Sulfadoxine/pyrimethamine, sold under the brand name Fansidar, is a combination medication used to treat

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

. It contains sulfadoxine (a sulfonamide) 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 dise ...

(an antiprotozoal). 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 naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young ...

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 ma ...

. 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, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

, rash, itchiness, headache, and hair loss. Rarely a severe

allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

or rash such as

toxic epidermal necrolysis Toxic epidermal necrolysis (TEN) 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 flu-like symptoms. A few days later ...

, may occur. It is not generally recommended in people with a

sulfonamide allergy Sulfonamide is a functional group (a part of a molecule) that is the basis of several groups of drugs, which are called sulphonamides, sulfa drugs or sulpha drugs. The original antibacterial sulfonamides are synthetic (nonantibiotic) antimi ...

or significant

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

or kidney disease. 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 a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medi ...

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,Medical Treatment - Sulphadoxine and Pyrimethamine . 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 specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...

(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 effec ...

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 mont ...

and ''

Pneumocystis jiroveci ''Pneumocystis jirovecii'' (previously ''P. carinii'') is a yeast-like fungus of the genus ''Pneumocystis''. The causative organism of ''Pneumocystis'' pneumonia, it is an important human pathogen, particularly among immunocompromised hosts. Pr ...

'' 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 Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema ...

Toxic epidermal necrolysis Toxic epidermal necrolysis (TEN) 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 flu-like symptoms. A few days later ...

* Agranulocytosis *

Aplastic anaemia Aplastic anemia is a cancer in which the body fails to make blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood c ...

* Disorder of haematopoietic structure * Drug-induced eosinophilia *

Thrombocytopaenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...

* Liver necrosis *

Hepatitis Hepatitis is inflammation of the 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), poor appetite, vomiting, tiredness, abdominal ...

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

Polyneuritis Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or o ...

* Atrophic

glossitis Glossitis can mean soreness of the tongue, or more usually inflammation with depapillation of the dorsal surface of the tongue (loss of the lingual papillae), leaving a smooth and erythematous (reddened) surface, (sometimes specifically termed atro ...

Gastritis Gastritis is 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). Other possi ...

* 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 Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are ...

Pharmacology

Sulfadoxine is a sulfonamide antibiotic that competes with

p-aminobenzoic acid 4-Aminobenzoic acid (also known as ''para''-aminobenzoic acid or PABA because the two functional groups are attached to the benzene ring across from one another in the ''para'' position) is an organic compound with the formula H2NC6H4CO2H. PABA ...

in the biosynthesis of folate. Pyrimethamine serves as a selective inhibitor of protozoal dihydrofolate reductase, hence preventing the synthesis of

tetrahydrofolate Tetrahydrofolic acid (THFA), or tetrahydrofolate, is a folic acid derivative. Metabolism Human synthesis Tetrahydrofolic acid is produced from dihydrofolic acid by dihydrofolate reductase. This reaction is inhibited by methotrexate. It is co ...

— 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

External links

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