Primsol

Overdose

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.

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.

Primsol price

Contraindications

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

Undesirable effects

To report SUSPECTED ADVERSE REACTIONS, contact FSC Laboratories , Inc. at 1-866-764- 7822, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 PRIMSOL, 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 PRIMSOL or sulfamethoxazole + trimethoprim oral suspension.

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

Therapeutic indications

PRIMSOL Solution is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below.

For the treatment of acute otitis media due to susceptible strains of Streptococcus pneumoniae and Haemophilus influenzae.

NOTE: Moraxella catarrhalis isolates were found consistently resistant to trimethoprim in vitro.

Therefore, when infection with Moraxella catarrhalis is suspected, the use of alternative antimicrobial agents should be considered. PRIMSOL is not indicated for prophylactic or prolonged administration in otitis media at any age.

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.

Fertility, pregnancy and lactation

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 Pursell3, 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, PRIMSOL 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.

Qualitative and quantitative composition

PRIMSOL (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 13551-501-01: 20 mL (3/4 ounce)
NDC 13551-501-05: 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.

REFERENCES

1. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically - -Third Edition. Approved Standard NCCLS Document M7-A3, Vol. 13, No. 25, NCCLS, Villanova, PA, December, 1993.

2. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests - Fifth Edition. Approved Standard NCCLS Document M2-A5, Vol. 13, No. 24, NCCLS, Villanova, PA, December, 1993.

3. Brumfitt W, Pursell R: Trimethoprim/Sulfamethoxazole in the Treatment of Bacteriuria in Women, J Infect Dis 128 (suppl): S657-S663, 1973.

Manufactured for: FSC Laboratories , Inc., Charlotte, NC 28210 USA. Manufactured by: Halo Pharmaceutical Inc., Whippany, NJ 07981 USA, U. S. Patent No. 5,698,562, FSC laboratories. Revised April 2013

Special warnings and precautions for use

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.

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.

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 PRIMSOL. 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 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 Pursell3, 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, PRIMSOL 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.

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

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.

Dosage (Posology) and method of administration

The recommended dose for pediatric patients with acute otitis media is 10 mg/kg trimethoprim per 24 hours, given in divided doses every 12 hours for 10 days. The following table is a guideline for the attainment of this dosage:

Pediatric patients 6 months of age or older

The usual oral adult dosage is 100 mg (10 mL) every 12 hours or 200 mg (20 mL) 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. Patients with a creatinine clearance of 15 to 30 mL/min should receive half the dose recommended for patients of the same age with normal renal function.

Interaction with other medicinal products and other forms of interaction

To report SUSPECTED ADVERSE REACTIONS, contact FSC Laboratories , Inc. at 1-866-764- 7822, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 PRIMSOL, 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 PRIMSOL or sulfamethoxazole + trimethoprim oral suspension.

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

PRIMSOL 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.

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.