Animal Drug Safety-Related Labeling Changes
This online resource provides information on recently approved safety-related labeling changes for animal drugs from January 2021 forward in an effort to improve transparency and communication with veterinarians and the public.
When adverse events are reported or safety concerns are identified for an animal drug, the FDA may work with the sponsor to revise the labeling to reflect this information. This webpage includes safety-related labeling changes initiated by the company or the FDA. Safety-related labeling changes include updates or revisions to any section of the label containing safety information. Awareness of these safety-related labeling changes is essential for the safe use and administration of FDA-approved animal products.
There is often a lag between the approval of labeling changes and the new labeling becoming available in the marketplace. You can check this webpage for recent safety-related labeling changes as it will be updated on a regular basis when changes to the drug labeling are approved by the FDA.
For more information about the most current labeling for a particular animal drug, veterinarians should reach out to the drug’s sponsor.
Disclaimer
This webpage reflects recently approved safety-related labeling changes for FDA approved brand name new animal drugs and is also applicable to any generics of those products. Generic new animal drugs are copies of brand name new animal drugs approved by the FDA and must provide the same labeling information (e.g., Indications, Warnings, Cautions, etc.). Therefore, the safety-related labeling changes reflected on this webpage also apply to generic new animal drugs.
The labeling for an approved animal drug, such as its carton or package insert, might not reflect the changes for a year or more in the marketplace as the drug company distributes its inventory of the drug with labeling printed prior to the approval of the labeling changes.
Any reference to a commercial product, process, service, or company is not an endorsement or recommendation by the U.S. government, the Department of Health and Human Services, the FDA or any of its components. The FDA is not responsible for the contents of any non-FDA website referenced by or linked to the agency's website.
Animal Drug Safety-Related Labeling Changes 2022-present:
Indications:
RESFLOR GOLD is indicated for treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, and control of BRD-associated pyrexia in beef and non-lactating dairy cattle.
Summary of Changes:
- The Precautions section was revised to alert users to periparturient safety concerns in cows and heifers administered flunixin either before or after calving.
The following safety-related changes were made to the labeling:
Precautions
(Additions and/or revisions are underlined)
…
Not for use in animals intended for breeding purposes.
The effects of RESFLOR GOLD on bovine reproductive performance, pregnancy, and lactation have not been determined. Toxicity studies in dogs, rats, and mice have associated the use of florfenicol with testicular degeneration and atrophy. NSAIDs are known to have potential effects on both parturition and the estrous cycle. There may be a delay in the onset of estrus if flunixin is administered during the prostaglandin phase of the estrous cycle. Studies have associated the use of flunixin in cattle with a delay in parturition and prolonged labor (which may increase the risk of stillbirth), and interference with involution and expulsion of fetal membranes (which may increase the risk for placental retention and metritis).
…
Indications:
COMFORTIS kills fleas and is indicated for the prevention and treatment of flea infestations (Ctenocephalides felis), for one month, on cats and kittens 14 weeks of age and older and 4.1 pounds of body weight or greater.
Summary of Changes:
- A Post-Approval Experience subsection was added to the Adverse Reactions section.
- The Client Information Sheet was updated to reflect the adverse events included in the Post-Approval Experience subsection.
The following safety-related changes were made to the labeling:
Adverse Reactions
(Newly added subsection)
Post-Approval Experience (2023)
The following adverse events are based on post-approval adverse drug experience reporting for COMFORTIS. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.
The following adverse events reported for cats are listed in decreasing order of reporting frequency:
Vomiting, depression/lethargy, anorexia, behavioral changes, pruritus, diarrhea, ataxia, hyperactivity, hypersalivation, panting, vocalization, dyspnea, twitching, and seizures.
In some cases, death has been reported. Some of these reports involved cats with cardiac disease, including cats with previously undiagnosed cardiac disease.
Following concomitant extra-label use of ivermectin with COMFORTIS, some cats have experienced the following clinical signs:
Ataxia, trembling/twitching, seizures, mydriasis, disorientation, and transient blindness.
Post-approval experience continues to support the safety of COMFORTIS when used concurrently with heartworm preventatives according to label directions.
Indications:
COMFORTIS kills fleas and is indicated for the prevention and treatment of flea infestations (Ctenocephalides felis), for one month, on dogs and puppies 14 weeks of age and older and 5.0 pounds of body weight or greater.
Summary of Changes:
- The Post-Approval Experience subsection of the Adverse Reactions section was updated.
- The Client Information Sheet was updated to reflect the new adverse events added to the Post-Approval Experience subsection.
The following safety-related changes were made to the labeling:
Adverse Reactions
(Updated Post-Approval Experience subsection, additions are underlined)
Post-Approval Experience (2023)
The following adverse events are based on post-approval adverse drug experience reporting for COMFORTIS. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.
The following adverse events reported for dogs are listed in decreasing order of reporting frequency:
Vomiting, depression/lethargy, pruritus, anorexia, diarrhea, seizures, ataxia, trembling, behavioral changes, and hypersalivation.
Following concomitant extra-label use of ivermectin with COMFORTIS, some dogs have experienced the following clinical signs:
Trembling/twitching, salivation/drooling, seizures, ataxia, mydriasis, blindness, and disorientation.
Post-approval experience continues to support the safety of COMFORTIS when used concurrently with heartworm preventatives according to label directions.
Indications:
CREDELIO kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and the treatment and control of tick infestations [Amblyomma americanum (lone star tick), Dermacentor variabilis (American dog tick), Ixodes scapularis (black-legged tick) and Rhipicephalus sanguineus (brown dog tick)] for one month in dogs and puppies 8 weeks of age and older, and weighing 4.4 pounds or greater.
Summary of Changes:
- A Post-Approval Experience subsection was added to the Adverse Reactions section.
The following safety-related changes were made to the labeling:
Adverse Reactions
(Newly added subsection)
Post-Approval Experience (2023)
The following adverse events are based on post-approval adverse drug experience reporting for CREDELIO. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.
The following adverse events reported in dogs are listed in decreasing order of reporting frequency:
Vomiting, diarrhea (with and without blood), lethargy, anorexia, seizure, pruritus, ataxia, urinary-related signs (polyuria, polydipsia, urinary incontinence, and inappropriate urination), and muscle tremor.
Indications:
VETMEDIN (pimobendan) is indicated for the management of the signs of mild, moderate, or severe congestive heart failure in dogs due to clinical myxomatous mitral valve disease (MMVD) or dilated cardiomyopathy (DCM). VETMEDIN is indicated for use with concurrent therapy for congestive heart failure (e.g., furosemide, etc.) as appropriate on a case-by-case basis.
Summary of Changes:
- The Warnings section was revised to add an Animal Safety Warnings subsection and a statement to store Vetmedin in a secure location.
- A Post-Approval Experience subsection was added to the Adverse Reactions section.
The following safety-related changes were made to the labeling:
Warnings
(Newly added subsection, new information is underlined)
Animal Safety Warnings: Keep VETMEDIN in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.
