Sulfamethoxazole And Trimethoprim Oral Suspension, Usp 200 Mg/40 Mg Per 5 Ml

Drug Facts

Composition & Product

Active Ingredients

Sulfamethoxazole (200 mg) Trimethoprim (40 mg)

Inactive Ingredients

Citric Acid Monohydrate Sodium Benzoate Microcrystalline Cellulose Methylparaben Carboxymethylcellulose Sodium, Unspecified Form Fd&c Red No. 40 Saccharin Sodium Glycerin Alcohol Polysorbate 80 Water Sorbitol

Identifiers & Packaging

Pill Appearance

Color: pink

Marketing Status

ANDA Active Since 2022-07-05

Medication Information

Indications and Usage

To reduce the development of drug-resistant bacteria and maintain the eﬀectiveness of sulfamethoxazole and trimethoprim and other antibacterial drugs, sulfamethoxazole and trimethoprim 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 sulfamethoxazole and trimethoprim in pediatric patients under two years of age. Sulfamethoxazole and trimethoprim are 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 sulfamethoxazole and trimethoprim 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 jirovecii Pneumonia

For the treatment of documented Pneumocystis jirovecii pneumonia and for prophylaxis against P. jirovecii pneumonia in individuals who are immunosuppressed and considered to be at an increased risk of developing P. jirovecii pneumonia.

Traveler’s Diarrhea in Adults

For the treatment of traveler’s diarrhea due to susceptible strains of enterotoxigenic E. coli.

Dosage and Administration

Sulfamethoxazole and trimethoprim 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 4 teaspoonfuls (20 mL) of sulfamethoxazole and trimethoprim 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	Teaspoonfuls
22	10	1 (5 mL)
44	20	2 (10 mL)
66	30	3 (15 mL)
88	40	4 (20 mL)

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
15 - 30	1⁄2; 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 4 teaspoonfuls (20 mL) of sulfamethoxazole and trimethoprim every 12 hours for 14 days.

Pneumocystis jirovecii Pneumonia Treatment

Adults and Children:

The recommended dosage for treatment of patients with documented Pneumocystis jirovecii pneumonia is 75 to 100 mg/kg sulfamethoxazole and 15 to 20 mg/kg trimethoprim per 24 hours given in equally divided doses every 6 hours for 14 to 21 days. ¹²

The following table is a guideline for the upper limit of this dosage:

Weight	Dose - every 6 hours
lb	kg	Teaspoonfuls
18	8	1 (5 mL)
35	16	2 (10 mL)
53	24	3 (15 mL)
70	32	4 (20 mL)
88	40	5 (25 mL)
106	48	6 (30 mL)
141	64	8 (40 mL)
176	80	10 (50 mL)

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 4 teaspoonfuls (20 mL) of sulfamethoxazole and trimethoprim daily. ¹³

Children:

For children, the recommended dose is 750 mg/m ²/day sulfamethoxazole with 150 mg/m ²/day trimethoprim given orally in equally divided doses twice a day, on 3 consecutive days per week. The total daily dose should not exceed 1600 mg sulfamethoxazole and 320 mg trimethoprim. ¹⁴

The following table is a guideline for the attainment of this dosage in children:

Body Surface Area	Dose - every 12 hours
(m ²)	Teaspoonfuls
0.26	1⁄2; (2.5 mL)
0.53	1 (5 mL)
1.06	2 (10 mL)

Traveler’s Diarrhea in Adults

For the treatment of traveler’s diarrhea, the usual adult dosage is 4 teaspoonfuls (20 mL) of sulfamethoxazole and trimethoprim every 12 hours for 5 days.

Contraindications

Sulfamethoxazole and trimethoprim is contraindicated in the following situations:

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).

Adverse Reactions

The following adverse reactions associated with the use of 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 sulfamethoxazole and trimethoprim (see WARNINGS).

Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura.

Allergic/Immune Reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-Schöenlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria, rash, periarteritis nodosa, hemophagocytic lymphohistiocytosis (HLH), systemic lupus erythematosus, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized erythematous pustulosis (AGEP), and acute febrile neutrophilic dermatosis (AFND) (see WARNINGS).

Gastrointestional: Hepatitis (including cholestatic jaundice and hepatic necrosis), elevation of serum transaminase and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhea, anorexia.

