Drug information of Cotrimoxazole

Cotrimoxazole

Drug group: sulfonamide

Co-trimoxazol is fixed combination of sulfamethoxazole (intermediate-acting sulfonamide) and trimethoprim.

Mechanism of effect

A fixed combination of sulfamethoxazole and trimethoprim; both drugs are folate-antagonists and sequentially inhibit enzymes of the folic acid pathway in susceptible bacteria.

Sulfamethoxazole inhibits formation of dihydrofolic acid from p-aminobenzoic acid and trimethoprim inhibits formation of tetrahydrofolic acid (the metabolically active form of folic acid).

Sulfamethoxazole is bacteriostatic and trimethoprim usually is bactericidal; the fixed combination generally is bactericidal when synergism is achieved.

Pharmacodynamic

Spectrum of activity includes many gram-positive and -negative aerobic bacteria and some protozoa. Inactive against most anaerobic bacteria and inactive against fungi and viruses.
Gram-positive aerobes: Active against Staphylococcus aureus (including penicillinase-producing strains), Streptococcus pneumoniae, S. pyogenes (group A β-hemolytic streptococci), and some strains of enterococci (e.g., Enterococcus faecalis). Also active against Nocardia, but Bacillus anthracis may be resistant.
Gram-negative aerobes: Active against Acinetobacter, Enterobacter, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Salmonella, and Shigella. Also active against Haemophilus influenzae (including ampicillin-resistant strains), H. ducreyi, and Neisseria gonorrhoeae. Pseudomonas aeruginosa is resistant.
Other organisms: Active in vitro and in vivo against Pneumocystis jiroveci (Pneumocystis carinii). Most anaerobes, including Bacteroides and Clostridium, are resistant.
Resistance to co-trimoxazole has been reported in some Enterobacteriaceae and H. influenzae.

Pharmacokinetics

Sulfamethoxazole and trimethoprim are rapidly and well absorbed from the GI tract following oral administration of the fixed combination preparation (co-trimoxazole).
Peak serum concentrations of both sulfamethoxazole and trimethoprim are attained within 1–4 hours.Co-trimoxazole contains a 1:5 ratio of trimethoprim to sulfamethoxazole, but the trimethoprim:sulfamethoxazole ratio in serum after administration of the fixed-combination preparation is about 1:20 at steady-state.

Widely distributed into body tissues and fluids, including sputum, aqueous humor, middle ear fluid, bronchial secretions, prostatic fluid, vaginal fluid, and bile.In patients with uninflamed meninges, trimethoprim and sulfamethoxazole concentrations in CSF are about 50 and 40%, respectively, of concurrent serum concentrations.
Sulfamethoxazole is approximately 70% and trimethoprim is approximately 44% bound to plasma proteins.

Both sulfamethoxazole and trimethoprim are metabolized in the liver.
Both sulfamethoxazole and trimethoprim are rapidly excreted in urine by glomerular filtration and active tubular secretion.ab In adults with normal renal function, approximately 45–85% of a sulfamethoxazole dose and 50–67% of a trimethoprim dose are excreted in urine.Only small amounts of trimethoprim are excreted in feces via biliary elimination.
Serum half-lives of sulfamethoxazole and trimethoprim are approximately 10–13 and 8–11 hours, respectively, in adults with normal renal function.

Drug indications

Typhoid Fever , Toxoplasmosis

Alerts

1- Cough, shortness of breath, and pulmonary infiltrates are hypersensitivity reactions of the respiratory tact that have been reported with sulfonamides.Severe (sometimes fatal) reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias, have been reported with sulfonamides. Discontinue co-trimoxazole at the first appearance of rash or any sign of adverse reactions.Use with caution in patients with severe allergy or bronchial asthma.
2- Possible emergence and overgrowth of nonsusceptibleclostridia.if diarrhea develops and manage accordingly.
3- Hemolysis may occur in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency; this effect may be dose-related.Use with caution in patient with possible folate deficiency (e.g., geriatric patients, chronic alcoholics, patients receiving anticonvulsant therapy, patients with malabsorption syndrome, patients with malnutrition).
4- HIV-infected patients with Pneumocystis jiroveci pneumonia may have an increased incidence of adverse effects during co-trimoxazole therapy (particularly rash, fever, leukopenia, increased liver enzymes) compared with HIV-seronegative patients .
5- Use with caution in patients with impaired hepatic function. In patients with Clcr 15–30 mL/minute, use 50% of usual dosage.
6- Do not administer by rapid IV infusion or injection and do not administer IM.
7- Co-trimoxazole concentrate for injection must be diluted prior to IV infusion.Each 5 mL of the concentrate for injection containing 80 mg of trimethoprim should be added to 125 mL of 5% dextrose in water. In patients in whom fluid intake is restricted, each 5 mL of the concentrate may be added to 75 mL of 5% dextrose in water. IV solutions should be infused over a period of 60–90 minutes.

Points of recommendation

1- Importance of completing full course of therapy, even if feeling better after a few days.
2- If colitis or diarrhea occurs you must stop using drug, consult pharmacist or doctor.
3- Importance of discontinuing drug and informing clinician if rash or any sign of adverse reaction (sore throat, fever, arthralgia, pallor, purpura, jaundice) occurs.
4- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking co-trimoxazole, call your doctor immediately. Co-trimoxazole can harm the fetus.
5- Advise patients to maintain an adequate fluid intake to prevent crystalluria and stone formation.

Related drugs

Triplesulfa , Sulfadiazine


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