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               <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/>
               <text>
                  <paragraph>(spinosad + milbemycin oxime)</paragraph>
                  <paragraph>
                     <content styleCode="bold">Chewable Tablets</content>
                  </paragraph>
                  <paragraph>
                     <content styleCode="bold">Caution:</content> Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.</paragraph>
               </text>
               <effectiveTime value="20240610"/>
            </section>
         </component>
         <component>
            <section ID="s2">
               <id root="02b72677-340c-464a-8bb0-b49db53ff5db"/>
               <code code="34089-3" codeSystem="2.16.840.1.113883.6.1" displayName="DESCRIPTION SECTION"/>
               <title>Description: </title>
               <text>
                  <paragraph>TRIFEXIS (spinosad and milbemycin oxime) is available in five sizes for oral administration to dogs and puppies according to their weight. Each chewable flavored tablet is formulated to provide a minimum spinosad dose of 13.5 mg/lb (30 mg/kg) and a minimum milbemycin oxime dose of 0.2 mg/lb (0.5 mg/kg). Spinosad is a member of the spinosyns class of insecticides, which are non-antibacterial tetracyclic macrolides. Spinosad contains two major factors, spinosyn A and spinosyn D, derived from the naturally occurring bacterium, <content styleCode="italics">Saccharopolyspora spinosa</content>. Spinosyn A and spinosyn D have the chemical compositions C<sub>41</sub>H<sub>65</sub>NO<sub>10</sub> and C<sub>42</sub>H<sub>67</sub>NO<sub>10</sub>, respectively. Milbemycin oxime is a macrocyclic lactone anthelmintic, containing two major factors, A<sub>3</sub> and A<sub>4</sub> of milbemycin oxime. The approximate ratio of A<sub>3</sub>:A<sub>4</sub> is 20:80. Milbemycin A<sub>4</sub> 5-oxime has the chemical composition of C<sub>32</sub>H<sub>45</sub>NO<sub>7</sub> and milbemycin A<sub>3</sub> 5-oxime has the chemical composition of C<sub>31</sub>H<sub>43</sub>NO<sub>7</sub>.</paragraph>
               </text>
               <effectiveTime value="20240610"/>
            </section>
         </component>
         <component>
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               <title>Indications:</title>
               <text>
                  <paragraph>TRIFEXIS is indicated for the prevention of heartworm disease (<content styleCode="italics">Dirofilaria immitis</content>).</paragraph>
                  <paragraph>TRIFEXIS kills fleas and is indicated for the prevention and treatment of flea infestations (<content styleCode="italics">Ctenocephalides felis</content>), and the treatment and control of adult hookworm (<content styleCode="italics">Ancylostoma caninum</content>), adult roundworm (<content styleCode="italics">Toxocara canis</content> and <content styleCode="italics">Toxascaris leonina</content>) and adult whipworm (<content styleCode="italics">Trichuris vulpis</content>) infections in dogs and puppies 8 weeks of age or older and 5 pounds of body weight or greater.</paragraph>
               </text>
               <effectiveTime value="20240610"/>
            </section>
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               <code code="34068-7" codeSystem="2.16.840.1.113883.6.1" displayName="DOSAGE &amp; ADMINISTRATION SECTION"/>
               <title>Dosage and Administration:</title>
               <text>
                  <paragraph>TRIFEXIS is given orally, once a month at the minimum dosage of 13.5 mg/lb (30 mg/kg) spinosad and 0.2 mg/lb (0.5 mg/kg) milbemycin oxime body weight. For heartworm prevention, give once monthly for at least 3 months after exposure to mosquitoes (see <content styleCode="bold">
                        <linkHtml href="#s14">EFFECTIVENESS</linkHtml>
                     </content>).</paragraph>
                  <paragraph>
                     <content styleCode="italics">Dosage Schedule:</content>
                  </paragraph>
                  <table width="100%">
                     <col width="23%"/>
                     <col width="25%"/>
                     <col width="29%"/>
                     <col width="22%"/>
                     <tbody>
                        <tr>
                           <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top">
                              <paragraph>Body Weight </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule Toprule " valign="top">
                              <paragraph>Spinosad<br/>Per Tablet (mg) </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule Toprule " valign="top">
                              <paragraph>Milbemycin oxime<br/>Per Tablet (mg) </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule Toprule " valign="top">
                              <paragraph>Tablets<br/>Administered </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td align="center" styleCode="Rrule Lrule Botrule " valign="top">
                              <paragraph>5 to 10 lbs </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>140 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>2.3 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>One </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td align="center" styleCode="Rrule Lrule Botrule " valign="top">
                              <paragraph>10.1 to 20 lbs </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>270 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>4.5 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>One </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td align="center" styleCode="Rrule Lrule Botrule " valign="top">
                              <paragraph>20.1 to 40 lbs </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>560 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>9.3 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>One </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td align="center" styleCode="Rrule Lrule Botrule " valign="top">
                              <paragraph>40.1 to 60 lbs </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>810 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>13.5 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>One </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td align="center" styleCode="Rrule Lrule Botrule " valign="top">
                              <paragraph>60.1 to 120 lbs </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>1620 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>27 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>One </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td align="center" styleCode="Rrule Botrule Lrule " valign="top">
                              <paragraph>Over 120 lbs </paragraph>
                           </td>
                           <td align="center" colspan="3" styleCode="Rrule Botrule " valign="top">
                              <paragraph>Administer the appropriate combination of tablets </paragraph>
                           </td>
                        </tr>
                     </tbody>
                  </table>
                  <paragraph>Administer TRIFEXIS with food for maximum effectiveness. To ensure heartworm prevention, owners should observe the dog for one hour after dosing. If vomiting occurs within an hour of administration, redose with another full dose. If a dose is missed and a monthly interval between doses is exceeded, then immediate administration of TRIFEXIS with food and resumption of monthly dosing will minimize the opportunity for the development of adult heartworm infections and flea reinfestations.</paragraph>