Genitourinary: Renal failure, interstitial nephritis, BUN and serum creatinine elevation, renal insufficiency, oliguria and anuria, crystalluria and nephrotoxicity in association with cyclosporine.

Metabolic and Nutritional: Hyperkalemia, hyponatremia (see PRECAUTIONS: Electrolyte Abnormalities ), metabolic acidosis.

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.

Musculoskeletal: Arthralgia, myalgia, rhabdomyolysis.

Respiratory: Cough, shortness of breath and pulmonary infiltrates, acute eosinophilic pneumonia, acute and delayed lung injury, interstitial lung disease, acute respiratory failure (see WARNINGS).

Cardiovascular System: QT prolongation resulting in ventricular tachycardia and torsades de pointes, circulatory shock (see WARNINGS).

Miscellaneous: Weakness, fatigue, insomnia.

How Supplied

Sulfamethoxazole and Trimethoprim Oral Suspension USP, is supplied in a pink, syrupy, sour cherry flavored suspension containing 200 mg sulfamethoxazole and 40 mg trimethoprim per 5 mL (teaspoonful) and available as follows:

NDC 81033-012-20: 20 mL unit dose cup

NDC 81033-012-40: Carton of 40 (20 mL) unit dose cups each

Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature].

Protect from light.

DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER.

Shake well before using.

To report SUSPECTED ADVERSE REACTIONS, contact Kesin Pharma at 1-833-537-4679 or FDA at 1-800-FDA-1088 or

www.fda.gov/medwatch.

Description

Sulfamethoxazole and trimethoprim oral suspension is a synthetic antibacterial combination product available in a suspension for oral administration, with each teaspoonful (5 mL) containing 200 mg sulfamethoxazole and 40 mg trimethoprim.

Sulfamethoxazole is N ¹-(5-methyl-3-isoxazolyl) sulfanilamide; the molecular formula is C ₁₀H ₁₁N ₃O ₃S. 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 ₁₄H ₁₈N ₄O 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: alcohol 0.03% (v/v), methylparaben 0.1% and sodium benzoate 0.1% (added as preservatves), carboxymethylcellulose sodium, citric acid, glycerin, microcrystalline cellulose, polysorbate 80, purified water, saccharin sodium, sorbitol soluton, FD&C Red No. 40 and cherry flavoring.

Section 42229-5

To reduce the development of drug-resistant bacteria and maintain the effectiveness of sulfamethoxazole and trimethoprim oral suspension and other antibacterial drugs, sulfamethoxazole and trimethoprim oral suspension should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Section 51945-4

NDC 81033-012-40

Sulfamethoxazole and Trimethoprim

Oral Suspension, USP

800mg/160mg per 20mL

Delivers 20mL

Rx Only

FOR INSTITUTIONAL USE ONLY

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.
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.
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.
Moh R, et al. Haematological changes in adults receiving a zidovudine-containing HAART regimen in combination with cotrimoxazole in Côte d’Ivoire. Antivir Ther. 2005;10(5):615-24.
Al-Khatib SM, LaPointe N, Kramer JM, Califf RM. What Clinicians Should Know About the QT Interval. JAMA. 2003;289(16):2120-2127.
Boyer EW, Stork C, Wang RY. Review: The Pharmacology and Toxicology of Dofetilide. Int J Med Toxicol. 2001;4(2):16.
Kosoglou T, Rocci ML Jr, Vlasses PH. Trimethoprim alters the disposition of procainamide and N-acetylprocainamide. Clin Pharmacol Ther. Oct 1988;44(4):467-77.
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 Pharmacology

Sulfamethoxazole and trimethoprim 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-5-methylhydroxy-sulfamethoxazole metabolites, and an N-glucuronide conjugate. The formation 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.

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-U.S. 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

Microbiology

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 studies have shown that bacterial resistance develops more slowly with both sulfamethoxazole and trimethoprim in combination than with either sulfamethoxazole or trimethoprim alone.

Antimicrobial Activity

Sulfamethoxazole and trimethoprim have been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Aerobic gram-positive bacteria

Streptococcus pneumoniae

Aerobic gram-negative bacteria

Escherichia coli (including susceptible enterotoxigenic strains implicated in traveler’s diarrhea)

Klebsiella species

Enterobacter species

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.fda.gov/STIC.

Structured Label Content

Section 42229-5 (42229-5)