Approval Date: October 22, 1990
Freedom of Information Summary
NADA 095-735
I. GENERAL INFORMATION:
NADA 095-735 Sponsor: Elanco Products Company
A Division of Eli Lilly and Company
Lilly Corporate Center
Indianapolis, IN 46285Generic Name: monensin (as monensin sodium) Trade Name: Rumensin Marketing Status: Over the Counter (OTC) Effect of Supplement: This supplement provides for an additional claim for the use of monensin in the prevention and control of coccidiosis in feedlot cattle. II. INDICATIONS FOR USE
III. DOSAGE:For the prevention and control of coccidiosis in feedlot cattle due to Eimeria bovis and Eimeria zuernii.
IV. EFFECTIVENESS:
A. DOSAGE FORM
The Type A Medicated Article is to be incorporated into complete feeds to provide levels of 10 to 30 g monensin per ton or may be included in Type B or Type C medicated feeds. Type B or Type C medicated feeds are to be mixed with grain and roughage to provide 10-30 g/ton in complete feed. Feed to provide 100 to 360 mg monensin per head daily.
B. ROUTE OF ADMINISTRATION See above C. RECOMMENDED DOSAGES: See above NOTES
V. ANIMAL SAFETY:Clinical Effectiveness in Monensin Fed to Cattle Inoculated With Coccidia Oocysts in a Four-Trial Dose Titration Experiment
Investigators:
Study No. 1 (T1F278303)
Bert E. Stromberg, Ph.D.
University of Minnesota
St. Paul, MN 55108
Study No. 2 (T1F178304)
Dr. Paul Fitzgerald
University of Illinois
Urbana, IL 61801
Study No. 3 (T1F398306)
Dr. Gary Davis
Greenbrier Veterinary Services, Inc.
Delaware, Ohio 43015
Study No. 4 (T1F278401)
Bert E. Stromberg, Ph.D.
John E. Schlotthaues, D.V.M., Ph.D
University of Minnesota
St. Paul, MN 55108
One hundred and twenty-three ruminating cattle weighing approximately 150 to 188 pounds were used in 4 trials to confirm the effectiveness of monensin fed at 0, 10, 20 or 30 g/ton against coccidiosis. The cattle were orally challenged with sporulated Eimeria bovis and/or Eimeria zuernii oocysts on the third day after monensin feeding began. The experimental design used was a randomized block at several locations with the challenge type (coccidia species) as the blocking factor. Oocyst counts and fecal score data were collected over time on several days throughout the 33 to 38-day trials. These data were viewed as sub-sampling units and analyzed accordingly. Animal weights and feed intakes were measured weekly, but analyzed over the entire length of the trial. Mortality within each treatment group was recorded upon occurrence. The least squares treatment means for pair-wise comparisons to the control treatment (0 g/ton monensin) were as follows:
--------Monensin Level (g/ton)-------- Variable 0 10 20 30 Ave. Daily Weight Gain 1.310 1.592 1.941 1.960 (lbs/h/d) Ave. Daily Dry Matter Intake 5.488 5.578 6.033 6.168 (lbs/h/d) E. bovis oocysts 49.936 29.077 15.894 11.163 (sq. root,1000 g/feces) E. zuernii oocysts 18.472 7.032 2.313 2.214 (sq. root,1000 g/feces) Other oocysts 19.275 9.233 8.666 4.710 (sq. root,1000 g/feces) Feces scores 1.40 1.28 1.12 1.09 (sq. root, scale1-5)* Mortality 16 0 0 0 (% of initial number)*** 1 = normal, 2 = slight diarrhea, 3 = diarrhea, 4 = diarrhea/blood, 5 = diarrhea/mucus
** Calculated percent (No. died/No. initially) x 100); not analyzed statisticallyFor both E. bovis and E. zuernii oocyst counts, the 10-gram level showed significant reduction as compared to controls. A statistically significant decrease in both oocyst counts was seen through 20 grams per ton. Although the 30 gram per ton level gave directionally lower oocyst counts than the 20-gram per ton level, the difference was not significant. Medical judgment was utilized in deciding that the 30-gram per ton level was medically meaningful.
