FDA SIDE EFFECTS UPDATE: Migraine Drug Constipation Risk, Boxed Warning Update for Methotrexate

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<p>Welcome to the FDA Side Effects Update. This series is designed to keep you informed about the latest safety advisories and newly documented side effects of your medications. In this installment, we’re highlighting safety updates concerning Ajovy, Emgality, Jylamvo, Methotrexate, and Xatmep.  </p>
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<p>This report is prepared using the most recent information posted in the<a href="https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm"> SrLC database</a>. It highlights recent safety labeling changes. It includes only newly reported side effects and safety information; additional side effects and warnings will appear on the drug label. Not all recent changes to the SrLC database or the label may be listed here. For all changes and the complete list of warnings and side effects, please click on the drug label link.</p>
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<p>Each of the items (approval and update dates, drug names, etc.) contained in this report are obtained from the SrLC. The side effects and medication descriptions are simplified and made clearer, if needed. Sometimes, additional sources, like a medical dictionary, may be used to translate technical medical phrases. Other sources (company news, FDA press releases, etc.) may be used to learn about some label changes.</p>
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<h2 class="wp-block-heading">Migraine Drugs Side Effect Update</h2>
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<h3 class="wp-block-heading">Ajovy (fremanezumab-vfrm) injection, for subcutaneous use</h3>
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<p><strong>Initial FDA Approval</strong>: 2018<br><strong>Side Effect Update Date</strong>: June 5, 2026<br><strong>Medication Description</strong>: Monthly or quarterly treatment used to prevent migraines. Ajovy is a calcitonin gene-related peptide (CGRP) inhibitor and is also a <a href="https://www.merriam-webster.com/dictionary/monoclonal%20antibody#medicalDictionary">monoclonal antibody</a> (“large molecule”) drug. <a href="https://my.clevelandclinic.org/health/treatments/cgrp-inhibitors">CGRP medications</a> work by blocking the activity of migraine-triggering CGRP molecules.<br><strong>Updated Side Effects/Safety Information</strong>: A new warning of the risk of severe constipation complications that can result in hospitalization or surgery. Using Ajovy along with medications that slow the movement of stomach contents (such as GLP-1 drugs like Ozempic) may increase the risk of constipation. Patients experiencing symptoms of constipation, including severe or constant belly pain, vomiting, swelling of the belly, or bloating, should contact their healthcare provider.<br><strong>Essential Extras</strong>: In the fourth quarter of 2024, the <a href="https://www.fda.gov/drugs/fda-adverse-event-monitoring-system-aems/october-december-2024-new-safety-information-or-potential-signals-serious-risks-identified-fda">FDA reported</a> receiving several adverse event reports of severe constipation associated with CGRP migraine drugs and said it would “evaluate the need for regulatory action.” In January 2026, the FDA <a href="https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/761089Orig1s036ltr.pdf">notified sponsor Teva</a> of the new safety information to be added to the labels of monoclonal antibody calcitonin gene-related peptide (CGRP) antagonists, including Ajovy.<br><strong>FDA Safety Announcement</strong>: <a href="https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=2185">Ajovy FDA Safety Label Change</a> and <a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/761089s036lbl.pdf">Revised Drug Label</a></p>
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<h3 class="wp-block-heading">Emgality (galcanezumab-gnlm) injection, for subcutaneous use</h3>
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<p><strong>Initial FDA Approval:</strong> 2018<br><strong>Side Effect Update Date</strong>: June 5, 2026<br><strong>Medication Description</strong>: Preventive treatment for migraines; also treats episodic cluster headaches. Emgality is a calcitonin gene-related peptide (CGRP) inhibitor and is also a<a href="https://www.merriam-webster.com/dictionary/monoclonal%20antibody#medicalDictionary"> monoclonal antibody</a> (“large molecule”) drug. <a href="https://my.clevelandclinic.org/health/treatments/cgrp-inhibitors">CGRP medications</a> work by blocking the activity of migraine-triggering CGRP molecules.<br><strong>Updated Side Effects/Safety Information</strong>: A new warning of the risk of severe constipation complications that can result in hospitalization or surgery. Using Emgality along with medications that slow the movement of stomach contents (such as GLP-1 drugs like Ozempic) may increase the risk of constipation. Patients experiencing symptoms of constipation, including severe or constant belly pain, vomiting, swelling of the belly, or bloating, should contact their healthcare provider.<br><strong>Essential Extras</strong>: In the fourth quarter of 2024, the <a href="https://www.fda.gov/drugs/fda-adverse-event-monitoring-system-aems/october-december-2024-new-safety-information-or-potential-signals-serious-risks-identified-fda">FDA reported</a> receiving several adverse event reports of severe constipation associated with CGRP migraine drugs and said it would “evaluate the need for regulatory action.” In January 2026, the FDA <a href="https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/761063Orig1s013ltr.pdf">notified sponsor Eli Lilly</a> of the new safety information to be added to the labels of monoclonal antibody calcitonin gene-related peptide (CGRP) antagonists, including Emgality.<br><strong>FDA Safety Announcement</strong>: <a href="https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=1966">Emgality FDA Safety Label Change</a> and <a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/761063s013lbl.pdf">Revised Drug Label</a></p>
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<h2 class="wp-block-heading">Oral Methotrexate Side Effect Update</h2>
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<h3 class="wp-block-heading">Jylamvo (methotrexate) oral solution</h3>
