LongRange: Product Information (Page 2 of 3)

WARNINGS AND PRECAUTIONS

Withdrawal Periods and Residue Warnings

Animals intended for human consumption must not be slaughtered within 48 days of the last treatment.

This drug product is not approved for use in female dairy cattle 20 months of age or older, including dry dairy cows. Use in these cattle may cause drug residues in milk and/or in calves born to these cows.

A withdrawal period has not been established for pre-ruminating calves. Do not use in calves to be processed for veal.

User Safety Warnings

Not for Use in Humans. Keep this and all drugs out of the reach of children. The Safety Data Sheet (SDS) contains more detailed occupational safety information. To report adverse effects, to obtain an SDS, or for assistance, contact Boehringer Ingelheim Animal Health USA Inc. at 1-888-637-4251. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS, or http://www.fda.gov/AnimalVeterinary/SafetyHealth.

Animal Safety Warnings and Precautions

The product is likely to cause tissue damage at the site of injection, including possible granulomas and necrosis. These reactions have disappeared without treatment. Local tissue reaction may result in trim loss of edible tissue at slaughter.

Observe cattle for injection site reactions. If injection site reactions are suspected, consult your veterinarian. This product is not for intravenous or intramuscular use. Protect product from light. LONGRANGE^® (eprinomectin) has been developed specifically for use in cattle only. This product should not be used in other animal species.

When to Treat Cattle with Grubs

LONGRANGE effectively controls all stages of cattle grubs. However, proper timing of treatment is important. For the most effective results, cattle should be treated as soon as possible after the end of the heel fly (warble fly) season. Destruction of Hypoderma larvae (cattle grubs) at the period when these grubs are in vital areas may cause undesirable host-parasite reactions, including the possibility of fatalities. Killing Hypoderma lineatum when it is in the tissue surrounding the esophagus (gullet) may cause salivation and bloat; killing H. bovis when it is in the vertebral canal may cause staggering or paralysis. These reactions are not specific to treatment with LONGRANGE, but can occur with any successful treatment of grubs. Cattle should be treated either before or after these stages of grub development. Consult your veterinarian concerning the proper time for treatment.

Environmental Hazards

Studies indicate that when eprinomectin comes in contact with soil, it readily and tightly binds to the soil and becomes inactive over time. Free eprinomectin may adversely affect fish and certain aquatic organisms. Do not contaminate water by direct application or by improper disposal of drug containers. Dispose of containers in an approved landfill or by incineration.

As with other avermectins, eprinomectin is excreted in the dung of treated animals and can inhibit the reproduction and growth of pest and beneficial insects that use dung as a source of food and for reproduction. The magnitude and duration of such effects are species and life-cycle specific. When used according to label directions, the product is not expected to have an adverse impact on populations of dung-dependent insects.

Not for use in cattle managed in feedlots or under intensive rotational grazing because the environmental impact has not been evaluated for these scenarios.

Other Warnings: Parasite resistance may develop to any dewormer, and has been reported for most classes of dewormers.

Treatment with a dewormer used in conjunction with parasite management practices appropriate to the geographic area and the animal(s) to be treated may slow the development of parasite resistance.

Fecal examinations or other diagnostic tests and parasite management history should be used to determine if the product is appropriate for the herd/flock, prior to the use of any dewormer. Following the use of any dewormer, effectiveness of treatment should be monitored (for example, with the use of a fecal egg count reduction test or another appropriate method).

A decrease in a drug’s effectiveness over time as calculated by fecal egg count reduction tests may indicate the development of resistance to the dewormer administered. Your parasite management plan should be adjusted accordingly based on regular monitoring.

Macrocyclic lactones provide prolonged drug exposure that may increase selection pressure for resistant parasites. This effect may be more pronounced in extended-release formulations.

CLINICAL PHARMACOLOGY

Due to its unique formulation characteristics, when LONGRANGE is injected subcutaneously in the shoulder area of cattle, a polymeric PLGA matrix is formed. The biodegradable matrix solidifies in vivo to form an in situ forming gel, which allows a gradual release of eprinomectin from the formulation. The rate-limiting step is diffusion of the drug through the gel matrix. Because of its mechanism of release, absorption characteristics can be highly dependent upon the injection technique used and the corresponding surface to volume ratio of the gel.

Clinical efficacy of avermectins and milbemycins is closely related to their pharmacokinetic behavior, and the time of parasite exposure to active drug concentrations is relevant to obtain optimal and persistent antiparasitic activity (Lanusse et al., 1997; Lifschitz et al., 1999; Lifschitz et al., 2004; Shoop et al., 1996). Lifschitz et al. (1999) indicated that plasma concentrations between 0.5 and 1 ng/mL would represent the minimal drug level required for optimal nematocidal activity, while others have suggested minimum levels of 1 to 2 ng/mL. Pharmacokinetic studies of LONGRANGE in cattle indicate that effective plasma levels remain for an extended period of time (at least 100 days).

Mean Eprinomectin B1a Plasma Concentration Versus Time Following a Single Subcutaneous Injection of LONGRANGE® at a Dose Rate of 1 mg Eprinomectin per kg Body Weight in Beef Cattle

(click image for full-size original)

Mode of Action

The macrocyclic lactones have a unique mode of action. Compounds of this class bind selectively and with high affinity to glutamate-gated chloride ion channels that are present in invertebrate nerve and muscle cells. This leads to an increase in the permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell, resulting in paralysis and death of the parasite. Compounds of this class may also interact in other ligand-gated chloride ion channels, such as those gated by the neurotransmitter gamma-aminobutyric acid (GABA).

The margin of safety for compounds of this class is at least partially attributable to the fact that mammals do not have glutamate-gated chloride ion channels, and that the macrocyclic lactones have low affinity for other mammalian ligand-gated channels and do not readily cross the blood-brain barrier.

TARGET ANIMAL SAFETY

Clinical studies have demonstrated the wide margin of safety of LONGRANGE^® (eprinomectin). Overdosing at 3 to 5 times the recommended dose resulted in a statistically significant reduction in average weight gain when compared to the group tested at label dose. Treatment-related lesions observed in most cattle administered the product included swelling, hyperemia, or necrosis in the subcutaneous tissue of the skin. The administration of LONGRANGE at 3 times the recommended therapeutic dose had no adverse reproductive effects on beef cows at all stages of breeding or pregnancy or on their calves.

Not for use in bulls, as reproductive safety testing has not been conducted in males intended for breeding or actively breeding. Not for use in calves less than 3 months of age because safety testing has not been conducted in calves less than 3 months of age.

HOW SUPPLIED

LONGRANGE is available in three ready-to-use glass bottle sizes. The 100, 250 and 500 mL bottles contain sufficient solution to treat 20, 50 and 100 head of 550 lb (250 kg) cattle, respectively. The 250 and 500 mL bottles are supplied in a removable plastic protector.