Prior to initiation of the above studies, two preliminary studies were conducted as follows:
Study No. 665
L. R. McDougald and W. H. Henry
Lilly Research Laboratories
Greenfield, IN
Study No. 715
L. R. McDougald, W. H. Henry and L. L. Schenck
Lilly Research Laboratories
Greenfield, IN
The design and conduct of each pivotal or preliminary study are discussed under
A. Pivotal Studies
Study No. 1
1. The Clinical Effectiveness of Monensin in Controlling Bovine Coccidiosis. (T1F278303)
2. Investigator:
Bert E. Stromberg, Ph.D.
University of Minnesota
St. Paul, MN 55108
3. General Design:
a. Objective: To determine the effect of monensin on coccidial oocysts production, weight gain, feed intake, clinical signs, and mortality of ruminating cattle challenged with E. bovis or E. zuernii oocysts.
b. Test Animals: Thirty-six male Holstein-Friesian cattle approximately 8 weeks of age.
c. Each animal constituted an experimental unit. The four non-challenged animals served as controls for baseline performance and were confined in separate tie stalls adjacent to the coccidial challenged animals. The challenged controls and treated animals were blocked by inoculum (E. zuernii or E. bovis) into treatment groups of four animals each. Treatments (0, 10, 20, or 30 g/ton monensin) were assigned at random to each group as follows:
Monensin No. of Coccidial g/ton Animals Challenge 0 4 None 0 4 E. zuernii 10 4 E. zuernii 20 4 E. zuernii 30 4 E. zuernii 0 4 E. bovis 10 4 E. bovis 20 4 E. bovis 30 4 E. bovisd. Treatment:
1) Treatment feeds were offered three days prior to E. bovis or E. zuernii inoculation to establish acceptance and normal intake.
2) The cattle challenged with E. zuernii received an essentially pure inoculum containing about 235,000 sporulated oocysts in an oral gavage.
3) The cattle challenged with E. bovis received an essentially pure inoculum containing about 150,000 sporulated oocysts in an oral gavage.
e. Dosage Form:
Rumensin Premix, 60 g monensin/lb. incorporated into complete feeds at levels of 0, 10, 20 and 30 monensin/ton.
f. Test Duration:
35 days
g. Parameters Measured:
1) Body weights were recorded and average daily gain was calculated.
2) Feed intake was recorded.
3) Fecal character for each animal was recorded daily on the following scale: 1 = normal, 2 = slight diarrhea, 3 = diarrhea, 4 = diarrhea/blood, and 5 = diarrhea/mucus.
4) Oocyst counts were made. Oocysts were identified and recorded by species.
4. Results (eds. note, the following table includes 11 columns)
Cumulative Fecal --------Cumulative Oocysts-------- Character Monensin No. -----Days 19-23 Post Challenge---- Days 19-23 Trt. Coccidia of ADG* ADF** Post (g/ton) Challenge An. Mortality (lbs) (lbs) E.zuernii E.bovis Other Total Challenge 0 None 4 0 1.91 5.93 50 70 10 130 1.25 0 E.zuernii 4 0 1.63 5.75 110 100 10 220 1.25 10 E.zuernii 4 0 1.62 5.51 0 0 0 0 1.10 20 E.zuernii 4 0 1.69 5.70 0 10 0 10 1.10 30 E.zuernii 4 0 1.47 5.18 10 0 0 10 1.10 0 E.bovis 4 0 1.93 5.46 750 1260 40 2050 2.05 10 E.bovis 4 0 1.78 5.74 710 1670 0 2380 1.85 20 E.bovis 4 0 1.60 6.05 20 60 0 80 1.45 30 E.bovis 4 0 1.38 5.65 0 90 0 90 1.00*ADG = Average daily gain.
