PMRA Guidance Document, Label Improvements for Spot-on Pesticides Used on Companion Animals

Pest Management Regulatory Agency
6 December 2019

(PDF Version)

Table of Contents

1.0 Purpose

The purpose of this document is to outline recent label improvements for spot-on pesticides used on companion animals. The improvements are intended to better inform the consumer as to the possible effects that may occur following product use, and to clarify the use directions on product labels. Listing of possible side effects aligns with practices already in place for drugs and companion animal products in other areas of Health Canada and in other jurisdictions such as the United States and Europe.

This document should be used in concert with Regulatory Directive DIR2002-01, Canadian Label Improvement Program for Pesticides Used on Companion Animals and Regulatory Directive DIR2010-02, Label Improvements for Spot-on Pesticides Used for Flea and Tick Control on Companion Animals.

2.0 Background

In April 2009, Health Canada’s Pest Management Regulatory Agency (PMRA) published an Advisory to inform consumers about the potential adverse reactions in pets that may be associated with flea, tick and mosquito pest control products applied to cats and dogs and to remind them to follow label directions. An in-depth review of spot-on incident data was performed in conjunction with the United States Environmental Protection Agency (USEPA). As a result of the review of the incidents, the PMRA released the findings in a March 2010 Update to the Public Advisory, and implemented label changes in 2011 under the Regulatory Directive DIR2010-02, Label Improvements for Spot-on Pesticides Used for Flea and Tick Control on Companion Animals, to address the key concerns. Specifically, the words “Toxic to cats” and a corresponding pictogram were added to the principal display panel of the label of spot-on products containing permethrin, since the application to cats of permethrin-containing products intended for use on dogs represented a high number of cases of misuse. Despite a decrease in incidents related to misuse since the implementation of these label amendments, animal incidents related to spot-on flea, tick and mosquito products continued to be frequently reported. An in-depth review was therefore conducted on all spot-on incident data reported to Health Canada’s PMRA from 2007 to the end of 2015.

In September 2018, Health Canada’s PMRA published the Regulatory Proposal PRO2018-01, Consultation on Proposed Regulatory Changes for Pesticide Products Used on Companion Animals. The purpose of PRO2018-01 was:

  1. to obtain input on a proposal requiring registrants and applicants of spot-on products to list potential side effects on the product label; and,
  2. to propose that the data requirements for pesticide products for use on companion animals under Use-site Category 24 be amended to include a clinical safety study, in addition to the previously required companion animal safety study (DACO 4.6.9).

This document addresses the labelling of side effects. A separate PMRA Guidance Document (Revisions to Data Requirements for Pesticide Products used on Companion Animals) has been published regarding data requirements for companion animals.

3.0 Outcome of the Science Evaluation

Overall, Health Canada’s PMRA analyzed 5928 incident reports for dogs and cats involving spot-on products. The analysis encompassed 4359 incidents reported to Health Canada’s PMRA that occurred in Canada, with the remainder being the most serious incidents that occurred in the United States with similar products.

Most Canadian incidents were considered to be related to appropriate product use and the majority were minor or moderate in severity. Incidents involving skin effects were commonly reported, with medical treatment provided in almost half of the cases. Other commonly reported effects in animal incidents included behavioural, gastrointestinal or systemic findings such as lethargy, hyperactivity, abnormal behaviour, vocalization, anorexia, emesis or hypersalivation. Neurological effects were frequently observed in the more serious cases with muscle tremors, paraesthesia, ataxia or convulsions reported. In most cases of death, no association was determined between exposure to the product and the reported effects. Often there was either insufficient information contained in the incident report to assess cases where the animal died, or the death was considered to be unlikely related to the pesticide, based on the exposure information provided in the report, or the available scientific information for the pesticide. For the deaths that were considered to be associated with exposure to the product, it was determined that several factors could have contributed to these deaths, and details such as medical testing and residue analysis (that might have otherwise provided further insights into an association with the pesticide) were limited or unavailable in the reports. Almost all reported deaths were from the United States, with only 24 occurring in Canada, which comprised 0.4% of all incidents included in the analysis. When considered in conjunction with the total number of doses of product sold, these cases of death were quite rare. Given this rarity and the lack of information available to definitively determine the cause of death in these animals, no further action was warranted for this outcome.

