Drug Safety Updates: February 2024 Part 2
Label updates for estradiol and other menopausal hormone therapy products; fluconazole (diflucan); Vytorin; Warning from Public Citizen on PPIs
Menopausal Hormone Therapy Products
Labels for the menopausal hormone therapy (MHT) products listed below were changed to provide information on the risk of breast cancer associated with the duration of use of MHT products. These include pills, patches, and vaginal creams. Note- these labeling changes were first reported on February 15 and were added to the database on February 20. Update: These links have been updated to go to the Safety Labeling update.
Labels for each were updated, at the direction of the U.S. Food & Drug Administration, to include risk information stating that results of a large cohort review study suggest that increased cancer risks are dependent upon duration of use and could last up to >10 years after discontinuation of estrogen plus progestin therapy and estrogen- alone therapy; the WHI (Women's Health Initiative*) extension trials also demonstrated increased breast cancer risk associated with estrogen plus progestin therapy.
*The Women’s Health Initiative (WHI) is a long-term national health study funded by the National Heart, Lung, and Blood Institute, or NHLBI. The original WHI study began in the early 1990s and concluded in 2005. Since 2005, the WHI has continued as Extension Studies, which are annual collections of health updates and outcomes in active participants. The second Extension Study enrolled 93,500 women in 2010 and follow-up of these women continues annually.
As with the original WHI study, the main areas of research are cardiovascular disease, cancers, and osteoporotic fractures. While WHI continues to focus on strategies to prevent the major causes of death, disability, and frailty in older women, the breadth and richness of the WHI data allow for the exploration and investigation of many more research questions on women’s health and aging."
ALORA (ABBVIE)
Diflucan (Fluconazole) Label Update
The label for fungal yeast infection drug Diflucan (fluconazole) was updated to include pediatric patient clinical trials data for premature infants receiving Diflucan prophylaxis and clinical trials data for children receiving Diflucan with extracorporeal membrane oxygenation (ECMO). For premature infants weighing less than 750 grams at birth, the incidence of intestinal perforation in infants receiving DIFLUCAN prophylaxis was higher compared to infants receiving placebo.
In a trial of 20 pediatric patients age 1 day to 17 years, the adverse reaction profile of DIFLUCAN in the ECMO patients was similar to that of adult and pediatric non-ECMO patients.
https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=1428
The FDA also reports that Difuclan "precautions" section received "significant changes." Check page 14 of the label for the precautions section.
Patient reviews of Diflucan on Ask a Patient website:
https://www.askapatient.com/viewrating.asp?drug=19949&name=DIFLUCAN
Vytorin (Ezetimibe; Simvastatin) Label Change
Cholesterol drug Vytorin had extensive safety label updates to include specific dosing for pediatric use (age 10 and up), risk factors for myopathy (it's contra-indicated in patients with liver failure or risk of liver problems), and it includes disclosure of rare reports of new-onset or exacerbation of myasthenia gravis. For patients age 65+ , there is greater risk factor for Vytorin-associated myopathy and rhabdomyolysis. https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=1460
Warning from Public Citizen on Long-term Use of PPIs
This month, Public Citizen's Health Research Group released a report warning about long term use of Proton Pump Inhibitors (PPIs) such as omeprazole (example brand is Prilosec). "PPIs are one of the most commonly prescribed drugs in the U.S. and their use has increased in recent years. When used once daily over a few days, PPIs can reduce the amount of stomach acid by about two-thirds." Long term use can cause problems like magnesium deficiency, bone fractures, stomach polyps, kidney injury, drug interactions, C. difficile infections, dependency because of “rebound acid hypersecretion” and more.
In 2011, Public Citizen petitioned the FDA and was partially successful in having the agency strengthen the warnings on the labels of these drugs. The FDA agreed to include warning language for some of these risks on the product labels of all PPIs. However, the agency declined the request to require black-box warnings.
https://www.worstpills.org/newsletters/view/1579 (this article is paywalled; abstract available)
Read AskaPatient’s case study describing a doctor's own experience with an unusual symptom that eventually was linked to omeprazole:
https://www.askapatient.com/news/strange-symptoms-iron-deficiency-anemia.asp
Please note that this article was updated to include links to the Safety Label Changes for the MHT (menopausal hormone therapy) drugs.