Safe “-sartans”

Key Points

  • Several Angiotensin Receptor Blockers (ARBs) have been recalled by the Federal Drug Administration (FDA). An updated list of affected manufacturers can be found online at https://www.fda.gov/Drugs/DrugSafety/ucm634620.htm
  • The risk of cancer from taking contaminated ARBs is low.
  • Patients should continue taking ARBs, even if affected by the recall, until they have a replacement from their pharmacy. If their pharmacy cannot obtain uncontaminated product, providers should write a prescription for a different ARB or a different drug class altogether.

ARB Recall

In July 2018, the Federal Drug Administration (FDA) announced a recall on valsartan after finding N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA). These substances are both types of nitrosamines, which are probable human carcinogens. At that time, only three manufacturers of the angiotensinogen receptor blocker (ARB) were affected. Now, more than 67 different products have been recalled along with valsartan. This list includes losartan, irbesartan, telmisartan, candesartan, azilsartan, and olmesartan. The number of affected products continues to rise as the FDA runs tests on more and more products.

Risk

Carcinogens in medications sounds like a very concerning problem, and it certainly is. However, it is important to quantify that risk. First of all, Americans are exposed to small amounts of this substance in things that we consume every day such as water, smoked and processed meats, and fresh vegetables. Secondly, it is estimated that if 8,000 people took the highest daily valsartan dose (320 mg) that contained NDMA, for four years (the amount of time it is believed the affected products had been on the U.S. market), there may be one additional case of cancer beyond the average cancer rate among Americans. To help put that into perspective, 1 out of 3 Americans will receive a cancer diagnosis over their lifetime.

These statistics should help put minds of both patients and practitioners more at ease, and hopefully it allows them to understand why the FDA still encourages patients to continue taking contaminated ARBs until they are able to obtain an unaffected drug. Medicine is all about balancing risk and benefit, and the FDA has determined that the risk of having a cardiac event while not taking an ARB is greater than the relatively low risk of developing cancer due to taking an affected medication.

Next Steps for Patients and Providers

Clearly communicating the risk to patients is key, but healthcare providers should also provide consistent instructions on what patients need to do next if they are on an ARB. Patients should be instructed that if they received a recalled ARB, they should expect to be contacted by their retail pharmacy. (If patients are afraid they were dispensed an impure medication but have not received any notification, they certainly are feel free to talk to their retail pharmacist.) Patients should continue taking the tablets they already have at home, recalled or not, until they receive a replacement from their pharmacist. If their retail pharmacy is unable to obtain a non-affected batch for dispensing, patients should contact their primary care physician to pursue other treatment options.

As providers, it is important to know what those “other treatment options can be.” It is important to keep the indication in mind. ARBs are shown to have mortality benefit for heart failure with reduced ejection fraction, so prescribing a therapeutically equivalent dose of another ARB is advisable (Table 1). Consider that the patient may be a good candidate for valsartan-sacubitril. If the ARB is being used for hypertension, remember that thiazides and calcium channel blockers are considered first-line agents unless there is otherwise a compelling indication.

Table 1: ARB Equivalent Dosing

Staying Up-to-Date On ARB Recalls

For the benefit of both patients and practitioners, the FDA has put together a list that lays out which products do not have nitrosamines present, which products still need to be tested, and which products have been removed from the market. This list is updated regularly and is posted on the FDA’s website to keep the public up to date. This list can be accessed at https://www.fda.gov/Drugs/DrugSafety/ucm634620.htm

References:

  1. Drug Safety and Availability – FDA’s Assessment of Currently Marketed ARB drug products. Center for Drug Evaluation and Research – https://www.fda.gov/Drugs/DrugSafety/ucm634620.htm
  2. Drug Safety and Availability – FDA’s Assessment of Currently Marketed ARB drug products Center for Drug Evaluation and Research – https://www.fda.gov/Drugs/DrugSafety/ucm634620.htm
  3. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, et al. ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017;136:e137–e161. DOI: 10.1161/CIR.0000000000000509.
  4. James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507–520. doi:10.1001/jama.2013.284427

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