The science evaluation considered a number of elements including the age and body weight of the affected animal, applied dose and point of sale (for example, retail outlet or veterinary clinic), in relation to the severity and nature of the reported signs. These elements were not the main contributing factors in the overall number of incidents submitted, although, in some cases, patterns of involvement with these elements were noted for specific active ingredients and/or products. Despite these specific patterns, the most frequently reported effects tended to be common amongst all spot-on products, and were generally minor in nature. The high number of minor incidents submitted for spot-on products is offset by the value that these products have in the marketplace; flea and tick infestations can be quite severe in animals in some instances, and spot-on products are a vital and cost-effective tool in controlling infestations. Notwithstanding these benefits, there is a need to communicate to consumers the potential side effects in dogs and cats from use of these products, and to clarify the use directions on product labels.

As part of the consultation process, Health Canada’s PMRA received comments related to the proposed label changes outlined in PRO2018-01. These comments and Health Canada PMRA’s responses are summarized in Appendix I of this document.

4.0 Spot-on Product Label Requirements

Labelling of Potential Side Effects

To better inform the consumer as to the possible effects that may be expected following product use, registrants of spot-on products have voluntarily agreed to list potential side effects on the product label and applicants of spot-on products are required to list potential side effects on the product label. These label changes align with practices already in place for veterinary drugs and companion animal products in other areas of Health Canada and in other jurisdictions such as the United States and Europe.

For currently registered spot-on products, the registrant will be including a box on the product label under the precautions section for pets entitled “Side Effects”. Registrants will either use the wording provided below or propose alternate label language based on incident reports, companion animal safety studies, and/or clinical trials, if available. Proposed amendments to the label language and any submitted information will be subject to review by Health Canada’s PMRA, which includes a confirmation of the adequacy of this information to support the underlying label amendments.

For products used on dogs:

“Monitor your dog after application. Side effects may include: skin irritation such as redness or scratching; changes in behaviour such as agitation or lethargy; or gastrointestinal effects such as vomiting or loss of appetite. If these or other side effects occur consult your veterinarian or [Registrant at 1-800-number].”

For products used on cats:

“Monitor your cat after application. Side effects may include: skin irritation such as scratching or hair loss at the application site, or changes in behaviour such as agitation or lethargy. Gastrointestinal effects such as drooling, vomiting, or loss of appetite may also occur. If these or other side effects occur consult your veterinarian or [Registrant at 1-800-number].”

For spot-on products currently under review by Health Canada’s PMRA at the time of the publication of this document, and for any future submissions to register a spot-on product for Use-site Category 24 (Companion Animals), the product labels will be amended to include the label language above. In the future, these registrants of spot-on products can also propose amendments to the label language based on incident reports, companion animal safety studies, and/or clinical trial data, if available. Proposed amendments will be subject to review by Health Canada’s PMRA, as outlined above for current registrants of spot-on products.

Label Improvements

Health Canada PMRA’s review also highlighted the lack of consistency in the use directions on product labels and registrants have voluntarily agreed to the following label improvements, which will be applied to all spot-on product labels. These label changes will also be required for any subsequent submissions to register spot-on products. These improvements consider comments received in response to PRO2018-01 (Appendix I). Registrants or applicants will either use the label language in bullet 2 below, or submit an application to Health Canada’s PMRA to modify the label language through the submission of product-specific scientific data to support a more frequent product re-application period and/or concomitant use of multiple products with a common pesticidal active ingredient. Hereafter, registrants must submit an application to:

As previously noted, any supporting scientific data must be submitted to Health Canada’s PMRA as part of the application or amendment request. Alternatively, as with any data requirement, applicants and registrants may provide a scientifically sound justification in support of a data waiver request. Applicants are also encouraged to undertake a pre-submission consultation with Health Canada’s PMRA for specific recommendations on proposed study protocols prior to study conduct.

5.0 Implementation

To comply with this decision, registrants have agreed to implement the required label amendments on all spot-on product labels sold by registrants no later than 24 months from the date of publication of this document. Appendix II lists the spot-on products that are registered under the authority of the Pest Control Products Act.

For spot-on products currently under review by Health Canada’s PMRA at the time of the publication of this PMRA Guidance Document, and for any subsequent submissions to register spot-on products, these label improvements will be required as part of the evaluation.

