BACTRIM DS- sulfamethoxazole and trimethoprim_tablet

BACTRIM is rapidly absorbed following oral administration. Both sulfamethoxazole and trimethoprim exist in the blood as unbound, protein-bound and metabolized forms; sulfamethoxazole also exists as the conjugated form. Sulfamethoxazole is metabolized in humans to at least 5 metabolites: the N 4 4 4 4 via Trimethoprim is metabolized in vitro The free forms of sulfamethoxazole and trimethoprim are considered to be the therapeutically active forms. In vitro Approximately 70% of sulfamethoxazole and 44% of trimethoprim are bound to plasma proteins. The presence of 10 mg percent sulfamethoxazole in plasma decreases the protein binding of trimethoprim by an insignificant degree; trimethoprim does not influence the protein binding of sulfamethoxazole. Peak blood levels for the individual components occur 1 to 4 hours after oral administration. The mean serum half-lives of sulfamethoxazole and trimethoprim are 10 and 8 to 10 hours, respectively. However, patients with severely impaired renal function exhibit an increase in the half-lives of both components, requiring dosage regimen adjustment (see DOSAGE AND ADMINISTRATION 1 4 2 Both sulfamethoxazole and trimethoprim distribute to sputum, vaginal fluid and middle ear fluid; trimethoprim also distributes to bronchial secretion, and both pass the placental barrier and are excreted in human milk. Pharmacokinetics in Pediatric Patients A simulation conducted with data from a pharmacokinetic study in 153 infants and children demonstrated that mean steady state AUC and maximum plasma concentration of trimethoprim and sulfamethoxazole would be comparable between pediatric patients 2 months to 18 years receiving 8/40 (trimethoprim/ sulfamethoxazole) mg/kg/day divided every 12 hours and adult patients receiving 320/1600 (trimethoprim/ sulfamethoxazole) mg/day. Pharmacokinetics in Geriatric Patients The pharmacokinetics of sulfamethoxazole 800 mg and trimethoprim 160 mg were studied in 6 geriatric subjects (mean age: 78. 6 years) and 6 young healthy subjects (mean age: 29. 3 years) using a non-US approved formulation. Pharmacokinetic values for sulfamethoxazole in geriatric subjects were similar to those observed in young adult subjects. The mean renal clearance of trimethoprim was significantly lower in geriatric subjects compared with young adult subjects (19 mL/h/kg vs. 55 mL/h/kg). However, after normalizing by body weight, the apparent total body clearance of trimethoprim was on average 19% lower in geriatric subjects compared with young adult subjects. 3 Mechanism of Action Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA). Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding to and reversibly inhibiting the required enzyme, dihydrofolate reductase. Thus, sulfamethoxazole and trimethoprim blocks two consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria. Resistance In vitro Antimicrobial Activity BACTRIM has been shown to be active against most isolates of the following microorganisms, both in vitro INDICATIONS AND USAGE Aerobic gram-positive bacteria Streptococcus pneumoniae Aerobic gram-negative bacteria Escherichia coli Klebsiella Enterobacter Haemophilus influenzae Morganella morganii Proteus mirabilis Proteus vulgaris Shigella flexneri Shigella sonnei Other Microorganisms Pneumocystis jirovecii Susceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of BACTRIM (sulfamethoxazole and trimethoprim) tablets and other antibacterial drugs, BACTRIM (sulfamethoxazole and trimethoprim) tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to empiric selection of therapy. Urinary Tract Infections For the treatment of urinary tract infections due to susceptible strains of the following organisms: Escherichia coli Klebsiella Enterobacter Morganella morganii Proteus mirabilis Proteus vulgaris Acute Otitis Media For the treatment of acute otitis media in pediatric patients due to susceptible strains of Streptococcus pneumoniae Haemophilus influenzae Acute Exacerbations of Chronic Bronchitis in Adults For the treatment of acute exacerbations of chronic bronchitis due to susceptible strains of Streptococcus pneumoniae Haemophilus influenzae Shigellosis For the treatment of enteritis caused by susceptible strains of Shigella flexneri Shigella sonnei Pneumocystis jirovecii For the treatment of documented Pneumocystis jirovecii P. jirovecii P. jirovecii Traveler's Diarrhea in Adults For the treatment of traveler's diarrhea due to susceptible strains of enterotoxigenic E.

