Basic information Pharmacology and mechanism of action Indications Side effects Contraindications and precautions Interactions Preparations References Safety Related Supplier
Sulfadoxine Chemical Properties
- Melting point:190-194°C
- Boiling point:298°C (rough estimate)
- Density 1.4006 (rough estimate)
- refractive index 1.6270 (estimate)
- storage temp. 2-8°C
- solubility Soluble in ethanol & ammonium hydroxide (9:1) at 20mg/ml
- form powder
- color white
- Water Solubility 209.8mg/L(temperature not stated)
- Merck 14,8906
- BRN 625453
Sulfadoxine Usage And Synthesis
- Pharmacology and mechanism of action The efficacy of sulphadoxine for the treatment of human malaria was first reported in 1964 . Soon thereafter it was found that potentiation took place when sulphadoxine was combined with pyrimethamine for treatment of malaria and monotherapy was abandoned.
Malaria parasites synthesize their folate co-factors and cannot use dietary folic acid as the human host can. Sulphadoxine competes with para-aminobenzoic acid (PABA) for binding to the enzyme dihydropteroate synthetase in the synthesis of dihydropteroate which is an essential substance for the formation of folic acid . It is active against asexual blood forms of P. falciparum but less active against other species. The action is too slow to be used alone for malaria treatment .
- IndicationsSulphadoxine is used only in combination with pyrimethamine for the treatment of falciparum malaria. It should generally not be used for malaria prophylaxis except perhaps in long-term travellers who have previously tolerated the combination.
- Side effectsSulphadoxine is usually well tolerated. Vomiting, skin rashes, pruritus and haematological reactions such as haemolysis and leucopenia occur . Hypersensitivity pneumonitis is reported[5, 6]. Cases of liver injury alone (hepatitis of hepatocellular, mixed hepatocellular, or aggressive type) or as part of a generalized allergic syndrome are well known[4, 6], and one case of fatal hepatic failure has also been reported .
Severe cutaneous adverse reactions (erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis) have been reported in persons taking prophylactic doses of sulphadoxine/pyrimethamine[6, 8]. Sulphadoxine has been incriminated as the most probable cause of these reactions. They all occurred within 7 weeks after start of prophylaxis.
The reported incidence was 1/5,000–8,000 users in USA and approximately 1/10,000 users in Sweden with fatality rates of 1/11,000–25,000 and 1/50,000, respectively. In Mozambique, when sulphadoxine was given alone in a single dose for cholera prophylaxis to 149,000 inhabitants, a total of 22 cases of Stevens-Johnson syndrome was seen with 3 deaths .
- Contraindications and precautions The drug or its combination should not be given to patients allergic to sulphonamides. It should not be used in persons with severe blood, kidney or liver diseases.
- InteractionsIncreased impairment of folic acid synthesis and consequent haematological adverse effects may occur if trimethoprim or its combination with sulphonamide is administered concurrently. Sulphadoxine potentiates the action of warfarin and thiopentone .
- PreparationsSulphadoxine combined with pyrimethamine.
• Fansidar® (Roche). Tablets (sulphadoxine 500 mg+pyrimethamine 25 mg), solution for intramuscular injection (sulphadoxine 200 mg/ml+pyrimethamine 10 mg/ml).
- References1. Laing ABG (1964). Antimalarial effect of sulphorthodimethoxine (Fanasil). BMJ, 2, 1439–1440.
2. The biology of malaria parasites. Technical Report Series no. 743 (1987). (Geneva: World Health Organization).
3. Chemotherapy of Malaria. Monograph series No. 27, 2nd edn, (1986), (Geneva: World Health Organization).
4. Hoigné R, Malinverni R, Sonntag R (1992). Sulfonomides, other folic acid antagonists and miscellaneous antibacterial drugs. In: Meyler’s Side Effects of Drugs, 12th edn, edited by M.N.G.Dukes (Amsterdam: Elsevier), pp. 715–722.
5. Svanbom M, Rombo L, Gustafsson L (1984). Unusual pulmonary reaction during short term prophylaxis with pyrimethamine-sulphadoxine (Fansidar). BMJ, 1, 1876.
6. Hellgren U, Rombo L, Berg B, Carlson J, Wiholm B-E (1987). Adverse reactions to sulphadoxinepyrimethamine in Swedish travellers: implications for prophylaxis. BMJ, 295, 365–366.
7. Zitelli BJ, Alexander J, Taylor S (1987). Fatal hepatic necrosis due to pyrimethamine-sulphadoxine (Fansidar). Ann Intern Med, 106, 393–395. 25. Miller KD, Lobel HO, Satriale RF, Kirutsky JN, Stern R, Campell CC (1986). Severe cutaneous reactions among American travellers using pyrimethamine-sulphadoxine (Fansidar) for malaria prophylaxis. Am J Trop Hyg, 35, 451–458.
8. Hernberg A (1985). Stevens-Johnson syndrome after mass prophylaxis with sulphadoxine for cholera in Mozambique. Lancet, 2, 1072–1073.
9. Sulfadoxine. Therapeutic Drugs, edited by Sir Colin Dollery (1991), (London: Churchill Livingstone), pp. S115–S119.
- Chemical PropertiesWhite Crystalline Solid
- UsesUsed as an antibacterial
- DefinitionChEBI: A sulfonamide consisting of pyrimidine having methoxy substituents at the 5- and 6-positions and a 4-aminobenzenesulfonamido group at the 4-position. In combination with the antiprotozoal pyrimethamine (CHEBI:8673) it is used as an antimalarial.
- brand nameFanasil (Hoffmann-LaRoche-International); Fanzil (Hoffmann-LaRoche).
- Antimicrobial activityIts antibacterial activity is relatively poor. Used alone it has a slow and uncertain effect against malaria parasites. Resistance of malaria parasites to the combination with pyrimethamine is common in many endemic areas.
- Pharmaceutical ApplicationsAn ultra-long-acting sulfonamide. It is no longer prescribed alone, but is used in combination with pyrimethamine as the antimalarial agent Fansidar. It is poorly soluble in water.
- PharmacokineticsOral absorption ：Extensive
Cmax 500 mg oral： c. 60 mg/L after 3–4 h
Plasma half-life：c.6 days
Volume of distribution：0.13 L/kg
Plasma protein binding：94%
The extremely long half-life allows administration at weekly intervals. The acetyl metabolite has a similarly long half-life, but sulfadoxine is less extensively metabolized than many other sulfonamides.
- Clinical UseSulfadoxine is used only in combination with pyrimethamine.
- Side effectsSide effects are those common to the group. There have been many reports of Stevens–Johnson syndrome following its use and the combination with pyrimethamine is no longer recommended for the prophylaxis of malaria.
- Sulfadimethoxine sodium salt Glycine Fomesafen 6-Aminocaproic acid 5,6-Dimethoxypyrimidin-4-ylamine 4-Amino-6-methoxypyrimidine Sulfadoxine-d3 Sulfadoxine Sulfanilamide Sulfamonomethoxine Sulfasalazine Tris Base Silver sulfadiazine Sulfadiazine 3-Aminophenol ALTRENOGEST Sulfadimethoxine Trimethoprim
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