Population Impact of Generic Valsartan Recall

Jackevicius, Cynthia A.; Krumholz, Harlan M.; Chong, Alice; Koh, Maria; Ozaki, Aya; Austin, Peter C.; Udell, Jacob A.; Ko, Dennis T.

doi:10.1161/circulationaha.119.044494

Cited by 23 publications

(46 citation statements)

References 3 publications

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“…The data, therefore, suggest that patients were primarily switched within the class of ARBs, mostly from valsartan to candesartan. Interestingly, and in contrast to other medication safety warnings/recalls and subsequent drug shortages, the data do not suggest an under-treatment on a population level during this period [7][8][9][10]19].…”

Section: Discussioncontrasting

confidence: 75%

“…Recently, two studies investigated the consequences of ARB recalls in North-America [19,23]. Analyzing a database in Ontario, Canada, covering 55,461 patients, 73.8% of recalled valsartan users switched to non-valsartan ARBs and 8.8% to a non-recalled valsartan product within one month after the recall, but 10.7% of patients did not fill an alternative medication at 3 month after the recall [19]. The lack of replacement of recalled valsartan was associated with increased healthcare utilization [19].…”

Section: Discussionmentioning

confidence: 99%

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Impact of angiotensin receptor blocker product recalls on antihypertensive prescribing in Germany

Rudolph

Enners²,

Kieble³

et al. 2020

J Hum Hypertens

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In Germany, ~8 million patients take angiotensin receptor blockers (ARBs) and 2.25 million of them valsartan. In 2018, contamination of generic ARBs with probable carcinogenic nitrosamines resulted in more than 30 recalls. The impact of such a huge recall has never been explored in Europe. We analyzed the utilization of valsartan, all ARBs, and other alternative antihypertensive drugs in Germany. We used our database of anonymized dispensing data from >80% of community pharmacies at the expense of the statutory health insurance (SHI) funds from January 2017 to December 2019. We analyzed 290.8 million prescriptions, including all oral mono- and fixed-dose combinations of ARBs and plausible alternatives, i.e. ACE inhibitors (ACEi), beta-blockers (BB), and calcium channel blockers (CCB). Utilization was calculated by defined daily doses per 1000 SHI-insured persons per day (DID). Valsartan use decreased substantially after the recalls in July 2018 from 39.0 to 14.2 DID (−64%) in the second quarter of 2019 and to 16.9 DID (−57%) in the fourth quarter of 2019. Simultaneously, the use of alternative ARBs increased from 77.7 DID in the second quarter of 2018 to 121.9 DID (+57%) in the fourth quarter of 2019, mainly due to an increase of candesartan dispensing to 99.8 DID (+73%). There were no changes in the utilization of ACEi, BB, or CCB. The majority of recalled generic valsartan products were replaced by other ARBs, predominantly candesartan, despite documented drug shortages. In contrast to previous safety warnings/recalls, our data do not suggest an under-prescription of antihypertensives during this period.

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Section: Discussioncontrasting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Impact of angiotensin receptor blocker product recalls on antihypertensive prescribing in Germany

Rudolph

Enners²,

Kieble³

et al. 2020

J Hum Hypertens

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“…Finally, fifty-one (51) published articles and recent newspaper reports and press releases as obtained from Google were considered for this review. Amongst the included published studies, publication date ranges from October 2018 5 to February 2020 6 .…”

Section: Literature Search and Resultsmentioning

confidence: 99%

Understanding the molecular–pharmaceutical basis of sartan recalls focusing on valsartan