BACTRIM is contraindicated in pediatric patients less than 2 months of age. Urinary Tract Infections and Shigellosis in Adults and Pediatric Patients, and Acute Otitis Media in Children Adults: Children: Children 2 months of age or older: Weight Doseen dashevery 12 hours lb kg Tablets 22 10 en dash 44 20 1 66 30 1½ 88 40 2 or 1 DS tablet For Patients with Impaired Renal Function When renal function is impaired, a reduced dosage should be employed using the following table: Creatinine Clearance (mL/min) Recommended Dosage Regimen Above 30 Usual standard regimen 15en dash30 ½ the usual regimen Below 15 Use not recommended Acute Exacerbations of Chronic Bronchitis in Adults Pneumocystis jirovecii Treatment Adults and Children: Pneumocystis jirovecii 12 Weight Doseen dashevery 6 hours lb kg Tablets 18 8 en dash 35 16 1 53 24 1½ 70 32 2 or 1 DS tablet 88 40 2½ 106 48 3 or 1½ DS tablets 141 64 4 or 2 DS tablets 176 80 5 or 2½ DS tablets For the lower limit dose (75 mg/kg sulfamethoxazole and 15 mg/kg trimethoprim per 24 hours) administer 75% of the dose in the above table. Prophylaxis Adults: The recommended dosage for prophylaxis in adults is 1 BACTRIM DS (double strength) tablet daily. 13 Children: 2 2 14 Body Surface Area Doseen dashevery 12 hours (m 2 Tablets 0.26 en dash 0.53 ½ 1.06 1 Traveler’s Diarrhea in Adults

The following adverse reactions associated with the use of BACTRIM or sulfamethoxazole and trimethoprim were identified in clinical trials, postmarketing or published reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most common adverse reactions are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash and urticaria). Fatalities and serious adverse reactions, including severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute febrile neutrophilic dermatosis (AFND), acute generalized erythematous pustulosis (AGEP); fulminant hepatic necrosis; agranulocytosis, aplastic anemia and other blood dyscrasias; acute and delayed lung injury; anaphylaxis and circulatory shock have occurred with the administration of sulfamethoxazole and trimethoprim products, including BACTRIM(see WARNINGS Hematologic: Allergic Reactions: WARNINGS Gastrointestinal: Genitourinary: Metabolic and Nutritional: PRECAUTIONS: Electrolyte Abnormalities Neurologic: Psychiatric: Endocrine: Musculoskeletal: Respiratory: WARNINGS Cardiovascular System: torsades de pointes WARNINGS . Miscellaneous:

BACTRIM is contraindicated in the following situations: a known hypersensitivity to trimethoprim or sulfonamides history of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides documented megaloblastic anemia due to folate deficiency pediatric patients less than 2 months of age marked hepatic damage severe renal insufficiency when renal function status cannot be monitored concomitant administration with dofetilide (see PRECAUTIONS

