TRIMETHOPRIM TABLETS, USP, Rx Only

/TRIMETHOPRIM TABLETS, USP, Rx Only
TRIMETHOPRIM TABLETS, USP, Rx Only2018-09-06T09:12:40+00:00

Prescription Drug Name:

TRIMETHOPRIM TABLETS, USP, Rx Only

ID:

65482e08-b343-50f6-e053-2991aa0a2437

Code:

34391-3

DESCRIPTION


id: 65482e08-b345-50f6-e053-2991aa0a2437
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Trimethoprim is a synthetic antibacterial available as 100 mg tablets for oral administration. Trimethoprim is 5-[(3,4,5-trimethoxyphenyl) methyl]-2,4-pyrimidinediamine. It is a white to cream colored, odorless, bitter compound. The structural formula is represented below: C
14H
18N
4O
3      M.W. 290.32
Trimethoprim tablets, USP, 100 mg contain the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, magnesium stearate, sodium lauryl sulfate, sodium starch glycolate and stearic acid.

CLINICAL PHARMACOLOGY


id: 65482e08-b346-50f6-e053-2991aa0a2437
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

Trimethoprim is rapidly absorbed following oral administration. It exists in the blood as unbound, protein-bound, and metabolized forms. Ten to twenty percent of trimethoprim is metabolized, primarily in the liver; the remainder is excreted unchanged in the urine. The principal metabolites of trimethoprim are the 1- and 3-oxides and the 3ʹ- and 4ʹ-hydroxy derivatives. The free form is considered to be the therapeutically active form. Approximately 44% of trimethoprim is bound to plasma proteins. Mean peak serum concentrations of approximately 1 mcg/mL occur 1 to 4 hours after oral administration of a single 100 mg dose. A single 200 mg dose will result in serum levels approximately twice as high. The half-life of trimethoprim ranges from 8 to 10 hours. However, patients with severely impaired renal function exhibit an increase in the half-life of trimethoprim, which requires either dosage regimen adjustment or not using the drug in such patients (see
DOSAGE
AND ADMINISTRATION ). During a 13 week study of trimethoprim administered at a daily dosage of 200 mg (50 mg q.i.d.), the mean minimum steady-state concentration of the drug was 1.1 mcg/mL. Steadystate concentrations were achieved within 2 to 3 days of chronic administration and were maintained throughout the experimental period.
Excretion of trimethoprim is primarily by the kidneys through glomerular filtration and tubular secretion. Urine concentrations of trimethoprim are considerably higher than are the concentrations in the blood. After a single oral dose of 100 mg, urine concentrations of trimethoprim ranged from 30 to 160 mcg/mL during the 0 to 4 hour period and declined to approximately 18 to 91 mcg/mL during the 8 to 24 hour period. A 200 mg single oral dose will result in trimethoprim urine levels approximately twice as high. After oral administration, 50% to 60% of trimethoprim is excreted in the urine within 24 hours, approximately 80% of this being unmetabolized trimethoprim. Since normal vaginal and fecal flora are the source of most pathogens causing urinary tract infections, it is relevant to consider the distribution of trimethoprim into these sites. Concentrations of trimethoprim in vaginal secretions are consistently greater than those found simultaneously in the serum, being typically 1.6 times the concentrations of simultaneously obtained serum samples. Sufficient trimethoprim is excreted in the feces to markedly reduce or eliminate trimethoprim-susceptible organisms from the fecal flora. Trimethoprim also passes the placental barrier and is excreted in human milk.

INDICATIONS AND USAGE


id: 65482e08-b34a-50f6-e053-2991aa0a2437
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

To reduce the development of drug-resistant bacteria and maintain the effectiveness of trimethoprim tablets, USP and other antibacterial drugs, trimethoprim tablets, USP 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 the empiric selection of therapy. For the treatment of initial episodes of uncomplicated urinary tract infections due to susceptible strains of the following organisms:
Escherichia coli,
Proteus mirabilis,
Klebsiella pneumoniae,
Enterobacter species, and coagulase-negative
Staphylococcus species, including
S. saprophyticus.
Cultures and susceptibility tests should be performed to determine the susceptibility of the bacteria to trimethoprim. Therapy may be initiated prior to obtaining the results of these tests.