Only for use in dogs with clinical evidence of heart failure. At 3 and 5 times the recommended dosage, administered over a 6-month period of time, pimobendan caused an exaggerated hemodynamic response in the normal dog heart, which was associated with cardiac pathology (See Target Animal Safety).
Adverse Reactions
(Newly added subsection)
Post-Approval Experience (2023)
The following adverse events are based on post-approval adverse drug experience reporting for VETMEDIN. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.
The following adverse events reported in dogs are listed in decreasing order of reporting frequency:
Diarrhea, lethargy, anorexia, emesis, cough, tachycardia, ataxia, dyspnea, convulsion, liver enzymes (ALT, ALP), increased BUN and/or creatinine, tremors, hyperactivity, pruritus, syncope, allergic reactions (including allergic edema/facial edema, erythema, and hives), hypotension, hypertension, coagulation abnormalities (including thrombocytopenia, hemorrhage and petechia), and hyperglycemia (with or without diabetes mellitus). Death has been reported in some cases.
Indications:
NexGard kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis), and the treatment and control of Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), Amblyomma americanum (lone star tick), Rhipicephalus sanguineus (brown dog tick), and Haemaphysalis longicornis (longhorned tick) infestations in dogs and puppies 8 weeks of age and older, weighing 4 pounds of body weight or greater, for one month. NexGard is indicated for the prevention of Borrelia burgdorferi infections as a direct result of killing Ixodes scapularis vector ticks.
Summary of Changes:
- Information was added to the Adverse Reactions section about adverse reactions observed in a second US field safety and effectiveness study.
Note: A new indication was added for the treatment and control of Haemaphysalis longicornis (longhorned tick) infestations in dogs and puppies 8 weeks of age and older, weighing 4 pounds of body weight or greater, for one month.
This new indication is listed here for informational purposes only; it does not affect the safe use of the product.
The following safety-related changes were made to the labeling:
Adverse Reactions
(Additions and/or revision are underlined)
...
In a second US field safety and effectiveness study, NexGard was administered to 130 dogs with fleas. Adverse reactions included pruritus, diarrhea (with or without blood), vomiting, anorexia, and lethargy.
Indications:
SILEO is indicated for the treatment of noise aversion in dogs.
Summary of Changes:
- Due to reports of accidental overdosing, a new dosing syringe will be included with the product that will require the user to twist the dosing ring along a threaded plunger. The dosing ring will not move freely along the plunger and will not require a separate locking step once the dose has been selected.
- the new dosing syringe will be packaged in an updated carton to distinguish it from the previous version and is expected to be available in 2024.
- The Client Information Sheet was updated to provide instructions for operating the new dosing syringe. The pictograms and associated text were revised to reflect how to use the new dosing syringe.
Indications:
REVOLUTION PLUS is indicated for the prevention of heartworm disease caused by Dirofilaria immitis. REVOLUTION PLUS kills adult fleas (Ctenocephalides felis) and is indicated for the treatment and prevention of flea infestations, the treatment and control of tick infestations with Ixodes scapularis (black-legged tick), Amblyomma maculatum (Gulf Coast tick) and Dermacentor variabilis (American dog tick), the treatment and control of ear mite (Otodectes cynotis) infestations, and the treatment and control of roundworm (Toxocara cati) and intestinal hookworm (Ancylostoma tubaeforme) infections for one month in cats and kittens 8 weeks and older, and weighing 2.8 pounds or greater.
Summary of Changes:
- The Dosage and Administration section was revised to emphasize protective measures for users to minimize contact with the product during application.
- The Warnings section was revised to include the statement to avoid contact with the application site for 4 hours post application.
- A Post-Approval Experience subsection was added to the Adverse Reactions section.
The following safety-related changes were made to the labeling:
Dosage and Administration
(Additions and/or revisions are underlined)
…
Do not massage the product into the skin. Due to alcohol content, do not apply to broken skin. Avoid contact between the product and fingers. Do not apply when the hair coat is wet. Stiff hair, clumping of hair, hair discoloration, or a slight powdery residue may be observed at the treatment site in some cats. These effects are temporary and do not affect the safety or effectiveness of the product. Discard empty tubes in your ordinary household refuse.
…
Warnings
(Additions and/or revisions are underlined)
Human warnings:
Not for human use. Keep this and all drugs out of the reach of children.
Do not come into contact with or allow children to contact the application site until 4 hours post application.
In humans, REVOLUTION PLUS may be irritating to skin and eyes. REVOLUTION PLUS and selamectin topical solution contain isopropyl alcohol and the preservative butylated hydroxytoluene (BHT). Reactions such as hives, itching and skin redness have been reported in humans after accidental dermal contact with selamectin topical solution. Individuals with known hypersensitivity to selamectin topical solution should use caution or consult a health care professional before applying this product on a cat. Wash hands after use and wash off any product in contact with the skin immediately with soap and water.
…
Adverse Reactions
(Newly added subsection)
Post-Approval Experience (2022)
The following adverse events are based on post-approval adverse drug experience reporting for REVOLUTION PLUS. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.
The following adverse events reported in cats are listed in decreasing order of reporting frequency:
Application site reactions (including alopecia, lesions, erythema, and pruritus), lethargy, anorexia, vomiting, generalized pruritus, behavioral disorders (including hiding, hyperactivity, and vocalization), ataxia, muscle tremor, diarrhea, generalized alopecia, and seizure.
Indications:
For use in dogs to prevent canine heartworm disease by eliminating the tissue stage of heartworm larvae (Dirofilaria immitis) for a month (30 days) after infection and for the treatment and control of roundworms (Toxocara canis, Toxascaris leonina) and hookworms (Ancylostoma caninum, Uncinaria stenocephala, Ancylostoma braziliense).
Summary of Changes:
- The Administration section was revised to add information about the risk of choking or intestinal obstruction if the chewable is swallowed whole.
- The Precautions section was revised to add a statement about the risk of choking or intestinal obstruction if the chewable is swallowed whole.
- A Post-Approval Experience subsection was added to the Adverse Reactions section.
The following safety-related changes were made to the labeling:
Administration
(Additions and/or revisions are underlined)
Remove only one chewable at a time from the foil-backed blister card. Return the card with the remaining chewables to its box to protect the product from light.
Because most dogs find HEARTGARD PLUS palatable, the product can be offered to the dog by hand. To avoid the risk of choking or intestinal obstruction, the chewable should be administered in a manner that encourages the dog to chew, rather than to swallow without chewing (see Precautions and Post-Approval Experience). Chewables may be broken into pieces and fed to dogs that normally swallow treats whole. Alternatively, it may be added intact to a small amount of dog food to encourage chewing, but care should be taken to ensure that the dog consumes the complete dose at one time.
Treated animals should be observed for a few minutes after administration to ensure that part of the dose is not lost or rejected. If it is suspected that any of the dose has been lost, redosing is recommended.
