CATTLE: 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 (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
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 control of
infections of Dictyocaulus viviparus and Ostertagia ostertagi for
21 days after treatment, and Oesophagostomum radiatum, Haemonchus
placei, Trichostrongylus axei, Cooperia punctata, and
Cooperia oncophora for 14 days after treatment in cattle.
Data demonstrating the effectiveness of IVOMEC Injection for Cattle for
previously registered indications are discussed in the parent NADA 128-409
FOI Summary (approval date February 7, 1984). Data from the following dose
confirmation trials demonstrate that IVOMEC Injection for Cattle given at the
recommended dosage controls infections of Dictyocaulus viviparus and
Ostertagia ostertagi for 21 days after treatment, and Oesophagostomum
radiatum, Haemonchus placei, Trichostrongylus axei,
Cooperia punctata, and Cooperia oncophora for 14 days after
treatment.
A. Dose Confirmation
Trial ASR 14553
1. Type of study: Dose confirmation study in cattle with induced infections of
gastrointestinal roundworms.
2. Investigator:
Bruce N. Kunkle, D.V.M., M.S., Ph.D.
Merck & Co., Inc.
Fulton, Missouri
3. General design:
a. Purpose: To determine the period after treatment during which infections
of gastrointestinal roundworms are controlled.
b. Animals: Twenty-eight (28) crossbred calves (7 per group). Animals were
approximately 6 months old and weighed 152 to 221 kg at the start of the study.
All animals were treated with another anthelmintic during the acclimation
period to eliminate any existing infections.
c. Controls: Negative controls received no treatment. Two groups received
medications which are not pertinent to this document.
d. Infection: Infective larvae were given to each animal daily, starting on
the day of treatment, according to the following schedule: Ostertagia
ostertagi (1000 per day for 22 days); Haemonchus placei (500 per day
for 15 days); Trichostrongylus axei (1000 per day for 15 days);
Cooperia punctata (500 per day for 15 days); Cooperia oncophora
(500 per day for 15 days); and Oesophagostomum radiatum (100 per day for
22 days, except that 1000 per day were erroneously given for 2 days).
e. Dosage form: The dosage form was the approved formulation of injectable
solution containing 10 mg ivermectin per mL.
f. Route of administration: Subcutaneous injection
g. Dose: 1 mL/50 kg body weight (200 mcg ivermectin/kg body weight) once.
h. Test duration: 49 to 51 days after treatment
i. Pertinent variables measured: Worm counts were determined at necropsy
which was 49 to 51 days after treatment, 34 to 36 days after the last
Haemonchus placei, Trichostrongylus axei, Cooperia punctata, and
Cooperia oncophora larvae were administered, and 27 to 29 days after the
last Ostertagia ostertagi and Oesophagostomum radiatum larvae
were administered.
4. Results - The following parasites had a minimum of six adequately infected
control animals:
Arithmetic mean
------------------- Percent
Parasite Control IVOMEC reduction
--------------------- --------- -------- ---------
Ostertagia ostertagi 4214.3 0.0 100
Haemonchus placei 1345.7 54.3 96.0
Trichostrongylus axei 5491.4 14.3 99.7
Cooperia punctata 3082.8 0.0 100
Cooperia oncophora 300.0 0.0 100
Oesoph. radiatum 121.4 1.4 98.8
5. Statistical methods:
Nematode percentage efficacies
were calculated using the following formula:
[Arithmetic mean number of
nematodes in non-medicated cattle) - (Arithmetic mean number of nematodes
in ivermectin-treated cattle)] ÷ (Arithmetic mean number of nematodes
in non-medicated cattle) x 100 = Percentage Efficacy
6. Conclusion:
Under the conditions of this
study, IVOMEC Injection for Cattle controlled infections of Ostertagia
ostertagi and Oesophagostomum radiatum for 21 days after treatment,
and Haemonchus placei, Trichostrongylus axei, Cooperia
punctata and Cooperia oncophora for 14 days after treatment.