Appendix I Comments and Responses

Six sets of comments were received during the 45-day consultation period for PRO2018-01. Commenters included the pesticide industry, non-governmental association groups representing the interests of public and animal health, as well as a member of the public. Commenters were generally supportive of the proposed label amendments for spot-on products outlined. Additional comments were provided that were general in nature or specific to certain sections. These comments have been summarized and where relevant, grouped by theme. The summarized comments and Health Canada’s responses are outlined below.

1.0 Comments Related to Health Canada’s PMRA Analysis

Comments were received from a registrant and a member of the public regarding a number of aspects of the incident report analysis for spot-on products, including inquiries as to the types of incident reports considered in the analysis, the incident reporting rates, and the causality assessments.

Health Canada’s PMRA Response:

Health Canada’s PMRA considered the concerns regarding the analysis of incidents related to spot-on products. These concerns have been generally addressed in the responses to the comments received regarding the proposed label amendments (refer to responses 2.0 to 4.0 below).

Health Canada’s PMRA will continue to monitor incident reports related to companion animal products and continue to advise Canadians about the importance of following the labels of pest control products. It is anticipated that the label changes described in this document for companion animal products will help to communicate to consumers the potential side effects in dogs and cats from the use of spot-on products, and that the amended data requirements (refer to PMRA Guidance Document, Revisions to Data Requirements for Pesticide Products used on Companion Animals) will improve the current animal safety testing strategy for pesticide products used on companion animals.

2.0 Comments Related to Labelled Symptoms

2.1 Comments related to the specificity of listed symptoms to individual products

Comments were received from a registrant and a non-governmental association that suggested that labelled side effects should be specific to individual products. The registrant indicated that further clarity and guidance is necessary, regarding the criteria that Health Canada’s PMRA will use to establish specific statements and whether alternate statements would be considered.

Health Canada’s PMRA Response:

Generic statements of potential side effects were developed for spot-on products for dogs and cats, as the analysis of related incident reports indicated that the spectrum of reported effects was generally common across the spot-on incidents for each species.

The intent of the labelling proposed in the PRO2018-01 is to better inform the consumer as to the possible effects that may be expected following product use; the label statement directs the user to then contact either the registrant or a veterinarian for advice.

As indicated in the PRO2018-01, as well as in Section 3.0 of this document, registrants can propose alternate label language to describe specific side effects based on incident reports, companion animal safety studies and/or clinical trials, if available.

2.2 Comment indicating that death should be listed as a symptom on the spot-on product labels

Comments were received from a member of the public that stated that labels of spot-on products should advise the consumer that death is a possible adverse health effect, particularly since cats are sensitive to permethrin toxicity and misuse of this spot-on product can result in death. The individual also indicated that the labels should specify that the products only be used on healthy animals.

Health Canada’s PMRA Response:

Although death did occur in 24 cases related to a spot-on product, when considered relative to product sales, it is considered to be a rare adverse effect (less than 1 death in 1 million doses sold). Given this rarity and the lack of information available to definitively determine the cause of death in these cases, no further action was warranted for this outcome. If concerns pertaining to serious adverse effects were identified in companion animals, Health Canada’s PMRA would take appropriate measures to mitigate this risk.

A statement warning of the risk of death to cats is currently required on all spot-on products containing permethrin. As per the Regulatory Directive DIR2010-02, Label Improvements for Spot-on Pesticides Used for Flea and Tick Control on Companion Animals, products containing permethrin must include a pictogram on the label of a cat’s silhouette within a red circle with a diagonal line through the picture of the cat; the words ‘Toxic to cats’ underneath the pictogram; and under Precautions, Pets: “Cats that actively groom or engage in close physical contact with recently treated dogs may be at risk of serious harm, including death.”

In addition, companion animal product labels also specify that the products not be used on sick animals. The Regulatory Directive DIR2002-01, Canadian Label Improvement Program for Pesticides Used on Companion Animals indicates that all labels must specify the statement “Consult a veterinarian before using on sick, aged, pregnant or nursing animals or animals receiving drug or other pesticide treatment.” Therefore, no additional label statements are needed at this time.

