Recall continues for some of the most common blood pressure medications
When the popular blood pressure medication valsartan was pulled from pharmacy shelves late last summer, pharmacy staff at Dilworth Drug & Wellness Center in North Carolina reached out to patients taking the medication and notified them of the recall before it became national news.
But like many pharmacies around the country, Dilworth Drug & Wellness Center had difficulty getting the medication from any other manufacturer of valsartan because the recall was so widespread.
“This prompted us to start considering other ARBs—drugs in the same class—that we could still provide for patients at around the same copay,” said Jenny Doughty, PharmD, pharmacy manager at Dilworth Drug & Wellness Center. With permission from each patient, Doughty and other staff pharmacists worked with patients’ physicians—with whom they already had established relationships—on selecting the best substitutes for each patient.
However, to date, the recall has escalated to include not only valsartan, but also losartan and irbesartan as well as combination medications.
“It just seems to be this slow trickle of more medications,” said Doughty.
The recalls are being traced to the way some manufacturers synthesize the active pharmaceutical ingredient (API) in valsartan, causing impurities in the form of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA), which are suspected human carcinogens. The steps for synthesizing other ARBs are similar to those for valsartan.
FDA’s investigation all started back in June 2018, when the agency was informed that Prinston Pharmaceuticals had stopped manufacturing valsartan products because it had detected trace amounts of NDMA in valsartan API supplied by the Chinese manufacturer Zhejiang Huahai Pharmaceutical (ZHP) Co. FDA put ZHP on import alert, blocking all API from legally entering the United States. Another supplier of tainted valsartan API was identified in India. In general, factories in China and India make and supply API to worldwide drug companies that sell generics.
FDA has acknowledged that the manufacturing issue at ZHP occurred sometime after 2010, when the company changed its processes.
Doughty and pharmacy staff at Dilworth Drug & Wellness Center have been able to provide appropriate blood pressure medications to patients during the shortage because some manufacturers are not affected by the recall, and the wholesalers the pharmacy works with still have medications in stock.
“They haven’t had much of an issue with the losartan or losartan combinations, and a lot of patients we switched out from valsartan weren’t switched to losartan; they went with a different ARB like telmisartan or candesartan, which haven’t been affected just yet,” said Doughty.
In February, FDA said it was still continuing its investigation of tainted ARBs and that more recalls are expected. As of March 1, the presence of a third carcinogen, N-nitroso-N-methyl-4-aminobutyric acid (NMBA), was found in lots of losartan potassium (25 mg, 50 mg, and 100 mg) made by Hetero Labs in India and distributed by Camber Pharmaceuticals. In March, FDA also announced that it approved a new generic of valsartan (Diovan) and that it was prioritizing the review to help alleviate the recent shortage of valsartan in the wake of the recalls. Approval of the new generic was given to Alkem Laboratories Ltd.
FDA noted that for this new approval, it evaluated Alkem's manufacturing processes and verified that they used appropriate testing methods to demonstrate that the valsartan product does not contain NDMA or NDEA.
Pharmacists should keep on top of information as it becomes available by checking updates on FDA’s site.
For the full article, please visit www.pharmacytoday.org for the April 2019 issue of Pharmacy Today.