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Dosing & Administration | AMVUTTRA® (vutrisiran)

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class="touch-none close" src="/themes/amvuttra/assets/images/0.0-icn-x-lg.svg" width="30" height="30" alt="Close menu"> </div> </div> </div> </div> </header> <main class="main " role="main"> <a id="main-content" tabindex="-1"></a> <div class="main__content relative"> <div class="region region--content"> <div data-drupal-messages-fallback class="hidden"></div> <div id="block-amvuttra-page-title" class="container page-title"> <h1><span>Dosing &amp; Administration</span> </h1> </div> <div id="block-amvuttra-content"> <article data-history-node-id="9" class="node node--basic-page-with-sections --view-mode--full"> <div class="node__content"> <div class="sections basic_page_with_sections__item"> <div class="sections__item --collection_of_blocks"> <div class="blocks"> <div class="blocks__item --container_block"> <div class="blocks"> <div class="blocks__item --large_text"> <h2>AMVUTTRA® is HCP-administered 4 times a year, providing the opportunity for consistent touchpoints in your patients’ healthcare routine<sup>1</sup></h2> </div> <div class="blocks__item --image"> <div class="image-default"> <div class="image-default__item"> <div class="media media--image --view-mode--full"> <div class="media-image"> <div class="media-image__item"> <img src="/sites/default/files/2022-09/4.0-BoxSyringe_ANGLED_LAYERED_nobckgrnd.svg" alt="AMVUTTRA® (vutrisiran) product image" loading="lazy" /> </div> </div> </div> </div> </div> </div> <div class="blocks__item --modal_trigger"> <div class="trigger"> <div class="trigger__item --link_icon"><a class="link modal-trigger-link" onclick="event.preventDefault()" href="#administering-amvuttra" title="Watch the administration video" muted="muted"> Watch the administration video <div class="media media--svg --view-mode--default"> <div class="media-svg-1"> <div class="media-svg-1__item"> <svg xmlns="http://www.w3.org/2000/svg" id="red_play_button_50px" data-name="red play button 50px" width="50" height="50" viewBox="0 0 50 50"> <g id="Group"> <circle id="Oval" cx="25" cy="25" r="25" fill="#e7004c"/> <path id="Triangle" d="M11.981,0,23.962,15.746H0Z" transform="translate(35.279 13.189) rotate(90)" fill="#fff"/> </g> </svg> </div> </div> </div> </a> </div> </div> </div> </div> </div> <div class="blocks__item --container_block"> <div class="blocks"> <div class="blocks__item --large_text"> <h2>AMVUTTRA® is HCP-administered 4 times a year, providing the opportunity for consistent touchpoints in your patients’ healthcare routine<sup>1</sup></h2><ul><li><p>The recommended dose of AMVUTTRA is 25 mg administered by subcutaneous injection once every 3 months by a healthcare professional.<sup>1</sup></p><p>AMVUTTRA is provided as a fixed dose (25&nbsp;mg/0.5&nbsp;mL) prefilled syringe—no dose adjustments are recommended.<sup>1</sup></p><p><em>(See section 2.2 of full Prescribing Information for complete Administration Instructions.)</em></p></li><li>If a dose is missed, administer AMVUTTRA as soon as possible. Resume dosing every 3 months from the most recently administered dose.<sup>1</sup></li></ul> </div> <div class="blocks__item --callout_box"> <div class="large-text"> <div class="large-text__item"><p>HCP administration helps ensure confidence that each dose is administered fully and properly, without the need for premedication or laboratory monitoring.<sup>1</sup></p></div> </div> </div> <div class="blocks__item --container_block"> <div class="blocks"> <div class="blocks__item --image"> <div class="image-default"> <div class="image-default__item"> <div class="media media--image --view-mode--full"> <div class="media-image"> <div class="media-image__item"> <img src="/sites/default/files/2023-03/AMVUTTRA-vutrisiran-Dosing-and-Administration-Guide%402x.png" width="360" height="430" alt="Picture of dosing and administration brochure" loading="lazy" /> </div> </div> </div> </div> </div> </div> <div class="blocks__item --container_block"> <div class="blocks"> <div class="blocks__item --large_text"> <p>Learn more about dosing and administration.