** ADF = Average daily feed.Animals inoculated with E. bovis exhibited more marked signs of bovine coccidiosis than those inoculated with E. zuernii. A monensin dose related oocyst passage response was observed in cattle receiving each challenge.
The daily fecal character indicated in reduction in diarrhea of monensin treated cattle when compared to non-treated challenged control animals.
All species of coccidial oocyst isolations following challenge were considerably reduced in the monensin treated groups of cattle when compared ton non-treated challenged control animals
There were no mortalities in this study.
5. Statistical Analysis
This trial was part of a four trial experiment. Statistical analysis was performed on the whole experiment run under a common protocol.
6. Conclusions
The cattle in the monensin treated groups demonstrated reduced coccidial oocyst shedding and diarrhea, over the non-treated challenged control animals.
7. Adverse Reactions
There were no adverse reactions attributable to the drug.
A. Pivotal Studies
Study No. 2
1. The Clinical Effectiveness of Monensin in Controlling Bovine Coccidiosis. (T1F178304)
2. Investigator:
Dr. Paul Fitzgerald
University of Illinois
Urbana, IL 61801
3. General Design
a. Objective: To determine the effect of monensin on coccidial oocysts production, weight gain, feed intake, clinical signs, and mortality of ruminating cattle challenged with E. bovis or E. zuernii oocysts.
b. Test Animals: Thirty-six male Holstein-Friesian cattle approximately 8 weeks of age.
c. Each animal constituted an experimental unit. The four non-challenged animals served as controls for baseline performance and were confined in separate tie stalls adjacent to the coccidial challenged animals. the challenged controls and treated animals were blocked by inoculum (E. zuernii or E. bovis) into treatment groups of four animals each. Treatments (0, 10, 20, or 30 g/ton monensin) were assigned at random to each group as follows:
Monensin No. of Coccidial g/ton Animals Challenge0 4 None 0 4 E. zuernii 10 4 E. zuernii 20 4 E. zuernii 30 4 E. zuernii 0 4 E. bovis 10 4 E. bovis 20 4 E. bovis 30 4 E. bovisd. Treatment
1) Treatment feeds were offered three days prior to E. bovis or E. zuernii inoculation to establish acceptance and normal intake.
2) The cattle challenged with E. zuernii received an inoculum containing about 228,000 sporulated oocysts in an oral gavage as follows: E. zuernii, 76%; E. bovis, 4%; E. auburnensis, 6%; and E. ellipsoidalis/cylindrica, 14%.
3) The cattle challenged with E. bovis received an inoculum containing about 250,000 sporulated oocysts in an oral gavage as follows: E. bovis, 99%; less than 1% of E. zuernii, E. auburnensis, or
E. ellipsoidalis/cylindrica.
e. Dosage Form
Rumensin Premix, 60 g monensin/lb. incorporated into complete feeds at levels of 0, 10, 20, and 30 g monensin/ton.
f. Test Duration: 35 days
g. Parameters Measured
1) Body weights were recorded and average daily gain calculated.
2) Feed intake was recorded.
3) Fecal character for each animal was recorded daily on the following scale: 1 = normal, 2 = slight diarrhea, 3 = diarrhea, 4 = diarrhea/blood, and 5 = diarrhea/mucus.
4) Oocyst counts were made. Oocysts were identified and recorded by species.
4. Results (eds. note, the following table includes 11 columns of results)
Cumulative Fecal --------Cumulative Oocysts-------- Character Monensin No. -----Days 19-23 Post Challenge---- Days 19-23 Trt. Coccidia of ADG* ADF** Post (g/ton) Challenge An. Mortality (lbs) (lbs) E.zuernii E.bovis Other Total Challenge 0 None 4 0 2.12 5.84 30 1120 410 1560 1.00 0 E.zuernii 4 0 1.36 4.23 1580 3970 6410 11960 1.85 10 E.zuernii 4 0 2.28 5.84 110 870 3260 4240 1.15 20 E.zuernii 4 0 2.31 6.10 220 270 4030 4520 1.05 30 E.zuernii 4 0 2.11 5.24 60 200 3070 3330 1.00 0 E.bovis 4 3 0.02 3.71 8107 87493 2227 97827 4.20 10 E.bovis 4 0 0.70 3.70 1965 22710 840 25515 3.20 20 E.bovis 4 0 1.73 4.49 350 13030 180 13560 1.60 30 E.bovis 4 0 1.62 4.85 740 10680 30 11450 1.75*ADG = Average daily gain.