               </text>
               <effectiveTime value="20240610"/>
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                     <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/>
                     <title>
                        <content styleCode="italics">Heartworm Prevention:</content>
                     </title>
                     <text>
                        <paragraph>TRIFEXIS should be administered at monthly intervals beginning within 1 month of the dog's first seasonal exposure and continuing until at least 3 months after the dog's last seasonal exposure to mosquitoes (see <content styleCode="bold">
                              <linkHtml href="#s14">EFFECTIVENESS</linkHtml>
                           </content>). TRIFEXIS may be administered year round without interruption. When replacing another heartworm preventative product, the first dose of TRIFEXIS should be given within a month of the last dose of the former medication.</paragraph>
                     </text>
                     <effectiveTime value="20240610"/>
                  </section>
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                     <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/>
                     <title>
                        <content styleCode="italics">Flea Treatment and Prevention:</content>
                     </title>
                     <text>
                        <paragraph>Treatment with TRIFEXIS may begin at any time of the year, preferably starting one month before fleas become active and continuing monthly through the end of flea season. In areas where fleas are common year-round, monthly treatment with TRIFEXIS should continue the entire year without interruption.</paragraph>
                        <paragraph>To minimize the likelihood of flea reinfestation, it is important to treat all animals within a household with an approved flea protection product.</paragraph>
                     </text>
                     <effectiveTime value="20240610"/>
                  </section>
               </component>
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                     <id root="51553c8f-bbf5-40b3-861b-482277ef35e0"/>
                     <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/>
                     <title>
                        <content styleCode="italics">Intestinal Nematode Treatment and Control:</content>
                     </title>
                     <text>
                        <paragraph>TRIFEXIS also provides treatment and control of roundworms (<content styleCode="italics">T. canis, T. leonina</content>), hookworms (<content styleCode="italics">A. caninum</content>) and whipworms (<content styleCode="italics">T. vulpis</content>). Dogs may be exposed to and can become infected with roundworms, whipworms and hookworms throughout the year, regardless of season or climate. Clients should be advised of measures to be taken to prevent reinfection with intestinal parasites. </paragraph>
                     </text>
                     <effectiveTime value="20240610"/>
                  </section>
               </component>
            </section>
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               <id root="13166438-0130-4f27-b251-a9fe534dc971"/>
               <code code="34070-3" codeSystem="2.16.840.1.113883.6.1" displayName="CONTRAINDICATIONS SECTION"/>
               <title>Contraindications:</title>
               <text>
                  <paragraph>There are no known contraindications to the use of TRIFEXIS. </paragraph>
               </text>
               <effectiveTime value="20240610"/>
            </section>
         </component>
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            <section ID="s9">
               <id root="a2fa6e04-9939-49b9-9957-733c66960456"/>
               <code code="34071-1" codeSystem="2.16.840.1.113883.6.1" displayName="WARNINGS SECTION"/>
               <title>Warnings:</title>
               <text>
                  <paragraph>Not for human use. Keep this and all drugs out of the reach of children. </paragraph>
                  <paragraph>Serious adverse reactions have been reported following concomitant extra-label use of ivermectin with spinosad alone, a component of TRIFEXIS (see <content styleCode="bold">
                        <linkHtml href="#s11">ADVERSE REACTIONS</linkHtml>
                     </content>). </paragraph>
               </text>
               <effectiveTime value="20240610"/>
            </section>
         </component>
         <component>
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               <code code="42232-9" codeSystem="2.16.840.1.113883.6.1" displayName="PRECAUTIONS SECTION"/>
               <title>Precautions:</title>
               <text>
                  <paragraph>Treatment with fewer than 3 monthly doses after the last exposure to mosquitoes may not provide complete heartworm prevention (see <content styleCode="bold">
                        <linkHtml href="#s14">EFFECTIVENESS</linkHtml>
                     </content>). </paragraph>
                  <paragraph>Prior to administration of TRIFEXIS, dogs should be tested for existing heartworm infection. At the discretion of the veterinarian, infected dogs should be treated with an adulticide to remove adult heartworms. TRIFEXIS is not effective against adult <content styleCode="italics">D. immitis</content>. While the number of circulating microfilariae may decrease following treatment, TRIFEXIS is not indicated for microfilariae clearance (see <content styleCode="bold">
                        <linkHtml href="#s18">ANIMAL SAFETY</linkHtml>
                     </content>).</paragraph>
                  <paragraph>Mild, transient hypersensitivity reactions manifested as labored respiration, vomiting, salivation and lethargy, have been noted in some dogs treated with milbemycin oxime carrying a high number of circulating microfilariae. These reactions are presumably caused by release of protein from dead or dying microfilariae.</paragraph>
                  <paragraph>Use with caution in breeding females (see <content styleCode="bold">
                        <linkHtml href="#s18">ANIMAL SAFETY</linkHtml>
                     </content>). The safe use of TRIFEXIS in breeding males has not been evaluated.</paragraph>
                  <paragraph>Use with caution in dogs with pre-existing epilepsy (see <content styleCode="bold">
                        <linkHtml href="#s11">ADVERSE REACTIONS</linkHtml>
                     </content>).</paragraph>
                  <paragraph>Puppies less than 14 weeks of age may experience a higher rate of vomiting (see <content styleCode="bold">
                        <linkHtml href="#s18">ANIMAL SAFETY</linkHtml>
                     </content>).</paragraph>
               </text>
               <effectiveTime value="20240610"/>
            </section>
         </component>
         <component>
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               <id root="79010862-3d84-4a4e-82d1-c57f445d558a"/>
               <code code="34084-4" codeSystem="2.16.840.1.113883.6.1" displayName="ADVERSE REACTIONS SECTION"/>
               <title>Adverse Reactions:</title>
               <text>
                  <paragraph>In a well-controlled US field study, which included a total of 352 dogs (176 treated with TRIFEXIS and 176 treated with an active control), no serious adverse reactions were attributed to administration of TRIFEXIS. All reactions were regarded as mild. </paragraph>
