Sulfamethoxazole-trimethoprime association

Another example of a complex formed through hydrogen bonds is given by the sulfamethoxazole-trimethoprime association ... 

Alberti-Flor, J.J., Hernandez, M.E., Ferrer, J.P., Howell, S., Jeffers, L. Fulminant liver failure and pancreatitis associated with the use of sulfamethoxazole-trimethoprim. Amer. X Gastroenterol. 1989 84 1577-1579... 

Tulloch AL. Pancytopenia in an infant associated with sulfamethoxazole-trimethoprim therapy. J Pediatr 1976 88(3) 499-500. 

Trimethoprim-sulfamethoxazole is used frequently for preventive or active treatment of Pneumocystis carinii pneumonia in patients with the AIDS. Adverse reactions to trimethoprim-sulfamethoxazole have been observed to occur much more frequently in these patients compared with those without AIDS. Adverse effects to trimethoprim-sulfamethoxazole occur in 50% to 80% of AIDS patients compared with 10% of other immunocompromised patients. Trimethoprim-sulfamethoxazole was associated with an adverse-event rate of 26.3 per 100 person-years and hypersensitivity events at 22 per 100 person-years. Adverse-event rate was related to lower CD4+ cell count. When the CD4+ cell count was less than 100/mm , the adverse drug event rate was 31 per 100 person-years. ... 

Ransohoff DF, Jacobs G (1981) Terminal Hepatic Failure Following a Small Dose of Sulfamethoxazole-Trimethoprim. Gastroenterology 80 816 Rao KG (1974) Pseudotumor cerebri associated with nalidixic acid. Urology 4 204 Rea TH, Levan NE (1975) Erythema nodosum leprosum in a general hospital. Arch Dermatol 3 1575... 

Overproduction of the chromosomal genes for the dihydrofolate reductase (DHFR) and the dihydroptero-ate synthase (DHPS) leads to a decreased susceptibility to trimethoprim and sulfamethoxazol, respectively. This is thought to be the effect of titrating out the antibiotics. However, clinically significant resistance is always associated with amino acid changes within the target enzymes leading to a decreased affinity of the antibiotics. 

Trimethoprim (Trimpex) interferes with the ability of bacteria to metabolize folinic acid, thereby exerting bacteriostatic activity. Trimethoprim is used for UTIs that are caused by susceptible microorganisms. Trimethoprim administration may result in rash, pruritus, epigastric distress, nausea, and vomiting. When trimethoprim is combined with sulfamethoxazole (Septra), the adverse effects associated with a sulfonamide may also occur. The adverse reactions seen with other anti-infectives, such as ampicillin, the sulfonamides, and cephalosporins, are given in their appropriate chapters. 

Treatment with trimethoprim-sulfamethoxazole or parenteral pentamidine is associated with a 60% to 100% response rate. Trimethoprim-sulfamethoxazole is the regimen of choice for treatment and subsequent prophylaxis of PCP in patients with and without HIV. 

In women who experience symptomatic reinfections in association with sexual activity, voiding after intercourse may help prevent infection. Also, self-administered, single-dose prophylactic therapy with trimethoprim-sulfamethoxazole taken after intercourse has been found to significantly reduce the incidence of recurrent infection in these patients. 

Co-trimoxazole refers to the combination of sulfamethoxazole and trimethoprim, which offers synergistic activity. Co-trimoxazole is associated... 

Note that in addition to the adverse events due to trimethoprim the combination trimethoprim-sulfamethoxazole may cause all of the untoward reactions associated with sulfonamides. In HIV positive patients the incidence of rashes can increase to 50%. Desensibilisation with increasing doses of co-trimoxazole has been successful. 

Serious adverse effects are rare except in AIDS patients. TMP-SMX can cause the same adverse effects as those associated with sulfonamide administration, including skin rashes, central nervous system (CNS) disturbances, and blood dyscrasias. Blood dyscrasias, hepatotoxicity, and skin rashes are particularly common in patients with AIDS. Most of the adverse effects of this combination are due to the sulfamethoxazole component. Trimethoprim may increase the hematological toxicity of sulfamethoxazole. Long-term use of trimethoprim in persons with borderline foUc acid deficiency, such as alcoholics and the malnourished, may result in megaloblastic anemia, thrombocytopenia, and granulocytopenia. 

Important specifications for the manufacture of all solutions include assay and microbial limits. Additional important specifications for suspensions include particle size of the suspended drug, viscosity, pH, and in some cases, dissolution. Viscosity can be important, from a processing aspect, to minimize segregation. In addition, viscosity has also been shown to be associated with bioequivalency. pH may also have some meaning regarding effectiveness of preservative systems and may even have an effect on the amount of drug in solution. With regard to dissolution, there are at least three products that have dissolution specifications. These products include pheny-toin suspension, carbamazepine suspension, and sulfamethoxazole and trimethoprim suspension. Particle size is also important, and at this point it would seem that any... 

Hughes WT, LaFon SW, Scott JD, Masur H. Adverse events associated with trimethoprim-sulfamethoxazole and atovaquone during the treatment of AIDS-related Pneumocystis carinii pneumonia. J Infect Dis 1995 171(5) 1295-301. 

Auxier GG. Aseptic meningitis associated with administration of trimethoprim and sulfamethoxazole. Am J Dis Child 1990 144(2) 144-5. 

Joffe AM, Farley JD, Linden D, Goldsand G. Trimethoprim-sulfamethoxazole-associated aseptic meningitis case reports and review of the literature. Am J Med 1989 87(3) 332-8. 

Safrin S, Lee BL, Sande MA. Adjunctive fohnic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death. I Infect Dis 1994 170(4) 912-17. 

Munoz SJ, Martinez-Hemandez A, Maddrey WC. Intrahepatic cholestasis and phospholipidosis associated with the use of trimethoprim-sulfamethoxazole. Hepatology 1990 12(2) 342-7. 

Antonow DR. Acute pancreatitis associated with trimethoprim-sulfamethoxazole. Ann Intern Med 1986 104(3) 363-5. 

Bedford S J, McDonnell S M 1999 Measurements of reproductive function in stallions treated with trimethoprim-sulfamethoxazole and pyrimethamine. Journal of the American Veterinary Medical Association 215 1317-1319... 

The sulfonamides and pyrimethamine (e.g. for equine protozoal myeloencephalitis (EPM) can cause abortion in mares and abnormalities in newborn foals (see Chs 2 and 3) even when the mares received folic acid supplementation. Trimethoprim-sulfamethoxazole given to mares for up to 1 week prior to and after breeding does not appear to potentiate early embryonic death and has not been associated with an increase in birth defects in foals (J. Brendemuehl, personal communication, 2001). Birth defects have not been identified in foals born to mares undergoing... 

Several other agents have been used to prevent recurrence of ANCA-associated diseases. Mycophenolate mofetU has been used anecdotally with favorable results for remission maintenance. Methotrexate has also been used however, it should not be given when the creatinine clearance is <50 mL/min. Trimethoprim-sulfamethoxazole was found to reduce ANCA-associated vasculitis, especially in the upper respiratory tract. 

Hayman M, Seidl EC, Ah M, Malik K. Acute tubular necrosis associated with propylene glycol from concomitant administration of intravenous lorazepam and trimethoprim-sulfamethoxazole. Pharmacotherapy 2003 23 1190-1194. 

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