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 2023-present:
Indications:
STELFONTA injection is indicated for use in dogs for the treatment of:
- non-metastatic cutaneous mast cell tumors
- non-metastatic subcutaneous mast cell tumors located at or distal to the elbow or the hock.
Summary of Changes:
- The Dosage and Administration section was updated to highlight the importance of appropriate administration of the required concomitant medications and to clarify the dosing instructions for both the concomitant medications and STELFONTA.
- Safety and risk information was updated in the Animal Safety Warnings, Precautions, and Information for Dog Owners sections to reflect post-approval experience, including extensive wound formation, limb amputation, and death.
- A Post-Approval Experience subsection was added to the Adverse Reaction section.
- The Client Information Sheet was updated to emphasize the potential for serious side effects and reflect the new safety and risk information and post-approval experience information, including diagrams illustrating extensive wound formation.
In addition, a fillable medication schedule and explanatory language were added to facilitate correct administration of concomitant medications.
The following safety-related changes were made to the labeling:
Dosage and Administration
(Additions and/or revision are underlined)
ALWAYS PROVIDE THE CLIENT INFORMATION SHEET TO THE DOG OWNER BEFORE DOSE ADMINISTRATION.
Carefully consider the potential benefits and risks of STELFONTA before deciding to use STELFONTA.
It is crucial to follow the dosing and administration instructions to use the product safely and effectively (see Boxed Warning, Animal Warnings, Precautions, Clinical Pharmacology).
Concomitant medications
Administer the following medications to decrease the potential for severe systemic adverse reactions from mast cell degranulation (see Effectiveness). Do not underdose concomitant medications and confirm that the dog owner administered the medications as prescribed prior to the day of STELFONTA treatment.
- Corticosteroid (oral prednisone or prednisolone at anti-inflammatory dose): Start medication 2 days prior to STELFONTA treatment at a dose of 0.5 mg/kg orally every 12 hours for 7 days (2 days prior, the day of treatment, and 4 days after treatment), then 0.5 mg/kg orally every 24 hours for an additional 3 days (10 days total).
- H1 receptor blocking agent (oral diphenhydramine): Start medication on the day of STELFONTA treatment at a dose of 2 mg/kg orally every 12 hours and continue for a total of 8 days (the day of treatment and 7 days after treatment).
- H2 receptor blocking agent (oral famotidine): Start medication on the day of STELFONTA treatment at a dose of 0.5 mg/kg orally every 12 hours and continue for a total of 8 days (the day of treatment and 7 days after treatment).
- Fill out the medication schedule (drug name, dose, route of administration, date) on the Client Information Sheet to help the dog owner administer these medications correctly.
Consider administering analgesic medications prior to, during, and after treatment with STELFONTA.
Dosing Instructions
Administer STELFONTA as an intratumoral injection at a dose of 0.5 mL per cm3 of tumor volume, as determined by the following calculations:
STEP 1. Calculate Tumor Volume:
- Measure the tumor dimensions (Length, Width and Height) with calipers on the day of STELFONTA injection.
- Determine the Tumor Volume using the modified ellipsoid formula (cube volume x ½) as below:
- Confirm the Tumor Volume does not exceed 10 cm3.
- Do not use STELFONTA if the tumor volume is >10 cm3.
STEP 2. Calculate the mL of STELFONTA to inject:
- Confirm the dose of STELFONTA does not exceed 0.25 mL/kg body weight and do not use if the calculated dose exceeds this.
- Do not exceed 5 mL per dog, regardless of tumor volume or body weight.
- The minimum dose of STELFONTA is 0.1 mL, regardless of tumor volume or body weight. If the calculated dose is <0.1 mL, administer 0.1 mL.
- Confirm the calculated dose of STELFONTA using the online calculator at www.stelfonta.com/calculator
(or scan the QR code to the right).
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Warnings
(Additions and/or revision are underlined)
Human Safety Warnings
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Animal Safety Warnings
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Always administer the concomitant medications (prednisone or prednisolone, diphenhydramine, and famotidine), as directed in the Dosage and Administration section, with STELFONTA in order to decrease the potential for severe systemic adverse reactions, including death, from mast cell degranulation (see Adverse Reactions).
