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BACTRIM™
sulfamethoxazole and trimethoprim DS
(double strength) tablets and tablets USP
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 bacteria.
DESCRIPTION BACTRIM (sulfamethoxazole and trimethoprim) is a synthetic antibacterial combination product available in DS (double strength) tablets, each containing 800 mg sulfamethoxazole and 160 mg trimethoprim; in tablets, each containing 400 mg sulfamethoxazole and 80 mg trimethoprim for oral administration.
Sulfamethoxazole is N^1 -(5-methyl-3-isoxazolyl)sulfanilamide; the molecular formula is C 10 H 11 N 3 O 3 S. It is an almost white, odorless, tasteless compound with a molecular weight of 253.28 and the following structural formula:
Trimethoprim is 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine; the molecular formula is C 14 H 18 N 4 O 3. It is a white to light yellow, odorless, bitter compound with a molecular weight of 290.3 and the following structural formula:
Inactive ingredients: Docusate sodium 85%, sodium benzoate 15%, sodium starch glycolate, magnesium stearate and pregelatinized starch.
CLINICAL PHARMACOLOGY 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 -acetyl-, N 4 -hydroxy-, 5-methylhydroxy-, N 4 -acetyl-
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5-methylhydroxy- sulfamethoxazole metabolites, and an N-glucuronide conjugate. The formulation of N 4 -hydroxy metabolite is mediated via CYP2C9.
Trimethoprim is metabolized in vitro to 11 different metabolites, of which, five are glutathione adducts and six are oxidative metabolites, including the major metabolites, 1- and 3-oxides and the 3- and 4-hydroxy derivatives.
The free forms of sulfamethoxazole and trimethoprim are considered to be the therapeutically active forms.
In vitro studies suggest that trimethoprim is a substrate of P-glycoprotein, OCT1 and OCT2, and that sulfamethoxazole is not a substrate of P-glycoprotein.
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 section). Detectable amounts of sulfamethoxazole and trimethoprim are present in the blood 24 hours after drug administration. During administration of 800 mg sulfamethoxazole and 160 mg trimethoprim b.i.d., the mean steady-state plasma concentration of trimethoprim was 1.72 μg/mL. The steady-state mean plasma levels of free and total sulfamethoxazole were 57.4 μg/mL and 68.0 μg/mL, respectively. These steady-state levels were achieved after three days of drug administration.^1 Excretion of sulfamethoxazole and trimethoprim is primarily by the kidneys through both glomerular filtration and tubular secretion. Urine concentrations of both sulfamethoxazole and trimethoprim are considerably higher than are the concentrations in the blood. The average percentage of the dose recovered in urine from 0 to 72 hours after a single oral dose of sulfamethoxazole and trimethoprim is 84.5% for total sulfonamide and 66.8% for free trimethoprim. Thirty percent of the total sulfonamide is excreted as free sulfamethoxazole, with the remaining as N 4 -acetylated metabolite.^2 When administered together as sulfamethoxazole and trimethoprim, neither sulfamethoxazole nor trimethoprim affects the urinary excretion pattern of the other.
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.
Geriatric Pharmacokinetics: 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,
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Diffusion Techniques: Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method14,15. This procedure uses paper disks impregnated with 1.25/23.75 μg of trimethoprim/sulfamethoxazole to test the susceptibility of microorganisms to trimethoprim/sulfamethoxazole. The disc diffusion interpretive criteria are provided in Table 1.
Table 1: Susceptibility Test Interpretive Criteria for Trimethoprim/Sulfamethoxazole
Bacteria
Minimal Inhibitory Concentration (mcg/mL)
Zone Diameter (mm) S I R S I R Enterobacteriaceae (^) ≤ 2/38 - ≥ 4/76 ≥ 16 11 – 15 ≤ 10 Haemophilus influenzae (^) ≤ 0.5/9.5 1/19 – 2/38 ≥ 4/76 ≥ 16 11 – 15 ≤ 10 Streptococcus pneumoniae ≤ 0.5/9.5 1/19 – 2/38 ≥ 4/76 ≥ 19 16 – 18 ≤ 15
A report of Susceptible indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations at the site of infection necessary to inhibit growth of the pathogen. A report of Intermediate indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected.