CONTRAINDICATIONS


id: 65482e08-b34b-50f6-e053-2991aa0a2437
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Trimethoprim is contraindicated in individuals hypersensitive to trimethoprim and in those with documented megaloblastic anemia due to folate deficiency.

WARNINGS


id: 65482e08-b34c-50f6-e053-2991aa0a2437
displayName: WARNINGS SECTION
FDA Article Code: 34071-1

Serious hypersensitivity reactions have been reported rarely in patients on trimethoprim therapy. Trimethoprim has been reported rarely to interfere with hematopoiesis, especially when administered in large doses and/or for prolonged periods. The presence of clinical signs such as sore throat, fever, pallor, or purpura may be early indications of serious blood disorders (see
OVERDOSAGE
,
Chronic ).
Complete blood counts should be obtained if any of these signs are noted in a patient receiving trimethoprim and the drug discontinued if a significant reduction in the count of any formed blood element is found. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including trimethoprim tablets, USP, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of
C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of
C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antiobiotic 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.

ADVERSE REACTIONS


id: 65482e08-b35c-50f6-e053-2991aa0a2437
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

The adverse effects encountered most often with trimethoprim were rash and pruritus.

DOSAGE AND ADMINISTRATION


id: 65482e08-b367-50f6-e053-2991aa0a2437
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

The usual oral adult dosage is 100 mg of trimethoprim every 12 hours or 200 mg of trimethoprim (two 100 mg tablets) every 24 hours, each for 10 days. The use of trimethoprim in patients with a creatinine clearance of less than 15 mL/min is not recommended. For patients with a creatinine clearance of 15 to 30 mL/min, the dose should be 50 mg every 12 hours.

HOW SUPPLIED


id: 65482e08-b368-50f6-e053-2991aa0a2437
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Trimethoprim tablets, USP, 100 mg are scored, oval-shaped, white tablets imprinted
DAN DAN and
5571 supplied in bottles of 10 (NDC 55289-746-10). Store at 20° to 25°C (68° to 77°F) in a dry place. [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP with a child-resistant closure (as required).

REFERENCES


id: 65482e08-b369-50f6-e053-2991aa0a2437
displayName: REFERENCES SECTION
FDA Article Code: 34093-5

Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Ninth Edition. CLSI Document M07-A9, Vol. 32, No. 2, CLSI, Wayne, PA, January, 2012.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard-Eleventh Edition. CLSI Document M02-A11, Vol. 32, No. 1, CLSI, Wayne, PA, January, 2012.
Brumfitt W, Pursell R. Trimethoprim-sulfamethoxazole in the treatment of bacteriuria in women. J Infect Dis. 1973;128(suppl): S657-S663.
Lacey RW, Simpson MHC, Fawcett C, et al. Comparison of single-dose trimethoprim with a five-day course for the treatment of urinary tract infections in the elderly. Age and Ageing 10: 179-185, 1981.
Ewer TC, Bailey RR, Gilchrist NL, et al. Comparative study of norfloxacin and trimethoprim for the treatment of elderly patients with urinary tract infection. NZ Med J 101: 537-539, 1988.
Marinella MA. Trimethopriminduced hyperkalemia: An analysis of reported cases. Gerontology 45: 209-212, 1999.
Clinical Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement. CLSI Document M100-S22, Vol. 32, No. 3, CLSI, Wayne, PA, January 2012.
Manufactured by:

Watson Pharma Private Ltd.

Verna, Salcette Goa 403 722 INDIA  Distributed by:

Actavis Pharma, Inc.

Parsippany, NJ 07054 USA Revised: August 2015                                                                                               

PRINCIPAL DISPLAY PANEL


id: 65482e08-b36a-50f6-e053-2991aa0a2437
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

Trimethoprim

Tablets, USP

100 mg

Rx Only