</p> </div> <div class="blocks__item --link_icon"><a class="link" href="/sites/default/files/pdfs/AMVUTTRA-vutrisiran-Administration-Guide-for-Healthcare-Professionals.pdf" title="Download brochure" muted="muted"> Download brochure <div class="media media--svg --view-mode--default"> <div class="media-svg-1"> <div class="media-svg-1__item"> <svg xmlns="http://www.w3.org/2000/svg" width="18.152" height="19.5" viewBox="0 0 18.152 19.5"><g transform="translate(0.75 0.75)"><path d="M0,18.5v2.157A2.071,2.071,0,0,0,2.109,22.74H14.543a2.135,2.135,0,0,0,2.109-2.157V18.5" transform="translate(0 -4.74)" fill="none" stroke="#e7004c" stroke-linecap="round" stroke-linejoin="round" stroke-miterlimit="10" stroke-width="1.5"/><path d="M4.3,10l5.163,5.281L14.626,10" transform="translate(-1.174 -2.56)" fill="none" stroke="#e7004c" stroke-linecap="round" stroke-linejoin="round" stroke-miterlimit="10" stroke-width="1.5"/><path d="M11.4,0V12.72" transform="translate(-3.111)" fill="none" stroke="#e7004c" stroke-linecap="round" stroke-linejoin="round" stroke-miterlimit="10" stroke-width="1.5"/></g></svg> </div> </div> </div> </a> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="sections__item --collection_of_blocks"> <div class="blocks"> <div class="blocks__item --large_text"> <h2>AMVUTTRA requires the fewest doses to treat the polyneuropathy of hATTR amyloidosis<sup>1-4</sup></h2> </div> <div class="blocks__item --custom_html_code"> <div class="html-code"> <div class="html-code__item"><ul><li><img src="/sites/default/files/2024-01/4.0-dosing-amvuttra.svg" alt="AMVUTTRA® (vutrisiran) is HCP-administered 4 times a year." width="255" height="499" loading="lazy" typeof="foaf:Image"></li><li><img src="/sites/default/files/2024-01/4.0-dosing-eplontersen.svg" alt="Eplontersen is self-administered monthly." width="237" height="499" loading="lazy" typeof="foaf:Image"></li><li><img src="/sites/default/files/2024-01/4.0-dosing-patisiran.svg" alt="Patisiran is HCP-administered every 3 weeks." width="237" height="499" loading="lazy" typeof="foaf:Image"></li><li><img src="/sites/default/files/2024-01/4.0-dosing-inotersen.svg" alt="Inotersen is self-administered weekly." width="237" height="499" loading="lazy" typeof="foaf:Image"></li></ul></div> </div> </div> <div class="blocks__item --large_text"> <ul><li><strong>AMVUTTRA offers you and your patient</strong> the flexibility to decide the best place to receive treatment—whether in your office, at a local clinic (one of the &gt;1000 in the Alnylam Treatment Center Directories), or in the patient's home<sup>a</sup></li></ul><p class="footnote"><sup>a</sup>If covered by patient's insurance.</p> </div> <div class="blocks__item --callout_box"> <div class="large-text"> <div class="large-text__item"><p>More than 1,000 patients are receiving treatment with AMVUTTRA in the US, making it the <span class="nowrap">#1-prescribed</span> treatment for the polyneuropathy of hATTR amyloidosis in adults.<sup>5</sup></p></div> </div> </div> </div> </div> <div class="sections__item --single_video"><div class="inner" id="administering-amvuttra" > <div class="lg:hidden"> <div class="title"> <div class="title__item">Administering AMVUTTRA</div> </div> </div> <div class="video-item"> <div class="video-item__item --video"> <div class="image"> <div class="image__item"> <img src="/sites/default/files/2024-01/administering-video-poster.png" width="1456" height="820" alt="Administration of AMVUTTRA® (vutrisiran) video" loading="lazy" /> </div> </div> <div class="video"> <div class="video__item"> <div class="media media--video --view-mode--default"> <div class="media-video-file"> <div class="media-video-file__item"><a id="video"></a> <video width="640" height="480" playsinline="playsinline"> <source src="/sites/default/files/2023-04/administering-amvuttra.mp4" type="video/mp4" /> </video> <button 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<div class="current">00:00</div> </div> <div class="timeline"> <input type="range" name="" id="" min="0" max="100" value="0" step="0.01"> <div class="inner"></div> <div class="bar"></div> </div> <div class="volume-control"> <button class="volume"></button> <input type="range" name="" id="" min="0" max="100" value="100" step="0.05"> <div class="bar"></div> </div> <!-- <button class="options"></button> --> <button class="fullscreen"></button> </div> </div> </div> </div> </div> </div> </div> </div> <div class="right"> <div class="hidden lg:block"> <div class="title"> <div class="title__item">Administering AMVUTTRA</div> </div> </div> <div class="large-text"> <div class="large-text__item"><h3>Watch this instructional video for healthcare professionals</h3><p>Walk through the steps for AMVUTTRA administration.