Quality Control Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay and the techniques of the individuals performing the test4, 14, 15. Standard trimethoprim/sulfamethoxazole powder should provide the following range of MIC values noted in Table 2. For the diffusion technique using the 1.25/23.75 μg trimethoprim/sulfamethoxazole disk the criteria in Table 2 should be achieved.
Table 2: Acceptable Quality Control Ranges for Susceptibility Testing for Trimethoprim/Sulfamethoxazole
QC Strain Minimal Inhibitory Zone Diameter Concentration (mm) (mcg/mL) Escherichia coli ATCC 25922 ≤ 0.5/9.5 23– Haemophilus influenzae ATCC 49247 0.03/0.59 – 0.25/4.75 24– Streptococcus pneumoniae ATCC 49619 0.12/2.4 – 1/19 20–
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INDICATIONS AND USAGE
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 species, Enterobacter species, Morganella morganii , Proteus mirabilis and Proteus vulgaris. It is recommended that initial episodes of uncomplicated urinary tract infections be treated with a single effective antibacterial agent rather than the combination.
Acute Otitis Media: For the treatment of acute otitis media in pediatric patients due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae when in the judgment of the physician sulfamethoxazole and trimethoprim offers some advantage over the use of other antimicrobial agents. To date, there are limited data on the safety of repeated use of BACTRIM in pediatric patients under two years of age. BACTRIM is not indicated for prophylactic or prolonged administration in otitis media at any age.
Acute Exacerbations of Chronic Bronchitis in Adults: For the treatment of acute exacerbations of chronic bronchitis due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae when a physician deems that BACTRIM could offer some advantage over the use of a single antimicrobial agent.
Shigellosis: For the treatment of enteritis caused by susceptible strains of Shigella flexneri and Shigella sonnei when antibacterial therapy is indicated.
Pneumocystis jiroveci Pneumonia: For the treatment of documented Pneumocystis jiroveci pneumonia and for prophylaxis against P. jiroveci pneumonia in individuals who are immunosuppressed and considered to be at an increased risk of developing P. jiroveci pneumonia.
Traveler’s Diarrhea in Adults: For the treatment of traveler’s diarrhea due to susceptible strains of enterotoxigenic E. coli.
CONTRAINDICATIONS BACTRIM is contraindicated in patients with a known hypersensitivity to trimethoprim or sulfonamides, in patients with a history of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides, and in patients with documented megaloblastic anemia due to folate deficiency.
BACTRIM is contraindicated in pediatric patients less than 2 months of age. BACTRIM is also contraindicated in patients with marked hepatic damage or with severe renal insufficiency when renal function status cannot be monitored.
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If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.
Adjunctive treatment with Leucovorin for Pneumocystis jiroveci pneumonia Treatment failure and excess mortality were observed when trimethoprim-sulfamethoxazole was used concomitantly with leucovorin for the treatment of HIV positive patients with Pneumocystis jiroveci pneumonia in a randomized placebo controlled trial.^6 Co-administration of trimethoprim sulfamethoxazole and leucovorin during treatment of Pneumocystis jiroveci pneumonia should be avoided.
PRECAUTIONS Development of drug resistant bacteria Prescribing Bactrim (sulfamethoxazole and trimethoprim) tablets in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Folate deficiency BACTRIM should be given with caution to patients with impaired renal or hepatic function, to those with possible folate deficiency (e.g., the elderly, chronic alcoholics, patients receiving anticonvulsant therapy, patients with malabsorption syndrome, and patients in malnutrition states) and to those with severe allergies or bronchial asthma.
Hematological changes indicative of folic acid deficiency may occur in elderly patients or in patients with preexisting folic acid deficiency or kidney failure. These effects are reversible by folinic acid therapy.
Hemolysis In glucose-6-phosphate dehydrogenase deficient individuals, hemolysis may occur. This reaction is frequently dose-related (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION ).
Hypoglycemia Cases of hypoglycemia in non-diabetic patients treated with BACTRIM are seen rarely, usually occurring after a few days of therapy. Patients with renal dysfunction, liver disease, malnutrition or those receiving high doses of BACTRIM are particularly at risk.
Phenylalanine metabolism Trimethoprim has been noted to impair phenylalanine metabolism, but this is of no significance in phenylketonuric patients on appropriate dietary restriction.
Porphyria and Hypothyroidism As with all drugs containing sulfonamides, caution is advisable in patients with porphyria or thyroid dysfunction.