                  <paragraph>Over the 180-day study period, all observations of potential adverse reactions were recorded. Reactions that occurred at an incidence &gt;1% (average monthly rate) within any of the 6 months of observation are presented in the following table. The most frequently reported adverse reaction in dogs in the TRIFEXIS group was vomiting. </paragraph>
                  <paragraph>
                     <content styleCode="italics">Average Monthly Rate (%) of Dogs With Adverse Reactions</content>
                  </paragraph>
                  <table width="100%">
                     <col width="37%"/>
                     <col width="36%"/>
                     <col width="27%"/>
                     <tfoot>
                        <tr>
                           <td align="left" colspan="3" valign="top">
                              <sup>a</sup>n=176 dogs </td>
                        </tr>
                     </tfoot>
                     <tbody>
                        <tr>
                           <td styleCode="Rrule Botrule Lrule Toprule " valign="top">
                              <paragraph>
                                 <content styleCode="bold">Adverse Reaction</content>
                              </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule Toprule " valign="top">
                              <paragraph>
                                 <content styleCode="bold">TRIFEXIS Chewable</content>
                                 <br/>
                                 <content styleCode="bold">Tablets<sup>a</sup>
                                 </content>
                              </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule Toprule " valign="top">
                              <paragraph>
                                 <content styleCode="bold">Active Control</content>
                                 <br/>
                                 <content styleCode="bold">Tablets<sup>a</sup>
                                 </content>
                              </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td styleCode="Rrule Lrule Botrule " valign="top">
                              <paragraph>Vomiting </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>6.13 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>3.08 </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td styleCode="Rrule Lrule Botrule " valign="top">
                              <paragraph>Pruritus </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>4.00 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>4.91 </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td styleCode="Rrule Lrule Botrule " valign="top">
                              <paragraph>Lethargy </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>2.63 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>1.54 </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td styleCode="Rrule Lrule Botrule " valign="top">
                              <paragraph>Diarrhea </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>2.25 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>1.54 </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td styleCode="Rrule Lrule Botrule " valign="top">
                              <paragraph>Dermatitis </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>1.47 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>1.45 </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td styleCode="Rrule Lrule Botrule " valign="top">
                              <paragraph>Skin Reddening </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>1.37 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>1.26 </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td styleCode="Rrule Lrule Botrule " valign="top">
                              <paragraph>Decreased appetite </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>1.27 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>1.35 </paragraph>
                           </td>
                        </tr>
                        <tr>
                           <td styleCode="Rrule Botrule Lrule " valign="top">
                              <paragraph>Pinnal Reddening </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>1.18 </paragraph>
                           </td>
                           <td align="center" styleCode="Rrule Botrule " valign="top">
                              <paragraph>0.87 </paragraph>
                           </td>
                        </tr>
                     </tbody>
                  </table>
                  <paragraph>In the US field study, one dog administered TRIFEXIS experienced a single mild seizure 2 ½ hours after receiving the second monthly dose. The dog remained enrolled and received four additional monthly doses after the event and completed the study without further incident. </paragraph>
                  <paragraph>Following concomitant extra-label use of ivermectin with spinosad alone, a component of TRIFEXIS, some dogs have experienced the following clinical signs: <content styleCode="italics">trembling/twitching, salivation/drooling, seizures, ataxia, mydriasis, blindness and disorientation</content>. Spinosad alone has been shown to be safe when administered concurrently with heartworm preventatives at label directions. </paragraph>
                  <paragraph>In US and European field studies, no dogs experienced seizures when dosed with spinosad alone at the therapeutic dose range of 13.5-27.3 mg/lb (30-60 mg/kg), including 4 dogs with pre-existing epilepsy. Four epileptic dogs that received higher than the maximum recommended dose of 27.3 mg/lb (60 mg/kg) experienced at least one seizure within the week following the second dose of spinosad, but no seizures following the first and third doses. The cause of the seizures observed in the field studies could not be determined. </paragraph>
                  <paragraph>For technical assistance or to report suspected adverse drug events, contact 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 </paragraph>
               </text>
               <effectiveTime value="20240610"/>
            </section>
         </component>
         <component>
            <section ID="s12">
               <id root="3769417a-3690-41f9-af13-56eb2b4463a7"/>
               <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/>
               <title>Post Approval Experience (Mar 2012): </title>
               <text>
                  <paragraph>The following adverse reactions are based on post-approval adverse drug event reporting. The adverse reactions are listed in decreasing order of frequency: vomiting, depression/lethargy, pruritus, anorexia, diarrhea, trembling/shaking, ataxia, seizures, hypersalivation, and skin reddening. </paragraph>
               </text>
               <effectiveTime value="20240610"/>
            </section>
         </component>
         <component>
            <section ID="s13">
               <id root="9da68bd0-22c9-4088-89ca-8acc63016932"/>
               <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/>
               <title>Mode of Action: </title>
               <text>
                  <paragraph>The primary target of action of spinosad, a component of TRIFEXIS, is an activation of nicotinic acetylcholine receptors (nAChRs) in insects. Spinosad does not interact with known insecticidal binding sites of other nicotinic or GABAergic insecticides such as neonicotinoids, fiproles, milbemycins, avermectins and cyclodienes. Insects treated with spinosad show involuntary muscle contractions and tremors resulting from activation of motor neurons. Prolonged spinosad-induced hyperexcitation results in prostration, paralysis and flea death. The selective toxicity of spinosad between insects and vertebrates may be conferred by the differential sensitivity of the insect versus vertebrate nAChRs. </paragraph>