3.0 Comments related to the concomitant use of multiple pesticide products with a common active ingredient

Comments were received from registrants and interested non-governmental associations regarding the proposal to add label language to restrict the use of other flea control products with the same active ingredients as in the spot-on products. Comments indicated that such practices may be necessary in a flea, and tick management plan, and that any restrictions on the product label should be based on scientific evidence.

Health Canada’s PMRA Response:

Health Canada’s PMRA acknowledges that application of other types of products, including shampoos, powders and sprays may be a component of an integrated pest management program. Health Canada’s PMRA concurs that there can be value to, for example, first using products such as flea control shampoos and then following up with the application of a spot-on product if there is an insufficient response. Use of other flea control products, including those with the same pesticidal active ingredient, to use sites other than direct application to the animal (for example, the house, bedding) may be part of a pest management program and will not typically be contraindicated on spot-on products.

The proposed label statement restricting the use of additional products containing the same active ingredient on the treated animal is due to the concern with applying such products following the application of a spot-on product. While application of these types of products to the animal prior to use of a spot-on product may help with management of the pest problem, use of other products during the control period of a spot-on product should not be necessary, as spot-on products are expected to provide sufficient control of the pest when used according to label directions. In addition, such applications may result in the over-application of the same active ingredient, and in some cases may reduce the efficacy of the spot-on product (for example, the use of a shampoo following application of a spot-on).

For improved clarity, the required label statement for spot-on products will be amended from that proposed in the PRO2018-01 to “This product contains [name of active ingredient(s)]. Do not apply another pest control product such as a shampoo, collar, or powder that contains [name of active ingredient(s)] to the treated animal after applying [name of spot-on product]”. These statements may be modified on a case-by-case basis upon submission of scientific data generated to support the concomitant use of the multiple companion animal products in question, during the course of field safety and/or efficacy trials. Any supporting scientific data must be submitted to Health Canada’s PMRA as part of the application or amendment request. Alternatively, as with any data requirement, applicants and registrants may provide a scientifically sound justification in support of a data waiver request. Applicants are also encouraged to undertake a pre-submission consultation with Health Canada’s PMRA for specific recommendations on proposed study protocols prior to study conduct.

4.0 Comments related to re-application prior to end of effective control period

Comments were received from registrants and interested non-governmental associations regarding the proposal to remove label language that allows re-application of the product before the end of the effective control period. Comments indicated that reapplication may be necessary in scenarios such as during active flea infestations, with seasonal variations, or following frequent swimming or bathing. The comments indicated that any restrictions on the product label should be based on scientific evidence.

Health Canada PMRA Response:

Removal of label instructions regarding early re-application (prior to end of effective control period) is consistent with the Regulatory Directive DIR2002-01, Canadian Label Improvement Program for Pesticides Used on Companion Animals. This directive specifies that the minimum interval between applications “must not be shorter than that which would result in acceptable efficacy”. Current label statements do not provide clear direction on when early re-application may be required, and to-date, scientific data have not been submitted to support or justify existing label statements for early re-application. However, it may be possible to add label directions for shorter re-application intervals on a case-by-case basis, provided that the directions are supported by scientific data to justify when to reapply prior to the end of the complete control period. Any such directions must provide clear instruction on when re-application may be necessary. Any supporting scientific data must be submitted to Health Canada’s PMRA as part of the application or amendment request. Alternatively, as with any data requirement, applicants and registrants may provide a scientifically sound justification in support of a data waiver request. Applicants are also encouraged to undertake a pre-submission consultation with Health Canada’s PMRA for specific recommendations on proposed study protocols prior to study conduct.

Appendix II   Spot-on products that are registered in Canada, excluding discontinued products or products with a submission for discontinuation as of 31 December 2018, based upon Health Canada PMRA’s Electronic Pesticide Regulatory System (e-PRS) database.