Use in the Treatment of and Prophylaxis for Pneumocystis jiroveci Pneumonia in Patients with Acquired Immunodeficiency Syndrome (AIDS): AIDS patients may not tolerate or respond to
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BACTRIM in the same manner as non-AIDS patients. The incidence of side effects, particularly rash, fever, leukopenia and elevated aminotransferase (transaminase) values, with BACTRIM therapy in AIDS patients who are being treated for P. jiroveci pneumonia has been reported to be greatly increased compared with the incidence normally associated with the use of BACTRIM in non-AIDS patients. Adverse effects are generally less severe in patients receiving BACTRIM for prophylaxis. A history of mild intolerance to BACTRIM in AIDS patients does not appear to predict intolerance of subsequent secondary prophylaxis.^7 However, if a patient develops skin rash or any sign of adverse reaction, therapy with BACTRIM should be reevaluated (see WARNINGS ).
Co-administration of BACTRIM and leucovorin should be avoided with P. jiroveci pneumonia (see WARNINGS ).
Electrolyte Abnormalities High dosage of trimethoprim, as used in patients with P. jiroveci pneumonia, induces a progressive but reversible increase of serum potassium concentrations in a substantial number of patients. Even treatment with recommended doses may cause hyperkalemia when trimethoprim is administered to patients with underlying disorders of potassium metabolism, with renal insufficiency, or if drugs known to induce hyperkalemia are given concomitantly. Close monitoring of serum potassium is warranted in these patients.
Severe and symptomatic hyponatremia can occur in patients receiving BACTRIM, particularly for the treatment of P. jiroveci pneumonia. Evaluation for hyponatremia and appropriate correction is necessary in symptomatic patients to prevent life-threatening complications.
During treatment, adequate fluid intake and urinary output should be ensured to prevent crystalluria. Patients who are “slow acetylators” may be more prone to idiosyncratic reactions to sulfonamides.
Information for Patients: Patients should be counseled that antibacterial drugs including Bactrim (sulfamethoxazole and trimethoprim) tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Bactrim (sulfamethoxazole and trimethoprim) tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Bactrim (sulfamethoxazole and trimethoprim) tablets or other antibacterial drugs in the future.
Patients should be instructed to maintain an adequate fluid intake in order to prevent crystalluria and stone formation.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
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In the literature, a single case of toxic delirium has been reported after concomitant intake of sulfamethoxazole/trimethoprim and amantadine (an OCT2 substrate). Cases of interactions with other OCT2 substrates, memantine and metformin, have also been reported.
In the literature, three cases of hyperkalemia in elderly patients have been reported after concomitant intake of sulfamethoxazole/trimethoprim and an angiotensin converting enzyme inhibitor.8,
Drug/Laboratory Test Interactions: BACTRIM, specifically the trimethoprim component, can interfere with a serum methotrexate assay as determined by the competitive binding protein technique (CBPA) when a bacterial dihydrofolate reductase is used as the binding protein. No interference occurs, however, if methotrexate is measured by a radioimmunoassay (RIA).
The presence of sulfamethoxazole and trimethoprim may also interfere with the Jaffé alkaline picrate reaction assay for creatinine, resulting in overestimations of about 10% in the range of normal values.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenesis: Sulfamethoxazole was not carcinogenic when assessed in a 26-week tumorigenic mouse (Tg-rasH2) study at doses up to 400 mg/kg/day sulfamethoxazole; equivalent to 2.4-fold the human systemic exposure (at a daily dose of 800 mg sulfamethoxazole b.i.d. ).
Mutagenesis: In vitro reverse mutation bacterial tests according to the standard protocol have not been performed with sulfamethoxazole and trimethoprim in combination. An in vitro chromosomal aberration test in human lymphocytes with sulfamethoxazole/trimethoprim was negative. In in vitro and in vivo tests in animal species, sulfamethoxazole/trimethoprim did not damage chromosomes. In vivo micronucleus assays were positive following oral administration of sulfamethoxazole/trimethoprim. Observations of leukocytes obtained from patients treated with sulfamethoxazole and trimethoprim revealed no chromosomal abnormalities.
Sulfamethoxazole alone was positive in an in vitro reverse mutation bacterial assay and in in vitro micronucleus assays using cultured human lymphocytes.
