Lidaprim

Trimethoprim:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• Lidaprim (Trimethoprim) reviews

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Lidaprim (Trimethoprim) tablets, USP and other antibacterial drugs, Lidaprim (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 Lidaprim (Trimethoprim). Therapy may be initiated prior to obtaining the results of these tests.

CONTRAINDICATIONS

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

WARNINGS

Serious hypersensitivity reactions have been reported rarely in patients on Lidaprim (Trimethoprim) therapy. Lidaprim (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 Lidaprim (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 Lidaprim (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.

PRECAUTIONS

General

Prescribing Lidaprim tablets, USP 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.

Lidaprim (Trimethoprim) should be given with caution to patients with possible folate deficiency. Folates may be administered concomitantly without interfering with the antibacterial action of Lidaprim (Trimethoprim). Lidaprim (Trimethoprim) should also be given with caution to patients with impaired renal or hepatic function (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Information for Patients

Patients should be counseled that antibacterial drugs including Lidaprim (Trimethoprim) tablets, USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Lidaprim (Trimethoprim) tablets, USP 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 Lidaprim (Trimethoprim) tablets, USP or other antibacterial drugs in the future.

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 and 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.

Drug Interactions

Lidaprim may inhibit the hepatic metabolism of phenytoin. Lidaprim (Trimethoprim), given at a common clinical dosage, increased the phenytoin half-life by 51% and decreased the phenytoin metabolic clearance rate by 30%. When administering these drugs concurrently, one should be alert for possible excessive phenytoin effect.

Drug/Laboratory Test Interactions

Lidaprim (Trimethoprim) 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 Lidaprim (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

Long-term studies in animals to evaluate carcinogenic potential have not been conducted with Lidaprim.

Mutagenesis

Lidaprim (Trimethoprim) was demonstrated to be nonmutagenic in the Ames assay. In studies at two laboratories, no chromosomal damage was detected in cultured Chinese hamster ovary cells at concentrations approximately 500 times human plasma levels; at concentrations approximately 1000 times human plasma levels in these same cells, a low level of chromosomal damage was induced at one of the laboratories. No chromosomal abnormalities were observed in cultured human leukocytes at concentrations of Lidaprim (Trimethoprim) up to 20 times human steady-state plasma levels. No chromosomal effects were detected in peripheral lymphocytes of human subjects receiving 320 mg of Lidaprim (Trimethoprim) in combination with up to 1600 mg of sulfamethoxazole per day for as long as 112 weeks.

Impairment of Fertility

No adverse effects on fertility or general reproductive performance were observed in rats given Lidaprim in oral dosages as high as 70 mg/kg/day for males and 14 mg/kg/day for females.

Pregnancy

Teratogenic Effects

Pregnancy category C

Lidaprim has been shown to be teratogenic in the rat when given in doses 40 times the human dose. In some rabbit studies, the overall increase in fetal loss (dead and resorbed and malformed conceptuses) was associated with doses six times the human therapeutic dose.

While there are no large, well-controlled studies on the use of Lidaprim (Trimethoprim) in pregnant women, Brumfitt and Pursell,³ in a retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or Lidaprim (Trimethoprim) in combination with sulfamethoxazole. 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 Lidaprim (Trimethoprim) and sulfamethoxazole. 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 Lidaprim (Trimethoprim) and sulfamethoxazole at the time of conception or shortly thereafter.

Because Lidaprim (Trimethoprim) may interfere with folic acid metabolism, Lidaprim (Trimethoprim) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

The oral administration of Lidaprim (Trimethoprim) to rats at a dose of 70 mg/kg/day commencing with the last third of gestation and continuing through parturition and lactation caused no deleterious effects on gestation or pup growth and survival.

Nursing Mothers

Lidaprim is excreted in human milk. Because Lidaprim (Trimethoprim) may interfere with folic acid metabolism, caution should be exercised when Lidaprim (Trimethoprim) is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 2 months have not been established. The effectiveness of Lidaprim (Trimethoprim) as a single agent has not been established in pediatric patients under 12 years of age.

Geriatric Use

Clinical studies of Lidaprim (Trimethoprim) tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience^4,5 has not identified differences in response between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Case reports of hyperkalemia in elderly patients receiving trimethoprim-sulfamethoxazole have been published.⁶ Lidaprim (Trimethoprim) is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor potassium concentrations and to monitor renal function by calculating creatinine clearance.

ADVERSE REACTIONS

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

Dermatologic

Rash, pruritus, and phototoxic skin eruptions. At the recommended dosage regimens of 100 mg b.i.d. or 200 mg q.d., each for 10 days, the incidence of rash is 2.9% to 6.7%. In clinical studies which employed high doses of Lidaprim (Trimethoprim), an elevated incidence of rash was noted. These rashes were maculopapular, morbilliform, pruritic, and generally mild to moderate, appearing 7 to 14 days after the initiation of therapy.

Hypersensitivity

Rare reports of exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylaxis have been received.

Gastrointestinal

Epigastric distress, nausea, vomiting, and glossitis. Elevation of serum transaminase and bilirubin has been noted, but the significance of this finding is unknown. Cholestatic jaundice has been rarely reported.

Hematologic

Thrombocytopenia, leukopenia, neutropenia, megaloblastic anemia, and methemoglobinemia.

Metabolic

Hyperkalemia, hyponatremia.

Neurologic

Aseptic meningitis has been rarely reported.

Miscellaneous

Fever, and increases in BUN and serum creatinine levels.

OVERDOSAGE

Acute

Signs of acute overdosage with Lidaprim may appear following ingestion of 1 gram or more of the drug and include nausea, vomiting, dizziness, headaches, mental depression, confusion, and bone marrow depression (see Chronic subsection).

Treatment consists of gastric lavage and general supportive measures. Acidification of the urine will increase renal elimination of Lidaprim (Trimethoprim). Peritoneal dialysis is not effective and hemodialysis is only moderately effective in eliminating the drug.

Chronic

Use of Lidaprim (Trimethoprim) 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, Lidaprim (Trimethoprim) should be discontinued and the patient should be given leucovorin; 5 to 15 mg leucovorin daily has been recommended by some investigators.

DOSAGE AND ADMINISTRATION

The usual oral adult dosage is 100 mg of Lidaprim (Trimethoprim) every 12 hours or 200 mg of Lidaprim (Trimethoprim) every 24 hours, each for 10 days. The use of Lidaprim (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

Lidaprim (Trimethoprim) tablets, USP, 100 mg: White, round, convex tablet, debossed “9”, scored, “3” on one side and debossed “21 58” on the other, in bottles of 100.

Store at 20° to 25°C (68° to 77°F).

Dispense in a tight, light-resistant container as defined in the USP with a child-resistant closure (as required).

REFERENCES

• Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition. CLSI document M07-A10 [2015], Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
• Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard-Twelfth Edition. CLSI document M02-A12 [2015], Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
• 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 Lidaprim (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 Lidaprim (Trimethoprim) for the treatment of elderly patients with urinary tract infection. NZ Med J 101: 537-539, 1988.
• Marinella MA. Trimethoprim-induced hyperkalemia: An analysis of reported cases. Gerontology 45: 209-212, 1999.
• Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-sixth Informational Supplement, CLSI document M100-S26 [2016], Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.

Manufactured In Canada By:

TEVA CANADA LIMITED

Toronto, Canada M1B 2K9

Manufactured For:

TEVA PHARMACEUTICALS USA, INC.

North Wales, PA 19454

Rev. K 6/2016

NDC 0093-2158-01

Lidaprim (Trimethoprim)

Tablets USP

100 mg

Rx only

100 TABLETS

TEVA