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<p><strong>Initial FDA Approval</strong>: 1953 (active ingredient); 2022 (this product)<br><strong>Side Effect Update Date</strong>: May 27, 2026<br><strong>Medication Description</strong>: Treats cancer and autoimmune conditions, including leukemia, Hodgkin's lymphoma, rheumatoid arthritis, polyarticular juvenile idiopathic arthritis (pJIA), and severe psoriasis.<br><strong>Updated Side Effects/Safety Information</strong>: The boxed warning and patient medication guide were updated to include a warning that medication errors have caused patient deaths. Severe side effects and deaths have happened when Jylamvo was taken every day instead of one time each week.<br><strong>Essential Extras</strong>: Methotrexate medication errors that result in patient harm <a href="https://nabp.pharmacy/news/blog/regulatory_news/ismp-safety-brief-prevent-harm-from-methotrexate/">have been recognized for years</a>, but until now, the labels did not include this risk in the boxed warning. In the fourth quarter of 2024, the <a href="https://www.fda.gov/drugs/fda-adverse-event-monitoring-system-aems/october-december-2024-new-safety-information-or-potential-signals-serious-risks-identified-fda">FDA reported</a> a potential signal of serious risks associated with medication errors involving oral methotrexate products. In February 2026, the <a href="https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/212479Orig1s009ltr.pdf">FDA notified</a> drug sponsor Shorma Oncology about the required label change.<br><strong>FDA Safety Announcement:</strong> <a href="https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=2197">Jylamvo MPC FDA Safety Label Change</a> and<a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/212479s009lbl.pdf"> Revised Drug Label</a><br>The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.</p>
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<h3 class="wp-block-heading">Methotrexate Sodium tablets</h3>
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<p><strong>Initial FDA Approval</strong>: 1953<br><strong>Side Effect Update Date</strong>: May 27, 2026<br><strong>Medication Description</strong>: Treats cancer and autoimmune conditions, including adult and pediatric leukemia, adults with mycosis fungoides, non-Hodgkin lymphoma, rheumatoid arthritis, and pediatric patients with polyarticular (affecting five or more joints) juvenile idiopathic (unknown cause) arthritis (pJIA).<br><strong>Updated Side Effects/Safety Information</strong>: The boxed warning and patient medication guide were updated to include a warning that medication errors have caused patient deaths. Methotrexate is taken one time each week for rheumatoid arthritis, polyarticular juvenile idiopathic arthritis (pJIA), and severe psoriasis. Deaths have happened when oral methotrexate was taken every day instead of once a week.<br><strong>Essential Extras</strong>: Methotrexate medication errors that result in patient harm <a href="https://nabp.pharmacy/news/blog/regulatory_news/ismp-safety-brief-prevent-harm-from-methotrexate/">have been recognized for years</a>, but until now, the labels did not include this risk in the boxed warning. In the fourth quarter of 2024, the <a href="https://www.fda.gov/drugs/fda-adverse-event-monitoring-system-aems/october-december-2024-new-safety-information-or-potential-signals-serious-risks-identified-fda">FDA reported</a> the potential signal of serious risks related to medication errors for oral methotrexate products. In February 2026, the <a href="https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/008085Orig1s072ltr.pdf">FDA notified</a> drug sponsor Strides Pharma about the required label change. While Strides Pharma has discontinued its production of methotrexate tablets, as the drug sponsor, it is required to make all labeling updates, which will be followed by associated generics.<br><strong>FDA Safety Announcement</strong>: <a href="https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=1479">Methotrexate FDA Safety Label Change</a> and<a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/008085s072lbl.pdf"> Revised Drug Label</a><br>The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.</p>
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<h3 class="wp-block-heading">Xatmep (methotrexate) oral solution</h3>
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<p><strong>Initial FDA Approval</strong>: 1953 (active ingredient); 2017 (this product)<br><strong>Side Effect Update Date</strong>: May 27, 2026<br><strong>Medication Description</strong>: Treats pediatric patients with acute lymphoblastic leukemia (ALL) and polyarticular juvenile idiopathic arthritis (pJIA), a form of arthritis that affects five or more joints. In pJIA, the immune system mistakenly attacks healthy tissues, causing inflammation.<br><strong>Updated Side Effects/Safety Information</strong>: The boxed warning and patient medication guide were updated to include a warning that medication errors have caused patient deaths. Oral methotrexate, including Xatmep, when administered daily, has caused deaths in patients. Xatmep should be taken once a week.<br><strong>Essential Extras</strong>: Methotrexate medication errors that result in patient harm <a href="https://nabp.pharmacy/news/blog/regulatory_news/ismp-safety-brief-prevent-harm-from-methotrexate/">have been recognized for years</a>, but until now, the labels did not include this risk in the boxed warning. In the fourth quarter of 2024, the <a href="https://www.fda.gov/drugs/fda-adverse-event-monitoring-system-aems/october-december-2024-new-safety-information-or-potential-signals-serious-risks-identified-fda">FDA reported</a> a potential signal of serious risks associated with medication errors involving oral methotrexate products. In February 2026, the <a href="https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/208400Orig1s005ltr.pdf">FDA notified</a> drug sponsor Azurity Pharmaceuticals of the required label change.<br><strong>FDA Safety Announcement:</strong> <a href="https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=1475">Xatmep FDA Safety Label Change</a> and<a href="https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/208400s005lbl.pdf"> Revised Drug Label</a><br>The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.</p>
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