October 2024 Drug Safety Update Part 1: Sickle cell drug withdrawn; Quviviq, Aldara, Xeljanz, Dupixent and cancer drugs; breast feeding and meds
Consumer-friendly summaries of new safety information added to FDA drug labels
Oxbryta (voxelotor)
Pfizer is withdrawing sickle cell anemia drug Oxbryta (voxelotor) from the market due to safety problems discovered during post-approval clinical trials. Participants receiving Oxbryta had a higher rate of vaso-occlusive crisis (severe pain caused by sickled red blood cells blocking blood flow and oxygen delivery to tissues) compared to placebo. Also, more deaths were reported in the Oxbryta treatment group as compared to the placebo group. Pfizer has discontinued all Oxbryta trials.
In an announcement, the Food and Drug Administration (FDA) says that health care professionals should stop prescribing Oxbryta and patients and caregivers should contact their health care professional about stopping Oxbryta and starting another treatment option. Oxbryta was initially approved in 2019 under the accelerated approval pathway for the treatment of sickle cell disease in patients 12 years of age and older, and in 2021 it gained approval for patients age 4 to 11 years.
FDA Safety Announcement about Oxbryta (voxelotor)
Many patients and doctors say that the market withdrawal came as a complete surprise and complain that they have not been given good advice about how to stop taking the drug. While tapering is not recommended by Pfizer, many doctors are recommending a gradual reduction in dose amounts because of concerns about withdrawal symptoms.
https://www.statnews.com/2024/09/27/sickle-cell-disease-oxbryta-patients-doctors/
Drug Label Updates: Aldara (imiquimod) cream
Aldara is a topical medication used to treat skin cancer growths and genital warts. Its label was updated with new warnings and some formatting changes. Users are advised not to use Aldara with other imiquimod-containing products because of increased risk of skin reactions. The drug's medication guide now also warns to avoid application on skin that is not intact (such as skin with an abrasion, cut, or burns).
A warning about possible hypopigmentation (lightening of skin in patches) was added to the Warnings and Precautions section of the label. Both hypopigmentation and complete depigmentation (loss of all skin pigment) were reported during post-marketing use and patients are advised to discontinue treatment if this condition develops. This is Aldara’s first safety label change. Aldara was initially approved in 1997.
Aldara FDA Safety Label Change
Patient reviews of Aldara at AskaPatient
Dupixent (dupilumab)
In conjunction with eczema drug Dupixent’s recent approval as an add-on treatment for adults with controlled chronic obstructive pulmonary disease (COPD), the drug label had extensive safety updates. Additional side effects added to the list include viral infection, headache, back pain, urinary tract infection, and inflammation inside the nose (rhinitis). Dupixent was initially approved in 2017.
Dupixent FDA Safety Label Change
Patient reviews of Dupixent at AskaPatient
Quviviq (daridorexant) tablets
Insomnia drug Quviviq had a safety label update to warn that the medication may increase the risk of falls and of a “temporary weakness in your legs that can happen during the day or at night.” As part of its approval requirements, drug sponsor Idorsia conducted a post-marketing study (called a “middle-of-the-night safety study”) to assess the "ability to awaken to sound in the middle of the night and postural stability and cognitive function following awakening.” Results of that study led to some of the new label updates.
Under the medication guide’s list of the most common side effects, “tiredness” was added as one of the top three, joining headache and sleepiness. The national Poison Help Line number (1-800-222-1222) was added to the section on what to do if you take too much Quviviq.
A section was added for patients with breathing problems to warn that the effects on respiratory functions should be considered, based on a study on use of the drug in patients with mild to moderate obstructive sleep apnea (OSA) NOT using a CPAP device. Also, results from a lactation study were included to report that “daridorexant is present in human breast milk in low amounts.” Quviviq was initially approved in 2022.
Quviviq FDA Safety Label Change
Patient reviews of Quviviq at AskaPatient
Xeljanz and Xeljanz XR (tofacitinib)
Rheumatoid arthritis (RA) and ulcerative colitis (UC) drugs Xeljanz and Xeljanz XR (tablets and oral solution) had label updates to add safety information related to pregnancy and lactation based on data for 11 patients in the Tofacitinib Pregnancy Exposure Registry and from medical literature and market surveillance.