                  <paragraph>Milbemycin oxime, a component of TRIFEXIS, acts by binding to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells. Increased permeability by the cell membrane to chloride ions causes hyperpolarization of affected cells and subsequent paralysis and death of the intended parasites. Milbemycin oxime may also act by disrupting the transmission of invertebrate neurotransmitters, notably gamma amino butyric acid (GABA). </paragraph>
               </text>
               <effectiveTime value="20240610"/>
            </section>
         </component>
         <component>
            <section ID="s14">
               <id root="c7a5e731-a425-4f2b-a8f8-12718b03ee96"/>
               <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/>
               <title>Effectiveness: </title>
               <text>
                  <paragraph>
                     <content styleCode="italics">Heartworm Prevention:</content>
                  </paragraph>
                  <paragraph>In a well-controlled laboratory study, TRIFEXIS was 100% effective against induced heartworm infections when administered for 3 consecutive monthly doses. </paragraph>
                  <paragraph>Two consecutive monthly doses did not provide 100% effectiveness against heartworm infection. In another well-controlled laboratory study, a single dose of TRIFEXIS was 100% effective against induced heartworm infections. </paragraph>
                  <paragraph>In a well-controlled six-month US field study conducted with TRIFEXIS, no dogs were positive for heartworm infection as determined by heartworm antigen testing performed at the end of the study and again three months later.</paragraph>
                  <paragraph>
                     <content styleCode="italics">Flea Treatment and Prevention:</content>
                  </paragraph>
                  <paragraph>In a well-controlled laboratory study, TRIFEXIS demonstrated 100% effectiveness on the first day following treatment and 100% effectiveness on Day 30. In a well-controlled laboratory study, spinosad, a component of TRIFEXIS, began to kill fleas 30 minutes after administration and demonstrated 100% effectiveness within 4 hours. Spinosad, a component of TRIFEXIS, kills fleas before they can lay eggs. If a severe environmental infestation exists, fleas may persist for a period of time after dose administration due to the emergence of adult fleas from pupae already in the environment. In field studies conducted in households with existing flea infestations of varying severity, flea reductions of 98.0% to 99.8% were observed over the course of 3 monthly treatments with spinosad alone. Dogs with signs of flea allergy dermatitis showed improvement in erythema, papules, scaling, alopecia, dermatitis/pyodermatitis and pruritus as a direct result of eliminating the fleas. </paragraph>
                  <paragraph>
                     <content styleCode="italics">Treatment and Control of Intestinal Nematode Infections:</content>
                  </paragraph>
                  <paragraph>In well-controlled laboratory studies, TRIFEXIS was ≥ 90% effective in removing naturally and experimentally induced adult roundworm, whipworm and hookworm infections. </paragraph>
                  <paragraph>
                     <content styleCode="italics">Palatability:</content>
                  </paragraph>
                  <paragraph>TRIFEXIS is a flavored chewable tablet. In a field study of client-owned dogs where 175 dogs were each offered TRIFEXIS once a month for 6 months, dogs voluntarily consumed 54% of the doses when offered plain as if a treat, and 33% of the doses when offered in or on food. The remaining 13% of doses were administered like other tablet medications. </paragraph>
               </text>
               <effectiveTime value="20240610"/>
            </section>
         </component>
         <component>
            <section ID="s18">
               <id root="c8960a3b-9523-43bd-89ed-9eccbc51eb8c"/>
               <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/>
               <title>Animal Safety: </title>
               <text>
                  <paragraph>TRIFEXIS was tested in pure and mixed breeds of healthy dogs in well-controlled clinical and laboratory studies. No dogs were withdrawn from the field studies due to treatment- related adverse reactions. </paragraph>
                  <paragraph>In a margin of safety study, TRIFEXIS was administered orally to 8-week-old Beagle puppies at doses of 1, 3, and 5 times the upper half of the therapeutic dose band, every 28 days for 6 dosing periods. Vomiting was seen in all groups including control animals with similar frequency. Adverse reactions seen during the course of the study were salivation, tremors, decreased activity, coughing and vocalization. </paragraph>
                  <paragraph>Body weights were similar between control and treated groups throughout the study. Treatment with TRIFEXIS was not associated with any clinically significant hematology, clinical chemistry or gross necropsy changes. One 5X dog had minimal glomerular lipidosis observed microscopically. The clinical relevance of this finding is unknown. </paragraph>
                  <paragraph>Plasma spinosyn A, spinosyn D, milbemycin A<sub>3</sub> 5-oxime and milbemycin A<sub>4</sub> 5-oxime concentrations increased throughout the study. At each dosing period, plasma spinosyn A and spinosyn D concentrations were greater than proportional across the dose range 1 to 5X. Plasma milbemycin A<sub>4</sub> 5-oxime concentrations appeared to be dose proportional across range 1 to 5X by the end of the study. Plasma concentrations of spinosad and milbemycin oxime indicate that expected systemic exposures were achieved throughout the study. </paragraph>
                  <paragraph>In an avermectin-sensitive Collie dog study, TRIFEXIS was administered orally at 1, 3, and 5 times the upper half of the recommended therapeutic dose band every 28 days. No signs of avermectin sensitivity were observed after administration of TRIFEXIS during the study period to avermectin-sensitive Collie dogs. The adverse reactions observed in the treatment groups were vomiting and diarrhea. Body weights in all treatment groups were comparable to the control group. Hematology and clinical chemistry parameters showed no clinically significant changes from study start to end, and all dogs were considered healthy throughout the study. </paragraph>
                  <paragraph>In a heartworm positive safety study, TRIFEXIS was administered orally at 1, 3, and 5 times the upper half of the therapeutic dose band to Beagle dogs with adult heartworm infections and circulating microfilariae, every 28 days for 3 treatments. Vomiting was observed in one dog in the 1X group, in three dogs in the 3X group, and in one dog in the 5X group. All but one incident of vomiting was observed on the treatment day during the first treatment cycle. The vomiting was mild and self-limiting. Hypersensitivity reactions were not observed in any of the treatment groups. Microfilariae counts decreased with treatment. </paragraph>