Trimethoprim alone was negative in in vitro reverse mutation bacterial assays and in in vitro chromosomal aberration assays with Chinese Hamster ovary or lung cells with or without S activation. In in vitro Comet, micronucleus and chromosomal damage assays using cultured human lymphocytes, trimethoprim was positive. In mice following oral administration of trimethoprim, no DNA damage in Comet assays of liver, kidney, lung, spleen, or bone marrow was recorded.
Impairment of Fertility: No adverse effects on fertility or general reproductive performance were observed in rats given oral dosages as high as 350 mg/kg/day sulfamethoxazole plus 70 mg/kg/day trimethoprim, doses roughly two times the recommended human daily dose on a body surface area basis.
Pregnancy: While there are no large, well-controlled studies on the use of sulfamethoxazole and trimethoprim in pregnant women, Brumfitt and Pursell,^10 in a retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or sulfamethoxazole and
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trimethoprim. The incidence of congenital abnormalities was 4.5% (3 of 66) in those who received placebo and 3.3% (4 of 120) in those receiving sulfamethoxazole and trimethoprim. There were no abnormalities in the 10 children whose mothers received the drug during the first trimester. In a separate survey, Brumfitt and Pursell also found no congenital abnormalities in 35 children whose mothers had received oral sulfamethoxazole and trimethoprim at the time of conception or shortly thereafter.
Because sulfamethoxazole and trimethoprim may interfere with folic acid metabolism, BACTRIM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Teratogenic Effects: Pregnancy Category D.
Human Data: While there are no large prospective, well controlled studies in pregnant women and their babies, some retrospective epidemiologic studies suggest an association between first trimester exposure to sulfamethoxazole/trimethoprim with an increased risk of congenital malformations, particularly neural tube defects, cardiovascular abnormalities, urinary tract defects, oral clefts, and club foot. These studies, however, were limited by the small number of exposed cases and the lack of adjustment for multiple statistical comparisons and confounders. These studies are further limited by recall, selection, and information biases, and by limited generalizability of their findings. Lastly, outcome measures varied between studies, limiting cross-study comparisons. Alternatively, other epidemiologic studies did not detect statistically significant associations between sulfamethoxazole/trimethoprim exposure and specific malformations.
Animal Data: In rats, oral doses of either 533 mg/kg sulfamethoxazole or 200 mg/kg trimethoprim produced teratologic effects manifested mainly as cleft palates. These doses are approximately 5 and 6 times the recommended human total daily dose on a body surface area basis. In two studies in rats, no teratology was observed when 512 mg/kg of sulfamethoxazole was used in combination with 128 mg/kg of trimethoprim. In some rabbit studies, an overall increase in fetal loss (dead and resorbed conceptuses) was associated with doses of trimethoprim 6 times the human therapeutic dose based on body surface area.
Nonteratogenic Effects: See CONTRAINDICATIONS section.
Nursing Mothers: Levels of trimethoprim/sulfamethoxazole in breast milk are approximately 2– 5% of the recommended daily dose for infants over 2 months of age. Caution should be exercised when BACTRIM is administered to a nursing woman, especially when breastfeeding, jaundiced, ill, stressed, or premature infants because of the potential risk of bilirubin displacement and kernicterus.
Pediatric Use: BACTRIM is contraindicated for infants younger than 2 months of age (see INDICATIONS and CONTRAINDICATIONS sections).
Geriatric Use: Clinical studies of BACTRIM did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
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Genitourinary: Renal failure, interstitial nephritis, BUN and serum creatinine elevation, toxic nephrosis with oliguria and anuria, crystalluria and nephrotoxicity in association with cyclosporine.
Metabolic and Nutritional: Hyperkalemia, hyponatremia (see PRECAUTIONS: Electrolyte Abnormalities ).
Neurologic: Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache.
Psychiatric: Hallucinations, depression, apathy, nervousness.
Endocrine: The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides.
Musculoskeletal: Arthralgia and myalgia. Isolated cases of rhabdomyolysis have been reported with BACTRIM, mainly in AIDS patients.
Respiratory: Cough, shortness of breath and pulmonary infiltrates (see WARNINGS ).
Miscellaneous: Weakness, fatigue, insomnia.
Postmarketing Experience The following adverse reactions have been identified during post-approval use of trimethoprim sulfamethoxazole. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure:
Thrombotic thrombocytopenia purpura
Idiopathic thrombocytopenic purpura
QT prolongation resulting in ventricular tachycardia and torsade de pointes
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
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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.
