Proloprim Information
Proloprim (Trimethoprim) Description:
Proloprim (Trimethoprim) is a synthetic antibacterial available in tablet form for oral administration. Each scored white tablet contains 100 mg trimethoprim and the inactive ingredients corn starch, lactose, magnesium stearate, and sodium starch glycolate. Each scored yellow tablet contains 200 mg trimethoprim and the inactive ingredients corn starch, D & C Yellow No. 10, magnesium stearate, and sodium starch glycolate.
Trimethoprim is 5-[(3,4,5,-trimethoxyphenyl)methyl]-2,4-pyrimidinediamine. It is a white to light yellow, odorless, bitter compound with a molecular weight of 290.32 and the molecular formula CHNO. The structural formula is:
Proloprim (Trimethoprim) Clinical Pharmacology:
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 3’- and 4’- 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 1.0 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 ). During a 13-week study of trimethoprim administered at a daily dosage of 200 mg (50 mg qid), the mean minimum steady-state concentration of the drug was 1.1 mcg/mL. Steady-state 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.
Proloprim (Trimethoprim) Indications And Usage:
For the treatment of initial episodes of uncomplicated urinary tract infections due to susceptible strains of the following organisms: , , , species, and coagulase-negative species, including .
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.
Proloprim (Trimethoprim) Contraindications:
Proloprim (Trimethoprim) is contraindicated in individuals hypersensitive to trimethoprim and in those with documented megaloblastic anemia due to folate deficiency.
Proloprim (Trimethoprim) Warnings:
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 ).
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.
Proloprim (Trimethoprim) Precautions:
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.
Clinical studies of Proloprim (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 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-sulfaethoxazole have been published. 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.
Proloprim (Trimethoprim) Adverse Reactions:
The adverse effects encountered most often with trimethoprim were rash and pruritus.
Proloprim (Trimethoprim) Overdosage:
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 subsection).
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 is only moderately effective in eliminating the drug.
Proloprim (Trimethoprim) Dosage And Administration:
The usual oral adult dosage is 100 mg of Proloprim (Trimethoprim) every 12 hours or 200 mg Proloprim (Trimethoprim) 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.
Proloprim (Trimethoprim) How Supplied:
100-mg Tablets (white, scored, round-shaped), containing 100 mg trimethoprim–bottle of 100 (NDC 61570-057-01). Imprint on tablets “Proloprim (Trimethoprim) 09A.”
200-mg Tablets (yellow, scored, round-shaped), containing 200 mg trimethoprim–bottle of 100 (NDC 61570-058-01). Imprint on tablets “Proloprim (Trimethoprim) 200.”
Proloprim (Trimethoprim) References:
Prescribing Information as of February 2003.
Distributed by: Monarch Pharmaceuticals, Inc. Bristol, TN 37620
Manufactured by: DSM Pharmaceuticals, Inc. Greenville, NC 27834