                  <paragraph>In a reproductive safety study, TRIFEXIS was administered orally to female dogs at 1 and 3 times the upper half of the therapeutic dose band every 28 days prior to mating, during gestation and during a six-week lactation period. Dogs with confirmed fetal heartbeats on ultrasound examination were evaluated for reproductive safety. One 3X and one 1X group female did not become pregnant. No treatment-related adverse reactions or signs of avermectin toxicosis were noted for adult females. Adult females in the 3X group lost weight during the 6-week pre-mating period, while control group females gained weight during that time. The body weights of the treated groups were comparable to the control group during gestation and post-parturition phases of the study. Gestation length, litter average body weight, litter size, stillborn pups, pup survival and the proportion of pups with malformations were comparable between treated and control dam groups. Malformations in the 1X group included a pup with cleft palate and a littermate with anophthalmia, fused single nares, misshapen palate, hydrocephalus, omphalocele and malpositioned testes; a pup with a malformation of the anterior tip of the urinary bladder and umbilical blood vessel; and a pup with patent ductus arteriosus (PDA). Malformations in the 3X group included three littermates with PDA. Malformations in the control group included a pup with a malformed sternum and a pup with PDA and a malpositioned superior vena cava. Clinical findings in pups of the treated groups were comparable to the control group except for one 1X group pup that was smaller and less coordinated than its littermates and had tremors when excited. The relationship between spinosad and milbemycin oxime treatment and the 1X and 3X dogs that did not become pregnant, the specific pup malformations and the unthrifty 1X group pup are unknown. The incidence of cleft palate is not unexpected based on the historical data collected at the breeding site. </paragraph>
                  <paragraph>In a margin of safety study with spinosad alone, 6-week old Beagle puppies were administered average doses of 1.5, 4.4, and 7.4 times the maximum recommended dose at 28-day intervals over a 6-month period. Vomiting was observed across all treatments, including controls, and was observed at an increased rate at elevated doses. Vomiting most often occurred 1 hour following administration and decreased over time and stabilized when puppies reached 14 weeks of age. </paragraph>
               </text>
               <effectiveTime value="20240610"/>
            </section>
         </component>
         <component>
            <section ID="s19">
               <id root="aeb9c005-3234-4739-8ebe-77fe71062534"/>
               <code code="44425-7" codeSystem="2.16.840.1.113883.6.1" displayName="STORAGE AND HANDLING SECTION"/>
               <title>Storage Information: </title>
               <text>
                  <paragraph>Store at 20-25°C (68-77°F), excursions permitted between 15-30°C (59-86°F). </paragraph>
               </text>
               <effectiveTime value="20240610"/>
            </section>
         </component>
         <component>
            <section ID="s20">
               <id root="6d466b9c-4560-4232-95ed-16dc852aa770"/>
               <code code="34069-5" codeSystem="2.16.840.1.113883.6.1" displayName="HOW SUPPLIED SECTION"/>
               <title>How Supplied: </title>
               <text>
                  <paragraph>TRIFEXIS is available in five tablet sizes. Each tablet size is available in color-coded packages of 6 tablets. </paragraph>
                  <paragraph>5-10 lbs (140 mg spinosad and 2.3 mg milbemycin oxime) </paragraph>
                  <paragraph>10.1-20 lbs (270 mg spinosad and 4.5 mg milbemycin oxime) </paragraph>
                  <paragraph>20.1-40 lbs (560 mg spinosad and 9.3 mg milbemycin oxime) </paragraph>
                  <paragraph>40.1-60 lbs (810 mg spinosad and 13.5 mg milbemycin oxime) </paragraph>
                  <paragraph>60.1-120 lbs (1620 mg spinosad and 27 mg milbemycin oxime) </paragraph>
                  <paragraph>Approved by FDA under NADA # 141-321 </paragraph>
                  <paragraph>Manufactured for: <br/>Elanco US Inc.<br/>Greenfield, IN 46140 </paragraph>
                  <paragraph>www.trifexis.com </paragraph>
                  <paragraph>Trifexis, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates. </paragraph>
                  <paragraph>CA4332 </paragraph>
                  <paragraph>CA4333 </paragraph>
                  <paragraph>CA4334 </paragraph>
                  <paragraph>CA4335 </paragraph>
                  <paragraph>CA4336 </paragraph>
                  <paragraph>Revised:  July 2024 </paragraph>
                  <paragraph>
                     <content styleCode="bold">
                        <content styleCode="italics">Elanco</content>
                     </content>™ </paragraph>
               </text>
               <effectiveTime value="20241001"/>
            </section>
         </component>
         <component>
            <section ID="s21">
               <id root="84f3724c-39bf-452b-bf94-d06ee007f875"/>
               <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/>
               <title>Information for Dog Owners </title>
               <text>
                  <paragraph>Your veterinarian has chosen to prescribe TRIFEXIS Chewable Tablets for the prevention of heartworm disease (<content styleCode="italics">Dirofilaria immitis</content>), to kill fleas and for the prevention and treatment of flea infestations (<content styleCode="italics">Ctenocephalides felis</content>), and the treatment and control of adult hookworm (<content styleCode="italics">Ancylostoma caninum</content>), adult roundworm (<content styleCode="italics">Toxocara canis</content> and <content styleCode="italics">Toxascaris leonina</content>) and adult whipworm (<content styleCode="italics">Trichuris vulpis</content>) infections in dogs and puppies 8 weeks of age or older and 5 pounds of body weight or greater. Controlling these parasites is very important to the health of your dog. Please read this leaflet, which describes the proper use of TRIFEXIS. If you have any questions about this information, please consult your veterinarian. Additional information can be found at www.trifexis.com. </paragraph>
                  <paragraph>
                     <content styleCode="bold">What is TRIFEXIS?</content>
                  </paragraph>
                  <paragraph>TRIFEXIS is a chewable, flavored tablet that you give orally to your dog once-a-month to kill fleas, to prevent flea infestations, to treat and control hookworms, whipworms and roundworms, and to prevent heartworm disease. TRIFEXIS is for monthly use in dogs and puppies 8 weeks of age or older and 5 pounds of body weight or greater. If you do not administer TRIFEXIS monthly throughout the year, the final dose must be given no fewer than three months following the last exposure to mosquitoes. </paragraph>
                  <paragraph>
                     <content styleCode="bold">Why has my veterinarian prescribed TRIFEXIS?</content>
                  </paragraph>
                  <paragraph>Your veterinarian has prescribed TRIFEXIS as a way of preventing your dog from developing problems caused by infection with three commonly occurring parasite categories. <content styleCode="bold">Heartworm infection</content> can make dogs very sick and can even be fatal. This parasite is spread to dogs by mosquitoes. TRIFEXIS can prevent <content styleCode="bold">flea infestations</content> from becoming established, and can also remove any fleas that are on your dog at the time of treatment. TRIFEXIS will also treat and control common adult <content styleCode="bold">intestinal worm infections</content> (roundworms, hookworms and whipworms). </paragraph>
                  <paragraph>
                     <content styleCode="bold">Should I give TRIFEXIS each month all year round?</content>
                  </paragraph>
                  <paragraph>Consult your veterinarian regarding the need for year round use of TRIFEXIS. If you do not administer TRIFEXIS monthly throughout the year, the final dose must be given no fewer than three months following the last exposure to mosquitoes. </paragraph>