DOSAGE AND ADMINISTRATION 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: The usual adult dosage in the treatment of urinary tract infections is 1 BACTRIM DS (double strength) tablet or 2 BACTRIM tablets every 12 hours for 10 to 14 days. An identical daily dosage is used for 5 days in the treatment of shigellosis.
Children: The recommended dose for children with urinary tract infections or acute otitis media is 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim per 24 hours, given in two divided doses every 12 hours for 10 days. An identical daily dosage is used for 5 days in the treatment of shigellosis. The following table is a guideline for the attainment of this dosage:
Children 2 months of age or older: Weight Dose–every 12 hours lb kg Tablets 22 10 – 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 Recommended Clearance (mL/min) Dosage Regimen Above 30 Usual standard regimen 15–30 ½ the usual regimen Below 15 Use not recommended
Acute Exacerbations of Chronic Bronchitis in Adults: The usual adult dosage in the treatment of acute exacerbations of chronic bronchitis is 1 BACTRIM DS (double strength) tablet or 2 BACTRIM tablets every 12 hours for 14 days.
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HOW SUPPLIED
BACTRIM™ TABLETS are supplied as follows:
BACTRIM™ DS (double strength) TABLETS (white, oval shaped, scored) containing 160 mg trimethoprim and 800 mg sulfamethoxazole – bottles of 100 (NDC 13310-146-01) and 500 (NDC 13310-146-05). Imprint on tablets (debossed): (front) BACTRIM DS
BACTRIM™ TABLETS (white, round, scored) containing 80 mg trimethoprim and 400 mg sulfamethoxazole – bottles of 100 (NDC 13310-145-01) and 500 (NDC 13310-145-05). Imprint on tablets (debossed): (front) BACTRIM
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]
DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.
REFERENCES:
- Kremers P, Duvivier J, Heusghem C. Pharmacokinetic Studies of Co-Trimoxazole in Man after Single and Repeated Doses. J Clin Pharmacol. Feb-Mar 1974; 14:112–117.
- Kaplan SA, et al. Pharmacokinetic Profile of Trimethoprim-Sulfamethoxazole in Man. J Infect Dis. Nov 1973; 128 (Suppl): S547–S555.
- Varoquaux O, et al. Pharmacokinetics of the trimethoprim-sulfamethoxazole combination in the elderly. Br J Clin Pharmacol. 1985;20:575–581.
- Rudoy RC, Nelson JD, Haltalin KC. Antimicrobial Agents Chemother. May 1974;5:439–443.
- Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – 9th^ ed. CLSI document M07– A9, CLSI, Wayne, PA, 2012.
- Safrin S, Lee BL, Sande MA. Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death. J Infect Dis. 1994 Oct;170(4):912–7.
- Hardy DW, et al. A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. N Engl J Med. 1992; 327: 1842–1848.
- Marinella Mark A. 1999. Trimethoprim-induced hyperkalemia: An analysis of reported cases. Gerontol. 45:209–212.
- Margassery, S. and B. Bastani. 2002. Life threatening hyperkalemia and acidosis secondary to trimethoprim-sulfamethoxazole treatment. J. Nephrol. 14:410–414.
- Brumfitt W, Pursell R. Trimethoprim/Sulfamethoxazole in the Treatment of Bacteriuria in Women. J Infect Dis. Nov 1973; 128 (Suppl):S657–S663.
- Masur H. Prevention and treatment of Pneumocystis pneumonia. N Engl J Med. 1992; 327: 1853–1880.
- Recommendations for prophylaxis against Pneumocystis carinii pneumonia for adults and adolescents infected with human immunodeficiency virus. MMWR. 1992; 41(RR–4):1–11.
- CDC Guidelines for prophylaxis against Pneumocystis carinii pneumonia for children infected with human immunodeficiency virus. MMWR. 1991; 40(RR–2):1–13.
- Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard – 11th^ ed. CLSI document M02–A11, CLSI, Wayne, PA, 2012.
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- Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-third Informational Supplement , CLSI document M100–S23. CLSI document M100–S23, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2013.
BACTRIMTM^ and BACTRIMTM^ DS are trademarks of Hoffmann-La Roche Inc.
Manufactured for: AR SCIENTIFIC, INC. Philadelphia, PA 19124 USA by: MUTUAL PHARMACEUTICAL COMPANY, INC. Philadelphia, PA 19124 USA
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