SULFADIMETHOXINE

Sulfadimethoxine Injection 40%
(sulfadimethoxine)

ANTIBACTERIAL
Each mL contains 400 mg Sulfadimethoxine
Caution: Federal law restricts this drug to use by or on the order of a
licensed veterinarian.

RESTRICTED DRUG (California), USE ONLY AS DIRECTED
NOT FOR USE IN HUMANS
KEEP OUT OF REACH OF CHILDREN

DESCRIPTION: Sulfadimethoxine Injection 40% is a low-dosage, rapidly absorbed, long-acting sulfonamide, effective for the
treatment of shipping fever complex, bacterial pneumonia, calf diphtheria and foot rot in cattle. Sulfadimethoxine is a white,
almost tasteless and odorless compound. Chemically, it is N¹-(2,6 dimethoxy-4-pyrimidinyl) sulfanilamide. The structural
formula is:

SDM Formula

ACTIONS: Sulfadimethoxine has been demonstrated clinically or in the laboratory to be effective against a variety of organisms,
such as streptococci, klebsiella, proteus, shigella, staphylococci, escherichia, and salmonella.^1,2 The systemic 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.

   The tissue distribution of sulfadimethoxine, as with all sulfonamides, is a function of plasma levels, degree of plasma protein binding,
and subsequent passive distribution in the tissues of the lipid-soluble un-ionized form. The relative amounts are determined by both
its pKa and by the pH of each tissue. Therefore, levels tend to be higher in less acid tissue and body fluids or those diseased tissues
having high concentrations of leucocytes.²

   Slow renal excretion results from a high degree of tubular reabsorption,³ and plasmaprotein 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.¹

   To assure successful sulfonamide therapy (1) the drug must be given early in the course of the disease, and it must produce a high
sulfonamide level in the body rapidly after administration, (2) therapeutically effective sulfonamide levels must be maintained in the
body throughout the treatment period, (3) treatment should continue for a short period of time after the clinical signs have disappeared,
and (4) the causative organisms must be sensitive to this class of drugs.

TOXICITY AND SAFETY: Data regarding acute (LD₅₀) and chronic toxicities of sulfadimethoxine indicate the drug is very safe.
The LD₅₀ in mice is greater than 2 g/kg body weight when administered intraperitoneally and greater than 16 g/kg when
administered orally.
   In dogs receiving massive single oral doses of 3.2 g/kg body weight, diarrhea was the only adverse effect observed. Dogs given
160 mg/kg body weight orally daily for 13 weeks showed no sign of toxicity.
   In cattle sulfadimethoxine has been shown to be safe through extensive clinical use with other dosage forms. In addition, studies
with intravenous administration of Sulfadimethoxine Injection 40% have demonstrated that hemolysis of erythrocytes does not occur
by this route of administration. Sulfadimethoxine has a relatively high solubility at the pH normally occurring in the kidney, precluding
the possibility of precipitation and crystalluria.

INDICATIONS: Sulfadimethoxine Injection 40% is indicated for the treatment of bovine respiratory disease complex (shipping fever
complex) and bacterial pneumonia associated with Pasteurella spp. sensitive to sulfadimethoxine; necrotic pododermatis (foot rot)
and calf diphtheria caused by Fusobacterium necrophorum (Sphaerophorus necrophorus), sensitive to sulfadimethoxine.

LIMITATIONS: Sulfadimethoxine is not effective in viral or rickettsial infections, and as with any anti-bacterial agent, occasional
failures in therapy may occur due to resistant microorganisms. The usual precautions in sulfonamide therapy should be observed.

RESIDUE WARNINGS: Milk taken from animals during treatment and for 60 hours (5 milkings) after the latest treatment must not
be used for food. Do not administer within 5 days of slaughter. A withdrawal period has not been established for this product in
pre-ruminating calves. Do not use in calves to be processed for veal.

PRECAUTIONS: During treatment period, make certain that animals maintain adequate water intake.
If animals show no improvement within 2 or 3 days, consult your veterinarian.
Tissue damage may result from perivascular infiltration.

DOSAGE AND ADMINSTRATION: Sulfadimethoxine Injection 40% must be administered only by the intravenous route in cattle.
Cattle should receive 1 mL of Sulfadimethoxine Injection 40% per 16 pounds of body weight (55 mg/kg) as an initial dose,
followed by 0.5 mL per 16 pounds of body weight (27.5 mg/kg) every 24 hours thereafter. Sulfadimethoxine boluses may be
utilized for maintenance therapy in cattle. Representative weights and doses are indicated in the following table:

SDM Chart

Length of treatment depends on the clinical response. In most cases treatment for 3 to 5 days is adequate. Treatment should be
continued until the animal is asymptomatic for 48 hours.

