Sulfadoxine/pyrimethamine, sold under the brand name Fansidar, is a combination 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 ...

. It contains

sulfadoxine Sulfadoxine (also spelled sulphadoxine) is an ultra-long-lasting sulfonamide used in combination with pyrimethamine to treat malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''A ...

sulfonamide In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the Chemical structure, structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this gro ...

) and

pyrimethamine Pyrimethamine, sold under the brand name Daraprim among others, is a medication used with leucovorin (leucovorin is used to decrease side effects of pyrimethamine; it does not have intrinsic anti-parasitic activity) to treat the parasitic disea ...

(an

antiprotozoal Antiprotozoal agents ( ATC code: ATC P01) is a class of pharmaceuticals used in treatment of protozoan infection. A paraphyletic group, protozoans have little in common with each other. For example, '' Entamoeba histolytica'', a unikont eukary ...

). For the treatment of malaria it is typically used along with other

antimalarial medication Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often natural product, naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target ...

such as

artesunate 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 ...

. In areas of Africa with moderate to high rates of malaria, three doses are recommended during the second and third trimester of pregnancy. Side effects include

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

, rash, itchiness,

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

, and hair loss. Rarely a severe

allergic reaction Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...

or rash such as

toxic epidermal necrolysis Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and f ...

, may occur. It is not generally recommended in people with a sulfonamide allergy or significant

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an Inflammation, inflammatory kidney disease and has several types according to the location of the inflammation. Infla ...

. It works by blocking malaria's ability to use

folinic acid Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to ...

. Sulfadoxine/pyrimethamine was initially approved for medical use in the United States in 1981. 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 ...

. It is not commercially available in the United States.

Medical uses

Malaria

It is approved in the United States as a treatment and preventive measure against

. The combination is considered to be more effective in treating malaria caused by ''Plasmodium falciparum'' than that caused by '' P. vivax'', for which

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 ...

is considered more effective, though in the absence of a species-specific diagnosis, the sulfadoxine-pyrimethamine combination may be indicated. Due to side effects, however, it is no longer recommended as a routine preventive, but only to treat serious malaria infections or to prevent them in areas where other drugs may not work. However, it is recommended by 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) for seasonal preventative use in children when combined with

amodiaquine Amodiaquine (ADQ) is a medication used to treat malaria, 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 ef ...

Other

It has also be used as a treatment and prophylactic measure for

toxoplasmosis Toxoplasmosis is a parasitic disease caused by ''Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or month ...

and '' Pneumocystis jiroveci'' pneumonia.

Adverse effects

Adverse effects by incidence include: Common (>1% frequency): * Hypersensitivity reactions (e.g. itchiness, contact dermatitis, and hives) * Myelosuppression * Gastrointestinal effects (e.g. nausea, vomiting, and diarrhoea) * Headache Rare (<1% frequency): *

Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and #Classification, Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN) overlap, they are considered febrile mucocutaneous d ...

Toxic epidermal necrolysis Toxic epidermal necrolysis (TEN), also known as Lyell's syndrome, is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and f ...

Agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing neutropenia in the circulating blood. I ...

* Aplastic anaemia * Disorder of haematopoietic structure * Drug-induced

eosinophilia Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds . Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 billion/ L (1,500/ μL). The hypereosinophilic syndrome ...

Thrombocytopaenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coa ...

* Liver necrosis *

Hepatitis Hepatitis is inflammation of the liver parenchyma, liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), Anorexia (symptom), poor appetite ...

* Jaundice * Hepatomegaly * Nephrotoxicity Unknown frequency: * Weight loss * Abdominal cramps * Hair loss * Photosensitivity * Fatigue * Fever * Polyneuritis * Atrophic glossitis *

Gastritis Gastritis is the inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain (see dyspepsia). Othe ...

* Abnormal liver function test results (e.g. elevated serum ALT, AST, alkaline phosphatase, and bilirubin concentrations)

Contraindications

Use of this drug is contraindicated in: * Megaloblastic anaemia caused by folate deficiency * Hypersensitivity to pyrimethamine, sulfonamides, or any ingredient in the formulation * Repeated prophylactic (prolonged) use in patients with kidney or liver failure or blood dyscrasias * Infants <2 months of age * Prophylaxis in pregnancy at term * Prophylaxis in nursing women * Acute porphyria

Pharmacology

Sulfadoxine is a

antibiotic that competes with p-aminobenzoic acid in the biosynthesis of folate. Pyrimethamine serves as a selective inhibitor of protozoal

dihydrofolate reductase Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in one-carbon transfer chemistry. ...

, hence preventing the synthesis of tetrahydrofolate — the active form of folate. A great degree of synergy occurs between the two drugs due to their inhibition of two different steps in the biosynthesis of tetrahydrofolate.

References

{{DEFAULTSORT:Sulfadoxine Pyrimethamine Antimalarial agents Drugs developed by Hoffmann-La Roche World Health Organization essential medicines Wikipedia medicine articles ready to translate