The Culprit – NDEA
NDEA is the abbreviation of N-nitrosodiethylamine. It is the chemical that appears to have contaminated some lots of irbesartan, a type of antihypertensive drug. The chemical is described as a transparent synthetic oil which is sensitive to light, volatile, transparent and also soluble in water, lipids as well as other organic solvents. It was also used as an additive for gasoline and lubricants, as an antioxidant and also as a stabilizer for industrial materials. The chemical is also said to emit toxic fumes when heated to a sufficiently high temperature. It is used in laboratories to cause liver tumors for experimental purposes – making it highly likely for it to be a carcinogen. Although there has been some debate over its carcinogenic properties, it is safe to say that NDEA causes carcinogenic concerns.Trace amounts of NDEA are said to have appeared in irbesartan tablets sold by Sciegen Pharmaceuticals, Inc. NDEA is not normally expected to be part of these drugs.
Traces would be a contamination or an impurity. This impurity prompted the company to voluntarily recall specific batches of irbesartan tablets (75 mg, 150 mg, and 300 mg USP dosage forms), according to the FDA (Food and Drug Administration).
Irbesartan – The Drug in Question
Irbesartan is described as an angiotensin II receptor antagonist (ARB), which is actually a hormone that starts out being a protein produced by your liver, called angiotensinogen. Renin, which is a hormone produced by your kidneys, converts angiotensinogen to angiotensin I. After this an enzyme called angiotensin converting enzyme (ACE) produced by your lungs converts angiotensin I to angiotensin II. Angiotensin II can then bind to the receptors of your blood vessels throughout your body, causing your blood vessels to tighten. This process is said to help regulate the flow of blood throughout the body. However, high blood pressure can occur when your blood vessels are too narrow, which can occur when vessel walls become too stiff or thick. ARBs such as irbesartan can block these angiotensin II receptors, relaxing and enlarging your blood vessels. That’s why doctors use ARBs to control high blood pressure and improve blood circulation in patients with weakened hearts.
A few months ago, the FDA announced that Torrent Pharmaceuticals Limited voluntarily recalled a different type of ARB, valsartan. The recall included valsartan tablets and those associated with amlodipine and hydrochlorothiazide. The impurity, in this case, was identified as N-nitrosodimethylamine (NDMA), another chemical that is said to be reasonably likely to be a carcinogen to humans. Zhejiang Huahai Pharmaceuticals was the company that manufactured these drugs.
These concerns currently only relate to specific batches of blood pressure medications from specific manufacturers. This does not imply most drugs for blood pressure. Scientists use higher concentrations of these chemicals to induce tumor growth (in the liver, lungs, and gastrointestinal tract) in laboratory animals. But humans are not lab rats, not in the biological sense at least. There have been no studies in which humans have been given different levels of NDEA and followed to see if they develop tumors. Therefore, it is not yet known to what extent exposure to NDEA or NDMA can cause cancer in humans, and the threshold probably varies from person to person.
Cumulative exposure over time is a more important concern. Repeated exposure to small amounts of these chemicals or similar products from other sources, could mean the effects add up, causing a severe ailment. That’s why minimizing exposure to these chemicals as much as possible is always recommended.
These two reminders underscore the importance of monitoring manufacturing processes and drug supply chains. Impurities could slip at almost every step in the chain. That is why a company outsourcing part of these processes should make sure that everyone involved complies with all applicable guidelines and regulations. It is up to the pharmaceutical industry to take appropriate measures.