DIRECTIONS FOR INTRAVENOUS INJECTION:
Equipment needed-
1. A nose lead and/or halter sufficiently strong enough to effectively restrain or hold the animal's head steady so that the intravenous
    injection can be made with ease.
2. Hypodermic needles, 16 or 18 gauge and 2 inches long. Only new, sharp and sterile hypodermic needles should be used. Dull needles
    should be discarded. Extra needles should always be available in case of the needle being used should become clogged.
3. Hypodermic syringes, 40 or 50 mL sterile disposable or reusable glass syringes should be available.
4. Alcohol (70%) or equally effective antiseptic for disinfecting the skin.
Preparation of equipment - Glass syringes and regular hypodermic needles should be thoroughly cleaned and washed. Following this, the
needles and syringes should be immersed in boiling water for 30 minutes prior to each injection. Regular hypodermic needles should not
be used more than 3-4 times as repeated skin puncturing and boiling of the needles causes them to become quite dull. Disposable
hypodermic needles and syringes should not be used more than once.
Restraint of animal - The cow should preferably be in a stanchion for maximum restraint. If this is not possible, the animal should be
restrained in a manner to prevent excessive movement. A nose lead should be applied and the animal's head turned sidewise to stretch
the skin and tense the muscles of the neck region. (See Figure 1).
Locating the jugular vein - Once the animal has been restrained (as above), you will notice a long depression of the skin from below
the angle of the jaw to just above the shoulder. This is known as the jugular furrow or jugular groove. The jugular vein is located
just under the jugular groove. (See Fig. 1).
Preparation of Sulfadimethoxine Injection 40% for injection - The rubber cap of the bottle should be thoroughly cleaned with 70% alcohol
or other satisfactory antiseptic. The correct amount of Sulfadimethoxine Injection 40% for treatment should be calculated (see dosage
directions) and that amount withdrawn into a syringe. (See Figure 2). One or two syringefuls of air should be injected into the bottle
first to make withdrawing the drug easier. Sulfadimethoxine Injection 40% should preferably be at room temperature when filling syringes
and when injecting intravenously.
Entering the vein - The skin of the injection area should be clean and free of dirt. Cotton saturated with 70% alcohol (or suitable
antiseptic) should be used to wipe the injection site.
   Apply pressure over the jugular vein close to the shoulder. This will reduce the flow of blood to the heart and cause the jugular vein
to bulge or enlarge. (See Figure 3). When the jugular vein has been "raised", insert the hypodermic needle at a 45 degree angle through
the skin just underneath the jugular vein. The beveled edge of the hypodermic needle should be up. (See Figure 4).
   After the skin has been punctured, the point of the needle should be directed toward the side of the vein and pushed into the center of
the vein. (See Figure 5). When the needle is in the center of the vein, there will be a free flow of blood back through the needle.
Release external pressure when you are sure the needle is within the vein.
Injecting the Sulfadimethoxine Injection 40% - After the needle has been accurately inserted into the jugular vein, firmly attach the
syringe containing Sulfadimethoxine Injection 40% to the inserted hypodermic needle. Caution, be sure syringe is free of air. Exert
firm pressure on the plunger of the syringe to inject the Sulfadimethoxine Injection 40% while the barrel is held firmly. The injection
should be made moderately slow - never rapidly.
   If the animal moves, causing resistance in pushing the plunger of the syringe, or if a bubble of the drug is noted under the skin, the
needle is no longer within the vein. The needle should be repositioned.
   When the injection is completed, quickly withdraw the syringe and needle with a quick pull and apply light pressure over the injection
site with alcohol and cotton to minimize bleeding from the puncture site.

SDM Injections

To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet (SDS), contact
Huvepharma, Inc. at 1-877-994-4883 or www.huvepharma.us. For additional information about adverse drug experience reporting
for animal drugs, contact FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae.

NOTE: Store at room temperature. Should crystallization occur at cold temperatures, crystals will dissolve either by storing in room
temperature for several days or by heating the vial in warm water. Crystallization and redissolution do not impair the efficacy of the
product.

HOW SUPPLIED:Sulfadimethoxine Injection 40% is available in 250 mL sterile multiple dose containers.
Sulfadimethoxine Injection 40% – Each mL contains 400 mg sulfadimethoxine compounded with 20% propylene glycol, 1%
benzyl alcohol, 0.1 mg disodium edetate, 1 mg sodium formaldehyde sulfoxylate, and pH adjusted with sodium hydroxide.

REFERENCES
1. Data on file from Hoffmann-La Roche Inc., Nutley, New Jersey.
2. Stowe, C.M., THE SULFONAMIDES, in Jones. L.M. (ed.), Veterinary Pharmacology and Therapeutics, Ames, Iowa, Iowa State University Press. 1965, chapter 33.
3. Baggot, J.D., SOME ASPECTS OF DRUG PERSISTENCE IN DOMESTIC ANIMALS, Res. Vet. Sci. 11:2, 130, 1970

CONTENTS:
EACH mL CONTAINS: 400 mg sulfadimethoxine compounded with 20% propylene glycol, 1% benzyl alcohol, 0.1 mg disodium
edetate, 1 mg sodium formaldehyde sulfoxylate, and pH adjusted with sodium hydroxide.

DOSAGE:

To be administered in amounts to provide 25 mg/lb (55 mg/kg) for initial dose, followed by 12.5 mg/lb (27.5 mg/kg) for maintenance
doses every 24 hours.

During treatment period, make certain that animals maintain adequate water intake.

Approved by FDA under ANADA # 200-038

Manufactured for:
Aspen Veterinary Resources,® Ltd.
Liberty, MO 64068
www.aspenveterinaryresources.com

Take Time

AS SDM Unit

AS SDM Onsert