WARNINGS
Some epidemiologic studies suggest that exposure to BACTRIM during pregnancy may be associated with an increased risk of congenital malformations, particularly neural tube defects, cardiovascular malformations, urinary tract defects, oral clefts, and club foot. If BACTRIM is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be advised of the potential hazards to the fetus (see PRECAUTIONS Fatalities and serious adverse reactions including severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute febrile neutrophilic dermatosis (AFND), acute generalized erythematous pustulosis (AGEP); fulminant hepatic necrosis; agranulocytosis, aplastic anemia and other blood dyscrasias; acute and delayed lung injury; anaphylaxis and circulatory shock have occurred with the administration of sulfamethoxazole and trimethoprim products, including BACTRIM (see ADVERSE REACTIONS Hypersensitivity Reactions of the Respiratory Tract Cough, shortness of breath and pulmonary infiltrates potentially representing hypersensitivity reactions of the respiratory tract have been reported in association with sulfamethoxazole and trimethoprim treatment. Respiratory Failure Other severe pulmonary adverse reactions occurring within days to week of BACTRIM initiation and resulting in prolonged respiratory failure requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO), lung transplantation or death have also been reported in patients and otherwise healthy individuals treated with sulfamethoxazole and trimethoprim products. Circulatory Shock Circulatory shock with fever, severe hypotension, and confusion requiring intravenous fluid resuscitation and vasopressors has occurred within minutes to hours of re-challenge with sulfamethoxazole and trimethoprim products, including BACTRIM, in patients with history of recent (days to weeks) exposure to sulfamethoxazole and trimethoprim. Management of Hypersensitivity Reactions BACTRIM should be discontinued at the first appearance of skin rash or any sign of a serious adverse reaction. A skin rash may be followed by a more severe reaction, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, AFND, AGEP, hepatic necrosis, or serious blood disorders (see PRECAUTIONS ADVERSE REACTIONS The sulfonamides should not be used for treatment of group A beta-hemolytic streptococcal infections. In an established infection, they will not eradicate the streptococcus and, therefore, will not prevent sequelae such as rheumatic fever. BACTRIM-induced thrombocytopenia may be an immune-mediated disorder. Severe cases of thrombocytopenia that are fatal or life threatening have been reported. Thrombocytopenia usually resolves within a week upon discontinuation of BACTRIM. Clostridioides difficile C. difficile C. difficile If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile Treatment failure and excess mortality were observed when BACTRIM was used concomitantly with leucovorin for the treatment of HIV positive patients with P. jirovecii 4 P jirovecii.
OVERDOSAGE
Acute The amount of a single dose of BACTRIM that is either associated with symptoms of overdosage or is likely to be life-threatening has not been reported. Signs and symptoms of overdosage reported with sulfonamides include anorexia, colic, nausea, vomiting, dizziness, headache, drowsiness and unconsciousness. Pyrexia, hematuria and crystalluria may be noted. Blood dyscrasias and jaundice are potential late manifestations of overdosage. Signs of acute overdosage with trimethoprim include nausea, vomiting, dizziness, headache, mental depression, confusion and bone marrow depression. General principles of treatment include the institution of gastric lavage or emesis, forcing oral fluids, and the administration of intravenous fluids if urine output is low and renal function is normal. Acidification of the urine will increase renal elimination of trimethoprim. The patient should be monitored with blood counts and appropriate blood chemistries, including electrolytes. If a significant blood dyscrasia or jaundice occurs, specific therapy should be instituted for these complications. Peritoneal dialysis is not effective and hemodialysis is only moderately effective in eliminating sulfamethoxazole and trimethoprim. Chronic Use of BACTRIM at high doses and/or for extended periods of time may cause bone marrow depression manifested as thrombocytopenia, leukopenia and/or megaloblastic anemia. If signs of bone marrow depression occur, the patient should be given leucovorin 5 to 15 mg daily until normal hematopoiesis is restored.
REFERENCES
Kremers P, Duvivier J, Heusghem C. Pharmacokinetic Studies of Co-Trimoxazole in Man after Single and Repeated Doses. J Clin Pharmacol Kaplan SA, et al. Pharmacokinetic Profile of Trimethoprim-Sulfamethoxazole in Man. J Infect Dis Varoquaux O, et al. Pharmacokinetics of the trimethoprim-sulfamethoxazole combination in the elderly. Br J Clin Pharmacol Safrin S, Lee BL, Sande MA. Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii J Infect Dis Marinella Mark A. 1999. Trimethoprim-induced hyperkalemia: An analysis of reported cases. Gerontol Margassery, S. and B. Bastani. 2002. Life threatening hyperkalemia and acidosis secondary to trimethoprim-sulfamethoxazole treatment. J. Nephrol Moh R, et al. Haematological changes in adults receiving a zidovudine-containing HAART regimen in combination with cotrimoxazole in Côte d’Ivoire. Antivir Ther Al-Khatib SM, LaPointe N, Kramer JM, Califf RM. What Clinicians Should Know About the QT Interval. JAMA Boyer EW, Stork C, Wang RY. Review: The Pharmacology and Toxicology of Dofetilide. Int J Med Toxicol. Kosoglou T, Rocci ML Jr, Vlasses PH. Trimethoprim alters the disposition of procainamide and N- Clin Pharmacol Ther Brumfitt W, Pursell R. Trimethoprim/Sulfamethoxazole in the Treatment of Bacteriuria in Women. J Infect Dis Masur H. Prevention and treatment of Pneumocystis N Engl J Med Recommendations for prophylaxis against Pneumocystis carinii MMWR. CDC Guidelines for prophylaxis against Pneumocystis carinii MMWR

REMEDYREPACK INC.

BACTRIM DS- sulfamethoxazole and trimethoprim_tablet Product manual source documgent