Pregnancy: Although no adverse effects were observed in the infants when the drug was taken during pregnancy, the label says that there is insufficient data to draw conclusions about a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
Lactation: It was found that tofacitinib is present in breast milk and that "data on the effects of tofacitinib on the breastfed infant is limited to a small number of cases with no reported adverse effects." Xeljanz was initially approved in 2012 and carries a boxed warning about the risk of serious infections and major adverse cardiovascular events.
Xeljanz FDA Safety Label Change
Patient Reviews of Xeljanz at AskaPatient
Note: About 3.4% of the tofacitinib dosage taken by the mother was passed along to the infant as the worst-case daily infant dosage, according to studies referenced in the National Library of Medicine’s Drugs and Lactation Database (LactMed®).
LactMed® Database
Cancer Drugs Safety Updates
Infugem (Gemcitabine Hydrochloride)
Infugem and the generic gemacitabine are chemotherapy drugs that are administered intravenously and treat a variety of cancers. Their drug labels were updated with a new subsection on the risk of severe types of skin reactions called severe cutaneous adverse reactions (SCARs):
“SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which can be life threatening or fatal, have been reported in association with gemcitabine treatment. Monitor patients for signs and symptoms of severe cutaneous adverse reactions. Permanently discontinue gemcitabine in patients who develop SCARs.”
Gemcitabine was initially approved under the name Gemzar in 1996.
Gemciabine FDA Safety Label Change
Infugem FDA Safety Label Change
Gemcitabine and Gemzar patient ratings and reviews at AskaPatient
Tagrisso (osimertinib mesylate) tablets
In conjunction with its expanded approval to treat certain kinds of stage 3 lung cancer, Tagrisso had a label update to expand the information it provides in its warnings about the risk of interstitial lung disease (ILD) and also lung inflammation (pneumonitis). Clinical trials information was also updated with outcomes for patients who used Tagrisso after platinum-based chemoradiation therapy:
"In the LAURA study, following definitive platinum-based chemoradiation therapy, ILD/pneumonitis, including radiation pneumonitis, occurred in 80 of the 143 patients (56%) who received TAGRISSO monotherapy and 28 of the 73 patients (38%) who received placebo…..In the 80 TAGRISSO-treated patients, ILD/pneumonitis resolved in 40%, resolved with sequelae in 1.3%, were resolving in 16%, did not resolve in 41%, and resulted in death in 1.3%."
The clinical trial data also show that ILD occurred in only 3.3% of patients who had taken the drug in combination with pemetrexed and platinum-based chemotherapy. Tagrisso was initially approved in 2015.
Additional extensive clinical trial updates were added. Please check the FDA link for complete information, which also has a link to the new drug label.
Tagrisso FDA Safety Label Change
More on Tagrisso’s expanded approval: https://www.curetoday.com/view/fda-approves-tagrisso-for-some-with-advanced-nsclc
Retevmo (selpercatinib) capsule
In conjunction with its upgraded approval from "accelerated" to "traditional," medullary thyroid cancer and lung cancer drug Retevmo had a label update to report recent clinical trial results, including two pediatric studies where an adolescent taking Retevmo had a "slipped capital femoral epiphysis/slipped upper femoral epiphysis” (SCFE/SUFE).
SCFE is a hip disorder in which the head of the femur slips off the neck of the bone at the growth plate; it is the most common hip disorder in preteens and teens, and often requires surgery. Health care professionals are advised to monitor patients for symptoms of SCFE/SUFE and treat as medically and surgically appropriate. The label also includes other clinical trial updates. Retevmo was initially approved in 2020.
Retevmo FDA Safety Label Change
FDA announcement on Retevmo traditional approval
Cleveland Clinic explains the symptoms and typical causes of SCFE:
https://my.clevelandclinic.org/health/diseases/17485-slipped-capital-femoral-epiphysis-scfe
Did you miss previous Drug Safety Updates? Check out the list of them here:
https://news.askapatient.com/s/fda-drug-safety-warnings-for-popular
Please note: our regular “Drugs & Treatments” news for this week will be sent on Tuesday, October 8.
Visit us at AskaPatient.com for drug ratings and reviews and more news!