                  <paragraph>
                     <content styleCode="bold">Will TRIFEXIS kill heartworms?</content>
                  </paragraph>
                  <paragraph>TRIFEXIS prevents heartworm disease by killing certain stages that develop after an infected mosquito bites a dog. As with other heartworm preventatives, TRIFEXIS does not kill adult heartworms. Speak to your veterinarian about treatment options if your dog is diagnosed with an adult heartworm infection. </paragraph>
                  <paragraph>
                     <content styleCode="bold">Will my dog still need to be tested for heartworm infection while taking TRIFEXIS?</content>
                  </paragraph>
                  <paragraph>You should speak to your veterinarian about the frequency of heartworm testing while your dog is taking TRIFEXIS. </paragraph>
                  <paragraph>
                     <content styleCode="bold">How do I switch to TRIFEXIS from another heartworm preventative?</content>
                  </paragraph>
                  <paragraph>Follow the advice of your veterinarian about switching heartworm preventatives. </paragraph>
                  <paragraph>
                     <content styleCode="bold">What should I discuss with my veterinarian regarding TRIFEXIS for my dog?</content>
                  </paragraph>
                  <paragraph>Your veterinarian is your dog's healthcare expert and can make the best recommendation for medications for your dog. This includes the prevention, control and/or treatment of parasites such as fleas, heartworms and intestinal parasites that may cause conditions that include flea allergy dermatitis, anemia and heart disease. Key points of your discussion may include the following: </paragraph>
                  <list listType="unordered">
                     <item>
                        <caption>•</caption>As with other heartworm preventatives, dogs should be tested for heartworm prior to beginning treatment with TRIFEXIS. </item>
                     <item>
                        <caption>•</caption>If a dose is missed and a monthly interval between doses is exceeded, then immediately give TRIFEXIS with food and resume monthly dosing. This practice will minimize the opportunity for heartworms to grow. Also, continuing normal monthly dosing will allow you to gain control of any flea or intestinal parasites that might have infected your dog. </item>
                     <item>
                        <caption>•</caption>To minimize the likelihood of fleas continuing to jump onto your dog, it is important to treat all household pets with an approved flea protection product. </item>
                     <item>
                        <caption>•</caption>TRIFEXIS is not for use in humans. Like all medications, keep TRIFEXIS out of reach of children. </item>
                  </list>
                  <paragraph>
                     <content styleCode="bold">How should I give TRIFEXIS to my dog?</content>
                  </paragraph>
                  <paragraph>Give TRIFEXIS with food for maximum effectiveness. TRIFEXIS is a chewable tablet and may be offered as a treat. Consult your veterinarian regarding the need for year round administration of TRIFEXIS. </paragraph>
                  <paragraph>
                     <content styleCode="bold">What if I give more than the prescribed amount of TRIFEXIS to my dog?</content>
                  </paragraph>
                  <paragraph>Contact your veterinarian as soon as possible if you believe your dog has ingested more than the recommended dose of TRIFEXIS. In a study in which dogs were dosed at 1, 3, and 5 times the upper half of the recommended dose, dogs exhibited vomiting, tremors, decreased activity, salivation, coughing and vocalization. </paragraph>
                  <paragraph>
                     <content styleCode="bold">Should I restrict either my dog's activity or contact with my dog after the tablet is consumed?</content>
                  </paragraph>
                  <paragraph>Since TRIFEXIS is an oral formulation, you may maintain normal activities and interactions with your dog. </paragraph>
                  <paragraph>
                     <content styleCode="bold">How quickly will TRIFEXIS kill fleas?</content>
                  </paragraph>
                  <paragraph>In a laboratory study of spinosad alone, an active ingredient of TRIFEXIS, spinosad started to kill fleas within 30 minutes and killed 100% of the fleas within 4 hours. TRIFEXIS kills fleas before they can lay eggs. </paragraph>
                  <paragraph>
                     <content styleCode="bold">Does seeing fleas on my dog mean that the treatment is not working?</content>
                  </paragraph>
                  <paragraph>TRIFEXIS kills fleas before they can lay eggs when used monthly according to the label directions. Remember that all animals in the household should be treated with an approved flea product to help control the flea population. </paragraph>
                  <paragraph>Your dog can continue to be exposed to the fleas that live in the environment. When fleas jump onto your dog, they will be killed by TRIFEXIS. </paragraph>
                  <paragraph>If within a month after your dog receives TRIFEXIS you see fleas on your dog, it is most likely that these are new fleas. These new fleas will be killed before they can produce eggs that contaminate the environment. Continued monthly use of TRIFEXIS can prevent any new infestations. </paragraph>
                  <paragraph>
                     <content styleCode="bold">What if I see worms in my dog's stool during the month after administration of TRIFEXIS?</content>
                  </paragraph>
                  <paragraph>TRIFEXIS is indicated to treat and control intestinal parasite infections of adult hookworms, roundworms and whipworms. In occasional cases, it is possible that the action of TRIFEXIS in killing the intestinal worms will lead to the dog expelling them in the stool. If you have questions, consult with your veterinarian for measures you can take to prevent a reinfection with intestinal parasites. </paragraph>
                  <paragraph>
                     <content styleCode="bold">Is it safe to give my dog TRIFEXIS?</content>
                  </paragraph>
                  <paragraph>TRIFEXIS has been demonstrated to be safe in pure and mixed breeds of healthy dogs when used according to label directions for dogs and puppies 8 weeks of age and older and five pounds of body weight or greater. You should discuss the use of TRIFEXIS with your veterinarian prior to use if your dog has a history of epilepsy (seizures). Puppies less than 14 weeks of age may experience a higher rate of vomiting. </paragraph>
                  <paragraph>
                     <content styleCode="bold">Is it safe to give my breeding dogs TRIFEXIS?</content>
                  </paragraph>
                  <paragraph>Ask your veterinarian about the use of TRIFEXIS prior to use in breeding females. The safe use of TRIFEXIS in male dogs intended for breeding has not been evaluated. </paragraph>
                  <paragraph>
                     <content styleCode="bold">What side effects might occur with TRIFEXIS?</content>
                  </paragraph>
                  <paragraph>Like all medications, sometimes side effects may occur. In some cases, dogs vomited after receiving TRIFEXIS. To ensure heartworm prevention, observe your dog for one hour after administration. If vomiting occurs within an hour of administration, redose with another full dose. </paragraph>
