Medications may cause elevated lactate levels which could potentially lead to hyperlactatemia and lactic acidosis, according to a systematic review published in the journal Pharmacotherapy.

To improve clinical knowledge of this rare, but potentially deadly side effect, study authors used the PubMed database to search for articles related to medication-induced lactate level elevation in which at least 1 patient over the age of 12 years was diagnosed with hyperlactatemia or lactic acidosis resulting from medication use. A total of 286 patients were identified among 101 articles that met the inclusion criteria; these cases were tied to 59 unique drugs. 

Among the causative agents, epinephrine (n=74) and albuterol (n=72) were found to be most commonly tied to medication-induced lactate level elevation (metformin and nucleoside/nucleotide reverse transcriptase inhibitors were excluded from the analysis). Other agents implicated in ≥5 cases included linezolid, oxaliplatin, and acetaminophen.

The majority of these cases involved the use of FDA-approved doses (86%), while 10.8% and 3.1% of cases were related to intentional overdoses or higher prescribed doses, respectively; patients in 40.8% of these cases continued on the medication without any change. The authors identified 6 deaths that were attributed to medication-induced lactic acidosis; no deaths were reported for medication-induced hyperlactatemia.


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As for management strategies, 95.2% of patients received supportive care (ie, mechanical ventilation, renal replacement therapy, cardiac device support). In some cases (15.2%), patients were given medication-specific antidotes, the most common being N-acetylcysteine (n=11), as well as exogenous bicarbonate therapy (23.8%). 

“Medication-induced lactate level elevation is an uncommon adverse effect and may be underreported in the literature,” the authors concluded. They added that “Unexplained lactate level elevations should prompt clinicians to assess for medication-induced lactate level elevations.”

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