Because it can be difficult to metabolize, valsartan can severely affect the liver in some patients who take the medication. The risk may be exacerbated due to small amounts of carcinogenic toxins, known as nitrosamines, that have been discovered in some lots of valsartan and other medications of the ARB class.

What Is Valsartan and Why Is it Prescribed?

Valsartan, the generic version of Diovan, is part of the angiotensin II receptor blocker (ARB) class of blood pressure medications that also includes losartan and irbesartan. In addition to being indicated for hypertension, valsartan is also prescribed for the treatment of heart failure and diabetic kidney disease.

How Does Valsartan Work?

Valsartan’s mechanism of action is to disable cellular receptors on the muscles surrounding blood vessels that bind to angiotensin, an enzyme that causes them to constrict. By preventing these receptors from working, blood vessels are able to relax and open wider, reducing blood pressure.

How Does Valsartan Affect the Liver?

The National Institutes of Health report that valsartan can cause a liver condition known as cholestasis. This disease develops as a result of reduced flow of bile, a substance that plays an important role in digestion. Impaired bile flow can present any or all of the following symptoms:

• jaundice (yellowish skin and sclera)
• dark yellow or brown-colored urine
• pale-colored stools
• abdominal pain
• generalized fatigue
• nausea
• itchy skin

In addition to digestion, the liver is also largely responsible for processing, or metabolizing medications. Valsartan is among those drugs that are more difficult to metabolize. Because of this, valsartan is not recommended for patients with impaired liver function.

Do Nitrosamines Affect the Liver as Well?

Nitrosamines such as NDMA that have been detected in ARB medications are known to cause malignant tumors in several organs, including the liver, kidney, bladder, esophagus, lungs, and pancreas. According to a study published in the journal Oncotarget in December 2017, nitrosamines are “potent hepatotoxic agents” (i.e., poison to the liver) and can cause a condition known as hepatofibrosis, which can lead to cirrhosis and eventually, liver cancer.

Although NDMA may be found in common products including cured meats, tobacco, beer, cheese, shampoo, and detergents, the contaminant is deemed to be potentially dangerous to humans and consumers may want to limit their exposure. NDMA has caused tumors in animals and may be linked to gastric or colorectal cancer in humans.

Although the risk of NDMA exposure through medication is fairly low, any amount of exposure to it may be hazardous. The amount of NDMA found in valsartan and other medications has varied depending on the medication, the manufacturer, and the testing site.

How Did the Contamination Occur?

The initial NDMA contamination was traced to a factory in China, where the active ingredient was manufactured. The cause appears to have been the result of a change made in the production process, which was intended to increase efficiency. Unfortunately, it also resulted in an unexpected chemical reaction that caused the formation of NDMA.

Additionally, the way the drugs are stored may also affect the amount of NDMA found in them. According to Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, the temperature and length of time a drug is stored may increase the level of NDMA. “That explains a little bit why we saw NDMA in varying levels, even in the same drug from the same manufacturer,” she said.

Another source of nitrosamine contamination was traced to a factory in India, which had been cited by the FDA for violating good manufacturing practice rules.

According to USA Today, FDA inspectors who have visited some of the factories responsible for manufacturing valsartan and other drugs have reported broken or damaged machinery, a lack of quality control, and a failure to follow up on irregularities in the appearance of drugs, irregular testing results, or suspected contaminations. At one factory, employees were discovered shredding documents and records just before inspectors were scheduled to arrive.

Are There Alternatives That Do Not Affect the Liver?

Other medications that can treat hypertension include angiotensin-converting enzyme (ACE) inhibitors such as Zestril or Lotensin, although these medications have their own side effects. Those who are concerned about how valsartan or similar drugs may affect the liver should discuss the issues with their prescribing physician.