                  <paragraph>During field studies, no severe or prolonged vomiting occurred. </paragraph>
                  <paragraph>Additional adverse reactions observed in the clinical studies were itching, decreased activity, diarrhea, inflammation of the skin, redness of the skin, decreased appetite and redness of the ear. All reactions were regarded as mild. </paragraph>
                  <paragraph>Since the introduction of TRIFEXIS, additional side effects reported are trembling/shaking, ataxia, seizures and hypersalivation. </paragraph>
                  <paragraph>For technical assistance or to report suspected adverse drug events, contact 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 </paragraph>
                  <paragraph>
                     <content styleCode="bold">Can other medications be given while my dog is taking TRIFEXIS?</content>
                  </paragraph>
                  <paragraph>Yes, TRIFEXIS has been given safely with a wide variety of products and medications. Your veterinarian should be made aware of all products that you administered and/or intend to administer to your dog. </paragraph>
                  <paragraph>
                     <content styleCode="bold">How should TRIFEXIS be stored?</content>
                  </paragraph>
                  <paragraph>Store at 68-77°F (20-25°C). Temporary periods of time outside this range between 59-86°F (15 -30°C) are permitted. </paragraph>
                  <paragraph>www.trifexis.com </paragraph>
                  <paragraph>Trifexis, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates. </paragraph>
                  <paragraph>© 2024 Elanco or its affiliates</paragraph>
                  <paragraph>PA104092X </paragraph>
                  <paragraph>
                     <content styleCode="bold">
                        <content styleCode="italics">Elanco™</content>
                     </content>
                  </paragraph>
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               <title>Principal Display Panel - Trifexis 140 mg Carton Label </title>
               <text>
                  <paragraph>
                     <content styleCode="bold">Trifexis</content>™ </paragraph>
                  <paragraph>
                     <content styleCode="bold">(spinosad + milbemycin oxime)</content>
                  </paragraph>
                  <paragraph>FOR DOGS<br/>5-10 lbs </paragraph>
                  <paragraph>
                     <content styleCode="bold">6</content>
                     <br/>
                     <content styleCode="bold">CHEWABLE</content>
                     <br/>
                     <content styleCode="bold">TABLETS</content>
                  </paragraph>
                  <paragraph>140 mg spinosad/<br/>2.3 mg milbemycin oxime </paragraph>
                  <paragraph>
                     <content styleCode="bold">CAUTION:</content> Federal (USA) law restricts this drug to<br/>use by or on the order of a licensed veterinarian. </paragraph>
                  <paragraph>Prevents<br/>
                     <content styleCode="bold">HEARTWORM</content> Disease </paragraph>
                  <paragraph>Kills<br/>
                     <content styleCode="bold">FLEAS</content> &amp; Prevents Infestations </paragraph>
                  <paragraph>Treats and Controls<br/>
                     <content styleCode="bold">INTESTINAL WORMS</content>
                  </paragraph>
                  <paragraph>Adult Hookworm, Roundworm, and Whipworm </paragraph>
                  <paragraph>
                     <content styleCode="bold">For use in dogs and puppies 8 weeks of age</content>
                     <br/>
                     <content styleCode="bold">and older and 5 lbs of body weight or greater</content>
                  </paragraph>
                  <paragraph>
                     <content styleCode="bold">STARTS</content>
                     <br/>Killing Fleas<br/>in 30 mins. </paragraph>
                  <paragraph>
                     <content styleCode="bold">MONTHLY</content>
                     <br/>Use </paragraph>
                  <paragraph>
                     <content styleCode="bold">GIVE WITH</content>
                     <br/>A Meal </paragraph>
                  <paragraph>
                     <content styleCode="bold">
                        <content styleCode="italics">Elanco</content>
                     </content>™ </paragraph>
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               <title>Principal Display Panel - Trifexis 270 mg Carton Label </title>
               <text>
                  <paragraph>
                     <content styleCode="bold">Trifexis</content>™ </paragraph>
                  <paragraph>
                     <content styleCode="bold">(spinosad + milbemycin oxime)</content>
                  </paragraph>
                  <paragraph>FOR DOGS<br/>10.1-20 lbs </paragraph>
                  <paragraph>
                     <content styleCode="bold">6</content>
                     <br/>
                     <content styleCode="bold">CHEWABLE</content>
                     <br/>
                     <content styleCode="bold">TABLETS</content>
                  </paragraph>
                  <paragraph>270 mg spinosad/<br/>4.5 mg milbemycin oxime </paragraph>
                  <paragraph>
                     <content styleCode="bold">CAUTION:</content> Federal (USA) law restricts this drug to<br/>use by or on the order of a licensed veterinarian. </paragraph>
                  <paragraph>Prevents<br/>
                     <content styleCode="bold">HEARTWORM</content> Disease </paragraph>
                  <paragraph>Kills<br/>
                     <content styleCode="bold">FLEAS</content> &amp; Prevents Infestations </paragraph>
                  <paragraph>Treats and Controls<br/>
                     <content styleCode="bold">INTESTINAL WORMS</content>
                  </paragraph>
                  <paragraph>Adult Hookworm, Roundworm, and Whipworm </paragraph>
                  <paragraph>
                     <content styleCode="bold">For use in dogs and puppies 8 weeks of age</content>
                     <br/>
                     <content styleCode="bold">and older and 5 lbs of body weight or greater</content>
                  </paragraph>
                  <paragraph>
                     <content styleCode="bold">STARTS</content>
                     <br/>Killing Fleas<br/>in 30 mins. </paragraph>
                  <paragraph>
                     <content styleCode="bold">MONTHLY</content>
                     <br/>Use </paragraph>
                  <paragraph>
                     <content styleCode="bold">GIVE WITH</content>
                     <br/>A Meal </paragraph>
                  <paragraph>
                     <content styleCode="bold">
                        <content styleCode="italics">Elanco</content>
                     </content>™ </paragraph>
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               <effectiveTime value="20241001"/>
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                     <text>Figure</text>
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                        <reference value="tri0m-0005-02.jpg"/>
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               <title>Principal Display Panel - Trifexis 560 mg Carton Label </title>
               <text>
                  <paragraph>
                     <content styleCode="bold">Trifexis</content>™ </paragraph>
                  <paragraph>
                     <content styleCode="bold">(spinosad + milbemycin oxime)</content>
                  </paragraph>
                  <paragraph>FOR DOGS<br/>20.1-40 lbs </paragraph>
