Co-Trimoxazole

Cotrimoxazole is a combination of trimethoprim and sulfamethoxazole. Cotrimoxazole is used to treat a variety of bacterial infections such as uncomplicated UTIs, respiratory tract infections, and gastrointestinal infections.

Co-Trimoxazole is primarily indicated in conditions like Acute exacerbation of chronic bronchitis, Anorectal infections, Brucellosis, Chancroid, Cholera, Chronic bronchitis, Diarrhea, Genitourinary tract infections, GI infections, Gonorrhea, Metastatic germ cell cancer, Oliguria due to renal failure, Oropharyngeal candidiasis, Oropharyngeal infections, Osteomyelitis, Otitis media, Pneumocystis carinii infections, Pneumonia, Respiratory tract infections, Septicemia, Skin infections, Squamous cell carcinoma, Travelers diarrhea, Uncomplicated UTIs, and can also be given in adjunctive therapy as an alternative drug of choice in Cancer, Infections, Oliguria, Prostatic cancer, Salmonellosis.

Co-Trimoxazole is contraindicated in conditions like Impaired renal function, Liver parenchymal damage, Hypersensitivity, Haematological disorders.

The severe or irreversible adverse effects of Co-Trimoxazole, which give rise to further complications include Thrombocytopenia, Aplastic anemia, Hemolytic anemia, Stevens Johnson syndrome, Leucopenia, Neutropenia, Agranulocytosis, Interstitial nephritis, Acute renal failure, Methemoglobinemia, Hemolytic anemia, Megaloblastic anemia, Crystalluria, Methemoglobinemia, Aplastic anemia. The symptomatic adverse reactions produced by Co-Trimoxazole are more or less tolerable and if they become severe, they can be treated symptomatically, these include Nausea, Vomiting, Skin reactions, Skin rashes, GI symptoms, Exfoliative dermatitis, Skin rashes.

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. Rash, sore throat, fever, arthralgia, pallor, purpura, or jaundice may be early indications of serious reactions. Discontinue co-trimoxazole at the first appearance of rash or any sign of adverse reactions. Possible emergence and overgrowth of nonsusceptible bacteria or fungi. Institute appropriate therapy if superinfection occurs. Treatment with anti-infectives may permit overgrowth of clostridia. Consider Clostridium difficile -associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly. Some mild cases of C. difficile -associated diarrhea and colitis may respond to discontinuance alone. Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe. Cough, shortness of breath, and pulmonary infiltrates are hypersensitivity reactions of the respiratory tact that have been reported with sulfonamides. Use with caution in patients with severe allergy or bronchial asthma. Concentrate for injection contains a sulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals. 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). 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. The incidence of hyperkalemia and hyponatremia also may be increased in HIV-infected patients. Adverse effects generally are less severe in those receiving co-trimoxazole for prophylaxis rather than treatment. A history of mild intolerance to co-trimoxazole in HIV-infected patients does not appear to predict intolerance to subsequent use of the drug for secondary prophylaxis. However, use of the drug should be reevaluated in patients who develop rash or any sign of adverse reaction. Concomitant use of leucovorin and co-trimoxazole for acute treatment of P. jiroveci pneumonia in HIV-infected patients has been associated with increased rates of treatment failure and morbidity. Perform CBCs frequently during co-trimoxazole therapy; discontinue the drug if a significant reduction in any formed blood element occurs. Perform urinalysis with careful microscopic examination and renal function tests during co-trimoxazole therapy, especially in patients with impaired renal function. To reduce development of drug-resistant bacteria and maintain effectiveness of co-trimoxazole and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria. When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. Because S. pyogenes (group A β-hemolytic streptococci) may not be eradicated by co-trimoxazole, do not use the drug for treatment of infections caused by this organism since it cannot prevent sequelae such as rheumatic fever. Category C. Because sulfonamides may cause kernicterus in neonates, co-trimoxazole is contraindicated in pregnant women at term. Both sulfamethoxazole and trimethoprim distributed into milk. Co-trimoxazole contraindicated in nursing women. Safety and efficacy not established in children <2 months of age. Geriatric patients may be at increased risk of severe adverse reactions, particularly if they have impaired hepatic and/or renal function or are receiving concomitant drug therapy. The most frequent adverse reactions in geriatric patients are severe skin reactions, generalized bone marrow suppression, or a specific decrease in platelets (with or without purpura). Those receiving concurrent therapy with a diuretic (principally thiazides) are at increased risk of thrombocytopenia with purpura. Dosage adjustments are necessary based on age-related decreases in renal function. Use with caution in patients with impaired hepatic function. Use reduced dosage in patients with Cl cr 15–30 mL/minute. Do not use in patients with Cl cr <15 mL/minute.

