2023 Animal Drug Safety-Related Labeling Changes
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.