully assessed. Pregnant and lactating women should consult with their healthcare provider before using this medication. 
• Concomitant Use with Certain Medications: There may be potential drug interactions with other medications, including those that affect hepatic enzymes, which can influence the metabolism of sulphadoxine and pyrimethamine. Therefore, healthcare providers should assess interactions before prescribing this combination.

Caution: 

• Renal Impairment: Patients should be monitored closely while using this combination. sulphadoxine is primarily excreted by the kidneys, and its accumulation can occur in individuals with impaired renal function. Dose adjustments may be necessary in such cases. 
• Hepatic Impairment: Patients with hepatic (liver) impairment should also be monitored carefully. The medications in this combination are metabolized in the liver, and liver impairment can affect their metabolism. Dosing adjustments or alternative treatments may be considered in patients with severe hepatic impairment. 
• Drug Interactions: There may be potential drug interactions between this combination and other medications, particularly those that affect hepatic enzymes involved in drug metabolism. Healthcare providers should evaluate interactions before prescribing this combination.

Comorbidities: 

• HIV/AIDS: In areas where both malaria and HIV/AIDS are prevalent, co-infection is possible. Individuals with HIV/AIDS often have weakened immune systems, making them more susceptible to severe malaria. Special care and monitoring may be needed in these cases. 
• Malnutrition: Malnutrition, especially among children, can weaken the immune system and increase the severity of malaria. Adequate nutrition and nutritional support should be provided to individuals with malnutrition. 
• Other Chronic Illnesses: Patients with chronic conditions like diabetes, hypertension, or cardiovascular disease may experience complications if they contract malaria. These individuals should receive appropriate medical care and monitoring to manage both their chronic condition and malaria. 
• Immunosuppression: Individuals who are immunosuppressed, either due to medical conditions or medications (e.g., organ transplant recipients), may be at higher risk of severe malaria. Specialized care and monitoring are essential. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category: not assigned 

Lactation: excreted into human milk: 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: 

The combination of artesunate, sulphadoxine, and pyrimethamine is an antimalarial medication used to treat uncomplicated malaria, primarily caused by the Plasmodium falciparum parasite. Each component of this combination drug has a specific role in combating malaria. artesunate is a fast-acting antimalarial agent that rapidly reduces the parasite load in the bloodstream, relieving acute symptoms.

sulphadoxine and pyrimethamine, on the other hand, are antifolate drugs that inhibit the parasite’s ability to replicate DNA and RNA. This combination therapy is particularly effective because it targets different stages of the parasite’s life cycle, providing a synergistic effect. sulphadoxine also has a long half-life, which extends the duration of protection against recurring malaria infections. This pharmacological synergy makes artesunate, sulphadoxine, and pyrimethamine a valuable tool in regions where malaria is endemic, contributing to successful treatment outcomes and reduced transmission of the disease.  

Pharmacodynamics: 

• artesunate: artesunate is a fast-acting antimalarial drug that belongs to the artemisinin class. It has a potent and rapid schizonticidal effect. artesunate works by producing toxic-free radicals within the parasite, damaging its proteins and lipids, leading to parasite death. It is particularly effective in reducing the parasite load in the bloodstream and alleviating acute malaria symptoms. 
• sulphadoxine: sulphadoxine is a sulfonamide drug that belongs to the group of antifolate medications. It acts by inhibiting the enzyme dihydropteroate synthase, which is involved in the folate synthesis pathway of the malaria parasite. By interfering with folate production, sulphadoxine disrupts the parasite’s ability to replicate DNA and RNA, arresting its growth and multiplication. 
• pyrimethamine: pyrimethamine is also an antifolate drug but works by inhibiting another enzyme in the folate pathway, dihydrofolate reductase. This enzyme is essential for the parasite’s utilization of folate, a critical co-factor in nucleotide synthesis. By blocking dihydrofolate reductase, pyrimethamine further impairs the parasite’s ability to replicate its genetic material. 

The combination of these three drugs provides a synergistic effect against malaria. artesunate rapidly reduces the parasite load, relieving acute symptoms, while sulphadoxine and pyrimethamine act against the parasite’s ability to replicate and multiply. This multi-pronged approach makes this combination therapy highly effective against Plasmodium falciparum malaria and helps reduce the risk of developing drug resistance.  

Pharmacokinetics: 

artesunate: 

• Absorption: artesunate is rapidly absorbed after oral administration. 
• Distribution: It distributes well in the bloodstream and reaches high concentrations in the blood. 
• Metabolism: artesunate undergoes metabolic conversion to its active form, dihydroartemisinin, primarily in the liver. 
• Excretion: The metabolites are excreted through urine and bile. 

sulphadoxine: 

• Absorption: sulphadoxine is well-absorbed from the gastrointestinal tract after oral administration. 
• Distribution: It is distributed throughout the body, including in plasma and tissues. 
• Metabolism: sulphadoxine undergoes some hepatic metabolism. 
• Excretion: It is primarily excreted unchanged in the urine. 

pyrimethamine: 

• Absorption: pyrimethamine is well-absorbed after oral administration. 
• Distribution: It distributes widely in body tissues, including the liver and lungs. 
• Metabolism: It undergoes hepatic metabolism. 
• Excretion: The majority of the drug and its metabolites are excreted in the urine. 

Adminstartion

Administration: 

• Dosage Form: The combination of artesunate, sulphadoxine, and pyrimethamine is often available as a fixed-dose combination tablet. 
• Oral Administration: The tablets are usually administered orally with water. It is important to follow the healthcare provider’s instructions regarding when and how to take the medication. 
• Timing: The dosing regimen may vary depending on the specific product and local treatment guidelines. It may involve a single dose or a multi-day course of treatment. 
• Monitoring: During and after treatment, patients should be monitored for any adverse effects or signs of treatment failure. If symptoms worsen or do not improve, it is crucial to seek medical attention promptly. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: artesunate, sulphadoxine and pyrimethamine 

Pronounced: (Ar-tee-soon-ate, Sulf-a-dox-een, and Py-ri-meth-a-meen)  

Why do we use artesunate, sulphadoxine and pyrimethamine? 

• Treatment of Uncomplicated Malaria: This combination is effective against Plasmodium falciparum, the most common and deadly malaria parasite. It is used to treat uncomplicated malaria infections, including those caused by drug-resistant strains of the parasite. 
• Intermittent Preventive Treatment in Pregnancy (IPTp): In some regions with a high prevalence of malaria, pregnant women are at increased risk of malaria-related complications. This combination may be used as a preventive measure during pregnancy to decrease the risk of maternal anemia, and neonatal mortality associated with malaria infection. 
• Seasonal Malaria Chemoprevention (SMC): In areas with a seasonal pattern of malaria transmission, particularly in young children, this combination may be used to provide preventive treatment during the high transmission season.