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. Rash, sore throat, fever, arthralgia, pallor, purpura, or jaundice may be early indications of serious reactions. Discontinue co-trimoxazole at the first appearance of rash or any sign of adverse reactions. Possible emergence and overgrowth of nonsusceptible bacteria or fungi. Institute appropriate therapy if superinfection occurs. Treatment with anti-infectives may permit overgrowth of clostridia. Consider Clostridium difficile -associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly. Some mild cases of C. difficile -associated diarrhea and colitis may respond to discontinuance alone. Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe. Cough, shortness of breath, and pulmonary infiltrates are hypersensitivity reactions of the respiratory tact that have been reported with sulfonamides. Use with caution in patients with severe allergy or bronchial asthma. Concentrate for injection contains a sulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals. 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). 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. The incidence of hyperkalemia and hyponatremia also may be increased in HIV-infected patients. Adverse effects generally are less severe in those receiving co-trimoxazole for prophylaxis rather than treatment. A history of mild intolerance to co-trimoxazole in HIV-infected patients does not appear to predict intolerance to subsequent use of the drug for secondary prophylaxis. However, use of the drug should be reevaluated in patients who develop rash or any sign of adverse reaction. Concomitant use of leucovorin and co-trimoxazole for acute treatment of P. jiroveci pneumonia in HIV-infected patients has been associated with increased rates of treatment failure and morbidity. Perform CBCs frequently during co-trimoxazole therapy; discontinue the drug if a significant reduction in any formed blood element occurs. Perform urinalysis with careful microscopic examination and renal function tests during co-trimoxazole therapy, especially in patients with impaired renal function. To reduce development of drug-resistant bacteria and maintain effectiveness of co-trimoxazole and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria. When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. Because S. pyogenes (group A β-hemolytic streptococci) may not be eradicated by co-trimoxazole, do not use the drug for treatment of infections caused by this organism since it cannot prevent sequelae such as rheumatic fever. Category C. Because sulfonamides may cause kernicterus in neonates, co-trimoxazole is contraindicated in pregnant women at term. Both sulfamethoxazole and trimethoprim distributed into milk. Co-trimoxazole contraindicated in nursing women. Safety and efficacy not established in children <2 months of age. Geriatric patients may be at increased risk of severe adverse reactions, particularly if they have impaired hepatic and/or renal function or are receiving concomitant drug therapy. The most frequent adverse reactions in geriatric patients are severe skin reactions, generalized bone marrow suppression, or a specific decrease in platelets (with or without purpura). Those receiving concurrent therapy with a diuretic (principally thiazides) are at increased risk of thrombocytopenia with purpura. Dosage adjustments are necessary based on age-related decreases in renal function. Use with caution in patients with impaired hepatic function. Use reduced dosage in patients with Cl cr 15–30 mL/minute. Do not use in patients with Cl cr <15 mL/minute.

960 mg (960 (960)) 12 hourly PO —

24 mg/kg (24 (24)) 12 hourly Oral — - 24 mg/kg (24 (24)) 12 hourly Slow IV — -

15 to 30 mg/kg (22 (22.5)) 12 hourly Slow intravenous — 15 to 30 mg/kg (22 (22.5)) 12 hourly oral —

Co-Trimoxazole is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementCyclosporin ADigoxinFosphenytoinLamivudineMethotrexateNicoumalonePhenindionePhenytoin (Na)Procainamide (HCl)PyrimethaminePyrimethamineRifampicinSulphamethoxazoleWarfarin (Na)Zidovudine These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.

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