Appendix II   Spot-on products that are registered in Canada, excluding discontinued products or products with a submission for discontinuation as of 31 December 2018, based upon Health Canada PMRA’s Electronic Pesticide Regulatory System (e-PRS) database.
PCP No. Product Name
25127 Advantage 55 Flea and Lice Adulticide For dogs 8 weeks and older weighing between 11 and 25 kg
25128 Advantage 9 Flea Adulticide For cats 8 weeks and older weighing 4 kg and under
25129 Advantage 18 Flea Adulticide For cats 8 weeks and older weighing over 4 kg
25130 Advantage 10 Flea and Lice Adulticide For dogs 8 weeks and older weighing 4.5 kg and under
25131 Advantage 100 Flea and Lice Adulticide For dogs 8 weeks and older weighing more than 25 kg
25132 Advantage 20 Flea and Lice Adulticide For dogs 8 weeks and older weighing between 4.6 and 11 kg
31307 Primidacide < 4 Kg
31308 Primidacide < 4.5 Kg
31309 Primidacide 4.6-11 Kg
31310 Primidacide > 4 kg
31311 Primidacide > 25 Kg
31312 Primidacide 11-25 Kg
31507 Barrier 9
31508 Barrier 10
31509 Barrier 18
31510 Barrier 55
31511 Barrier 100
31512 Barrier 20
31980 Zodiac Infestop Topical Solution For Cats 4 Kg And Under
31982 Zodiac Infestop Topical Solution For Dogs 4.5 Kg And Under
31983 Zodiac Infestop Topical Solution For Dogs Between 4.6 And 11 Kg
31984 Zodiac Infestop Topical Solution For Cats Over 4 Kg
31985 Zodiac Infestop Topical Solution For Dogs Over 25 Kg
31986 Zodiac Infestop Topical Solution For Dogs Between 11 And 25 Kg
32573 EctoShield Topical Solution Medium and Large Cat
32574 EctoShield Topical Solution Small Cat
32581 EctoShield Topical Solution Small Dog
32584 EctoShieldTopical Solution Extra Large Dog
32585 EctoShield Topical Solution Medium Dog
32590 EctoShield Topical Solution Large Dog
33173 Bugwacker Flea Protector 9
27658 K9 Advantix 10 Flea, Tick, Mosquito and Lice Adulticide
27659 K9 Advantix 100 Flea, Tick, Mosquito and Lice Adulticide
27660 K9 Advantix 55 Flea, Tick, Mosquito and Lice Adulticide
27661 K9 Advantix 20 Flea, Tick, Mosquito and Lice Adulticide
32567 Preventic Topical Solution Extra Large Dog
32586 Preventic Topical Solution Large Dog
32588 Preventic Topical Solution Medium Dog
32589 Preventic Topical Solution Small Dog
29777 K9 Advantix II small dog
29778 K9 Advantix II medium dog
29779 K9 Advantix II extra large dog
29780 K9 Advantix II large dog
27581 Advantage II small dog
27582 Advantage II large dog
27583 Advantage II medium dog
27584 Advantage II extra large dog
27585 Advantage II small cat
27586 Advantage II large cat
31517 Advantage II kitten
26496 Zodiac Spoton Flea Control For Cats & Kittens
26497 Vet Kem Ovispot Flea Control For Cats & Kittens
28743 Zodiac Spot On II Flea Control for CATS & KITTENS
29930 Hartz UltraGuard OneSpot Drops for Cats and Kittens
31368 Zodiac Spot On II with Smart Shield Flea Control for Cats & Kittens
32717 Hartz First Defense OneSpot Treatment for Cats and Kittens
33044 Hartz InControl OneSpot Drops for Cats and Kittens
26489 Hartz UltraGuard Plus Flea & Tick Drops for Dogs & Puppies Under 14 kg (30 lbs)
26490 Hartz UltraGuard Plus Flea & Tick Drops for Dogs & Puppies Over 14 kg (30 lbs)
26492 Vet-Kem OviSpotTM Plus Flea & Tick Control for Dogs Under 14 kg (30 lbs)
26493 Zodiac Powerspot Flea & Tick Control for Dogs Over 14 kg (30 lbs)
26494 Zodiac Powerspot Flea & Tick Control for Dogs Under 14 kg (30 lbs)
26495 Vet Kem OviSpotTM Plus For Dogs Over 14 kg (30 lbs)
