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Salt in Fizzy Tablets Linked to Heart, Death Risk

— Warning signals seen for fast-acting acetaminophen and other drugs

MedpageToday
A photo of an effervescent tablet in water releasing bubbles.

Sodium-containing acetaminophen was associated with increased cardiovascular and mortality risk in older people, according to a report sounding the alarm on the potential dangers of fast-acting prescription and over-the-counter drugs alike.

A large U.K. database of electronic health records revealed significant excess in 1-year incidence of myocardial infarction, stroke, and heart failure associated with sodium-containing acetaminophen therapy use compared with standard formulations:

  • A 59% relative increase in risk for those with hypertension (5.6% vs 4.6%)
  • A 45% relative increase in risk for those without hypertension (4.4% vs 3.7%)

All-cause mortality risk over 1 year was twofold elevated in the hypertension patients taking sodium-containing acetaminophen and 87% elevated in users without hypertension. Risk increased in step with more prescriptions and longer durations of use of these medications, according to the study authors.

Similar risks were observed for the subgroups of patients also using sodium-containing ibuprofen or ranitidine, epidemiologist Yuqing Zhang, DSc, of Massachusetts General Hospital and Harvard Medical School, and colleagues reported in .

"Sodium-containing drugs are an important source of sodium intake that could be easily overlooked," study authors wrote. "Given that the pain-relief of non-sodium-containing acetaminophen is similar to that of sodium-containing acetaminophen, our results suggest re-visiting the safety profile of effervescent and soluble acetaminophen use."

Whereas traditional formulations in tablet, oral suspension, or capsule form do not contain sodium, fizzy or soluble drug preparations rely on it for fast-acting disintegration.

And the sodium can really add up, cautioned Aletta Schutte, PhD, and Bruce Neal, MBChB, PhD, both of The George Institute for Global Health in Sydney, Australia.

If a given fizzy acetaminophen tablet has 400 mg of sodium, a day's worth at full dose would add 3,000 mg of sodium per day -- far above the daily recommended sodium intake for an adult, they wrote in an .

"Large increments would also be anticipated for other types of effervescent medications, with a single 5 g sachet of effervescent antacids containing 850 mg of sodium, fizzy vitamins 280 mg of sodium per tablet, and urinary alkalinizers some 644 mg of sodium per dose," the editorialists estimated.

As such, Schutte and Neal urged "urgent action" on sodium-containing medications.

"Particularly concerning is the observation in some surveys that up to 94% of uses of fizzy medications are self-medication using over-the-counter preparations. There is an immediate need for protection of consumers against these risks. The most plausible and effective strategy is likely to be the mandatory labelling of all medications containing significant quantities of sodium with a front-of-pack warning label," they said.

"Information programmes that raise public and practitioner awareness of the hidden sodium in medications, and educate about the need to avoid effervescent, dispersible, and soluble medicines in all but essential circumstances should also be considered," according to the editorialists.

The study was based on the Health Improvement Network with patient records spanning 2000 to 2017. Included were nearly 300,000 people (average age in the early 70s) with physician-ordered acetaminophen prescriptions started during the study period.

Sodium-containing formulations were prescribed to 3.0% of individuals with hypertension and 3.6% of those without it. Significantly more women were in the group taking sodium-containing acetaminophen.

Zhang's team acknowledged that the study was limited by the potential for residual confounding and the lack of urinary sodium excretion or dietary sodium intake data. Investigators also couldn't adjust for over-the-counter acetaminophen use.

"The results are compelling. The effects were consistent across several different methodological approaches and in a series of sensitivity analyses," Schutte and Neal maintained.

"Large-scale supplementation of dietary sodium in a randomized trial studying cardiovascualr [sic] outcomes has never been done and would almost certainly be viewed as unethical. This type of analysis is as close as researchers are ever likely to come to doing that trial, and, while the current report is observational in nature, it provides strong evidence of harmful effects of adding large quantities of sodium to the diet," they said.

  • author['full_name']

    Nicole Lou is a reporter for ֱ, where she covers cardiology news and other developments in medicine.

Disclosures

The study was funded by Chinese national and local grants.

Zhang, Schutte, and Neal had no disclosures.

Primary Source

European Heart Journal

Zeng C, et al "Sodium-containing acetaminophen and cardiovascular outcomes in individuals with and without hypertension" Eur Heart J 2022; DOI: 10.1093/eurheartj/ehac059/6535634.

Secondary Source

European Heart Journal

Schutte AE, Neal B "The sodium hidden in medication: a tough pill to swallow" Eur Heart J 2022; DOI: 10.1093/eurheartj/ehab888/6535540.