...
STELFONTA can induce a substantial local inflammatory reaction which may result in severe pain and swelling, bruising, cellulitis, extensive wound formation, and severe tissue sloughing extending away from the treated site. Consider administering analgesic medications prior to, during, and after treatment with STELFONTA in addition to the use of corticosteroids and both H1 and H2 receptor blocking agents.
Amputation of an extremity has been reported in some cases (see Post-Approval Experience).
Some dogs require wound care and pain management for an extended period.
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Precautions
(Additions and/or revision are underlined)
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Some discharge from the site following treatment is expected. Wear disposable gloves to clean the site with warm water as necessary.
After treatment with STELFONTA, dogs may require additional care of the treated site to aid in the healing process, especially if there is extensive wound formation (see Animal Safety Warnings and Post-Approval Experience).
Tongue lesions have been reported (see Post-Approval Experience). Do not allow the dog to lick the site for the first few days after treatment. Discourage excessive licking for the remainder of the healing period.
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Adverse Reactions
(Newly added subsection)
Post-Approval Experience (2024)
The following adverse events are based on post-approval adverse drug experience reporting for STELFONTA. 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:
Injection site reactions (wound formation, swelling, pain, necrosis, skin sloughing, skin hemorrhage, bruising and erythema). These injection site reactions varied in severity and ranged from localized to extending away from the injection site.
Other signs reported include anorexia, lameness, lethargy, diarrhea, vomiting, fever, tachypnea/dyspnea, and ulceration or necrosis of tongue.
In some cases, when STELFONTA was used to treat a mast cell tumor on an extremity, the entire extremity became swollen, painful, and developed tissue sloughing. Some of these cases resulted in amputation.
In some cases, death (including euthanasia) has been reported as an outcome of the adverse events reported above.
Information for Dog Owners
(Additions and/or revision are underlined)
…
Owners should be advised to observe their dog for potential side effects, including signs of systemic mast cell degranulation, excessive pain and swelling, and excessive wound formation. Advise dog owners about the possibility of severe side effects, including amputation and death, when to contact a veterinarian, and how to care for the treated tumor site.
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Discuss the importance of the concomitant medications and ensure that the owner is aware of the schedule of medications that should be administered. The owner should use the Medication Schedule on the CIS to keep track of the medications they have administered.
Discuss with owners that they should not allow the dog to lick the site for the first few days after treatment and they should discourage excessive licking for the remainder of the healing period.
An Elizabethan Collar may be utilized to prevent self-trauma of the treatment site. After treatment the owner may need to separate the dog from other household animals to prevent grooming and trauma to the treated site.
Client Information Sheet
(Additions and/or revisions are underlined)
This Client Information Sheet contains important information about STELFONTA. Before your dog is treated, you should carefully read this information and discuss the following with your veterinarian:
- How STELFONTA works.
- All parts of your dog’s treatment plan. It is very important to follow the treatment plan exactly as directed.
- The risk and benefits of STELFONTA, including the potential for serious side effects.
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What additional medications need to be given to my dog before, on, and after the day of treatment with STELFONTA?
- To help prevent the potential for severe side effects that can occur, your veterinarian will prescribe three medications:
- You must start to give your dog the corticosteroid two days before the STELFONTA treatment day and continue for a total of 10 days.
- You will start giving your dog the H1 and H2 blockers on the STELFONTA treatment day and continue for a total of 8 days.
- Your veterinarian will fill out the medication schedule included in this Client Information Sheet for you to follow, so that you can give your dog the medications correctly.
- If you are unable to give your dog the medications as directed, talk to your veterinarian about other options. Do not skip these medications.
How will STELFONTA affect my dog?
…
- A wound will form where STELFONTA was administered. It is difficult to predict the size and severity of the wound formed. In some cases, an extensive wound that is deeper and/or larger than the original treatment site may develop, which may lead to unexpected complications.
- Tumors treated with STELFONTA typically go through a 4 to 6-week tumor breakdown and healing process.
… - During the tumor breakdown and healing process, your dog my require additional care of the treated tumor site to aid in the healing process.
…
Some dogs experience extensive wounds after STELFONTA treatment that take longer to heal, as in the case below.
