I. GENERAL INFORMATION
Norbrook Laboratories Limited
Northern Ireland BT35 6JP
Sterile Penicillin G Procaine Suspension USP
Over the Counter (OTC)
Effect of Supplement:
This supplement provides for the reduction of the milk withholding period from 72 hours (6 milkings) to 48 hours.
II. INDICATIONS FOR USE
Penicillin G Procaine is an antibacterial agent which is effective against a variety of pathogenic organisms, chiefly in the gram-positive category. Sterile Penicillin G Procaine Suspension is recommended for treatment of bacterial pneumonia (shipping fever) caused by Pasteurella multocida in cattle and sheep, erysipelas caused by Erysipelothrix insidiosa in swine and strangles caused by Streptococcus equi in horses.
A. DOSAGE FORM: Suspension
B. ROUTE OF ADMINISTRATION: intramuscular
C. RECOMMENDED DOSAGES:
3,000 units per pound of bodyweight (one ml per 100 lbs. bodyweight).
Sterile Penicillin G Procaine Suspension should be administered by the intramuscular route. The product is ready for injection after warming the vial to room temperature and shaking to insure a uniform suspension. The recommended daily dosage of penicillin is 3,000 units per pound of bodyweight (one ml per 100 lbs. bodyweight). Continue daily treatment until recovery is apparent and for at least one day after symptoms disappear, usually in two to three days. Treatment should not exceed four consecutive days. No more than 10 mL should be injected at any one site in adult livestock: rotate injection sites for each succeeding treatment.
Exceeding the recommended daily dosage of 3,000 units per pound of bodyweight, administering at the recommended level for more than four consecutive days and/or exceeding 10 mL intramuscularly per injection site, may result in antibiotic residues beyond the withdrawal time. Milk taken from treated dairy animals within 48 hours after the latest treatment must not be used for food. Discontinue use of this drug for the following time period before treated animals are slaughtered for food. Cattle - 10 days; Sheep - 9 days; Swine - 7 days. Not for use in horses intended for food.
IV. & V. EFFECTIVENESS AND ANIMAL SAFETY
The change provided by this supplement does not affect the underlying safety or effectiveness in the parent application.
VI. HUMAN FOOD SAFETY
A milk residue depletion study was performed by Norbrook Laboratories Limited at their research farm in Rostrevor, Co. Down, Northern Ireland. Twenty lactating Friesian cows weighing from 940 to 1480 pounds (average 1120 pounds) were given intramuscular injections of 3000 units of penicillin G procaine per pound of body weight, once daily for four days. During the study the cows were milked at 6-hour intervals (four times per day).
Average milk production during the study was 15 - 27 kg per cow per day (overall average of 20 kg/cow/day). Milk samples were stored frozen (at about -20 C) until assayed.
Milk samples were analyzed for penicillin G residues using the standard procedure from FDA's "Antibiotic Residues in Milk, Dairy Products, and Animal Tissues: Methods, Reports, and Protocols" (the "Green Book", revised October 1968), which employs the Sarcina lutea organism. The limit of detection was 0.0063 units/mL. The mean residues for the samples collected 6, 12, 18, 24, 30, and 36 hours after the last dose are shown below in the table.
Mean Penicillin G Residues* in Milk from Cows Treated Intramuscularly with 3000 units/lb of body weight Once Daily for Four Days.
|Withdrawal Time (Hours)||Residues (units/mL)|
* Mean of values for 20 cows unless otherwise noted.
** The samples from 12 of the 20 cows were below the limit of detection (LOD), and the mean was computed using the LOD (0.0063 units/mL) for those samples.
*** The samples from 19 of 20 cows were below the LOD.
Analysis of the data using the statistical method described in FDAs "General Principles for Evaluating the Safety of Compounds Used in Food-Producing Animals" (a 99% statistical tolerance limit and a 95% confidence interval) showed that the data support a 48-hour milk discard period.
VII. AGENCY CONCLUSIONS
Under the agency's supplemental approval policy, 21 CFR 514.106(b)(2)(x), this is a Category II change that did not require a reevaluation of the safety and effectiveness data in the parent application.
This supplemental application for sterile penicillin G procaine suspension provides for reduction of the milk withholding period from 72 hours to 48 hours and this is supported by a milk residue depletion study.
The agency has determined under 21 CFR 25.24(d)(1)(i) that this action is of a type that does not individually or cumulatively have a significant effect on the human environment. Therefore, neither an environmental assessment nor an environmental impact statement is required.
Under section 512(c)(2)(F)(iii) of the Federal Food, Drug, and Cosmetic Act, this approval does not qualify for marketing exclusivity because no new clinical or field investigations (other than bioequivalence or residue studies) and no new human food safety studies (other than bioequivalence or residue studies) were essential to the approval and conducted or sponsored by the applicant.
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 20857
Or requests may be sent via fax to: (301) 443-1726. If there are problems sending a fax, call (301) 443-2414.