Approval Date: December 19, 1997

Freedom of Information Summary
NADA 128-409

I. GENERAL INFORMATION:

NADA	128-409
Sponsor:	Merial Limited 2100 Ronson Road Iselin, New Jersey 08830-3800
Generic Name:	ivermectin
Trade Name:	IVOMEC® Injection for Cattle and Swine
Marketing Status:	Over the Counter (OTC)
Effect of Supplement:	New claim for the treatment and control of grubs (Hypoderma bovis in American bison.

II. INDICATIONS FOR USE

CATTLE: Ivomec injection is indicated for the effective treatment and control of the following harmful species of gastrointestinal roundworms, lungworms, sucking lice, and mange mites:

Gastrointestinal Roundworms(adults and 4th stage larvae):

Ostertagia ostertagi (including inhibited O. ostertagi)
O. lyrata
Haemonchus placei
Trichostrongylus axei
T. colubriformis
Cooperia oncophora
C. punctata
C. pectinata
Oesophagostomum radiatum
Bunostomum phlebotomum
Nematodirus helvetianus (adults only)
N. spathiger (adults only)

Lungworms (adults and fourth-stage larvae):

Dictyocaulus viviparus

Cattle Grubs (parasitic stages):

Hypoderma bovis
H. lineatum

Sucking Lice:

Linognathus vituli
Haematopinus eurysternus
Solenopotes capillatus

Mites (Scabies):

Psoroptes ovis (syn. P. communis var. bovis)
Sarcoptes scabiei var. bovis

Persistent Activity

IVOMEC Injection has been proved to effectively control infections and to protect cattle from re-infection with Dictyocaulus viviparus and Ostertagia ostertagi for 21 days after treatment; Oesophagostomum radiatum, Haemonchus placei, Trichostrongylus axei, Cooperia punctata and Cooperia oncophora for 14 days after treatment.

SWINE: Ivomec Injection is indicated for the effective treatment and control of the following harmful species of gastrointestinal roundworms, lungworms, lice, and mange mites:

Gastrointestinal Roundworms:

Large roundworm, Ascaris suum (adults and fourth-stage larvae)
Red stomach worm, Hyostrongylus rubidus (adults and fourth stage larvae)
Nodular worm, Oesophagostomum spp. (adults and fourth stage larvae)
Threadworm, Strongyloides ransomi (adults)

Somatic Roundworm Larvae:

Threadworm, Strongyloides ransomi (somatic larvae)
Sows must be treated at least seven days before farrowing to prevent infection in piglets.

Lungworms:

Metastrongylus spp. (adults)

Lice:

Haematopinus suis

Mange Mites:

Sarcoptes scabiei var. suis

REINDEER: For the treatment and control of warbles (Oedemagena tarandi)

Additional indications contained in this supplemental NADA are for the treatment and control of grubs (Hypoderma bovis) in American bison.

III. DOSAGE

A.	DOSAGE FORM	IVOMEC Injection is a sterile 1% solution available in 50, 200, 500, and 1000 mL plastic containers
B.	ROUTE OF ADMINISTRATION	IVOMEC Injection should be administered by subcutaneous injection
C.	RECOMMENDED DOSAGES:	200 g ivermectin/kg body weight (1 mL/110 lb body weight)
	NOTES	This FREEDOM OF INFORMATION SUMMARY references data in Public Master File (PMF) 5059, 61 FR 4442, February 6, 1996, in support of the supplemental new animal drug application. The data were generated by: Dr. T.W. Schillhorn van Veen College of Veterinary Medicine Michigan State University East Lansing, Michigan 48824

IV. EFFECTIVENESS

Effectiveness data from PMF 5059, 61 FR 4442, February 6, 1996, demonstrated that ivermectin injection, when administered subcutaneously at a dose of 200 g/kg body weight, was efficacious in treating and controlling grubs (Hypoderma bovis) in American bison.

V. ANIMAL SAFETY

Target animal safety data from PMF 5059, 61 FR 4442, February 6, 1996, demonstrated that based on clinical observation and evaluation of hematology, serum chemistry, and gross pathology, American bison treated with ivermectin at a dosage of 1000 g/kg body weight (5X the optimal dose) were not adversely affected by the elevated level of the drug. The data demonstrate that ivermectin injection, when administered subcutaneously at a dosage of 200 g/kg body weight, is safe to American bison.

VI. HUMAN SAFETY

The target tissue (liver) and marker residue (22,23-dihydroavermectin B_1a) for ivermectin residues in cattle were applied to the American bison because a residue depletion study submitted under PMF 5059, 61 FR 4442, February 6, 1996, had results showing similarity of residues in the liver and fat of American bison to residues in the liver and fat of reindeer, therefore, the tolerance assigned to reindeer (15 ppb) was used for American bison in calculating the withdrawal time. The withdrawal time was calculated to be 56 days.

VII. AGENCY CONCLUSIONS

The data submitted in support of this supplemental NADA comply with the requirements of section 512 of the Act and demonstrate that ivermectin injection, when used under the proposed conditions of use, is safe and effective for the treatment and control of grubs (Hypoderma bovis) in American bison.

Based on a tissue residue study in American bison, the similarity of those data to the residues in reindeer, and the current tolerance of 100 ppb for the marker residue (22, 23-dihydro-avermectin B_1a) of ivermectin in cattle (21 CFR 556.344), a 56-day withdrawal period is assigned for American bison treated with ivermectin at the recommended dose.

The original approval of ivermectin injection was as an over-the-counter drug. Accurate diagnosis of the need to treat for grub (Hypoderma bovis) infestations in American bison, which is the new species to be added to the label, can be made with a reasonable degree of certainty by the layman. Adequate directions for use have been written for the layman, and the conditions for use prescribed on the labeling are likely to be followed in practice. Therefore, the Center for Veterinary Medicine (CVM) has concluded that this product shall retain over-the-counter marketing status.

Under the Center's supplemental approval policy 21 CFR 514.106(b)(2)(vii), this is a Category II change. The approval of this change did not require a reevaluation of the safety or effectiveness data in the parent application.

VIII. LABELING (Attached)

Facsimile base label and package outsert for the 1000 mL container, bottle label and package insert for the 50, 200, 500, and 1000 mL containers, and box carton for the 50 mL container.

Copies of applicable labels may be obtained by writing to the:

Food and Drug Administration
Freedom of Information Staff (HFI-35)
5600 Fishers Lane
Rockville, MD 20857

Or requests may be sent via fax to: (301) 443-1726. If there are problems sending a fax, call (301) 443-2414.