What are some possible side effects of STELFONTA?
…
- In some cases, extensive swelling, severe pain, large amounts of discharge, odor, infection, or wound formation extending into the area surrounding the tumor site may develop, delaying wound healing and requiring additional management of the wound. If any of these occur, contact your veterinarian who will assess if your dog needs additional treatments during this time (e.g., pain medication, bandages, Elizabethan collar, antibiotics).
- Amputation has been reported as a result of extensive swelling and wound formation.
- Mast cell degranulation can occur, especially during the first 5-7 days after treatment. Mast cell degranulation is a type of allergic reaction that occurs when inflammatory substances are released from your dog’s tumor when mast cells are destroyed.
Mast cell degranulation can cause severe side effects and potentially be fatal. Contact your veterinarian if you notice any of the following signs:- trouble breathing or excessive panting
- excessive bruising and swelling
- vomiting
- diarrhea
- hives
- decreased appetite (refusal to eat for more than 1 day)
…
- Side effects can occur with or without warning, and in some cases may result in death.
Contact your veterinarian if you notice any of the following changes in your dog. These changes may mean your dog is experiencing a serious side effect.
...
- Excessive licking of the treatment site
- Tiredness, weakness, or refusal to eat for more than 1 day
… - Trouble breathing or excessive panting
- A rash or hives anywhere on the body
- Changes to the treated tumor site, including increased or excessive swelling and bruising, large amounts of discharge, strong odor, or extensive wound formation.
…
What do I need to know to safely care for my dog before and after treatment with STELFONTA (tigilanol tiglate injection)?
- Your veterinarian will prescribe medications to decrease the potential for allergic reactions due to mast cell degranulation that can occur during the treatment process. It is essential that you give the medications as prescribed (use the Medication Schedule below to help you keep track of the dosing schedule).
... - Notify your veterinarian if your dog seems uncomfortable. Your veterinarian may prescribe additional medications for pain.
… - Do not allow your dog to lick the tumor site for the first few days after treatment. Discourage excessive licking for the remainder of the healing period.
…
Use the Medication Schedule below to help you keep track of the medicine you need to give your dog.
Medication schedule
The following medications are to be given when your pet is treated with STELFONTA to help decrease and/or prevent side effects:
- Corticosteroid (prednisone or prednisolone): Start medication as directed two days before STELFONTA treatment day, continue on the treatment day, and for an additional 7 days after the treatment day, which will be a total of 10 days.
- H1 and H2 blockers (diphenhydramine and famotidine): Start medications as directed on STELFONTA treatment day and continue for an additional 7 days, which will be a total of 8 days.
- Use the following chart to help you keep track of the dosing schedule, make an ‘X’ in the box when that dose of medication is given. Do not administer the medication if the box is grayed out.
- If you are unable to give your dog the medications orally (by mouth), or your dog is vomiting or not eating, talk to your veterinarian to determine what other options may be used for administration. Do not skip these medications.
Note for veterinarian – the above chart is intended to be a visual aid for the client to administer the concomitant medications correctly. Fill in the chart with the specific dates of administration and the specific names of the medications prescribed.
Indications:
CREDELIO CAT kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) for one month in cats and kittens 8 weeks of age and older, and weighing 2.0 pounds or greater.
CREDELIO CAT is also indicated for the treatment and control of Ixodes scapularis (black-legged tick) infestations for one month in cats and kittens 6 months of age and older, and weighing 2.0 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 (2024):
The following adverse events are based on post-approval adverse drug experience reporting for CREDELIO CAT. 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:
Pruritus, vomiting, lethargy, behavioral changes (including hyperactivity, vocalization, and hiding), tachypnea, anorexia, muscle tremor, dyspnea, hyperthermia, and ataxia.
Indication:
GALLIPRANT (grapiprant tablets) is indicated for the control of pain and inflammation associated with osteoarthritis in dog.
Summary of Changes:
- Safety and risk information was updated in the Dosage and Administration, Warnings, Precautions, and Information for Dog Owners sections based on post-approval experience information for GALLIPRANT and to reflect that the safety profile is similar to other non-steroidal anti-inflammatory drugs approved for use in dogs.
