FULL PRESCRIBING INFORMATION: CONTENTS*
- INDICATIONS FOR USE
- DOSAGE AND ADMINISTRATION
- ADVERSE REACTIONS
- TARGET ANIMAL SAFETY
- STORAGE INFORMATION
- HOW SUPPLIED
- PRINCIPAL DISPLAY PANEL - 20 mL Bottle Label
FULL PRESCRIBING INFORMATION
Sterile Solution for Injection
Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.
IMPROVEST is a sterile solution containing Gonadotropin Releasing Factor Analog-Diphtheria Toxoid Conjugate. Each mL contains 0.2 mg Gonadotropin Releasing Factor Analog-Diphtheria Toxoid Conjugate, 150 mg of diethylaminoethyl-dextran hydrochloride, 1 mg chlorocresol, sodium hydroxide as needed to adjust pH and water for injection.
INDICATIONS FOR USE
IMPROVEST is indicated for the temporary immunological castration (suppression of testicular function) and reduction of boar taint in intact male pigs intended for slaughter.
DOSAGE AND ADMINISTRATION
IMPROVEST should be administered via subcutaneous injection into the post auricular region of the neck. A safety injector should be used, preferably one which has a dual safety system providing both a needle guard and a mechanism to prevent accidental operation of the trigger. Each intact male pig should receive two 2-mL doses of IMPROVEST. The first dose should be administered no earlier than 9 weeks of age. The second dose should be administered at least 4 weeks after the first dose. Pigs should be slaughtered no earlier than 4 weeks and no later than 8 weeks after the second dose. In case of misdosing, the animal should be re-dosed immediately.
Do not use IMPROVEST in intact male pigs intended for breeding because of the disruption of reproductive function. Not approved for use in female pigs and barrows.
No withdrawal period is required when used according to labeling.
Not for Human Use. Keep Out of Reach of Children.
USER SAFETY WARNINGS
Warning for person administering IMPROVEST
Accidental self injection could affect reproductive physiology of both men and women and may adversely affect pregnancy. Pregnant women should not administer this product. Women of childbearing age should exercise extreme caution when handling this product. Special care should be taken to avoid accidental self injection and needle stick injury when administering the product. Protective clothing including, but not limited to, safety glasses and gloves should be worn. Use a safety injector, preferably one which has a dual safety system providing both a needle guard and a mechanism to prevent accidental operation of the trigger. In case of eye contact, rinse immediately with copious amounts of water. In case of skin contact, wash immediately with soap and water. The product should be stored safely out of the reach of children. As a reminder, it is the prescribing veterinarian's responsibility to inform drug administrators of the user safety warnings associated with IMPROVEST.
Advice to the user in the event of accidental self injection
In the event of accidental self injection, wash the injury thoroughly with clean running water. Seek prompt medical attention and take the package leaflet with you. Do not administer the product, and/or any other product with a similar action, in the future.
Advice to the physician
Accidental self injection could affect reproductive physiology of both men and women and may adversely affect pregnancy. If self injection with IMPROVEST is suspected, reproductive physiology should be monitored by assay of testosterone or estrogen levels (as appropriate).
The risk of a physiological effect is greater after a second or subsequent accidental injection than after a first injection. The patient should be advised not to administer IMPROVEST, and/or any other product with a similar action, in the future.
For customer service, to report suspected adverse reactions or to obtain a copy of the Material Safety Data Sheet (MSDS) call 1-800-336-5288.
Subcutaneous injection in intact male pigs can cause a transient local injection site reaction that may result in trim loss at slaughter.
The field study observations from field effectiveness studies were consistent with the observations made during the target animal safety studies of transient inflammation at the injection sites. IMPROVEST did not cause unusual clinical signs or an unexpected frequency or severity of injection site reactions. Adverse events, as reported, were not uniquely attributable to IMPROVEST.
TARGET ANIMAL SAFETY
Margin of Safety
The safety of two doses of IMPROVEST was evaluated in intact male swine. Thirty 9-week old intact boars received two subcutaneous doses of IMPROVEST in the same location 14 days apart. The boars received one of three treatments: Saline Control (12-mL), IMPROVEST at the intended dose (2-mL, 1×), or IMPROVEST at 6 times the intended dose (12-mL, 6×). Boars were clinically monitored daily. In addition, observation and measurement of injection sites, body weight, quantitative feed consumption, hematology, and clinical chemistry analyses were also obtained. A complete postmortem examination was conducted on each boar 14 days after the second injection. IMPROVEST, administered subcutaneously at the label dose (2-mL) resulted in mild transient injection site reactions at the 1× dose and caused clinical signs of systemic inflammation at 6× the intended dose. The signs of inflammation included depression, stiffness of the neck lasting up to five days, reduction in feed intake, and lower body weights. Multiple swollen joints and associated lameness, which may be signs of systemic inflammation, were observed in one 6× boar. Evaluation of blood work revealed increased white blood cell counts (eosinophilia and neutrophilia); slight increases in total serum protein (above normal reference range in 50% of the 6× boars) and globulin (above the normal reference range in 40% of the 6× boars); and slight decreases in serum albumin in 6× boars. Injection sites for the 6× boars showed clinically detectable firmness persisting in all animals for 14 days after the second injection. Pain and sensitivity at the injection site persisted for up to five days, and erythema and heat were more prominent in the 6× boars than in the 1× boars. Mild to moderate chronic inflammation and discoloration in the subcutaneous tissues at the injection site were observed. In all IMPROVEST treated boars, atrophy of testes, prostate, and bulbourethral glands were observed as expected consequences associated with the intended effect of the drug. At the label 2-mL dose, IMPROVEST may cause transient injection site inflammation.