</p></div> </div> </div> </div> </div> <div class="sections__item --embed_blocks"> <div class="block-list"> <div class="block-list__item"> <div class="paragraphs"> <div 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</svg> </div> </div> </div> </div> </div> <div class="title"> <div class="title__item">Find a treatment center</div> </div> <div class="text"> <div class="text__item"><div class="title">Find a treatment center</div><p>Locate a treatment center closest to your patients.</p></div> </div> <div class="link-icon"> <div class="link-icon__item --link_icon"><a class="link" href="/treatment-center-directory" title="View the directory" muted="muted"> View the directory <div class="media media--svg --view-mode--default"> <div class="media-svg-1"> <div class="media-svg-1__item"> <svg xmlns="http://www.w3.org/2000/svg" width="18.809" height="18.809" viewBox="0 0 18.809 18.809"> <g id="pin" transform="translate(0.87 -0.553)"> <path id="Path_32092" data-name="Path 32092" d="M0,0H18.809V18.809H0Z" transform="translate(-0.87 0.553)" fill="none"/> <g id="CTA_arrow" data-name="CTA arrow" transform="translate(6.13 3.552)"> <path id="Path" d="M0,0,5.334,6.141,0,12.282" fill="none" stroke="#e7004c" 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</a></div> </div> </div> </article> </div> <div id="isi" id="block-isi" class="isi-inline"> <div class="container"> <div class="body"> <div class="body__item"><h1>Important Safety Information and Indication</h1> <h2>Important Safety Information</h2> <h3>Reduced Serum Vitamin A Levels and Recommended Supplementation</h3> <p>AMVUTTRA® (vutrisiran) treatment leads to a decrease in serum vitamin A levels.</p> <p>Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A levels do not reflect the total vitamin A in the body.</p> <p>Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).</p> <h3>Adverse Reactions</h3> <p>The most common adverse reactions that occurred in patients treated with AMVUTTRA were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%).</p> <h2>Indication</h2> <p>AMVUTTRA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.</p> <h3>For additional information about AMVUTTRA, please see the full <a href="https://www.alnylam.com/sites/default/files/pdfs/amvuttra-us-prescribing-information.pdf" target="_blank">Prescribing Information</a>.</h3> <ul> <li><a href="/sign-up">Sign up for updates</a></li> </ul> </div> </div> </div> </div> <div id="references" id="block-referencesindosingadministration" class="block-references"> <div class="container"> <div class="body"> <div class="body__item"><h2>References</h2> <ol> <li>AMVUTTRA Prescribing Information. Cambridge MA: Alnylam Pharmaceuticals, Inc.</li> <li>TEGSEDI Prescribing Information. Waltham, MA: Akcea Therapeutics, Inc.</li> <li>ONPATTRO Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.</li> <li>WAINUA Prescribing Information. Wilmington, DE: AstraZeneca Pharmaceuticals LP.</li> <li>Data on file. Alnylam Pharmaceuticals, Inc.</li> </ol> </div> </div> </div> </div><div class="isi-tray collapsed"> <div class="container relative"> <button class="toggle-isi"> <img class="open" src="/themes/amvuttra/assets/images/0.0-icn-plus.svg" alt="Open ISI" /> <img class="close" src="/themes/amvuttra/assets/images/0.0-icn-x-lg.svg" alt="Close ISI" /> </button> <div class="paragraphs"> <div class="paragraphs__item --collection_of_blocks"> <div class="blocks"> <div class="blocks__item --embed_blocks"> <div class="block-list"> <div class="block-list__item"> <div class="body"> <div class="body__item"><h1>Important Safety Information and Indication</h1> <h2>Important Safety Information</h2> <h3>Reduced Serum Vitamin A Levels and Recommended Supplementation</h3> <p>AMVUTTRA® (vutrisiran) treatment leads to a decrease in serum vitamin A levels.</p> <p>Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A levels do not reflect the total vitamin A in the body.</p> <p>Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).</p> <h3>Adverse Reactions</h3> <p>The most common adverse reactions that occurred in patients treated with AMVUTTRA were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%).</p> <h2>Indication</h2> <p>AMVUTTRA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.</p> <h3>For additional information about AMVUTTRA, please see the full <a href="https://www.alnylam.com/sites/default/files/pdfs/amvuttra-us-prescribing-information.pdf" target="_blank">Prescribing Information</a>.</h3> <ul> <li><a href="/sign-up">Sign up for updates</a></li> </ul> </div> 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