                  <paragraph>
                     <content styleCode="bold">6</content>
                     <br/>
                     <content styleCode="bold">CHEWABLE</content>
                     <br/>
                     <content styleCode="bold">TABLETS</content>
                  </paragraph>
                  <paragraph>560 mg spinosad/<br/>9.3 mg milbemycin oxime </paragraph>
                  <paragraph>
                     <content styleCode="bold">CAUTION:</content> Federal (USA) law restricts this drug to<br/>use by or on the order of a licensed veterinarian. </paragraph>
                  <paragraph>Prevents<br/>
                     <content styleCode="bold">HEARTWORM</content> Disease </paragraph>
                  <paragraph>Kills<br/>
                     <content styleCode="bold">FLEAS</content> &amp; Prevents Infestations </paragraph>
                  <paragraph>Treats and Controls<br/>
                     <content styleCode="bold">INTESTINAL WORMS</content>
                  </paragraph>
                  <paragraph>Adult Hookworm, Roundworm, and Whipworm </paragraph>
                  <paragraph>
                     <content styleCode="bold">For use in dogs and puppies 8 weeks of age</content>
                     <br/>
                     <content styleCode="bold">and older and 5 lbs of body weight or greater</content>
                  </paragraph>
                  <paragraph>
                     <content styleCode="bold">STARTS</content>
                     <br/>Killing Fleas<br/>in 30 mins. </paragraph>
                  <paragraph>
                     <content styleCode="bold">MONTHLY</content>
                     <br/>Use </paragraph>
                  <paragraph>
                     <content styleCode="bold">GIVE WITH</content>
                     <br/>A Meal </paragraph>
                  <paragraph>
                     <content styleCode="bold">
                        <content styleCode="italics">Elanco</content>
                     </content>™ </paragraph>
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               <effectiveTime value="20241001"/>
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                     <text>Figure</text>
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               <title>Principal Display Panel - Trifexis 810 mg Carton Label </title>
               <text>
                  <paragraph>
                     <content styleCode="bold">Trifexis</content>™ </paragraph>
                  <paragraph>
                     <content styleCode="bold">(spinosad + milbemycin oxime)</content>
                  </paragraph>
                  <paragraph>FOR DOGS<br/>40.1-60 lbs </paragraph>
                  <paragraph>
                     <content styleCode="bold">6</content>
                     <br/>
                     <content styleCode="bold">CHEWABLE</content>
                     <br/>
                     <content styleCode="bold">TABLETS</content>
                  </paragraph>
                  <paragraph>810 mg spinosad/<br/>13.5 mg milbemycin oxime </paragraph>
                  <paragraph>
                     <content styleCode="bold">CAUTION:</content> Federal (USA) law restricts this drug to<br/>use by or on the order of a licensed veterinarian. </paragraph>
                  <paragraph>Prevents<br/>
                     <content styleCode="bold">HEARTWORM</content> Disease </paragraph>
                  <paragraph>Kills<br/>
                     <content styleCode="bold">FLEAS</content> &amp; Prevents Infestations </paragraph>
                  <paragraph>Treats and Controls<br/>
                     <content styleCode="bold">INTESTINAL WORMS</content>
                  </paragraph>
                  <paragraph>Adult Hookworm, Roundworm, and Whipworm </paragraph>
                  <paragraph>
                     <content styleCode="bold">For use in dogs and puppies 8 weeks of age</content>
                     <br/>
                     <content styleCode="bold">and older and 5 lbs of body weight or greater</content>
                  </paragraph>
                  <paragraph>
                     <content styleCode="bold">STARTS</content>
                     <br/>Killing Fleas<br/>in 30 mins. </paragraph>
                  <paragraph>
                     <content styleCode="bold">MONTHLY</content>
                     <br/>Use </paragraph>
                  <paragraph>
                     <content styleCode="bold">GIVE WITH</content>
                     <br/>A Meal </paragraph>
                  <paragraph>
                     <content styleCode="bold">
                        <content styleCode="italics">Elanco</content>
                     </content>™ </paragraph>
                  <renderMultiMedia ID="id-92243210" referencedObject="ID_0cd84dad-683f-465b-9400-af5010a32b1b"/>
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               <effectiveTime value="20241001"/>
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                     <text>Figure</text>
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               <title>Principal Display Panel - Trifexis 1620 mg Carton Label </title>
               <text>
                  <paragraph>
                     <content styleCode="bold">Trifexis</content>™ </paragraph>
                  <paragraph>
                     <content styleCode="bold">(spinosad + milbemycin oxime)</content>
                  </paragraph>
                  <paragraph>FOR DOGS<br/>60.1-120 lbs </paragraph>
                  <paragraph>
                     <content styleCode="bold">6</content>
                     <br/>
                     <content styleCode="bold">CHEWABLE</content>
                     <br/>
                     <content styleCode="bold">TABLETS</content>
                  </paragraph>
                  <paragraph>1620 mg spinosad/<br/>27 mg milbemycin oxime </paragraph>
                  <paragraph>
                     <content styleCode="bold">CAUTION:</content> Federal (USA) law restricts this drug to<br/>use by or on the order of a licensed veterinarian. </paragraph>
                  <paragraph>Prevents<br/>
                     <content styleCode="bold">HEARTWORM</content> Disease </paragraph>
                  <paragraph>Kills<br/>
                     <content styleCode="bold">FLEAS</content> &amp; Prevents Infestations </paragraph>
                  <paragraph>Treats and Controls<br/>
                     <content styleCode="bold">INTESTINAL WORMS</content>
                  </paragraph>
                  <paragraph>Adult Hookworm, Roundworm, and Whipworm </paragraph>
                  <paragraph>
                     <content styleCode="bold">For use in dogs and puppies 8 weeks of age</content>
                     <br/>
                     <content styleCode="bold">and older and 5 lbs of body weight or greater</content>
                  </paragraph>
                  <paragraph>
                     <content styleCode="bold">STARTS</content>
                     <br/>Killing Fleas<br/>in 30 mins. </paragraph>
                  <paragraph>
                     <content styleCode="bold">MONTHLY</content>
                     <br/>Use </paragraph>
                  <paragraph>
                     <content styleCode="bold">GIVE WITH</content>
                     <br/>A Meal </paragraph>
                  <paragraph>
                     <content styleCode="bold">
                        <content styleCode="italics">Elanco</content>
                     </content>™ </paragraph>
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                     <text>Figure</text>
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