** ADF = Average daily feed.Animals inoculated with E. bovis exhibited more marked signs of bovine coccidiosis than those inoculated with E. zuernii. A monensin dose related response was observed in cattle receiving each challenge.
Monensin treated groups of cattle gained more weight than the non-treated, challenge control animals.
The daily fecal character indicated reduction in diarrhea of monensin treated cattle when compared to non-treated, challenged control animals.
All species of coccidial oocyst isolations following challenge were considerably reduced in the monensin treated groups of cattle when compared to non-treated, challenged control animals.
5. Statistical Analysis
This trial was part of a four trial experiment. Statistical analysis was performed on the whole experiment run under a common protocol.
6. Conclusions
The cattle in the monensin treated groups demonstrated improved performance and reduced coccidial oocyst shedding, diarrhea, and mortality over the non-treated, challenged control animals.
7. Adverse reactions
There were no adverse reactions attributable to the drug.
A. Pivotal Effectiveness Studies
Study No. 3
1. The Clinical Effectiveness of Monensin in Controlling Bovine Coccidiosis. (T1F398306)
2. Investigator:
Dr. Gary Davis
Greenbrier Veterinary Services, Inc.
Delaware, OH 43015
3. General Design
a. Objective: To determine the effect of monensin on coccidial oocysts production, weight gain, feed intake, clinical signs, and mortality or ruminating cattle challenged with E. bovis or E. zuernii oocysts.
b. Test Animals: Thirty-six male Holstein-Friesian cattle approximately 8 weeks of age.
c. Each animal constituted an experimental unit. The four non-challenged animals served as controls for baseline performance and were confined in separate tie stalls adjacent to the coccidial challenged animals. The challenged animals were blocked both by inoculum (E. zuernii or E. bovis) and location (four animals/block). All four treatments (0, 10, 20, or 30 g/ton monensin) were assigned to each block.
Monensin No. of Coccidial g/ton Animals Challenge 0 4 None 0 4 E. zuernii 10 4 E. zuernii 20 4 E. zuernii 30 4 E. zuernii 0 4 E. bovis 10 4 E. bovis 20 4 E. bovis 30 4 E. bovisd. Treatment
1) Treatment feeds were offered three days prior to E. bovis or E. zuernii inoculation to establish acceptance and normal intake.
2) The cattle challenged with E. zuernii received an inoculum containing about 475,000 sporulated oocysts in an oral dose.
3) The cattle challenged with E. bovis received an inoculum containing about 300,000 sporulated oocysts in an oral dose.
e. Dosage Form
Rumensin Premix, 60 g monensin/lb. incorporated into complete feeds at levels of 0, 10, 20, and 30 g monensin/ton.
f. Test Duration: 35 days
g. Parameters Measured
1) Body weights were recorded and average daily gain calculated.
2) Feed intake was recorded.
3) Fecal character for each animal was recorded daily on the following scale: 1 = normal, 2 = slight diarrhea, 3 = diarrhea, 4 = diarrhea/blood, and 5 = diarrhea/mucus.
4) Oocyst counts were made. Oocysts were identified and recorded by species.