7. Adverse reactions:
Some animals had loose stools
during the trial and one animal vomited. These health problems were not
believed to be related to the experimental treatments.
Trial ASR 15065
1. Type of study: Dose confirmation
study in cattle with induced infections of gastrointestinal roundworms.
2. Investigator:
Bruce N. Kunkle,
D.V.M., M.S., Ph.D.
Merck & Co., Inc.
Fulton, Missouri
3. General design:
a. Purpose: To determine
the period after treatment during which infections of gastrointestinal
roundworms are controlled.
b. Animals: Thirty (30) Holstein
calves (10 per group). Animals were approximately 4 to 5 months old and
weighed 157 to 234 kg at the start of the study. Animals were free of
patent infections at the time of treatment.
c. Controls: Negative controls
received the vehicle for IVOMEC Injection for Cattle subcutaneously at
1 mL/50 kg body weight. One group received a medication which is not pertinent
to this document.
d. Infection: Infective larvae
were given to each animal daily, starting on the day after treatment,
according to the following schedule: Ostertagia ostertagi (1000
per day for 21 days) and Dictyocaulus viviparus (50 per day for
28 days).
e. Dosage form: The dosage
form was the approved formulation of the injectable solution containing
10 mg ivermectin per mL.
f. Route of administration:
Subcutaneous injection
g. Dose: 1 mL/50 kg body
weight (200 mcg ivermectin/kg body weight) once.
h. Test duration: 49 to 50
days after treatment
I. Pertinent variables measured:
Worm counts were determined at necropsy which was 49 to 50 days after
treatment, 28 to 29 days after the last Ostertagia ostertagi larvae
were administered, and 21 to 22 days after the last Dictyocaulus viviparus
larvae were administered.
4. Results - The following
parasites had a minimum of six adequately infected control animals:
Arithmetic mean
------------------- Percent
Parasite Control IVOMEC reduction
---------------------- --------- ------ ---------
Dictyocaulus viviparus 20.3 0 100
Ostertagia ostertagi 1258.0 82.0 93.5
5. Statistical methods:
Nematode percentage efficacies
were calculated using the following formula:
[Arithmetic mean number of
nematodes in non-medicated cattle) - (Arithmetic mean number of nematodes
in ivermectin-treated cattle)] ÷ (Arithmetic mean number of nematodes
in non-medicated cattle) x 100 = Percentage Efficacy
6. Conclusion:
Under the conditions of this
study, IVOMEC Injection for Cattle controlled infections of Ostertagia
ostertagi for 21 days after treatment and Dictyocaulus viviparus
for 28 days after treatment.
7. Adverse reactions:
One animal died 22 days after
treatment. The apparent cause of death was an esophageal impaction, which
was not believed to be related to the experimental treatment.
Trial ASR 15071
1. Type of study: Dose confirmation
study in cattle with induced infections of gastrointestinal roundworms
and lungworms.
2. Investigator:
Bruce N. Kunkle,
D.V.M., M.S., Ph.D.
Merck & Co., Inc.
Fulton, Missouri
3. General design:
a. Purpose: To determine
the period after treatment during which infections of gastrointestinal
roundworms and lungworms are controlled.
b. Animals: Thirty (30) crossbred
calves (10 per group). Animals were approximately 8 to 9 months old and
weighed 235 to 275 kg at the start of the study. Animals were free of
patent infections at the time of treatment.
c. Controls: Negative controls
received the vehicle for IVOMEC Injection for Cattle subcutaneously at
1 mL/50 kg body weight. One group received a medication which is not pertinent
to this document.
d. Infection: Infective larvae
were given to each animal daily, starting on the day after treatment,
according to the following schedule: Haemonchus placei (500 per
day for 14 days); Trichostrongylus axei (1000 per day for 14 days);
and Cooperia punctata (1000 per day for 14 days).
e. Dosage form: The dosage
form was the approved formulation of the injectable solution containing
10 mg ivermectin per mL.
f. Route of administration:
Subcutaneous injection
g. Dose: 1 mL/50 kg body
weight (200 mcg ivermectin/kg body weight) once.
h. Test duration: 42 or 43
days after treatment
i. Pertinent variables measured:
Worm counts were determined at necropsy which was 42 or 43 days after
treatment and 28 or 29 days after the last larvae were administered.