…
Precautions
(Additions and/or revisions are underlined)
…
Choking or intestinal obstruction has been reported after dosing with HEARTGARD PLUS. For dogs that normally swallow treats whole, chewables may be broken into pieces (see Post-Approval Experience).
Keep this and all drugs out of the reach of children. In case of ingestion by humans, clients should be advised to contact a physician immediately. Physicians may contact a Poison Control Center for advice concerning cases of ingestion by humans.
Keep HEARTGARD PLUS in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.
Adverse Reactions
(Newly added subsection)
Post-Approval Experience (2022)
The following adverse events are based on post-approval adverse drug experience reporting for HEARTGARD PLUS. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.
The following adverse events reported in dogs are listed in decreasing order of reporting frequency:
Vomiting, diarrhea, lethargy, anorexia, seizures, ataxia, muscle tremors, hypersalivation, pruritus.
In some cases, choking or intestinal obstruction has been reported after administration of HEARTGARD PLUS.
Indications:
Indicated for the treatment of dermatophytosis caused by Microsporum canis in cats.
Summary of Changes:
- The Precautions section was revised to add information about the risk of liver dysfunction with Itrafungol use.
- A Post-Approval Experience subsection was added to the Adverse Reactions section.
The following safety-related changes were made to the labeling:
Precautions
(Additions and/or revisions are underlined)
…
ITRAFUNGOL oral solution is metabolized by the liver (mainly CYP3A) and can cause elevated liver enzymes (see Animal Safety). Use with caution in cats with impaired liver function and in cats currently being treated with other products that are metabolized by the liver. If clinical signs suggestive of liver disease develop, ITRAFUNGOL oral solution should be discontinued. Clinical signs of liver dysfunction requiring treatment have been observed in cats after ITRAFUNGOL oral solution use (see Post-Approval Experience).
…
Adverse Reactions
(Newly added subsection)
Post-Approval Experience (2021):
The following adverse events are based on post-approval adverse drug experience reporting for Itrafungol (itraconazole oral solution). Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.
The following adverse events reported in cats are listed in decreasing order of reporting frequency:
Anorexia, emesis, elevated liver enzymes, lethargy, weight loss, icterus, elevated total bilirubin, and diarrhea.
Death (including euthanasia) has been reported. Some of these deaths were associated with the adverse events reported above.
Indications:
For the prevention of heartworm disease caused by Dirofilaria immitis and the treatment of Dirofilaria immitis circulating microfilariae in heartworm-positive dogs. Advantage Multi for Dogs kills adult fleas and is indicated for the treatment of flea infestations (Ctenocephalides felis). Advantage Multi for Dogs is indicated for the treatment and control of sarcoptic mange caused by Sarcoptes scabiei var. canis. Advantage Multi for Dogs is also indicated for the treatment and control of hookworms, roundworms, and whipworms.
Summary of Changes:
- The Dosage and Administration section was revised to provide information regarding the risk of ocular irritation if the product gets into the dog’s eye.
- The Post-Approval Experience subsection of the Adverse Reactions section was updated.
The following safety-related changes were made to the labeling:
Dosage and Administration
(Additions and/or revisions are underlined)
…
Do not let this product get in your dog’s mouth or eyes. Do not allow the dog to lick any of the application sites for 30 minutes. In households with multiple pets, keep each treated dog separated from other treated dogs and other pets for 30 minutes after application to prevent licking the application sites. (See WARNINGS.) Contact with eyes can lead to eye irritation and corneal ulceration. If contact with eyes occurs, hold the dog’s eyelids open, flush thoroughly with water, and contact your veterinarian.
…
Adverse Reactions
(Updated Post-Approval Experience subsection, additions are underlined)
Post-Approval Experience Section (2022)
The following adverse events are based on post-approval adverse drug experience reporting for Advantage Multi for Dogs. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using this data.
The following adverse events reported in dogs are listed in decreasing order of reporting frequency:
depression/lethargy, pruritus, vomiting, diarrhea, anorexia, application site reactions (alopecia, pruritus, erythema, and lesions, including blisters), hyperactivity, ataxia, trembling, seizures, panting, hypersalivation, anaphylaxis/anaphylactic reactions (hives, facial swelling, edema of the head), and corneal ulceration.
Serious reactions, including neurologic signs and death have been reported when cats have been exposed (orally and topically) to this product.
In humans, nausea, numbness or tingling of the mouth/lips and throat, ocular and dermal irritation, pruritus, headache, vomiting, diarrhea, depression and dyspnea have been reported following exposure to this product.
Indications for use
LONGRANGE, when administered at the recommended dose volume of 1 mL per 110 lb (50 kg) body weight, is effective in the treatment and control of the following internal and external parasites of cattle:
- Gastrointestinal Roundworms
- Bunostomum phlebotomum - Adults and L4
- Cooperia oncophora - Adults and L4
- Cooperia punctata - Adults and L4
- Cooperia surnabada - Adults and L4
- Haemonchus placei - Adults
- Oesophagostomum radiatum - Adults
- Ostertagia lyrata - Adults
- Ostertagia ostertagi - Adults, L4, and inhibited L4
- Trichostrongylus axei - Adults and L4
- Trichostrongylus colubriformis - Adults
- Lungworms
- Dictyocaulus viviparus - Adults
- Grubs
- Hypoderma bovis
- Mites
- Sarcoptes scabiei var. bovis
Persistent Activity
LONGRANGE has been proven to effectively protect cattle from reinfection with the following parasites for the indicated amounts of time following treatment:
| Gastrointestinal Roundworms | Durations of Persistent Effectiveness |
|---|---|
| Bunostomum phlebotomum | 150 days |
| Cooperia oncophora | 100 days |
| Cooperia punctata | 100 days |
| Haemonchus placei | 120 days |
| Oesophagostomum radiatum | 120 days |
| Ostertagia lyrata | 120 days |
| Ostertagia ostertagi | 120 days |
| Trichostrongylus axei | 100 days |
| Lungworms | Durations of Persistent Effectiveness |
|---|---|
| Dictyocaulus viviparus | 150 days |
Summary of Changes:
- The User Safety Warnings section was revised to include information regarding reproductive and developmental toxicities in laboratory animals.
- Safety information for pregnant women was added to the User Safety Warnings section.
- Contact Information was updated.
The following safety-related changes were made to the labeling:
User Safety Warnings
(Additions and/or revisions underlined)
Not for Use in Humans. Keep this and all drugs out of the reach
of children. Reproductive and developmental toxicities have been
reported in laboratory animals following high, repeated exposures to
N-methyl-2-pyrrolidone (NMP). Pregnant women should wear gloves
and exercise caution or avoid handling this product. The Safety Data
Sheet (SDS) contains more detailed occupational safety information.
To report adverse effects, to obtain an SDS, or for assistance, contact Boehringer Ingelheim Animal Health USA Inc. at 1-888-637-4251. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae.
