Effervescent, dispersible and soluble drug formulations appear to increase the risk for myocardial infarction, stroke and other cardiovascular events compared with lower salt or no-salt versions of the same medications, study findings indicate.

After adjusting for smoking, BMI and other CVD risk factors, regular users of such medications had a 16% greater risk for nonfatal stroke, nonfatal MI and vascular death (P<0.01) compared to those who used low or no-sodium versions, Jacob George, MD of University of Dundee in Scotland and colleagues reported in BMJ.

“Our results suggest that [clinicians] should prescribe sodium-containing formulations with caution and only if there are compelling reasons to do so,” the researchers wrote. “Sodium-loaded effervescent, soluble or dispersible tablets should be avoided in patients at risk of hypertension and patients prescribed these drugs should be carefully monitored for the emergence of hypertension.”

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Sodium bicarbonate is the key ingredient in many effervescent, dispersible and soluble medications, but drug manufacturers are not currently required to list the sodium content on their labels, the researchers explained.

For example, the sodium content for the effervescent formulation of paracetamol 500 mg (acetaminophen), the most widely prescribed medication in the study sample, contains between 16.9 mmol to 18.6 mmol per tablet. Taking the maximum daily dose of eight tablets per day would put sodium consumption at 148.8 mmol to 135.2 mmol, depending on the formulation.

U.S. dietary guidelines recommend limiting sodium intake to no more than 2,300 mg – 100 mmol/L or 1 teaspoon – per day. High-risk populations, including people aged older than 50 years, black patients and those with diabetes, hypertension or chronic kidney disease, are advised to limit daily sodium intake to no more than 1,500 mg.

However, several previous studies have concluded there is little evidence to support reducing sodium intake below 2,300 mg per day to decrease MI and stroke risk, even in high-risk groups.

Despite the report, the American Heart Association continues to recommend limiting daily sodium consumption to less than 1,500 mg for everyone, and WHO recommends a cut-off point of no more than 2,000 mg per day.

To determine whether taking prescription drugs that contain higher levels of sodium increases CV risk, George and colleagues conducted a nested, case-control study that involved data from 3 million people enrolled in the UK Clinical Practice Research Datalink (CPRD) database from 1987 to 2010.

Adults with a prescription for one of 24 different sodium-containing effervescent, dispersible and soluble medications, or a matched nonsodium formulation of the same drug, were included. Medications included pain relievers, antiemetics, vitamins, zinc and calcium supplements. 

The researchers matched a total of 61,072 people who experienced a cardiovascular event during the average 7.2 year follow-up period with case controls based on birth year, sex and general practice attended. The median time from the date of first prescription to a CV event was 3.92 years.

For the primary endpoint of incident nonfatal MI, incident nonfatal stroke and vascular death, the adjusted odds ratio for sodium-containing drug exposure was 1.16 (95% CI: 1.12-1.21).

The aORs for the following secondary enpoints were:

  • Hypertension: 7.18 (95% CI: 6.74-7.65)
  • All-cause mortality: 1.28 (95% CI: 1.23-1.33)
  • Incident nonfatal stroke: 1.22 (95% CI: 1.16-1.29)
  • Heart failure: 0.98 (95% CI: 0.93-1.04)
  • Incident nonfatal MI: 0.94 (95% CI: 0.88-1.00)
  • Vascular death: 0.70 (95% CI: 0.31-1.59)

In an analysis of the effects of cumulative doses of these medications, the researchers found a significant linear trend indicating a dose-response relationship with an aOR of 1.10 for the lowest third (≤7120 mmol sodium), 1.33 for the middle third (7,121-30,285 mmol sodium) and 1.31 for the highest third (>30,285 mmol sodium; P<0.01 for all).

“The sodium content of medicines seems to be an important topic that needs to be dealt with by regulatory agencies,” the researchers wrote. “At a minimum, the public should be warned about the potential hazards of high sodium consumption in prescribed medicines, and these should be clearly labeled with the sodium content in the same way as foods are labeled.”


  1. George J et al. BMJ. 2013;347:f6954