PRIMOR- sulfadimethoxine and ormetoprim tablet

Primor by

Drug Labeling and Warnings

Primor by is a Animal medication manufactured, distributed, or labeled by Zoetis Inc.. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

SPL UNCLASSIFIED SECTION

Tablets

WARNINGS

CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian.

DESCRIPTION

DESCRIPTION: Primor is an antimicrobial drug containing sulfadimethoxine and ormetoprim in a 5 to 1 ratio. The combination of these 2 compounds results in the potentiation of sulfadimethoxine, providing increased efficacy, a broadened spectrum of activity to include some sulfonamide-resistant organisms, and reduction in the rate of resistance development.

Sulfadimethoxine is a white, almost tasteless and odorless powder. Chemically, it is N1-(2,6-dimethoxy-4-pyrimidinyl)-sulfanila-mide. The structural formula is:

Ormetoprim is a white, almost tasteless powder. Chemically, it is 2,4-diamino-5-(4,5-dimethoxy-2-methylbenzyl)-pyrimidine. The structural formula is:

CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY: Sulfadimethoxine is not acetylated in the dog, as in most other animals, and is excreted predominantly as the unchanged drug.3 Sulfadimethoxine has a relatively high solubility at the pH normally occurring in the kidney, precluding the possibility of precipitation and crystalluria. Slow renal excretion results from a high degree of tubular reabsorption. Plasma protein binding is very high, providing a blood reservoir of the drug. Thus sulfadimethoxine maintains higher blood levels than most other long-acting sulfonamides. Single, comparatively low doses of sulfadimethoxine give rapid and sustained therapeutic blood levels.4

The systemically active sulfonamides, which include sulfadimethoxine, are bacteriostatic agents. Sulfonamides competitively inhibit bacterial synthesis of folic acid (pteroylglutamic acid) from para-aminobenzoic acid. Mammalian cells are capable of utilizing folic acid in the presence of sulfonamides.

Ormetoprim, like other diaminopyrimidines, inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid by bacterial cells.

Sulfadimethoxine/ormetoprim thus blocks 2 sequential steps of the folic acid metabolism of bacteria, depriving them of folate coenzymes. Potentiated sulfonamides have been shown to exhibit bactericidal as well as bacteriostatic action.

Microbiology: Sulfadimethoxine is a low-dosage, rapidly absorbed, long-acting sulfonamide effective for the treatment of a wide range of bacterial infections commonly encountered in dogs. Sulfadimethoxine has been demonstrated under laboratory and field conditions to be effective against a variety of gram-positive and gram-negative, aerobic and anaerobic organisms belonging to the genera Streptococcus, Klebsiella, Proteus, Shigella, Staphylococcus, Escherichia, Salmonella, and Clostridium.1,2 Most strains of these organisms were found to be susceptible to Primor in vitro, but the in vivo significance has not been determined for some canine isolates.

Ormetoprim potentiates the activity of sulfadimethoxine. The in vitro antibacterial spectrum and activity of the 2 compounds are very similar. On a molar basis, ormetoprim is more active than sulfadimethoxine. Sulfadimethoxine/ormetoprim shows enhanced in vitro and in vivo activity (potentiation) over that of either compound used alone. In vitro, this potentiation results in a reduction of the minimum inhibitory concentration of each drug, and an increase in activity against sulfonamide-resistant organisms, such as Streptococcus, Staphylococcus, Corynebacterium, Escherichia, Klebsiella, Proteus, Brucella, Bordetella, and Clostridium.1 The susceptibility of organisms to Primor Tablets should be determined using a potentiated sulfonamide sensitivity disc such as sulfa-methoxazole and trimethoprim (BBL® Sensi-Disc® SXT1). Specimens for susceptibility testing should be collected prior to initiation of therapy.

In an experimentally induced, controlled soft tissue infection study in dogs, the therapeutic efficacy of Primor was significantly greater than the 2 individual components when administered separately, providing clear evidence of the potentiation of sulfa-dimethoxine by ormetoprim in the target species.1

1 BBL® and Sensi-Disc® are registered trademarks owned by Becton, Dickinson and Company, Paramus, New Jersey.

Blood Levels:1 Therapeutically effective blood levels of both sulfadimethoxine and ormetoprim are obtained and maintained in dogs when using the recommended Primor dosing regimen of 25 mg/lb on day one and of 12.5 mg/lb on following days. Blood levels of sulfadimethoxine and ormetoprim were studied in 2 male and 2 female dogs. The initial drug dose was administered at zero hours. Blood samples were taken at 11 intervals, 6 of which are reported in Table 1. A second dose of Primor was administered immediately following the 24-hour blood samples and blood values were determined 2 hours later (26 hours from the initial dose).

Table 1. Blood levels (mcg/mL) obtained with administration of a 25 mg/lb dose of Primor followed with a 12.5 mg/lb dose at 24 hours

Sample	2 hr	8 hr	24 hr*	26 hr	32 hr	48 hr
* Sample collected before administration of the second dose.
Sulfadimethoxine	23.00	41.00	39.00	60.00	67.00	36.00
Ormetoprim	1.04	0.55	0.09	1.08	0.44	0.03