4. Results - The following
parasites had a minimum of six adequately infected control animals:
Arithmetic mean
----------------- Percent
Parasite Control IVOMEC reduction
----------------------- ------- ------
Haemonchus placei 1022.0 16.0 98.4
Trichostrongylus axei 1578.0 4.0 99.7
Cooperia punctata 1996.2 11.0 99.4
5. Statistical methods:
Nematode percentage efficacies
were calculated using the following formula:
[Arithmetic mean number of
nematodes in non-medicated cattle) - (Arithmetic mean number of nematodes
in ivermectin-treated cattle)] ÷ (Arithmetic mean number of nematodes
in non-medicated cattle) x 100 = Percentage Efficacy
6. Conclusion:
Under the conditions of this
study, IVOMEC Injection for Cattle controlled infections Haemonchus
placei, Trichostrongylus axei and Cooperia punctata
for 14 days after treatment.
7. Adverse reactions:
One animal exhibited lameness
of the left rear leg during the trial. This event was not believed to
be related to the experimental treatments.
Trial ASR 15073
1. Type of study: Dose confirmation
study in cattle with induced infections of gastrointestinal roundworms
and lungworms.
2. Investigator:
Edward G. Johnson,
D.V.M.
Johnson Research
Parma, Idaho
3. General design:
a. Purpose: To determine
the period after treatment during which infections of gastrointestinal
roundworms and lungworms are controlled.
b. Animals: Thirty (30) crossbred
calves (10 per group). Animals were approximately 6 to 10 months old and
weighed 215 to 283 kg at the start of the study. Animals were free of
patent infections at the time of treatment.
c. Controls: Negative controls
received the vehicle for IVOMEC Injection for Cattle subcutaneously at
1 mL/50 kg body weight. One group received a medication which is not pertinent
to this document.
d. Infection: Infective larvae
were given to each animal daily, starting on the day after treatment,
according to the following schedule: Haemonchus placei (500 per
day for 14 days); Trichostrongylus axei (1000 per day for 14 days);
Cooperia punctata (1000 per day for 14 days); Cooperia oncophora
(1000 per day for 14 days); and Dictyocaulus viviparus (50 per
day for 21 days).
e. Dosage form: The dosage
form was the approved formulation of the injectable solution containing
10 mg ivermectin per mL.
f. Route of administration:
Subcutaneous injection
g. Dose: 1 mL/50 kg body
weight (200 mcg ivermectin/kg body weight) once.
h. Test duration: 42 or 43
days after treatment
i. Pertinent variables measured:
Worm counts were determined at necropsy which was 42 or 43 days after
treatment and 28 or 29 days the last Haemonchus placei, Trichostrongylus
axei, Cooperia punctata, and Cooperia oncophora larvae
were administered, and 21 or 22 days after the last Dictyocaulus viviparus
larvae were administered.
4. Results - The following
parasites had a minimum of six adequately infected control animals:
Arithmetic mean
----------------- Percent
Parasite Control IVOMEC reduction
---------------------- ------- ------ ---------
Haemonchus placei 1353.5 10.0 99.3
Trichostrongylus axei 1202.0 0.0 100
Cooperia punctata 3067.8 0.7 > 99.9
Cooperia oncophora 696.0 0.7 > 99.9
Dictyocaulus viviparus 32.4 0.0 100
5. Statistical methods:
Nematode percentage efficacies
were calculated using the following formula:
[Arithmetic mean number of
nematodes in non-medicated cattle) - (Arithmetic mean number of nematodes
in ivermectin-treated cattle)] ÷ (Arithmetic mean number of nematodes
in non-medicated cattle) x 100 = Percentage Efficacy
6. Conclusion:
Under the conditions of this
study, IVOMEC Injection for Cattle controlled infections of Dictyocaulus
viviparus for 21 days after treatment, and Haemonchus placei,
Trichostrongylus axei, Cooperia punctata and Cooperia
oncophora for 14 days after treatment.