Indications:
Bravecto kills adult fleas and is indicated for the treatment and
prevention of flea infestations (Ctenocephalides felis), and the
treatment and control of tick infestations Ixodes scapularis
(black-legged tick), Dermacentor variabilis (American dog tick),
Rhipicephalus sanguineus (brown dog tick), and Haemaphysalis
longicornis (Asian longhorned tick) for 12 weeks in dogs and puppies
6 months of age and older, and weighing 4.4 pounds or greater.
Bravecto is also indicated for the treatment and control of Amblyomma
americanum (lone star tick) infestations for 8 weeks in dogs and puppies
6 months of age and older, and weighing 4.4 pounds or greater.
Summary of Changes:
- A new indication was added for the treatment and control of Haemaphysalis longicornis (Asian longhorned tick) infestations for 12 weeks in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater.
- The Precautions section was revised to emphasize that adverse events have been reported following the use of Bravecto in breeding females.
- The Post-Approval Experience subsection of the Adverse Reactions section was updated.
The following safety-related changes were made to the labeling:
Indications
(Additions and/or revisions are underlined)
Bravecto kills adult fleas and is indicated for the treatment and
prevention of flea infestations (Ctenocephalides felis), and the
treatment and control of tick infestations Ixodes scapularis
(black-legged tick), Dermacentor variabilis (American dog tick),
Rhipicephalus sanguineus (brown dog tick), and Haemaphysalis
longicornis (Asian longhorned tick) for 12 weeks in dogs and puppies
6 months of age and older, and weighing 4.4 pounds or greater.
Bravecto is also indicated for the treatment and control of Amblyomma
americanum (lone star tick) infestations for 8 weeks in dogs and puppies
6 months of age and older, and weighing 4.4 pounds or greater.
Precautions
(Additions and/or revisions are underlined)
Fluralaner is a member of the isoxazoline class. This class has been
associated with neurologic adverse reactions including tremors, ataxia,
and seizures. Seizures have been reported in dogs receiving isoxazoline
class drugs, even in dogs without a history of seizures. Use with
caution in dogs with a history of seizures or neurologic disorders.
Adverse events have been reported following use in breeding females.
Before use in breeding female dogs, refer to Post-Approval Experience
and Animal Safety sections.
Bravecto has not been shown to be effective for 12-weeks duration in
puppies less than 6 months of age. Bravecto is not effective against
Amblyomma americanum ticks beyond 8 weeks after dosing (see
Effectiveness).
Adverse Reactions
(Updated Post-Approval subsection, additions are underlined)
Post-Approval Experience (2022)
The following adverse events are based on post-approval adverse drug experience reporting for fluralaner. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.
The following adverse events reported in dogs are listed in decreasing order of reporting frequency:
Vomiting, lethargy, diarrhea (with and without blood), anorexia, pruritis,
polydipsia, seizure, allergic reactions (including hives, swelling,
erythema), dermatitis (including crusts, pustules, rash), tremors and
ataxia. In some cases, birth defects (including limb deformities and cleft
palate), stillbirth, and abortion have been reported after treatment of
breeding females.
Indications:
Banamine Transdermal pour-on is indicated for the control of pyrexia associated with bovine respiratory disease and acute bovine mastitis, and the control of pain associated with foot rot in beef cattle 2 months of age and older and dairy cattle.
Not for use in beef and dairy bulls intended for breeding over 1 year of age, replacement dairy heifers over 20 months of age, dry dairy cows, dairy calves, or veal calves.
Summary of Changes:
- The Indications section was revised to add the control of pyrexia associated with acute bovine mastitis.
- The Indications section was revised to add lactating dairy cows as a subclass for all approved indications.
- The Withdrawal Periods and Residue Warnings section was revised to add a milk discard time, and to emphasize that Banamine Transdermal is approved only as a single topical dose in cattle.
- The Precautions section was revised to emphasize that the safety of repeated treatments has not been evaluated.
The following safety-related changes were made to the labeling:
Indications
(Additions and/or revisions are underlined)
Banamine Transdermal pour-on is indicated for the control of pyrexia associated with bovine respiratory disease and acute bovine mastitis, and the control of pain associated with foot rot in beef cattle 2 months of age and older and dairy cattle.
Not for use in beef and dairy bulls intended for breeding over 1 year of age, replacement dairy heifers over 20 months of age, dry dairy cows, dairy calves, or veal calves.
Withdrawal Periods and Residue Warnings:
(Additions and/or revisions are underlined)
Milk that has been taken during treatment and for 48 hours after treatment must not be used for human consumption. Cattle must not be slaughtered for human consumption within 8 days of treatment. Not for use in replacement dairy heifers 20 months of age or older or dry dairy cows; use in these cattle may cause drug residues in calves born to these cows or heifers. Not for use in beef calves less than 2 months of age, dairy calves, and veal calves. A withdrawal period has not been established for this product in pre-ruminating calves. Approved only as a single topical dose in cattle. Repeated treatments may result in violative residues in milk or in edible tissues.
Precautions:
(Additions and/or revisions are underlined)
As a class, cyclo-oxygenase inhibitory NSAIDs may be associated with gastrointestinal, renal, and hepatic toxicity. Sensitivity to drug-associated adverse events varies with the individual patient. Patients at greatest risk for adverse events are those that are dehydrated, on concomitant diuretic therapy, or those with renal, cardiovascular, and/or hepatic dysfunction. Banamine transdermal should be used with caution in animals with suspected pre-existing gastric erosions or ulcerations. Concurrent administration of other NSAIDs, corticosteroids, or potentially nephrotoxic drugs should be avoided or used only with careful monitoring because of the potential increase of adverse events. Banamine Transdermal is approved only as a single topical dose. The safety of repeated treatment has not been evaluated.
…
Indications:
For suppression of estrus in mares. Suppression of estrus allows for a predictable occurrence of estrus following drug withdrawal. This facilitates the attainment of regular cyclicity during the transition from winter anestrus to the physiological breeding season. Suppression of estrus will also facilitate management of prolonged estrus conditions. Suppression of estrus may be used to facilitate scheduled breeding during the physiological breeding season.
Summary of Changes:
- A new subsection, Reported Human Effects from Exposure, was added to the User Safety Warnings section.
- Labeling revisions emphasize protective measures for users, including the use of appropriate protective gloves. Adequate protection minimizes human exposure to the drug.
- New language alerts to the risk of non-user exposure to contaminated surfaces or equipment. Users are directed to prevent such exposure by adequately decontaminating any equipment or surfaces that come in contact with Regumate.
- Instructions for the correct use of the Regumate dosing device have been added, as a safety measure to minimize human exposure.
The following safety-related changes were made to the labeling:
(Additions and/or revisions underlined)
DOSAGE AND ADMINISTRATION:
Administer solution orally at the rate of 1 mL per 110 pounds body weight (0.044 mg/kg) once daily for 15 consecutive days. Administer solution directly on the base of the mare's tongue or on the mare's usual grain ration.
