FDA SIDE EFFECTS UPDATE: Paxlovid And Breast Milk & More

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 edition, we take a closer look at Paxlovid, Repatha, Stelara, Vraylar, Zanaflex and Fludaribine.

How to Read This Report

This report is prepared using the most recent information posted in the SrLC database. 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.

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.

Fludarabine phosphate (fludarabine phosphate) injection for intravenous administration

Initial FDA Approval: 1991

Side Effect Update Date: November 19, 2024

Medication Description: Treats B-cell chronic lymphocytic leukemia (CLL)

Updated Side Effects/Safety Information: This update includes new and revised treatment indications and dosing regimens. Includes a new section on central nervous system adverse reactions such as coma, seizures, agitation, and confusion. New section on myelosuppression (a decrease in bone marrow activity that reduces blood cell production) and the need for frequent monitoring of blood counts. Includes a warning about fetal toxicity and presents clinical trial data for patients age 65 and older. A boxed warning is moved to the Warnings and Precautions section.

Extensive other label changes; see revised label for details.

Essential Extras: This drug’s label change is part of the FDA’s “Project Renewal,” an effort to update labeling information for older cancer treatments to ensure information is clinically meaningful and scientifically up to date. The other two drugs updated so far under Project Renewal include: Xeloda (capecitabine) tablets for treating colon cancer and other cancer types (revised in December 2022) and Temodar (temozolomide) oral or I.V. chemotherapy medication for treating brain cancer (revised in September 2023).

FDA Safety Announcement: Fludarabine phosphate FDA Label Change and Revised Drug Label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Paxlovid (nirmatrelvir; ritonavir) copackaged tablet

Initial FDA Approval: 2023

Side Effect Update Date: November 19, 2024

Medication Description: Treats mild-to-moderate COVID-19 in adults at high risk for progression to severe COVID-19.

Updated Side Effects/Safety Information: Updated lactation information from a very small clinical trial study of 8 lactating women. The study found nirmatrelvir and ritonavir are present in human breast milk in small amounts (less than 2%). States there is no available data on the effects of nirmatrelvir or ritonavir on breastfed infants or on milk production.

FDA Safety Announcement: Paxlovid FDA Safety Label Change and Revised Drug Label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Repatha (evolocumab) subcutaneous injection

Initial FDA Approval: 2015

Side Effect Update Date: November 20, 2024

Medication Description: Used to reduce risk of major cardiovascular events, including chest pain requiring hospitalization, heart attacks, and strokes in adults with established cardiovascular disease; used as an adjunct to diet (and sometimes other cholesterol-lowering therapies) to reduce LDL-C cholesterol.

Updated Side Effects/Safety Information: Added latex sensitivity warning. The prefilled single-dose auto-injector and syringe presentations that contain dry natural rubber (a derivative of latex) in the needle cover may cause an allergic reaction in individuals sensitive to latex. Patients are instructed to inform their healthcare provider if they are sensitive to latex.

FDA Safety Announcement: Repatha FDA Safety Label Change and Revised Drug Label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Stelara (ustekinumab) injection for subcutaneous or intravenous use

Initial FDA Approval: 2009

Side Effect Update Date: November 15, 2024

Medication Description: Treats plaque psoriasis, psoriatic arthritis, Crohn’s disease, ulcerative colitis.

Updated Side Effects/Safety Information: The drug interactions section has been updated for patients also taking CYP450 substrates (enzymes that affect how medication is metabolized in the body). It suggests that healthcare providers monitor for therapeutic effects or drug concentration and adjust the individual dosage of the CYP substrate as needed. In clinical trials, Crohn’s patients taking Stelara along with the CYP450 substances caffeine, warfarin, omeprazole, dextromethorphan midazolam, did not experience the CYP450 drug interactions.

FDA Safety Announcement: Stelara FDA Safety Change and Revised Drug Label

The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Vraylar (cariprazine hydrochloride) capsules

Initial FDA Approval: 2015

Side Effect Update Date: November 22, 2024

Medication Description: Treats schizophrenia; bipolar disorder. Adjunct therapy to antidepressants for major depressive disorder in adults.

Updated Side Effects/Safety Information: Adds dosage modifications (dosage reduction) for patients also taking a strong or moderate CYP3A4 inhibitor, which may increase the concentration of Vraylar in the blood. Examples include antifungal medications like ketoconazole, Itraconazole, voriconazole, and posaconazole, protease inhibitors used to treat HIV, along with some antibiotics like clarithromycin and grapefruit juice components. Recommends not taking with a CYP3A4 inducer, as it may decrease the concentration of Vrayar in the blood. Examples include phenobarbital, phenytoin, rifampicin, St. John’s Wort, and glucocorticoids.

FDA Safety Announcement: Vraylar FDA Safety Change and Revised Label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.

Zanaflex: (tizanidine hydrochloride) tablets and capsules

Initial FDA Approval: 1996

Side Effect Update Date: November 20, 2024

Medication Description: Treats muscle spasms in adults.

Updated Side Effects/Safety Information: A new warning that the FDA has received postmarketing reports of decreased blood pressure (hypotension) and hallucinations has been added. Drug interaction information was added, as well as drugs to avoid while taking Zanaflex. Juvenile animal study toxicity data added; pediatric safety and effectiveness have not been established. Extensive prescribing information updated based on FDA regulation, guidance and current recommendations. See revised label for all changes.

Essential Extras: Frequently used by patients with multiple sclerosis, cerebral palsy, or those with spinal cord injuries.Used off-label for migraines.

FDA Safety Announcement: Zanaflex FDA Safety Label Change and  Revised Drug Label
The revised drug label contains a complete list of FDA-approved indications, side effects, warnings, and more.