Injection Site Safety
Injection site safety was evaluated following the injection of IMPROVEST into healthy 17-week old boars. The treated boars received two 2-mL doses of IMPROVEST into the same injection site location 28 days apart, while the control boars received saline. Daily monitoring included clinical evaluation and observation and measurement of injection sites. Two days after the second injection, postmortem observations of injection sites were conducted. All clinical signs of observable injection site swelling were resolved within 24 hours, and pain on palpation resolved by 48 hours post-injection. Firmness persisted for up to 11 days after the first injection in 10% of boars. Gross injection site alterations consisted of subcutaneous edema with tan or red discoloration. Two 2-mL injections of IMPROVEST, administered 28 days apart into the same location resulted in transient injection site reactions following each injection and resulted in discoloration of tissue at the injection site which was observable approximately 48 hours after the second injection.
During the conduct of the nine location field effectiveness study, IMPROVEST did not cause unusual clinical signs or an unexpected frequency or severity of injection site reactions. The field safety observations from this study were consistent with the observations made during the target animal safety studies of transient inflammation at the injection sites. Adverse events, as reported, were not uniquely attributable to IMPROVEST.
IMPROVEST is an injectable sterile solution containing an incomplete analog of natural gonadotropin releasing factor (GnRF) conjugated to diphtheria toxoid in an adjuvanted formulation. Immunization with a two dose regimen of IMPROVEST, with a four week interval between doses, stimulates the pig's immune system to produce antibodies which can neutralize its own GnRF. Pigs given an initial dose of IMPROVEST are immunologically primed but do not produce sufficient antibodies to have any physiological effect. Following receipt of the second dose, the pig's immune system responds with a strong antibody response. These antibodies bind to and neutralize circulating GnRF in the bloodstream. Neutralization of GnRF blocks the hypothalamic-pituitary-gonadal endocrine axis, thereby suppressing testicular function, including both sex hormone production and reproductive capability, thereby providing temporary immunological castration in these injected boars.
Evidence of temporary immunological castration was provided in a series of studies showing that within 1-2 weeks after the second injection of IMPROVEST, anti-GnRF antibody levels increase significantly. With this rise in anti-GnRF antibodies, the levels of gonadal sex hormones were substantially reduced, the size of the testes, and spermatogenesis suppressed, as was the expression of typical male behaviors (aggression and sexual, e.g., mounting). Full immunological castration was demonstrated to last from 4 to 8 weeks after the second dose. IMPROVEST injected boars will start to return to full reproductive function at a variable period after this time, as evidenced by increases in male sex hormones, testicle size, and intact male behavior. IMPROVEST should not be used in boars intended for breeding purposes.
Evidence to assess the acceptability of pork from IMPROVEST treated pigs was provided through a series of consumer taste panels using consumers deemed sensitive to the taste of "tainted" meat. The presence of boar taint was evaluated on the basis of pork aroma and flavor and not by chemical analysis. Three consumer taste panel studies were conducted to demonstrate the difference of pork generated from IMPROVEST treated and intact boars. A surgically castrated male group was not evaluated during these studies. In these three studies, 465 sensitive consumers evaluated cooked pork loin samples from IMPROVEST treated and intact boars. These pigs were raised to market weight, injected with IMPROVEST as per product labeling and slaughtered 4 to 8 weeks after receipt of the second IMPROVEST injection. The consumers found the aroma and flavor of pork from the IMPROVEST injected pigs to be more acceptable than from the intact boars in all three studies.
Store under refrigeration at 2°-8°C (36°-46°F). Once broached, product may be stored under refrigeration for 28 days. Store bottles in carton until used. Protect from light. Protect from freezing.
IMPROVEST is available in the following package sizes:
|20 mL bottle
100 mL bottle
250 mL bottle
500 mL bottle
NADA # 141-322, Approved by FDA
Pfizer Animal Health
Division of Pfizer Inc
New York, NY 10017
Revised: April 2011
PRINCIPAL DISPLAY PANEL - 20 mL Bottle Label
(Gonadotropin Releasing Factor
Conjugate, 0.2 mg/mL)
For subcutaneous injection in intact male
pigs intended for slaughter.
For use in animals only
CAUTION: Federal (USA) law restricts this
drug to use by or on the order of a licensed
20 mL (10 doses, 2-mL each)
NADA #141-322, Approved by FDA
gonadotropin releasing factor analog-diphtheria toxoid conjugate SOLUTION