TMP-SMZ

Anti-Pneumocystis Prophylaxis Sulfamethoxazole-trimethoprim (SMZ-TMP, cotrimoxazole) One SS tablet by mouth once a day3 One DS tablet by mouth once a day3 One DS tablet by mouth every MA/V/F3 Hyperkalemia Myelosuppression Nephrotoxicity Neutropenia Photosensitivity Rash... 

As indicated earher, sulfonamides are effective in both gram-positive and gramnegative bacteria. Mostly prescribed for humans in the United States, in this class is sulfamethoxazole, mostly in combination with trimethoprim (SMZ-TMP) in a 5 1 ratio. Trimethoprim inhibits dihydropholic acid reductase and this, just like sulfonamides, also interferes with the synthesis of folic acid (Fig. 1.8). As a matter of fact, use of the combined SMZ-TMP has been steadily increasing recently as is displayed by the number of prescriptions (Fig. 1.7). Oral doses of sulfonamides are absorbed well and eliminated by the liver and kidney with 20-60% excreted as the parent compound (Queener and Gutierrez, 2003). 

The risk of developing serious renal toxicity in people receiving TMP-SMZ, TMP alone, or cephalexin was also estimated in a large British population, and found to be extremely low [68]. Only five cases of acute parenchymal renal disease occurred in the almost 700,000 subjects evaluated, suggesting that none was likely to be caused by the study drugs. Nonetheless, since in these patients TMP-SMZ manifests considerable extrarenal toxicity, reduction of dosage according to GFR, Ccr or to measured blood levels should be considered in patients with impaired renal function. 

The risk of developing serious renal toxicity in people receiving TMP-SMZ, TMP alone, or cephalexin was recently estimated in a large British population, and found to be extremely low [66]. Only five cases of acute parenchymal renal disease occurred in the almost... 

Bactrim, Bactrim DS, Bactrim I.V. Infusion, Cotrim, Septra, Septra DS, Septra IV Infusion, SMZ-TMP, Sulfatrim, UroPlus SS, UroPlus OS)... 

Drugs Available Post-exposure prophylaxis may be tried with TMP-SMZ (trimethoprim/sulfamethoxazole). 

A solution-state and solid-state nuclear magnetic resonance study of the complex and its separate components in both their neutral and ionized (TMP hydrochloride and SMZ sodium salt) forms was undertaken in order to elucidate the TMP-SMZ interactions. Inspection of the data for the complex in the solid state shows that the 13C chemical shifts are consistent with the ionic structure proposed by Nakai and coworkers105 (14). Stabilization of the complex is achieved by the resulting ionic interaction and by the formation of two intermolecular hydrogen bonds. 

Treatment of acute and chronic prostatitis - 160 mg TMP/800 mg SMZ twice daily has been used for chronic bacterial prostatitis for up to 12 weeks. 

Pharmacology SMZ inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid. TMP blocks the production of tetrahydrofolic acid by inhibiting the enzyme dihydrofolate reductase. 

Absorption/Distribution - TMP-SMZ is rapidly and completely absorbed following oral administration. Approximately 44% of TMP and 70% of SMZ are protein bound. Following oral administration, the half-lives of TMP (8 to 11 hours) and SMZ (10 to 12 hours) are similar. Following IV administration, the mean plasma half-life was 11.3 hours for TMP and 12.8 hours for SMZ. 

Metabolism/Excretion-TMP is metabolized to a small extent SMZ undergoes biotransformation to inactive compounds. 

Flypersensitivity to TMP or SMZ megaloblastic anemia caused by folate deficiency ... 

IV use at high doses or for extended periods of time may cause bone marrow depression manifested as thrombocytopenia, leukopenia, or megaloblastic anemia. POP in patients with Acquired Immunodeficiency Syndrome (AIDS) A DS patients may not tolerate or respond to TMP-SMZ. 

Renal/Hepatic function impairment Use with caution. Maintain adequate fluid intake to prevent crystalluria and stone formation. Patients with severely impaired renal function exhibit an increase in the half-lives of both TMP and SMZ, requiring dosage regimen adjustment. 

Lactation TMP-SMZ is not recommended in the nursing period because sulfonamides are excreted in breast milk and may cause kernicterus. Premature infants and infants with hyperbilirubinemia or G-6-PD deficiency are also at risk for adverse effects. 

Drugs that may be affected by TMP-SMZ include anticoagulants, cyclosporine, dapsone, diuretics, hydantoins, methotrexate, sulfonylureas, and zidovudine. Drugs that may affect TMP-SMZ include dapsone. 

Pneumocystitis carinii pneumonia (PCP) Prevention of PCP in patients who are intolerant to trimethoprim-sulfamethoxazole (TMP-SMZ). 

Severe POP Clinical experience has been limited to patients with mild to moderate PCP. Treatment of more severe episodes of PCP has not been systematically studied. Atovaquone efficacy in patients who are failing therapy with TMP-SMZ has not been systematically studied. 

Drugs that may interact include rifamycins, TMP-SMZ, and zidovudine. 

As an alternative therapy with concurrent leucovorin administration (leucovorin protection) for the treatment of moderate to severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS), who are intolerant of or refractory to TMP-SMZ therapy, or for whom TMP-SMZ is contraindicated. 

Sulfamethoxazole (SMZ)/trimethoprim (TMP) has been shown to be the best regimen for both the treatment and prevention of PCP (Table 11). 

---