(Dosage Chart – no changes)
When handling Regu-Mate product, the dosing device, or syringes, always use vinyl, neoprene, or nitrile gloves. Latex gloves are not protective. The product may be dosed using Regumate Equine Dosing Device or a luer lock syringe. Use of the Regumate Equine Dosing Device is recommended to reduce the risk of human exposure. Follow all instructions when using the dosing device. Do not use any dosing device other than the Regumate Equine Dosing Device.
For use with Regumate Equine Dosing Device, first assemble the device according to directions supplied with the Regumate Equine Dosing Device. Remove the shipping cap and seal on Regumate (altrenogest) bottle. Store the cap in a clean and dry location. Apply downward force and fasten the quick connect cap with dip tube onto the product bottle. The flexible dip tube will contact the bottom of the product bottle and bend slightly. Turn the dose selection dial to 15. Hold the dosing device vertically with the nozzle on the top. Direct the opening of the nozzle away from any person and cover it with absorbent material. Slowly squeeze and release handle until air in the barrel is expelled and product starts to come out. Prime the device by expelling two (2) doses of 15 mL of product into a waste container or absorbent material. (Re-prime the dosing device by expelling two (2) doses if air is observed inside the barrel after switching to a fresh bottle or during dosing period). Set the dose according to DOSAGE CHART provided herein by turning the dose selection dial. The dosing device is ready for use. Refer to the Regumate Equine Dosing Device label for equipment cleaning instructions.
For use with a luer lock syringe, remove shipping cap and seal; replace with enclosed plastic dispensing cap. Remove cover from bottle dispensing tip and connect luer lock syringe (without needle). Draw out appropriate volume of Regumate solution and return bottle to upright position before detaching syringe. (Note: Do not remove syringe while bottle is inverted as spillage may result.) Replace cover on bottle dispensing tip to prevent leakage. Syringes used for administration should be replaced frequently and disposed of in a secure manner to prevent exposure to the product.
WARNINGS AND PRECAUTIONS:
User Safety Warnings:
Not for use in humans. Keep out of reach of children. Avoid skin contact. Regumate is absorbed through unbroken skin, and exposure may result in serious side effects to both women and men. Wear vinyl, neoprene, or nitrile gloves when handling or administering Regumate, or when touching contaminated surfaces or equipment. Latex gloves are not protective.
PREGNANT WOMEN OR WOMEN WHO MAY BE PREGNANT SHOULD NOT HANDLE REGU-MATE. WOMEN OF CHILDBEARING AGE SHOULD EXERCISE EXTREME CAUTION WHEN HANDLING THIS PRODUCT.
Accidental absorption, such as via direct contact with the skin, could lead to a disruption of the menstrual cycle or prolongation of pregnancy. Immediately wash off accidental spillage on the skin with soap and water. Any equipment or surfaces that come in contact with Regumate should be adequately cleaned and decontaminated to prevent human exposure (see Reported HUMAN Effects from Exposure).
Potential Effects of Human Exposure
There has been no human use of this specific product. The information contained in this section is extrapolated from data available on other products of the same pharmacological class that have been used in humans. Effects anticipated are due to the progestational activity of altrenogest.
Acute effects after a single exposure are possible; however, continued daily exposure has the potential for more untoward effects such as disruption of the menstrual cycle, uterine or abdominal cramping, increased or decreased uterine bleeding, prolongation of pregnancy, and headaches. The oil base may also cause complications if swallowed.
The list of people who should not handle this product (see below) is based upon the known effects of progestins used in humans on a chronic basis.
PEOPLE WHO SHOULD NOT HANDLE Regumate:
- Women who are or may be pregnant.
- Anyone with blood clots or clotting disorders, or with a history of these events.
- Anyone with a history of heart disease or stroke.
- Women with known or suspected breast cancer.
- People with known or suspected estrogen-dependent cancer.
- Women with vaginal bleeding of unknown cause.
- People with tumors which developed during the use of oral contraceptives or other estrogen-containing products.
- Anyone with liver dysfunction or disease.
ACCIDENTAL EXPOSURE:
Regumate is readily absorbed through the skin. In addition, this oil-based product can penetrate latex or other types of porous gloves. Always wear vinyl, neoprene, or nitrile gloves when handling Regumate. Latex gloves are not protective. If Regumate gets inside gloves by damage or spilling, the covered skin may absorb more of the drug.
IN CASE OF ACCIDENTAL EXPOSURE:
Skin exposure and/or clothing contamination: Wash skin immediately with soap and water, and launder clothing with detergent.
Eye exposure: Immediately flush with plenty of water for 15 minutes. Get medical attention. If wearing contact lenses, flush eyes immediately with water before removing lenses.
If swallowed: Do not induce vomiting. Seek medical attention immediately. Regumate contains an oil. Vomiting should be supervised by a physician because of possible pulmonary damage via aspiration of the oil base. If possible, bring the labeling to the physician.
Reported HUMAN Effects from Exposure:
These symptoms have been reported in women and men following accidental exposure to altrenogest products, including Regumate, either through handling of the product or contact with contaminated surfaces.
- Adverse reproductive effects reported in women included abnormal or absent menstrual cycles.
- Adverse reproductive effects in men included decreased libido.
- Other adverse effects reported in women and men included headaches, fever, abdominal pain, nausea, diarrhea, vomiting, and rashes.
ANIMAL SAFETY WARNINGS AND PRECAUTIONS:
Keep Regumate in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.
Various synthetic progestins, including altrenogest, when administered to rats during the embryogenic stage of pregnancy at doses manyfold greater than the recommended equine dose, caused fetal anomalies, specifically masculinization of the female genitalia.
OTHER WARNINGS:
Do not use in horses intended for human consumption.
HOW SUPPLIED:
Regumate (altrenogest) contains 2.2 mg/mL in an oil solution.
Product supplied in 1,000 mL plastic bottles.
Regumate Equine Dosing Device supplied separately.
STORAGE, HANDLING, AND DISPOSAL:
Store Regumate solution bottle and Dosing Device when loaded with solution for continued use at or below room temperature, 77°F (25°C). Close tightly. Refer to the Regumate Equine Dosing Device label for equipment cleaning instructions. Place empty drug containers, waste from rinsing the Dosing Device, protective gloves, or other articles that contact this product in a leak-resistant container for disposal in accordance with applicable Federal, state, and local regulations.
Indications:
METACAM Oral Suspension is indicated for the control of pain and inflammation associated with osteoarthritis in dogs.
Summary of Changes:
- A new syringe will be included with the 0.5 mg/mL product that is calibrated in one-pound increments, starting at 2 pounds of body weight. The syringe can no longer be used to dose dogs under 2 pounds (0.9 kg).
- new syringes are expected to be available in 2024
- The Directions for Administration section for Dogs under 10 pounds (4.5 kg) was revised to reflect the change in syringe.
- The Client Information Sheet was revised to reflect the change in syringe and that the syringe can no longer be used to dose dogs under 2 pounds (0.9 kg).
