Sulfamethoxazole and trimethoprim

Sulfamethoxazole and trimethoprim

Sulfamethoxazole-trimethoprim is a medicine that contains two active components, and belong to a group of antibiotics. These two components act synergistically to block the synthesis of folic acid in bacteria, therefore this drug exerts a bactericidal effect on a large number of bacteria. If used separately, these substances exhibit a bacteriostatic effect and bacteria may develop resistance against them. However, when used in combination, they show an extremely strong bactericidal effect, so the bacteria have no ability to develop resistance.

The bacteria that are sensitive to Sulfamethoxazole-trimethoprim are:

  • Haemophillus influenzae
  • Haemophillus parainfluenzae
  • Enterobacter aerogenes
  • Enterobacter cloacae
  • Klebsiella pneumoniae
  • Klebsiella oxztoca
  • Proteus mirabilis
  • Proteus vulgaris
  • Pneumocystis carinii
  • Shigella
  • Vibrio cholerae
  • Pseudomonas cepacia
  • Listeria monocytogenes
  • Nocardia
  • Staphilococcus aureus
  • MRSA
  • Streptococcus pneumoniae

Although this drug is effective against infections caused by all of abovementioned pathogens, this drug is most frequently used in the treatment of urinary and respiratory infections.

According to the Patient Information Leaflet, Sulfamethoxazole-trimethoprim is used in the treatment of the following infections:

  • Respiratory infections caused by bacteria Pneumocystitis carinii
  • Infections caused by a parasite called Toxoplasma
  • Urinary tract infections
  • Chronic bronchitis
  • Acute otitis media
  • Infections caused by bacteria called Nocardia (systemic or pulmonary nocardiosis)

Precautions

Sulfamethoxazole-trimethoprim can cause liver failure1, and should not be used in patients who already have liver injury.

There are reported cases of acute renal failure induced by Sulfamethoxazole-trimethoprim2, and this drug should not be used in patients who have kidney failure.

Since this drug acts by inhibiting the synthesis of folic acid (vitamin B9), it should not be used in patients who folic acid deficiency anemia.

Sulfamethoxazole-trimethoprim is contraindicated for use in the last trimester of pregnancy and in babies younger than 6 months.

Sulfamethoxazole-trimethoprim reduces the renal excretion of potassium, and there are reported cases of hyperkalemia induced by using this drug3. Caution should be exercised in patients taking other drugs that may increase potassium levels in the blood (e.g. diuretics, such as: spironolactone, amiloride and triamterene).

Serious side effects, such as: Stevens-Johnson syndrome, Lyle's syndrome and fulminant hepatic necrosis have rarely been reported.

Studies have shown that patients older than 65 years are significantly more sensitive to the use of this drug and the incidence of adverse effects (including the severe one) in elderly patients is significantly higher.

Consequently, treatment with this drug should be implemented as short as possible.

Sulfamethoxazole-trimethoprim, pregnancy and breastfeeding

In one study that included 4196 pregnant women who took this medicine during pregnancy, 232 infants (around 3.5%) had birth defects of which the most frequently reported defect was the neural tube defect.3 Since Sulfamethoxazole-trimethoprim inhibits the synthesis of folic acid which is essential for the development of the neural tube in newborns, this defect is completely expected if this drug is taken during pregnancy. For this reason, Sulfamethoxazole-trimethoprim should not be used during pregnancy.

This medicine is excreted into breast milk, and breastfeeding should be avoided while taking this drug.

Dosage

Sulfamethoxazole-trimethoprim is present in the form of tablets at a dose of 400 mg + 80 mg. The usual dose is two tablets twice a day. Take the tablets after a meal (after breakfast and after dinner) with plenty of liquid.

In children younger than 12 years Sulfamethoxazole-trimethoprim should be applied in the form of syrup.

The duration of therapy depends on the type of infection.

For the treatment of acute uncomplicated urinary tract infections in women, it is recommended to take 4-6 tablets as a one-time only dose, at bedtime.

For the treatment of infection caused by bacteria called Pneumocystis usual dose is 20 mg / kg of body weight.

For the treatment of nocardiosis recommended dose is 6-8 tablets daily for at least three months.

Interactions

Sulfamethoxazole-trimethoprim must not be used simultaneously with the following medicines:

  • Preparations of digitalis (e.g. digoxin and digitoxin). These drugs are used to treat heart failure. Sulfamethoxazole-trimethoprim increases the concentration of these drugs in the blood, which increases the risk of toxic side effects.
  • Phenytoin (a drug used to treat epilepsy). Sulfamethoxazole-trimethoprim increases the level of Phenytoin in the blood, and increases the risk of toxicity.
  • Methotrexate (a drug used in the treatment of cancer). Sulfamethoxazole-trimethoprim increases the level of Methotrexate in the blood, and increases the risk of side effects.
  • Thiazides, such as: hydrochlorothiazide (drugs used in the treatment of heart diseases). Concomitant use increases the risk of thrombocytopenia.
  • Potassium sparing diuretics, such as: spironolactone, triamterene and amiloride. Sulfamethoxazole-trimethoprim increases the level of potassium in the blood, as well as mentioned diuretics, so concomitant use should be avoided.
  • ACE inhibitors and angiotensin-receptor blockers (medicines used to treat heart diseases). These drugs increase levels of potassium in the blood.

Side effects

Sulfamethoxazole-trimethoprim may cause the following side effects:

  • Blood idiosyncrasies, such as: thrombocytopenia, agranulocytosis, granulocytopenia, leucopenia, anemia and methemoglobinemia
  • Digestive disorders
  • Hyperkalemia
  • Hallucinations
  • Delirium
  • Neuropathy
  • Ataxia
  • Tinnitus
  • Fungal Infections
  • Clostridium difficile colitis
  • Stevens-Johnson syndrome
  • Lyle syndrome
  • Hepatic necrosis
  • Rhabdomyolysis
  • Allergic reactions

References

  1. NCBI link 1
  2. NCBI link 2
  3. NCBI link 3