4. Results (eds. note, the following table includes 11 columns)
Cumulative Fecal --------Cumulative Oocysts-------- Character Monensin No. -----Days 19-23 Post Challenge---- Days 19-23 Trt. Coccidia of ADG* ADF** Post (g/ton) Challenge An. Mortality (lbs) (lbs) E.zuernii E.bovis Other Total Challenge 0 None 4 0 2.04 6.68 0 0 0 0 1.08 0 E.zuernii 4 0 2.12 6.44 25 0 5 70 1.53 10 E.zuernii 4 0 2.04 5.88 0 0 0 0 1.08 20 E.zuernii 4 0 1.96 6.01 0 5 0 5 1.58 30 E.zuernii 4 0 2.46 6.43 15 0 0 15 1.10 0 E.bovis 4 2 -0.25 4.11 1067 22008 4831 25420 3.88 10 E.bovis 4 0 0.21 4.65 265 2198 1337 10750 3.20 20 E.bovis 4 0 2.04 6.18 23 12175 1688 14065 2.23 30 E.bovis 4 0 2.25 6.12 0 630 125 2610 1.73*ADG = Average daily gain.
** ADF = Average daily feed.
Animals inoculated with E. bovis exhibited more marked signs of bovine coccidiosis than those inoculated with E. zuernii. A monensin dose related response was observed in cattle receiving each challenge.Monensin E. bovis treated groups of cattle gained more weight than the non-treated, challenged control animals.
The daily fecal character indicated reduction in diarrhea of monensin treated cattle when compared to non-treated, challenged control animals.
All species of coccidial oocyst isolations following challenge were considerably reduced in the monensin treated groups of cattle when compared to non-treated, challenged control animals.
5. Statistical Analysis
This trial was part of a four-trial experiment. Statistical analysis was performed on the whole experiment run under a common protocol.
6. Conclusions
The cattle in the monensin treated groups demonstrated reduced coccidial oocyst, shedding, diarrhea, and mortality from E. bovis over the non-treated, challenged control animals.
7. Adverse Reactions
There were no adverse reactions attributable to the drug.
Study No. 4
1. The Clinical Effectiveness of Monensin in Controlling Bovine Coccidiosis. (T1F278401)
2. Investigator:
Bert E. Stromberg, Ph.D.
John C. Schlotthaues, D.V.M., Ph.D.
William J. Bemrick, Ph.D.
University of Minnesota
St. Paul, MN 55108
3. General Design
a. Objective: To determine the effect of monensin on coccidial oocysts production, weight gain, feed intake, clinical signs, and mortality of ruminating cattle challenged with E. bovis or E. zuernii oocysts.
b. Test Animals: Thirty-six male Holstein-Friesian cattle approximately 8 weeks of age.
c. Each animal constituted an experimental unit. The four non-challenged animals served as controls for baseline performance and were confined in separate tie stalls adjacent to the coccidial challenged animals. The challenged controls and treated animals were blocked by inoculum (E. zuernii or E. bovis) into treatment groups of four animals each. Treatments (0, 10, 20, or 30 g/ton monensin) were assigned at random to each group as follows:
Monensin No. of Coccidial g/ton Animals Challenge 0 4 None 0 7 Mixed* 10 7 Mixed* 20 7 Mixed* 30 7 Mixed**Challenged with both E. bovis and E. zuernii.d. Treatment
1) Treatment feeds were offered three days prior to E. bovis or E. zuernii inoculation to establish acceptance and normal intake.
2) The cattle were challenged with predominantly (99+%) E. zuernii inoculum containing 500,000 sporulated oocysts and a predominantly (99+%) E. bovis inoculum containing 300,000 sporulated oocysts. Each animal received these inocula oral gavages.
e. Dosage Form
Rumensin Premix, 60 g monensin/lb incorporated into complete feeds at levels of 0, 10, 20 and 30 g monensin/ton.
f. Test Duration: 31 days
g. Parameters Measured
1) Body weights were recorded and average daily gain was calculated.
2) Feed intake was recorded.
3) Fecal character for each animal was recorded daily on the following scale: 1 = normal, 2 = slight diarrhea, 3 = diarrhea, 4 = diarrhea/blood, and 5 = diarrhea/mucus.
4) Oocysts counts were made. Oocysts were identified and recorded by species.