29282 Hartz UltraGuard Pro Flea and Tick Drops for Dogs and Puppies Weighing over 14KG (30lbs)
29283 Hartz Ultraguard Pro Flea And Tick Drops For Dogs And Puppies Weighing Up To 14kg (30lbs)
31366 Zodiac PowerSpot with Smart Shield Flea & Tick Control for DOGS OVER 14 kg (30 lbs)
31367 Zodiac PowerSpot with Smart Shield Flea & Tick Control for DOGS UNDER 14 kg (30 lbs)
30728 Hartz UltraGuard Pro Flea & Tick Treatment for Dogs and Puppies weighing 6 to 14 kg
30729 Hartz Ultraguard Pro Flea & Tick Treatment For Dogs And Puppies Weighing 2.5 Kg To 6 Kg
30730 Hartz UltraGuard Pro Flea & Tick Treatment for Dogs and Puppies weighing 14 to 28 kg
30731 Hartz UltraGuard Pro Flea & Tick Treatment for Dogs and Puppies weighing greater than 28 kg
31005 Hartz UltraGuard PLUS Flea & Tick Treatment for Dogs and Puppies Weighing more than 28 kg
31006 Hartz UltraGuard Plus Flea & Tick Treatment for Dogs and Puppies weighing 2.5 to 6 kg
31007 Hartz UltraGuard Plus Flea & Tick Treatment for Dogs and Puppies weighing 6 to 14 kg
31008 Hartz UltraGuard Plus Flea & Tick Treatment for Dogs and Puppies weighing 14 to 28 kg
32708 Hartz First Defense Flea & Tick Treatment for Dogs and Puppies Weighing 2.5 to 6 kg
32710 Hartz First Defense Flea & Tick Treatment for Dogs and Puppies Weighing 6 to 14 kg
32713 Hartz First Defense Flea & Tick Treatment for Dogs and Puppies Weighing 14 to 28 kg
32716 Hartz First Defense Flea & Tick Treatment for Dogs and Puppies weighing greater than 28 kg
25922 Hartz UltraGuard Flea & Tick Drops for Dogs & Puppies Over 14 Kg (30 lbs)
25923 Hartz UltraGuard Flea & Tick Drops for Dogs & Puppies under 14 kg (30 lbs)
33073 Hartz InControl Flea & Tick Drops for Dogs and Puppies Weighing over 14KG (30lbs)
33074 Hartz InControl Flea & Tick Drops for Dogs and Puppies Weighing up to 14KG (30lbs)
28113 Seargeant’s PreTect Squeeze-On Flea, Tick & Mosquito Control For Dogs (up to 15 kg)
28280 Seargeant’s PreTect Squeeze-On Flea, Tick & Mosquito Control for Dogs (over 30 kg)
28281 Seargeant’s PreTect Squeeze-On Flea, Tick & Mosquito Control for Dogs (15-30 kg)
31609 Sentry Squeez-On Flea, Tick & Mosquito Control for Dogs (15-30 kg)
31610 Sentry Squeez-On Flea, Tick & Mosquito Control for Dogs (over 30 kg)
31611 Sentry Squeez-On Flea, Tick & Mosquito Control For Dogs (up to 15 kg)
32546 Seargeant’s Guardian Flea, Tick & Mosquito Control for Dogs (15 to 30 kg)
32548 Seargeant’s Guardian Flea, Tick & Mosquito Control for Dogs (over 30 kg)
32549 Seargeant’s Guardian Flea, Tick & Mosquito Control for Dogs (up to 15 kg)
30732 Hartz UltraGuard Flea & Tick Treatment for Dogs and Puppies weighing 2.5kg to 6 kg
30733 Hartz UltraGuard Flea & Tick Treatment for Dogs and Puppies weighing 6 kg to 14 kg
30734 Hartz UltraGuard Flea & Tick Treatment for Dogs and Puppies weighing 14 kg to 28 kg
30735 Hartz UltraGuard Flea & Tick Treatment for Dogs and Puppies weighing greater than 28 kg
33041 Hartz InControl Flea & Tick Treatment for Dogs and Puppies weighing 2.5 kg to 6 kg
33042 Hartz InControl Flea & Tick Treatment for Dogs and Puppies weighing 6 kg to 14 kg
33043 Hartz InControl Flea & Tick Treatment for Dogs and Puppies weighing greater than 28 kg
33045 Hartz InControl Flea & Tick Treatment for Dogs and Puppies weighing 14 kg to 28 kg
28610 Seargeant’s PreTect Squeeze-On Flea Control for Cats and Kittens
31608 Sentry Flea Squeeze-On For Cats And Kittens
32547 Seargeant’s Guardian Flea Control for Cats & Kittens
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