- A Post-Approval Experience subsection was added to the Adverse Reactions section.
- The Client Information Sheet (Information for Dog Owners) was updated to reflect the new safety and risk information and post-approval experience information.
The following safety-related changes were made to the labeling:
Dosage and Administration
(Additions and/or revisions are underlined)
Always provide “Information for Dog Owners” Sheet with prescription. Carefully consider the potential benefits and risks of GALLIPRANT and other treatment options before deciding to use GALLIPRANT. Use the lowest effective dose for the shortest duration consistent with individual response.
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Warnings
(Additions and/or revisions are underlined)
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All dogs should undergo a thorough history and physical examination before the initiation of NSAID therapy. Appropriate laboratory tests to establish hematological and serum biochemical baseline data prior to and periodically during administration of any NSAID is recommended.
Owners should be advised to observe for signs of potential drug toxicity (see Adverse Reactions, Post-Approval Experience, and Animal Safety) and be given an “Information for Dog Owners” Sheet about GALLIPRANT.
Do not administer GALLIPRANT in conjunction with any other oral or injectable NSAID or corticosteroid.
Keep GALLIPRANT in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.
Precautions
(Additions and/or revisions are underlined)
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Adverse reactions in dogs receiving GALLIPRANT may include vomiting, diarrhea, decreased appetite, mucoid, watery, or bloody stools, and decreases in serum albumin and total protein (see Adverse Reactions and Post-Approval Experience).
If GALLIPRANT is used long term, appropriate monitoring is recommended.
GALLIPRANT is a non-cyclooxygenase (COX) inhibiting non-steroidal anti-inflammatory drug (NSAID). As a class, NSAIDs may be associated with gastrointestinal, renal, and hepatic toxicity. Sensitivity to drug-associated adverse events varies with the individual patient. Dogs that have experienced adverse reactions from one NSAID may experience adverse reactions from another NSAID. Patients at greatest risk for adverse events are those that are dehydrated, on concomitant diuretic therapy, or those with existing renal, cardiovascular, and/or hepatic dysfunction.
Anesthetic drugs may affect renal perfusion; approach concomitant use of anesthetics and NSAIDs cautiously. Appropriate monitoring procedures (including ECG, blood pressure, and temperature regulation) should be employed during all surgical procedures. The use of parenteral fluids during surgery is recommended to decrease potential renal complications when using NSAIDs perioperatively.
If additional pain medication is needed after a daily dose of GALLIPRANT, a non-NSAID/non-corticosteroid class of analgesic may be necessary. Concurrent administration of potentially nephrotoxic drugs should be carefully approached and monitored. NSAIDs may inhibit the prostaglandins that maintain normal homeostatic function. Galliprant blocks the activity of the specific prostaglandin E2 (PGE2). Such anti-prostaglandin effects may result in clinically significant disease in patients with underlying or pre-existing disease that has not been previously diagnosed. NSAIDs possess the potential to produce gastrointestinal ulceration and/or gastrointestinal perforation. Do not use GALLIPRANT concomitantly with other anti-inflammatory drugs, such as NSAIDs or corticosteroids. Consider appropriate washout times when switching from GALLIPRANT to another NSAID (or vice versa) or when switching from corticosteroid use to GALLIPRANT use.
The concomitant use of protein-bound drugs with GALLIPRANT has not been studied in dogs. Commonly used protein-bound drugs include cardiac, anticonvulsant and behavioral medications. The influence of concomitant drugs that may inhibit metabolism of GALLIPRANT has not been evaluated. Drug compatibility should be monitored in patients requiring adjunctive therapy.
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Adverse Reactions
(Newly added subsection)
Post-Approval Experience (2024)
The following adverse events are based on post-approval adverse drug experience reporting for GALLIPRANT. 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 in dogs are categorized in order of decreasing reporting frequency by body system and in decreasing order of reporting frequency within each body system:
GI: diarrhea (with or without blood), vomiting (with or without blood), elevated pancreatic enzymes/pancreatitis, melena, bloody stool, hypoalbuminemia, abdominal pain, gastrointestinal ulcer.
General: anorexia, lethargy, weight loss, panting, hyperactivity.
Hepatic: elevated liver enzymes.