4. Results (eds. note, the following table includes 11 columns)
Cumulative Fecal --------Cumulative Oocysts-------- Character Monensin No. -----Days 19-23 Post Challenge---- Days 19-23 Trt. Coccidia of ADG* ADF** Post (g/ton) Challenge An. Mortality (lbs) (lbs) E.zuernii E.bovis Other Total Challenge0 None 4 0 1.83 8.56 0 5 145 150 1.05 0 Mixed*** 7 0 2.21 8.19 651 8783 123 9614 1.94 10 Mixed*** 7 0 2.41 7.90 72 2623 54 4549 2.09 20 Mixed*** 7 0 2.39 8.37 0 103 3 106 1.06 30 Mixed*** 6**** 0 2.49 9.37 3 346 0 349 1.34*ADG = Average daily gain.
** ADF = Average daily feed.
*** Challenged with both E. zuernii and E. bovis.
**** One animal was removed due to inability to measure feed consumption.The signs of bovine coccidiosis exhibited by these animals inoculated with a mixture of E. zuernii and E. bovis were more severe than previous trials using pure E. zuernii inoculation. A monensin dose-related response was observed in the animals.
Monensin-treated groups of cattle gained more weight than the unmedicated, challenged control animals.
The daily fecal character indicated, in most cases, reduction in diarrhea of monensin treated cattle when compared to the unmedicated, challenged control animals.
There were no mortalities in this study.
5. Statistical Analysis
This trial was part of a four-trial experiment. Statistical analysis was performed on the whole experiment run under a common protocol.
6. Conclusions
The cattle in the monensin treated groups demonstrated improved performance and reduced coccidial oocyst shedding, and in most cases, diarrhea over the non-treated challenged control animals.
7. Adverse Reactions
There were no adverse reactions attributable to the drug.
4. A. Preliminary Effectiveness Studies
Study No. 665
1. Monensin Coccidiosis Experiment No. 665
2. Investigator:
L. R. McDougald and W. H. Henry
Lilly Research Laboratories
Greenfield, IN
3. General Design
a. The study was designed as a pilot experiment to evaluate the efficacy of monensin against Eimeria bovis and E. zuernii in calves.
b. Eight newborn male Holstein calves were acquired from Florida. They were fed milk replacer until weaning onto the calf starter ration and housed in isolation pens.
c. Treatment
Pen 19 Monensin - 30 g/ton
Pen 20 Infected controls
d. Coccidia Challenge
Each calf was orally administered sporulated oocysts of the following species:
E. bovis (LB7) 100,000 oocysts (passed 6-1-76)
E. zuernii (LB6) 100,000 oocysts (passed 6-1-76)
e. Rations and Administration
A calf starter ration containing monensin levels of 0 to 30 g/ton was fed during the 35-day experiment.
f. Experimental Design
Eight calves were divided into 2 groups of 4 calves/group on an equal weight pen basis. Treated calves were on medicated feed (8-3-76, day 1) prior to inoculation (8-10-76, day 7). The following data were collected: weight gains per pen, feed/gain by pen and mortality. All calves and feed were weighed as shown in the following tables.
4. Results
Mean Weight Gain Per Pen (lbs)
Monensin Day 7 Day 14 Day 21 Day 28 Day 35
(g/t) 30 27 69 109 157 168 0 38 76 98 132 170Mean Feed/Gain Per Pen
Monensin Day 7 Day 14 Day 21 Day 28 Day 35Oocysts Passage Per Pen*
(g/t) 30 2.87 2.39 2.46 2.07 2.68 0 2.38 2.38 2.72 2.38 2.55Days P.I. Monensin Infected Controls 15 0 0 16 0 Trace 17 0 Trace 18 0 Trace 19 0 4,442,000 20 0 603,000 21 0 670,000 22 0 Trace 23 0 Trace 24 0 Trace* Count based on 1 liter of fecal material.Percent Mortality Due to Coccidiosis
Monensin (g/t) Percent Mortality 30 0 0 05. Statistical Analysis
This was a preliminary pilot study. Statistical analysis is not applicable.
