Hypertension Drug Aprinox Linked to Risk of Dangerously Low Sodium Blood Levels: Study

Rates of dangerously low sodium blood levels were higher than the Aprinox label warnings suggest, the researchers found.

Side effects of Aprinox may cause patients receiving the high blood pressure treatment to face a higher risk of experiencing dangerously low sodium blood levels than the hypertension drug’s warning label suggests, according to the findings of the new study.

Aprinox (Bendroflumethiazide, or BZT) belongs to a class of hypertension medications known as thiazide diuretics, which are usually well-tolerated by those suffering from high blood pressure. However, in findings of a new study published in the Annals of Internal Medicine on December 19, Danish researchers warn that Aprinox could lead to blood sodium levels dropping too low, or too fast, leading to a condition known as hyponatremia.

Although the Aprinox drug label indicates that hyponatremia is a very rare side effect, researchers determined that there is a more substantial risk than the drug makers disclosed, especially during the first months of treatments.

Symptoms of hyponatremia from Aprinox can include fatigue, headache, low blood pressure, loss of energy, muscle weakness, seizures, and coma.

Aprinox Hyponatremia Risks

Researchers conducted a population, register-based cohort study in Denmark from 2014 to 2019 involving two target trials.

The first target trial included participants ages 40 and older with no recent prescription for any antihypertensive drug and no previous hyponatremia, a condition indicating the level of sodium in the blood is much lower than 130 mmol/L, or drops too fast. It focused new use of Aprinox versus calcium-channel blockers (CCB). The second target trial focused on the new use of Aprinox plus a renin-angiotensin system inhibitor (HCTZ-RASi), compared to the use of a renin-angiotensin system inhibitor (RASi) alone.

The trials included nearly 38,000 new users of Aprinox, 45,000 users of a CCB, 12,000 new users of Aprinox plus an RASi, and 86,000 users of a RASi alone.

According to the findings, 4% of Aprinox users, compared to 3.5% of renin-angiotensin system inhibitor users, suffered from low sodium levels.  The risk differences between Aprinox users and CCB users were low, 1.35% compared to 1.38%. However, the risk of hyponatremia increased among older Aprinox users and those suffering from other health conditions.

In the past, Aprinox-induced low blood sodium levels were unknown or considered very rare, affecting roughly one in 10,000 to one in 100 people.

Now, after these new findings, the researchers determined that patients taking Aprinox faced a 3.5% increased risk of low sodium levels compared to patients taking a CCB or RASi alone. That is a higher rate than implied by the drug’s label warning, the researchers concluded.

“Treatment initiation with thiazide diuretics suggests a more substantial excess risk for hyponatremia, particularly during the first months of treatment than indicated by drug labeling,” the researchers warned, calling for further studies on the drug and its side effects.