The following safety-related changes were made to the labeling:
Directions for Administration:
(Additions and/or revisions are underlined)
Dogs under 10 pounds (4.5 kg)
Shake well before use, then remove cap. Particular care should be given with regard to the accuracy of dosing. To prevent accidental overdosing of small dogs, administer drops on food only, never directly into the mouth. Carefully measure suspension onto food to assure that the correct dose is given before presentation of the food to the dog. The syringe provided with the meloxicam concentration of 0.5 mg/mL cannot be used to measure doses for dogs weighing less than 2 lbs (0.9 kg).
For dogs less than 2 lbs (0.9 kg), METACAM Oral Suspension can be given using the dropper bottle: two drops for each pound of body weight for the 0.5 mg/mL concentration (five drops for each kilogram of body weight), dropped directly onto the food.
For dogs between 2-10 pounds, METACAM Oral Suspension can be given by drops or by using the measuring syringe provided in the package (see dosing procedure below). The syringe fits on to the bottle and has a scale beginning at 2 lbs, designed to deliver the daily maintenance dose (0.05 mg/lb or 0.1 mg/kg). When using the syringe, the dog’s weight should be rounded down to the nearest 1 pound increment. Replace and tighten cap after use.
…
Client Information Sheet
(Additions and/or revisions are underlined)
…
To prevent accidental overdosing of small dogs, administer drops on food only, never directly into the mouth.
Carefully measure suspension onto food to assure that the correct dose is given before presentation of the food to the dog. The syringe provided with the meloxicam concentration of 0.5 mg/mL cannot be used to measure doses for dogs weighing less than 2 lbs (0.9 kg).
For dogs less than 2 lbs (0.9 kg), METACAM Oral Suspension can be given using the dropper bottle: two drops for each pound of body weight for the 0.5 mg/mL concentration (five drops for each kilogram of body weight), dropped directly onto the food.
For dogs between 2-10 pounds, METACAM Oral Suspension can be given by drops or by using the measuring syringe provided in the package (see dosing procedure below). The syringe fits on to the bottle and has a scale beginning at 2 lbs, designed to deliver the daily maintenance dose (0.05 mg/lb or 0.1 mg/kg). When using the syringe, the dog’s weight should be rounded down to the nearest 1 pound increment. Replace and tighten cap after use.
…
Indications:
For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida and Histophilus somni. For the treatment of ovine respiratory disease (ORD) associated with Mannheimia haemolytica. For the control of respiratory disease in cattle at high risk of developing BRD associated with Mannheimia haemolytica.
Summary of Changes:
- This product is newly enclosed in a unique safety shroud which prevents direct access to the vial.
- Administration of Micotil will require a quick-fit connector specific to the safety shroud, enabling connection to a tube-fed safety syringe.
- Label changes emphasize correct use of this safety equipment and the prevention of human exposure.
The following safety-related changes were made to the labeling:
Shroud Label
(Additions and/or revisions underlined)
Front panel
Administer only with a tube-fed safety syringe. Do not use in automatically powered syringes, single-use syringes, or other delivery devices. Contact Elanco at 1-800-428-4441, or your distributor, for a tube-fed safety syringe for use with this product.
Boxed Warnings
HUMAN WARNINGS: Not for human use. Injection of this drug in humans has been associated with fatalities. Keep out of reach of children. Administer only with a tube-fed safety syringe. Do not use in automatically powered syringes, single-use syringes, or other delivery devices. Exercise extreme caution to avoid accidental self-injection. In case of human injection, consult a physician immediately and apply ice or cold pack to injection site while avoiding direct contact with the skin. Emergency medical telephone numbers are 1-800-722-0987 or 1-800-428-4441. Avoid contact with skin, eyes, or mucous membranes.
Left panel
Micotil must be used with the quick-fit connector made specifically for its use. Contact Elanco or your distributor for this equipment. Read product labeling, including Safe Handling Practices, before use.
Dosage and Administration:
Follow instructions for activation of the shroud before first usage. Inject Subcutaneously in Cattle and Sheep Only. See Safe Handling Practices, Contraindications, and Warnings prior to use. In cattle, administer a single subcutaneous dose of 10 to 20 mg/kg of body weight (1 to 2 mL/30 kg or 1.5 to 3 mL per 100 lbs).
Contraindications:
Do not use in automatically powered syringes, single-use syringes, or other delivery devices not specified in the labeling. Do not administer intravenously to cattle or sheep. Intravenous injection in cattle or sheep will be fatal. Do not use in lambs less than 15 kg body weight. Do not administer to animals other than cattle or sheep. Injection of tilmicosin has been shown to be fatal in swine and non-human primates. Death following exposure to tilmicosin injection has been reported to FDA/CVM in goats, rabbits, pheasants, pigs, dogs, deer, cats, alpacas, and horses.
Full Product Information attached to shroud
(The following diagram and text have been added.)
Instructions for Activation of the Shroud
Before first usage activate the shroud-vial-system as shown in the pictures.
Administer only with a tube-fed safety syringe. Do not use in automatically powered syringes, single-use syringes, or other delivery devices. This product must be used with the quick-fit connector made specifically for use with Micotil that attaches to the shroud fitting. To obtain a tube-fed safety syringe and quick-fit connector, contact Elanco at 1-800-428-4441, or your distributor.
Step 1. Twist the two tamper-evident tabs to break them off the Shroud Base.
Step 2. Rotate the Shroud Top through a quarter-turn clockwise. The spike will pierce the vial closure, and the Shroud Top will lock into its final position by an audible “click”.
Step 3. The correct final position can be confirmed by the alignment of the 2 arrows as shown in the picture.
Step 4. Remove the flexible cap from the fluid connection. Attach the quick-fit connector to tubing if not already attached. Push the quick-fit connector downwards onto the shroud fitting until it clicks into place.
Step 5. Invert the Micotil Shroud, then prime the tube-fed safety syringe following manufacturer’s instructions.
Return shroud to upright position after finishing operation. Leave tubing attached to tube-fed safety syringe and quick-fit connector until dosing equipment has been removed from the shroud. Remove dosing equipment by pushing the trigger as shown in the picture, then disconnecting the quick-fit connector from the shroud.
Micotil should not be stored in dosing equipment. Dosing equipment should be disconnected from the shroud after each use. Store product upright. The dosing equipment should be cleaned according to the manufacturer’s instructions. Avoid contact with skin, eyes, or mucous membranes.
Safe Use and Handling Instructions attached to shroud
(The following information has been added.)
WHAT ARE SAFE WAYS TO REMOVE AND CHANGE NEEDLES?
- Always follow the manufacturer’s instruction of how to safely remove and change needles from the safety syringe.
- Plan for the safe handling and disposal of needles before use.
- Keep the needle capped until ready to use.
- Avoid recapping a used needle.
- To safely remove used needles, use tools appropriate for the specific type of safety syringe. Do not remove a used needle with your fingers.
- Dispose used needles in an appropriate sharps disposal container. Do not overfill sharps containers and do not put your fingers into a sharps container.