7. Adverse reactions:
Signs of respiratory disease,
arthritis and bloat were seen in two animals during the trial. These health
problems were not believed to be related to the experimental treatments.
Trial ASR 13980
1. Type of study: Dose confirmation
study in cattle with induced infections of gastrointestinal roundworms
and lungworms.
2. Investigator:
R.E. Plue, D.V.M.
Springdale, Arkansas
3. General design:
a. Purpose: To determine
the period after treatment during which infections of gastrointestinal
roundworms are controlled.
b. Animals: Thirty-five (35)
Holstein calves (7 per group). Animals were approximately 6 to 8 months
old and weighed 142.9 to 207.3 kg at the start of the study. Animals were
free of patent infections at the time of treatment.
c. Controls: Negative controls
were untreated. Three groups received a medication or were treated at
a time not pertinent to this document.
d. Infection: Infective larvae
were given to each calf 14 days after treatment, according to the following
schedule: Oesophagostomum radiatum (1000).
e. Dosage form: The dosage
form was the approved formulation of the injectable solution containing
10 mg ivermectin per mL.
f. Route of administration:
Subcutaneous injection
g. Dose: 1 mL/50 kg body
weight (200 mcg ivermectin/kg body weight) once.
h. Test duration: 49, 50,
or 51 days after treatment
i. Pertinent variables measured:
Worm counts were determined at necropsy which was 49, 50, or 51 days after
treatment and 35, 36, or 37 days after the last larvae were administered.
4. Results - The following
parasites had a minimum of six adequately infected control animals:
Arithmetic mean
----------------- Percent
Parasite Control IVOMEC reduction
------------------------ ------- ------ ---------
Oesophagostomum radiatum 76 1.3 98
5. Statistical methods:
Nematode percentage efficacies
were calculated using the following formula:
[Arithmetic mean number of
nematodes in non-medicated cattle) - (Arithmetic mean number of nematodes
in ivermectin-treated cattle)] ÷ (Arithmetic mean number of nematodes
in non-medicated cattle) x 100 = Percentage Efficacy
6. Conclusion:
Under the conditions of this
study, IVOMEC Injection for Cattle controlled infections of Oesophagostomum
radiatum for 14 days after treatment.
7. Adverse reactions:
There were no adverse reactions
reported.
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 control
of infections of Dictyocaulus viviparus and Ostertagia ostertagi
for 21 days after treatment, and Oesophagostomum radiatum, Haemonchus
placei, Trichostrongylus axei, Cooperia punctata, and
Cooperia oncophora for 14 days after treatment.
For cattle the tolerance
of residues are specified in 21 CFR 556.344. A tolerance for the marker
residue (22, 23-dihydro-avermectin B1a) of ivermectin is 100 ppb in the
liver (target tissue). The withdrawal time is 35 days following one subcutaneous
injection of IVOMEC as specified in 21 CFR 522.1192.
The original approval of
ivermectin injection was as an over-the-counter drug. 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), 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.
Under section 512(c)(2)(F)(iii)
of the FFDCA, this approval for food producing animals qualifies for THREE
years of marketing exclusivity beginning on the date of approval because
the supplemental application contains substantial evidence of the effectiveness
of the drug involved, any studies of animal safety, or, in the case of
food producing animals, human food safety studies (other than bioequivalence
or residue studies) required for the approval of the application and conducted
or sponsored by the applicant. The three years of marketing exclusivity
applies only to the new claim for the control of Dictyocaulus viviparus
and Ostertagia ostertagi for 21 days after treatment and Oesophagostomum
radiatum, Haemonchus placei, Trichostrongylus axei,
Cooperia punctata, and Cooperia oncophora for 14 days after
treatment in cattle for which the supplemental application was approved.
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.