6. Conclusions
Monensin was effective in prevention of bovine coccidiosis caused by Eimeria bovis when fed to calves at 30 g/ton in finished feed.
7. Adverse reactions
There were no adverse reactions attributable to the drug.
Study No. 715
1. Monensin Coccidiosis Experiment No. 715
2. Investigators:
L. R. McDougald, W. H. Henry and L. L. Schenck
Lilly Research Laboratories,
Greenfield, IN
3. General Design
a. The study was designed to test the prophylactic effectiveness of monensin against Eimeria bovis infections in calves.
b. Thirty-two calves, 6 weeks old, male Holstein, obtained as 1-3 day old calves and fed milk replacer until weaning at 4 weeks of age.
c. Treatments
1. Noninfected, nonmedicated controls (2 x 4 calves)
2. Infected, nonmedicated controls (2 x 4 calves)
3. Infected, monensin 15 g/ton (2 x 4 calves)
4. Infected, monensin 30 g/ton (2 x 4 calves)
d. Coccidia Challenge
72 hrs. after initiation of the feeding regiment, each calf was given 100,000 oocysts of E. bovis (isolate LB7, Lot 60176) by oral inoculation.
e. Rations and Administration
A pelleted cattle ration containing levels of 0, 15 and 30 g monensin per ton was fed during the 28-day experiment.
f. Experimental Design
Each treatment was fed to two groups of 4 calves each. Calves were distributed to pens on a weight basis, to achieve approximately equal pen weights.
Each pen was supplied with the appropriate feed ad libitum and pine shavings used for bedding. At the onset of oocyst passage, bedding material was removed and the total fecal output was collected on a daily basis. Calves were
weighed individually at the time of the infection and subsequently at 7-day intervals until termination at 28 days post-infection. The following data were collected: Clinical observations, daily oocyst passage per pen, weight gain, individual weight gain and feed consumption per pen.
4. Results
a. Clinical Observations
Diarrhea and anorexia were noted in both infected control groups from day 12 through day 21 post-infection. No untoward effects were seen in any other treatments.
b. Oocyst Passage per Pen
Substantial oocyst passage was noted on days 19-28 post-infection in both infected control groups.
Total Oocyst Passage Monensin (g/t) Infection Calf (x 10 degrees) 0 + 58.7 0 - 0 15 + ---* 30 + 0*Positive, but too few to countWeight Gain/Calf
Monensin Conc. Total Gain/ Average Daily (g/t) Infection Calf (lbs) Gain(lbs) 0 + 47.75 1.54 0 - 56.75 1.83 15 + 62.67 2.02 30 + 63.00 2.03Feed Consumption and Feed/GainMonensin Conc. Feed Consumption (g/t) Infection (lbs/calf) Feed/Gain 0 + 142.8 3.00 0 - 157.3 2.77 15 + 155.0 2.48 30 + 154.3 2.455. Statistical Analysis
The data from this equipment were not statistically analyzed.
6. Conclusions
Monensin was effective in preventing bovine coccidiosis due to Eimeria bovis and E. zuernii when fed continuously at 15 and 30 g/ton in a complete feed. Control animals suffered depressed weight gain during the patent period but recovered by the end of the experiment.
7. Adverse Reactions
There were no adverse reactions attributable to the drug.
4. B. Corroborative Effectiveness Study
B. Corroborative Study
1. Comparison of Two Forms and Two Levels of Lasalocid with Monensin on Feedlot Cattle Performance. Journal of Animal Science, Vol. 53, No. 6, 1981, pages 1440-1445.
2. Investigators:
L. L. Berger, S. C. Ricke and G. C. Fahey, Jr.
University of Illinois
Urbana, IL 61801
3. General Design:
The purpose of these trials as regards anticoccidial activity was to determine the effects of lasalocid and monensin on the incidence and concentrations of coccidia oocysts.
4. Summary and Conclusions
Results:
Refer to Tables 3 and 5 below of the study. Monensin and lasalocid decreased the incidence and concentration of coccidial oocysts.