- Never place loose needles in household or public trash cans.
Indications:
Revolution kills adult fleas and prevents flea eggs from hatching for one month and is indicated for the prevention and control of flea infestations (Ctenocephalides felis), prevention of heartworm disease caused by Dirofilaria immitis, and the treatment and control of ear mite (Otodectes cynotis) infestations in dogs and cats. Revolution also is indicated for the treatment and control of sarcoptic mange (Sarcoptes scabiei) in dogs, and the treatment of intestinal hookworm (Ancylostoma tubaeforme) and roundworm (Toxocara cati) infections in cats. Revolution is recommended for use in dogs and cats six weeks of age and older.
Summary of Changes:
- The User Safety Warnings section was revised to provide information regarding ocular exposure in humans.
- A Contact Information section was added.
- The Post-Approval Experience subsection of the Adverse Reactions section was updated.
- The Dosage and Administration section was updated on the carton to include bathing information for cats.
The following safety-related changes were made to the labeling:
(Additions and/or revisions underlined)
WARNINGS:
User Safety Warnings
Not for human use. Keep out of reach of children.
In humans, Revolution may be irritating to skin and eyes.
Reactions such as hives, itching and skin redness have been reported in humans. Individuals with known hypersensitivity to Revolution should use the product with caution or consult a health care professional. Revolution contains isopropyl alcohol and the preservative butylated hydroxytoluene (BHT).
Wash hands after use and wash off any product in contact with the skin immediately with soap and water.
If contact with eyes occurs, then flush eyes copiously with water; if wearing contact lenses, rinse the eyes first then remove contact lenses and continue to rinse for 5-10 minutes and seek medical attention.
In case of ingestion by a human, contact a physician immediately.
The safety data sheet (SDS) provides more detailed occupational safety information. To obtain a SDS contact Zoetis at 1-888-963-8471 or www.zoetisus.com.
Flammable - Keep away from heat, sparks, open flames or other sources of ignition.
Animal Safety Warnings
Do not use in sick, debilitated or underweight animals (see TARGET ANIMAL SAFETY).
CONTACT INFORMATION:
Contact Zoetis at 1-888-963-8471 or www.zoetis.com. To report suspected adverse drug experiences, contact Zoetis at 1-888-963-8471. For additional information about reporting adverse drug experiences for animal drugs, contact FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae.
ADVERSE REACTIONS:
(Updated Post-Approval Experience subsection)
Post-Approval Experience (2021):
The following adverse events are based on post-approval adverse drug experience reporting for Revolution. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using this data.
The following adverse events reported for dogs are listed in decreasing order of reporting frequency:
Lethargy, vomiting, diarrhea, anorexia, generalized pruritus, seizures, application site reactions (including alopecia, lesions, erythema, pruritis, and inflammation), tremors, ataxia, death, and dermatitis.
The following adverse events reported for cats are listed in decreasing order of reporting frequency:
Application site reactions (including alopecia, lesions, erythema, pruritus, inflammation, vesicles, blisters, and excoriations), lethargy, anorexia, vomiting, death, generalized pruritus, diarrhea, ataxia, fever, generalized alopecia, tremors, hypersalivation, dermatitis, and seizures.
CARTON
Puppy/kitten carton:
However, bathing or immersing your puppy in water 2 hours after application, and kittens 24 hours after application, will not reduce the effectiveness of this treatment.
Cat carton:
However, bathing or immersing your pet in water 24 hours after application will not reduce the effectiveness of this treatment.
Indication:
For synchronization of estrus in sexually mature gilts that have had at least one estrous cycle.
Summary of Changes:
- The User Safety Warnings section was revised to provide information regarding human exposure and safe handling of the product.
- A new subsection, Reported Human Effects from Exposure, was added to the User Safety Warnings section.
The following safety-related changes were made to the labeling:
(Additions and/or revisions underlined)
USES:
For synchronization of estrus in sexually mature gilts that have had at least one estrous cycle. Treatment with MATRIX results in estrus (standing heat) 4 to 9 days after completion of the 14-day treatment period.
It is a violation of Federal law to use this drug product other than as directed in the labeling or as directed by your veterinarian.
USER SAFETY WARNINGS:
Not for use in humans. Keep out of reach of children. Skin contact must be avoided as MATRIX is readily absorbed through unbroken skin, and exposure may result in serious side effects to both women and men. Always wear vinyl, neoprene, or nitrile protective gloves when handling MATRIX or when in contact with equipment or surfaces contaminated by this product. Latex gloves are not protective.
PREGNANT WOMEN OR WOMEN WHO MAY BE PREGNANT SHOULD NOT HANDLE MATRIX (altrenogest). WOMEN OF CHILDBEARING AGE SHOULD EXERCISE EXTREME CAUTION WHEN HANDLING THIS PRODUCT.
Accidental absorption, such as absorption through the skin, could lead to a disruption of the menstrual cycle or prolongation of pregnancy. Wash off accidental spillage on the skin immediately with soap and water. Any equipment or surfaces that come in contact with MATRIX should be adequately cleaned and decontaminated to prevent human exposure. Always use the MATRIX Dosing Device to administer this product. The MATRIX bottle is designed only for use with the MATRIX Dosing Device. Use without the device increases the risk of human exposure.
PEOPLE WHO SHOULD NOT HANDLE MATRIX:*
- Women who are or may be pregnant.
- Anyone with blood clots or clotting disorders, or with a history of these events.
- Anyone with a history of heart disease or stroke.
- Women with known or suspected breast cancer.
- People with known or suspected estrogen-dependent cancer.
- Women with vaginal bleeding of unknown cause.
- People with tumors which developed during the use of oral contraceptives or other estrogen-containing products.
- Anyone with liver dysfunction or disease.
*Based on known effects of long-term progestin use in humans.
ACCIDENTAL EXPOSURE:
MATRIX is readily absorbed from contact with the skin. In addition, this oil-based product can penetrate latex or other types of porous gloves. Always wear vinyl, neoprene, or nitrile gloves when handling MATRIX. Latex gloves are not protective. If MATRIX gets inside gloves by damage or spilling, the covered skin may absorb more of the drug. Side effects after a single exposure are possible; however, continued daily exposure has the potential for more serious effects.
IN CASE OF ACCIDENTAL EXPOSURE:
Skin exposure and/or clothing contamination: Wash skin immediately with soap and water, and launder clothing with detergent.
Eye exposure: Immediately flush with plenty of water for 15 minutes. Get medical attention. If wearing contact lenses, flush eyes immediately with water before removing lenses.
If swallowed: Do not induce vomiting. Seek medical attention immediately. MATRIX contains an oil. Vomiting should be supervised by a physician because of possible pulmonary damage via aspiration of the oil base. If possible, bring the labeling to the physician.
Reported HUMAN Effects from Exposure
Side effects have been reported in women and men following accidental exposure to altrenogest products, including MATRIX, either through handling of the product or contact with contaminated surfaces.
- Reproductive side effects reported in women included abnormal or absent menstrual cycles.
