Cotrimoxazole

Author: Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 12.11.2021

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Synonym(s)

Trimethoprim-Sulfamethoxazole

Definition
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Chemotherapeutic agent; mixture of sulfamethoxazole and trimethoprim.

Half-life
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9–12 h

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Pharmacodynamics (Effect)
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Inhibition of tetrahydrofolic acid production and competitive inhibition of dihydrofolate reductase.

Spectrum of action
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Acinetobacter spp., Bordetella pertussis, Brucella spp., Citrobacter spp., Enterobacter spp., Enterococcus spp., E. coli, Haemophilus influenzae, Klebsiella spp., Listeria monocytogenes, Morganella morganii, Nocardia spp, Plasmodium falciparum (only in combination), Pneumocystis carinii (in high dosage), Proteus spp., Rochalimaea spp., Salmonella spp., Serratia macescens, Shigella spp., Staphylococcus spp., Streptococcus spp., Vibrio spp., Yersinia spp.

Indication
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Respiratory tract infections, Pneumocystis carinii pneumonia, infections of the urinary tract, gastrointestinal tract, female genital tract (not syphilis!), prostatitis. Proph. of Pneumocystis carinii pneumonia in HIV patients.

Limited indication
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Pregnancy 2nd and 3rd trimester, impaired renal function, mild hepatic dysfunction, thyroid dysfunction, hypersensitivity to sulfonylureas, diuretics and sulfonamide-based antidiabetics, especially folic acid deficiency, fragile X chromosome in combination with mental retardation in children.

Dosage and method of use
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Standard therapy: 2 times/day 2 tbl (80 mg TMP + 400 mg SM) p.o.
For Pneumocystis carinii pneumonia:
- Light PCP: double dosage i.v.
- Heavy PCP: SM 1 time 100 mg/kg bw, TMP 20 mg/kg bw, e.g. 3 times 5 amp. in 500 ml NaCl over 90 min. for 21 days.
- Prophylaxis of PCP: 4 Tbl. forte (160 mg TMP + 800 mg SMZ) 3 times/week p.o.

Undesirable effects
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Pulmonary infiltrates, pneumonia, BB changes, gastrointestinal disorders, acute pancreatitis, petechiae, allergic reactions, Wissler syndrome, glossitis, gingivitis, headache, ataxia, hypoglycemia, metabolic acidosis, arthralgias. Cotrimoxazole is reported in versch. Cotrimoxazole is mentioned in various studies as the most frequent trigger of Stevens-Johnson syndrome (Micheletti RG et al. 2018).

Interactions
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s. Table 1.

Contraindication
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Pregnancy 1. Trimenon, lactation (newborns with hyperbilirubinemia or glucose-6-phosphate dehydrogenase deficiency as well as premature infants), hypersensitivity to sulfonamides and trimethoprim analogues, erythema exsudativum multiforme (also in the medical history), severe BB changes, glucose-6-phosphate dehydrogenase deficiency, hemoglobin abnormalities, kidney damage, decompensated renal insufficiency, severe liver damage, liver dysfunction, acute hepatic porphyria.

Preparations
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Bactoreduct, Berlocid, Cotrim, Cotrimox-Wolff, Drylin, Eusaprim, Kepinol, Supracombin, TMS

Note(s)
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Occurrence of sweet syndrome after taking cotrimoxazole has been described in the literature.

Literature
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Callen JP et al (2002) Neutrophilic dermatoses. Dermatol Clin 20: 409-419
Micheletti RG et al (2018) Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A Multicenter Retrospective Study of 377 Adult Patients from the United States. J Invest Dermatol 138:2315-2321.

Tables
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Major drug interactions of cotrimoxazole

Antacids	Absorption of the sulfonamide moiety ↓
Antidiabetics, oral	Hypoglycemic tendency↑
Anticoagulants, oral	bleeding tendency ↑
Barbiturates	Trimethoprim toxicity ↑
Indometacin	Sulfonamide action ↑
Methotrexate	MTX toxicity ↑
Phenylbutazone	Sulfonamide action ↑
Phenytoin	Phenytoin effect ↑ in individual cases.
Pyrimethamine (> 25 mg/week).	BB changes
Salicylates	Sulfonamide effect ↑
Sulfinpyrazone	Sulfonamide effect ↑