Renal/Urinary: increased BUN or creatinine, polydipsia, urinary incontinence/inappropriate urination, polyuria, renal failure.
Neurologic: ataxia, seizures.
Hematologic: anemia, thrombocytopenia.
Dermatologic/Immunologic: pruritus, allergic reactions (including facial edema and hives), immune mediated hemolytic anemia.
In some cases, death (including euthanasia) has been reported as an outcome of the adverse events listed above.
Information for Dog Owners
(Additions and/or revisions are underlined)
Owners should be advised of the potential for adverse reactions and be informed of the clinical signs associated with drug intolerance. Adverse reactions may include diarrhea, vomiting, decreased appetite, dark or tarry stools, increased water consumption, increased urination, pale gums due to anemia, jaundice (yellowing of gums, skin or white of the eye), lethargy, incoordination, seizures, and behavioral changes such as depression or restlessness. Serious adverse reactions associated with this drug class can occur without warning and, in some cases, result in death (see Adverse Reactions and Post-Approval Experience). Owners should be advised to discontinue GALLIPRANT therapy and contact their veterinarian immediately if signs of intolerance are observed. The vast majority of patients with drug related adverse reactions have recovered when the signs are recognized, the drug is withdrawn, and veterinary care, if appropriate, is initiated. Owners should be advised of the importance of periodic follow up for all dogs during administration of any NSAID.
Client Information Sheet (Information for Dog Owners)
(Additions and/or revisions are underlined)
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What is GALLIPRANT?
GALLIPRANT is an EP4 prostaglandin receptor antagonist non-steroidal, anti-inflammatory drug (NSAID). As an anti-inflammatory, GALLIPRANT is indicated for the control of pain and inflammation associated with osteoarthritis in dogs.
Control of pain and inflammation may vary from dog to dog. Consult your veterinarian if your dog appears to be uncomfortable. GALLIPRANT may need to be given for an extended period of time. Use the lowest dose to provide adequate pain control. Always consult with your veterinarian before altering the dose.
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Your dog should not take GALLIPRANT if:
- Your dog is presently taking aspirin, other NSAIDs (non-steroidal anti-inflammatory drugs such as carprofen or meloxicam) or corticosteroids (such as prednisone) unless directed by your veterinarian.
… - Your dog has bloody stool or vomit.
- Your dog has a pre-existing kidney or liver condition.
- Your dog has any condition predisposing to dehydration.
- Your dog is anorexic (loss of appetite).
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GALLIPRANT should only be given to dogs. Do not use in cats.
People should not take GALLIPRANT. Keep GALLIPRANT and all medications out of reach of children. Consult a physician if you accidentally take GALLIPRANT.
Keep GALLIPRANT in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.
Tell your veterinarian about:
- Any side effects your dog has experienced from GALLIPRANT or other NSAIDs. Dogs that have experienced side effects from one NSAID may experience adverse reactions from another NSAID.
… - If your dog has no appetite or a decreased appetite.
- Any heart, kidney, or liver disease your dog has had.
- Any other medical problems or allergies that your dog has now or has had in the past.
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Talk to your veterinarian about:
- The signs of osteoarthritis you have observed (for example, limping or stiffness).
- What tests should be done prior to administering GALLIPRANT.
- How often your dog may need to be examined by your veterinarian.
- The risks and benefits of using GALLIPRANT.
What are the possible side effects that may occur in my dog during therapy with GALLIPRANT?
GALLIPRANT may cause some side effects in individual dogs. Serious side effects associated with this drug can occur with or without warning and, in some cases, result in death. The most common side effects associated with GALLIPRANT therapy involve the digestive tract (diarrhea, soft, mucoid stools, vomiting, and decreased appetite). Liver and kidney problems have also been reported.
Look for the following side effects that may indicate that your dog is having a problem with GALLIPRANT or may have another medical problem:
- Change in bowel movements such as diarrhea, soft mucoid stool, or change in stool color (black, tarry, or bloody stool).
- Vomiting.
- Decrease in appetite.
- Change in behavior, such as depression or restlessness.
- Incoordination or seizures.
- Change in drinking or urination.
- Yellowing of gums, skin, or whites of the eyes (jaundice).