Table 3 (eds. note, the following table includes 7 columns)
Coccidiostatic Effect of Two Forms of Lasalocid and Monensin in Trial1
--% of Steers with Coccidia Oocysts-- ------------Oocysts/g*------------ Treatment --Day 1 Day 40 Day 120-- --Day 1 Day 40 Day 120-- Control 70.8 41.5 58.3 495 275 715 Pure Lasalocid 79 4.2 21.0 883 50 200 Mycelia-Cake Lasalocid 58.3 4.2 8.5 833 50 100 Monensin 62.9 4.2 4.2 1,104 50 100 SE** 7.2 4.6 5.4 172 40.4 105.3*Average concentration for those steers shedding oocysts.
** Standard error of the mean.
Table 5 (eds. note, the following table includes 7 columns)
Coccidiostatic Effect of Lasalocid at 30 and 45 g/ton and of Monensin at 30 g/ton
--% of Steers with Coccidia Oocysts-- ------------Oocysts/g*------------ Treatment --Day 1 Day 40 Day 120-- --Day 1 Day 40 Day 120-- Control 66.9 10.2 6.3 742 19.7 12.5 Lasalocid, 30 g/ton 71.5 4.2 0 703 12.0 0 Lasalocid, 45 g/ton 63.1 5.1 0 794 10.3 0 Monensin, 30 g/ton 69.3 0 0 603 0 0 SE** 10.3 2.7 3 179.7 6.3 6.2* Average concentration for those steers shedding oocysts.
** Standard error of the mean.
Monensin premix is the subject of an approved NADA 095-735. The conditions of the existing approval are described in 21CFR 558.355. The feeding levels and rates proposed in this supplemental NADA providing for the control of bovine coccidiosis are essentially the same as for the existing approval. The differences involve changing the lower feeding level/rates of 5-30 g/ton and 50-360 mg/hd/day and providing 10-30 g/ton and 100-360 mg/hd/day when used for the control of coccidiosis. The duration of feeding will not exceed that already approved in the cited regulation. There is no reason to conclude that this additional approval at essentially the same levels will adversely affect the safety of animals receiving monensin.VI. HUMAN FOOD SAFETY:
VII. AGENCY CONCLUSIONS:This information is addressed in the original FOI for monensin for cattle in confinement for slaughter (FR 58289-58290, Vol:40, No. 242, December 16, 1975).
The data submitted in support of this supplemental NADA satisfy the requirements of section 512 of the Act and 21CFR 558 of the implementing regulations. It demonstrates that monensin (Type A medicated article) is safe and effective for the indications stated on the product labeling. The supplement provides for a new claim, the use of monensin in feedlot cattle for the prevention of coccidiosis caused by Eimeria bovis and E. zuernii.
Monensin sodium for use in food producing animals is an over the counter product. Accurate diagnosis can be made with reasonable degree of certainty by the layman, and the conditions for use prescribed on the labeling are likely to be followed in the practice. Therefore, the Center for Veterinary Medicine has concluded that this product remains under over-the-counter marketing status.
According to the Center's provisions of 21CFR 514.106 (2) (vii) this is a Category II change because the claim was expanded for the use of monensin in feedlot cattle to prevent coccidiosis caused by E. bovis and E. zuernii. It was concluded that the approval of this supplement neither poses an increased human risk from exposure to the drug nor alters the condition of the drug's safety in cattle.
The approved monensin sodium premix is codified in section 21CFR 558.355 as a Type A medicated article for use in broiler chickens, turkeys, replacement chickens intended for use as cage layers, bobwhite quail, and goats for the prevention of coccidiosis, and in cattle for the improvement of feed efficiency. The tolerance is codified in section 21CFR 556.420 (a) and is established at 0.05 part per million for negligible residues of monensin in the edible tissues of cattle and goats. Withdrawal time before slaughter is not required.
VIII. LABELING (Attached)
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 20857Or requests may be sent via fax to: (301) 443-1726. If there are problems sending a fax, call (301) 443-2414.