Ray

Atal

Sadasivam

2020

gcsp

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Angiotensin receptor blockers (ARBs) or the ‘sartans’ are widely used for the management of hypertension and heart failure. There have been a series of recent incidents where drug formulations containing different ARBs as active pharmaceutical ingredients have been recalled by various pharmaceutical firms. This article addresses valsartan as well as other sartan recalls besides discussing the recent recalls of ranitidine and metformin, giving insights into the molecular-pharmaceutical basis of the recalls. A thorough literature search of PubMed/Medline and Google Scholar databases was performed to identify all relevant articles and information published up to 29th April 2020 using Medical Subject Headings (MeSH terms) and Boolean operators. We also searched for relevant information on the web using web-browsers and reference lists from original research papers and review articles. The main impurity found was N-nitrosodimethylamine (NDMA) which was thought to be formed due to a change in the manufacturing process of valsartan. Besides, other impurities such N- nitrosodiethylamine (NDEA) and N-nitroso-N-methyl-4-aminobutyric acid (NMBA) were found in batches of other sartans, such as losartan and irbesartan. All of these are carcinogens and harmful if consumed at a level beyond a certain acceptable daily limit. Ranitidine, and more recent metformin recalls, have also been linked with valsartan in view of the presence of NDMA, the same impurity. Safety of ARBs is a major concern among healthcare professionals after the recalls of valsartan in the recent years. Periodic quality assessment of the manufacturing process and the drugs is key to ensure safe, effective and high-quality drugs for the global population. Additionally, practising physicians need to be vigilant in reporting adverse events in their patients receiving treatments.

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“…A research letter published in Circulation related to the 2018 valsartan recall highlights the challenge our health system faces addressing these supply chain issues. 27 Jackevicius et al. 27 found that although most patients taking a recalled valsartan product switched to another antihypertensive drug, approximately 10% of the patients did not refill an alternative medication.…”

Section: Regulatory Challengesmentioning

confidence: 99%

“… 27 Jackevicius et al. 27 found that although most patients taking a recalled valsartan product switched to another antihypertensive drug, approximately 10% of the patients did not refill an alternative medication. They also reported a small but statistically significant increase in the rate of hypertension-related emergency department visits, which may be associated with the recall (from 0.11% to 0.17%; P = 0.02).…”

Section: Regulatory Challengesmentioning

confidence: 99%

The U.S. medicine chest: Understanding the U.S. pharmaceutical supply chain and the role of the pharmacist

Costantino¹

2021

Journal of the American Pharmacists Association

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The U.S. capacity to manufacture key essential medications has diminished. The U.S. pharmaceutical supply chain (USPSC) has diversified and now relies on international sources of active pharmaceutical ingredients and finished drug products (FDPs). Despite years of effort raising concerns about the USPSC, pharmacists and pharmacy technicians continue to spend a substantial amount of time and energy responding to, and mitigating the impact of, medication shortages, drug recalls, and the adverse outcomes related to low-quality medications. The extent of U.S. reliance on foreign sources of medications is largely unknown. Pharmacists do not have a reliable way to determine the country of origin (i.e., source), capacity, or geographic location of pharmaceutical manufacturers, limiting our ability to anticipate challenges or mitigate risks to our Nation’s drug supply. The U.S. Food and Drug Administration’s task of regulating quality and safety is challenging and will likely require additional safeguards and resources. In addition to pharmacists’ engagement, solutions will likely need to leverage a mix of policy, economic incentives, and expanded objective surveillance testing. The U.S. pharmaceutical supply chain is complex, global, and goes beyond FDPs. The 2020 American Pharmacists Association House of Delegates has rightly asserted that “The quality and safety of pharmaceutical and other medical products and the global pharmaceutical and medical product supply chain are essential to the United States national security and public health.” Pharmacy professionals on the front line engage with patients, identify medication-related issues, and engage in drug-procurement decisions. Pharmacists are essential to our nation’s overall health and must be engaged in the development and implementation of strategies to safeguard the USPSC.

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Population Impact of Generic Valsartan Recall

Cited by 23 publications

References 3 publications

Impact of angiotensin receptor blocker product recalls on antihypertensive prescribing in Germany

Impact of angiotensin receptor blocker product recalls on antihypertensive prescribing in Germany

Understanding the molecular–pharmaceutical basis of sartan recalls focusing on valsartan

The U.S. medicine chest: Understanding the U.S. pharmaceutical supply chain and the role of the pharmacist

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