It is important to stop the medication and contact your veterinarian immediately if you think your dog may have a medical problem or side effect while on GALLIPRANT.
If you have additional questions about possible side effects, talk with your veterinarian or call Elanco US Inc. at 1-888-545-5973. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae.
Can GALLIPRANT be given with other medications?
GALLIPRANT should not be given with aspirin, other non-steroidal anti-inflammatory drugs (such as carprofen or meloxicam) or corticosteroids (such as prednisone).
Tell your veterinarian about all medications that you have given your dog in the past, and any medications that you are planning to give with GALLIPRANT. This should include any medications that you can get without a prescription and any dietary supplements. Your veterinarian may want to evaluate the potential for any drug interactions and to assure drug compatibility.
What can I do in case my dog eats more than the prescribed amount of GALLIPRANT?
Contact your veterinarian immediately if your dog eats more than the prescribed amount of GALLIPRANT.
What else should I know about GALLIPRANT?
Keep GALLIPRANT in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.
If you have any questions or concerns about GALLIPRANT or osteoarthritis, talk to your veterinarian. GALLIPRANT should only be given to the dog for which it was prescribed. It should be given to your dog only for the condition for which it was prescribed, at the prescribed dose, as directed by your veterinarian. Your veterinarian will determine if your dog is responding as expected and if your dog should continue receiving GALLIPRANT.
Indications:
Bravecto 1-Month 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) 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.
Bravecto 1-Month is also indicated for the treatment and control of Amblyomma americanum (lone star tick) infestations for one month in dogs and puppies 6 months of age and older and weighing 4.4 pounds or greater.
Summary of Changes:
- The Precautions section was revised to add language about adverse events being reported in breeding females following use of Bravecto 1- Month.
- The Post-Approval Experience subsection of the Adverse Reactions section was updated, and new language was added regarding reproductive adverse events following use of Bravecto 1-Month.
The following safety-related changes were made to the labeling:
Precautions
(Additions and/or revisions are underlined)
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The safety of Bravecto 1-Month has not been evaluated in breeding, pregnant, and lactating dogs. Adverse events have been reported following use of Bravecto (fluralaner) Chews in breeding females.
Before use in breeding female dogs, refer to Post-Approval Experience and Animal Safety sections.
Adverse Reactions
(Updated Post-Approval Experience subsection, additions are underlined).
Post-Approval Experience (2024):
The following adverse events are based on post-approval adverse drug experience reporting for Bravecto 1-Month. 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, lethargy, diarrhea, anorexia, tremors, ataxia, seizure, pruritus, and allergic reactions (including hives, swelling, and erythema).
The following reproductive adverse events have been reported following use of Bravecto (fluralaner) Chews: birth defects (including limb deformities and cleft palate), stillbirth, and abortion.
Indications:
Synotic is indicated for the relief of pruritus and inflammation associated with acute and chronic otitis in the dog.
Summary of Changes:
- The Dosage and Administration section was updated to add a statement about reports of hearing loss with product use and instructions on how to proceed if hearing or vestibular dysfunction are noted during the course of treatment.
- The carton and bottle label were revised to add a pictogram, and the phrase “FOR OTIC USE IN DOGS ONLY” was revised to “FOR USE IN DOG EARS ONLY” to emphasize that the product is not for use in the eye.
The following safety-related changes were made to the labeling:
Dosage and Administration
(Additions and/or revision are underlined)
The recommended dose of SYNOTIC Otic Solution Veterinary is 4 to 6 drops (0.2 mL) per ear administered twice daily into the ear canal for a maximum period of 14 days. The total dosage used should not exceed 17 mL. It is recommended that the affected ear canal be cleansed by some appropriate method prior to the instillation of the solution. Following instillation, gentle external massage of the ear canal may aid in promoting an even distribution of the medication. Care should be taken to avoid contact of the medication with the dog’s eyes.
Contact of the bare hand with the medication should also be avoided.
Hearing loss has been reported in a small number of dogs after use. If hearing or vestibular dysfunction is noted during the course of treatment, discontinue use of Synotic immediately and flush the ear canal thoroughly with a nonototoxic solution.
Bottle Label
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).
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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.