Trimpex

Trimethoprim comes as a tablet to take by mouth. It usually is taken one or two times a day. Trimethoprim may be taken with or without food. Follow the directions on your prescription label carefully, and ask your pharmacist or doctor to explain any part you do not understand. Take trimethoprim exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Yes

Trimethoprim is used to treat infections of the urinary tract. It may also be used for other problems as determined by your doctor. It will not work for colds, flu, or other virus infections.

Trimethoprim is available only with your doctor's prescription.

This section provides information on the proper use of a number of products that contain trimethoprim. It may not be specific to Trimpex. Please read with care.

Do not give this medicine to infants or children under 12 years of age unless otherwise directed by your doctor.

Trimethoprim may be taken on an empty stomach or, if it upsets your stomach, it may be taken with food.

To help clear up your infection completely, keep taking this medicine for the full time of treatment even if you begin to feel better after a few days. If you stop taking this medicine too soon, your symptoms may return.

This medicine works best when there is a constant amount in the body. To help keep the amount constant, do not miss any doses. Also, it is best to take the doses at evenly spaced times day and night. For example, if you are to take 2 doses a day, the doses should be spaced about 12 hours apart. If this interferes with your sleep or other daily activities, or if you need help in planning the best times to take your medicine, check with your health care professional.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For the treatment of urinary tract infections :
  • Adults and children 12 years of age and older: 100 milligrams every twelve hours for ten days, or 200 milligrams once a day for ten days.
  • Children up to 12 years of age: Dose must be determined by the doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Trimpex (trimethoprim hydrochloride oral solution) is a solution of the synthetic antibacterial trimethoprim in water prepared with the aid of hydrochloric acid. Each 5 mL for oral administration contains trimethoprim hydrochloride equivalent to 50 mg trimethoprim and the inactive ingredients bubble gum flavor, fructose, glycerin, methylparaben, monoammonium glycyrrhizinate, povidone, propylparaben, propylene glycol, saccharin sodium, sodium benzoate, sorbitol, water and hydrochloric acid and/or sodium hydroxide to adjust pH to a range of 3.0 - 5.0. Trimethoprim is 2,4-diamino-5-(3,4,5-trimethoxybenzyl) pyrimidine. Trimethoprim is a white to cream-colored, odorless, bitter compound with a molecular formula of C14H18N4O3 and a molecular weight of 290.32 and the following structural formula:

Experience with trimethoprim alone is limited, but it 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.

General

Trimethoprim should be given with caution to patients with possible folate deficiency. Folates may be administered concomitantly without interfering with the antibacterial action of trimethoprim. Trimethoprim should also be given with caution to patients with impaired renal or hepatic function. If any clinical signs of a blood disorder are noted in a patient receiving trimethoprim, a complete blood count should be obtained and the drug discontinued if a significant reduction in the count of any formed blood element is found.

Drug Interactions

Trimpex may inhibit the hepatic metabolism of phenytoin. 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

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 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

Long-term studies in animals to evaluate carcinogenic potential have not been conducted with trimethoprim. Trimethoprim was demonstrated to be non-mutagenic in the Ames assay. No chromosomal damage was observed in human leukocytes cultured in vitro with trimethoprim; the concentration used exceeded blood levels following therapy with Trimpex. No adverse effects on fertility or general reproductive performance were observed in rats given trimethoprim in oral dosages as high as 70 mg/kg/day for males and 14 mg/kg/day for females.

Pregnancy

Pregnancy Category C

Trimethoprim 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 6 times the human therapeutic dose.

While there are no large well-controlled studies on the use of trimethoprim in pregnant women, Brumfitt and Pursell,4 in a retrospective study, reported the outcome of 186 pregnancies during which the mother received either placebo or 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 trimethoprim plus 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 trimethoprim plus sulfamethoxazole at the time of conception or shortly thereafter.

Because trimethoprim may interfere with folic acid metabolism, Trimpex should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The oral administration of 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

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

Pediatric Use

The safety of trimethoprim has not been established in pediatric patients below the age of 2 months. The effectiveness of trimethoprim in the treatment of acute otitis media has not been established in patients below the age of 6 months.

To report SUSPECTED ADVERSE REACTIONS, contact Key Therapeutics, LLC at 1-888-981-8337, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Adverse Events Reported During Pediatric Clinical Trials With Trimpex

The following table lists those drug-related adverse events reported most frequently during the clinical trials in pediatric patients aged 6 months to 12 years. Most of these events were determined to be mild. The incidence of drug related adverse events was significantly lower for Trimpex, which was most apparent for those events related to skin/appendages as a body system.

An increase in lymphocytes and eosinophils was noted in some pediatric patients following treatment with Trimpex or sulfamethoxazole + trimethoprim oral suspension.

Adverse Reactions Reported For Trimethoprim

In addition to the adverse events listed above which have been observed in pediatric patients receiving Trimpex, the following adverse reactions and altered laboratory tests have been previously reported for trimethoprim and therefore, may occur with Trimpex therapy:

Dermatologic reactions: pruritus and exfoliative dermatitis. At the recommended adult 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 trimethoprim in adults, 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.

Gastrointestinal reactions: Epigastric distress, nausea, and glossitis.

Hematologic reactions: Thrombocytopenia, leukopenia, neutropenia, megaloblastic anemia and methemoglobinemia.

Metabolic reactions: Hyperkalemia, hyponatremia.

Miscellaneous reactions: Fever, elevation of serum transaminase and bilirubin, and increases in BUN and serum creatinine levels.

Acute

Signs of acute overdosage with trimethoprim 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 OVERDOSAGE-Chronic).

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

Chronic

Use of 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, trimethoprim should be discontinued and the patient should be given leucovorin, 3 to 6 mg intramuscularly daily for three days, or as required to restore normal hematopoiesis.

Trimpex (trimethoprim hydrochloride oral solution) is a dye-free, alcohol-free, bubble gum flavored, oral solution containing trimethoprim hydrochloride equivalent to 50 mg of trimethoprim in each 5 mL.

NDC 70868-120-20: 20 mL (2/3 ounce)

NDC 70868-120-16: 473 mL (1 Pint)

Store between 15-25°C (59-77°F). Dispense in tight, light resistant glass or PET plastic containers as defined in USP.

Protect from light.

Rx only

REFERENCES

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility 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.
2. 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.
3. Clinical and Laboratory Standards Institute (CLSI).Performance Standards for Antimicrobial Susceptibility Tests; Twenty-sixth Informational Supplement, CLSI document M100-S26 [2016], Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
4. Brumfitt W, Prusell R: Trimethoprim/Sulfamethoxazole in the treatment of Bacteriuria in Women, J Infect Dis128 (suppl): S657-S663, 1973.

Rev. 09/2017

Manufactured for:
Key Therapeutics, LLC
Flowood, MS 39232

U. S. Patent No. 5,698,562