Sulfamethoxazole/trimethoprim: Indications, Side Effects

What Is Sulfamethoxazole

Sulfamethoxazole-trimethoprim is a compound anti-inflammatory medicine. Sulfamethoxazole-Tmp can cooperate to work. Sulfamethoxazole(SMZ) belongs to sulfa drugs and can be used in all parts of body system. SMZ is a broad-spectrum bacteriostatic agent. SMZ can form competitive effect with PABA (p-aminabenzoic acid) on dihydrofolate synthase in bacterial to prevent bacterial dihydrofolate synthesis and restrain growth and reproduction of bacteria. Trimethoprim (TMP) is a kind of bacterial dihydrofolate depressant. TMP belongs to synergistic sulfa drugs.

TMP can selectively restrain activity of dihydrofolate reductase to inhibit dihydrofolate to be reduced to tetrahydrofolic acid so as to restrain growth and reproduction of bacteria. The antibacterial spectrum of TMP is similar with sulfamethoxazole, but the antibacterial effect is 20~100 times stronger than SMZ. It is easy to produce drug resistance when TMP is used alone. When SMZ and TMP cooperate, SMZ impacts on dihydrofolate synthase to inhibit first step of synthesis of falic acid interference. And then, TMP restrains synthase of folic acid synthesis. Now bacteria’s folate metabolism is doubly hampered. The compound drug of SMZ and TMP can cooperate to restrain living of bacteria so that the activity of antibacterial is enhanced and the function of antibacterial can turn into bactericidal. Thus the generation of resistant strains is reduced.

Sulfamethoxazole

What Is Sulfamethoxazole Used For

Sulfamethoxazole-trimethoprim (SMZ/TMP) has excellent antibacterial activity on most Gram-positive and negative bacteria, including non-producing Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Escherichia coli, Klebsiella, Salmonella, Proteus, Morgan genus, Chi He Enterobacteriaceae spp, Neisseria gonorrhoeae, meningococcal, and Haemophilus influenza. SMZ/TMP is effective on sickness including urinary tract infections, intestinal infections, adult acute exacerbation of chronic bronchitis, and acute ear caused by bacteria which is sensitive to SMZ/TMP.

Sulfamethoxazole Dosage

Dosage is different because of individual difference. An adult should not take more than 0.2g SMZ/TMP. When creatinine clearance is 30ml/min. an adult can maintain the dosage. When creatinine clearance is 15~30 ml/min, intake dosage should be 50mg every 12 hours. When creatinine clearance is 15 ml/min, the drug is not fit for the body.

Sulfamethoxazole Side Effects

  1. Taking Sulfamethoxazole-trimethoprim can impact folate metabolism to produce adverse reactions in the blood system and there are symptoms of leucopenia, thrombocytopenia, anemia or methemoglobin. General leukopenia and thrombocytopenia is slight side effect and can resume by stop taking the drug, folic acid preparations is a plus assistance.
  2. Allergies: Taking Sulfamethoxazole-TMP might have symptoms of itching, rash; sometimes there is severe exudative erythema multiforme.
  3. Taking Sulfamethoxazole-TMP might have symptoms of nausea, vomiting, diarrhea and other gastrointestinal reactions. Generally symptoms aremild.
  4. Taking Sulfamethoxazole-TMP might have occasional symptoms of aseptic meningitis, headache, neck stiffness, nausea and other symptoms.

Precautions

The drug is forbidden to be taken by Sulfa drugs allergic patient because the drug prevents the metabolism of folic acid and increase lack of megaloblastic anemia folate. Pregnant, lactating women, baby below two months, and liver & kidney dysfunction are forbidden to take the drug.

  • Taking Sulfamethoxazole-trimethoprim might have cross-allergic reactions. Presented to one sulfa drug allergic patients may be allergic to other sulfa drugs as well.
  • Sulfamethoxazole-tmp may bring damage to the liver. Taking SMZ / TMP can cause jaundice, liver dysfunction. When damage is severe, patient may have acute liver necrosis. Therefore, patients who are in impaired liver function should avoid systemic application of sulfa drugs.
  • SMZ / TMP may bring kidney damage so that bring about crystallization of urine, hematuria and urinary tube. If the treatment period is long and dosage is large, it had better to serve with sodium bicarbonate and the water to prevent this adverse reactions. During treatment, there should be at least2 to 3 times weekly urine check. If patient is to be found suffering crystallized urine or hematuria, patient should be given sodium bicarbonate and drink plenty of water, until the crystallization of urine and hematuria disappeared. Dehydration, shock and elderly patients should be cautious to take the drug because the drug is easy to damage kidney function of these patients.Patients with renal dysfunction should not be aviod taking the drug.
  • Patients who are allergic to furosemide, sulfone, thiazide diuretics, sulfonylureas, carbonic anhydrase inhibitors, may also be allergic to sulfa drugs.
  • Patients should not be used SMZ / TMP include: lack of glucose-6-phosphate dehydrogenase, blood porphyria, folic acid deficiency hematological diseases, dehydration, AIDS, shock and elderly patients.
  • Patient shoud hold follwoing check while taking SMZ/TMP:peripheral blood check, which is especally important for patients whose treatment period is long, who take large dosages, who are old, who have malnutrition and are taking anti-epileptic drugs . Periodic urine check during treatment (once every 2-3 days ) in order to find crystallizationa urine during long-period of treatment or high dosage of treatment; liver and kidney function checks.
  • Patient should drink plenty of water when taking the drug and should maitain enough water during treatment. Adult should maintain daily urine output for 1200ml every day. If the treatment period is long and dosage is large, patient should drink enough water and take bicrbonate as the same time.
  • Severe infected patient should be measured plasma concentration. For most infected patients, free sulfa concentration of 50 ~ 150μg / ml is valid and for severe infected patient ,free sulfa concentration should be 120 ~ 150μg / ml. Total sulfonamide blood concentration should not exceed 200μg / ml, if not, the adverse reaction rate would increase.
  • Patient cannot arbitrarily increase the dose, increase the times of taking drugs or prolong treatment so as to prevent the accumulation of poisoning.
  • Because SMZ / TMP can inhibit the growth of E. coli, and impede the synthesis of B vitamins in the intestines, patient who take the drug more than one week, should take vitamin B at the same time so as to prevent vitamin B deficiency.

If patient has folate deficiency because taking the drug, the patient can take folic acid preparations at the same tiem. Folic acid formulation does not interfere with TMP antibacterial activity. Because the bacteria can not use the synthesized folic acid, if there is symptom of bone marrow suppression, patient should stop taking the drug and be injected with 3 ~ 6mg folic acid in muscle, once every day. Generally, patient’s hematopoietic function would return to normal when taking two days of drug or maintaining taking the drug according to requirement. Patient who takes the drug in long period treatment should take high dosage of folic acid and prolonged treatment.
Pregnant women, newborns and the elderly should be cautious to take SMZ/TMP.

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