- Reproductive side effects in men included decreased libido.
- Other side effects reported in women and men included headaches, fever, abdominal pain, nausea, diarrhea, vomiting, and rashes.
Indication:
For replacement therapy for diminished thyroid function in dogs.
Summary of Changes:
- The Dosage and Administration section was revised to emphasize the difference in dosing instructions from other levothyroxine products and to describe how to transition between levothyroxine products.
- A Post-Approval Experience subsection was added to the Adverse Reactions section.
The following safety-related changes were made to the labeling:
(Additions and/or revisions underlined)
Dosage and Administration:
The initial total daily dose is 0.1 mg/10 pounds (0.01 mg/lb; 0.022 mg/kg) body weight as a single dose every 24 hours or as a divided dose every 12 hours.
The dose may then be adjusted by monitoring the serum total thyroxine (TT4) concentrations 4 to 6 hours post-tablet administration, along with clinical response, of the dog every 4 to 8 weeks until an adequate maintenance dose is established.
To minimize day-to-day variations in serum TT4 concentrations (see CLINICAL PHARMACOLOGY), owners should consistently administer Thyro-Tabs Canine either with or without food.
When switching from another levothyroxine sodium formulation to Thyro-Tabs Canine, monitor serum TT4 concentrations and clinical response due to potential differences in recommended starting doses and potential differences in bioavailability.
Adverse Reactions:
(Newly added subsection)
Post-Approval Experience (2022):
The following adverse events are based on post-approval adverse drug experience reporting for Thyro-Tabs Canine. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.
The following adverse events reported in dogs, are listed in decreasing order of reporting frequency: Pruritus, high or low serum thyroxine (T4) concentrations, tachypnea, weight loss, lethargy, anorexia, vomiting, polydipsia, alopecia, dermatitis, hyperactivity, diarrhea, and polyuria.
Allergic-type hypersensitivity reactions (including pruritus, hives, facial swelling, and dermatitis) have also been reported.
Indications:
For antibacterial use in a variety of species including chickens, turkeys, sheep, swine, calves, beef cattle, and non-lactating dairy cattle, and honey bees.
Summary of Changes:
The labeling was updated to improve the clarity of the instruction for safe use in honey bees.
The following safety-related changes were made to the labeling:
- A complete honey bee section was added to the label for Pennox 50, Pennox 100 Hi-Flo, and Pennox 200 Hi-Flo Type A medicated articles. These revisions address the three modes of product feeding in honey bees: dusting, syrup, and extender patty.
- The Type C Medicated Feed Blue Bird label was updated to reflect the revisions to the Type A medicated article labeling.
- Updated or new sections include Indications for Use; Mixing Directions for Honey Bees; Dusting, Syrup, and Extender Patty Feeding Directions; Withdrawal Periods and Residue Warnings; and Regulatory warnings for use of the product in a manner consistent with State apiary laws and regulations.
- A revised Veterinary Feed Directive (VFD) for honey bee use is consistent with the labeling revisions for the drug.
Indications:
For treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni, and for the treatment of bovine interdigital phlegmon (foot rot, acute interdigital necrobacillosis, infectious pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus. Also, it is indicated for the control of respiratory disease in cattle at high risk of developing BRD associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni.
Summary of Changes:
- The User Safety Warnings section was revised to include information regarding reproductive and developmental toxicities in laboratory animals.
- Safety information for pregnant women was added to the User Safety Warnings section.
- The Contact Information section was updated.
The following safety-related changes were made to the labeling:
(Additions and/or revisions underlined)
User Safety Warnings:
NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. This product contains materials that can be irritating to skin and eyes. Avoid direct contact with skin, eyes, and clothing. In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental skin exposure, wash with soap and water. Remove contaminated clothing. Consult a physician if irritation persists.
Accidental injection of this product may cause local irritation.
Consult a physician immediately.
Reproductive and developmental toxicities have been reported in laboratory animals following high, repeated exposures to N-methyl-2-pyrrolidone (NMP). Pregnant women should wear gloves and exercise caution or avoid handling this product. The Safety Data Sheet (SDS) contains more detailed occupational safety information.
Contact Information:
For customer service, adverse effects reporting and/or a copy of the SDS, call 1-800-211-3573. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae.
Indications:
Bravecto kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and the treatment and control of Ixodes scapularis (black-legged tick) infestations for 12 weeks in cats and kittens 6 months of age and older, and weighing 2.6 pounds or greater.
Bravecto is also indicated for the treatment and control of Dermacentor variabilis (American dog tick) infestations for 8 weeks in cats and kittens 6 months of age and older, and weighing 2.6 pounds or greater.
Summary of Changes:
- The Dosage and Administration section was revised to emphasize that the veterinarian should demonstrate to the client how to properly apply the product and that the cap is designed to stay on the tube.
- The Human Warnings section was revised to provide information regarding accidental ocular exposure and contact with the skin.
- A Post-Approval Experience subsection was added to the Adverse Reactions section.
The following safety-related changes were made to the labeling:
(Additions and/or revisions underlined)
Dosage and Administration:
A veterinarian or veterinary technician should demonstrate or instruct the pet owner regarding the appropriate technique for applying Bravecto topically to cats prior to first use.
Step 1: Immediately before use, open the pouch and remove the tube. Put on gloves. Hold the tube at the crimped end with the cap in an upright position (tip up). The cap should be rotated clockwise or counter clockwise one full turn. The cap is designed to stay on the tube for dosing and should not be removed. The tube is open and ready for application when a breaking of the seal is felt.
Greasy, oily, or wet appearance may occur at the application site in some cats.
Human Warnings:
Not for human use. Keep this and all drugs out of the reach of children.
Do not contact or allow children to contact the application site until 2 hours post application.
Keep the product in the original packaging until use in order to prevent children from getting direct access to the product. Do not eat, drink, or smoke while handling the product. Avoid contact with skin and eyes. If contact with eyes occurs, then flush eyes slowly and gently with water.
If wearing contact lenses, eyes should be rinsed first, then remove contact lenses and continue rinsing, then seek medical advice immediately. Wash hands and contacted skin thoroughly with soap and water immediately after use of the product. If the product accidentally contacts skin and a sticky residue persists after washing, rubbing alcohol (70% isopropyl alcohol) can be applied to the area to remove the residue.
The product is highly flammable. Keep away from heat, sparks, open flame or other sources of ignition.
Adverse Reactions:
(Newly added subsection)
Post-Approval Experience (2020):
The following adverse events are based on post-approval adverse drug experience reporting for fluralaner. Not all adverse events are reported to FDA/CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data.
The following adverse events reported in cats are listed in decreasing order of reporting frequency:
Application site alopecia, lethargy, hypersalivation, anorexia, vomiting, behavioral disorders (including hyperactivity, hiding, and vocalization), generalized pruritus, application site disorders (including lesion, pruritus, and erythema), ataxia, alopecia, diarrhea, and muscle tremor.