Severe Lactic Acidosis and Acute Pancreatitis Associated with Cimetidine in a Patient with Type 2 Diabetes Mellitus Taking Metformin

Seo, Ji Ho; Lee, Da Young; Hong, Chang Woo; Lee, In Hee; Ahn, Ki Sung; Kang, Gun Woo

doi:10.2169/internalmedicine.52.0697

Cited by 13 publications

(3 citation statements)

References 13 publications

(11 reference statements)

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“…Thus, the risk of AP due to the suspected drug is more easily discerned through the confounding factors and often is different from that gleaned from case report data. For example, an association between oral hypoglycemics and AP has been speculated based upon numerous published case reports [73][74][75]126,159,[287][288][289][290][427][428][429][430][431]491,506,604]; however, systematic review and/or meta-analysis of trial data have demonstrated no association with AP for vildagliptin alone [612] or for dipeptidyl peptidase-4 inhibitors (DPP4i) as a group (i.e., vildagliptin, sitagliptin, saxagliptin, alogliptin, linagliptin, and dutogliptin) [613]. Another systematic review of various study designs concluded that AP during oral hypoglycemic therapy was a rare event and that if an association exists, it is not as strong as originally thought [614].…”

Section: Discussionmentioning

confidence: 99%

Drug induced pancreatitis: A systematic review of case reports to determine potential drug associations

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Drug induced pancreatitis: A systematic review of case reports to determine potential drug associations

et al. 2020

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“…Overall, 20.7% of these patients died; four patients died from multiorgan failure (three from acetaminophen and erlotinib), and two died from an infection (sulfamethoxazole-trimethoprim and cimetidine). 27,38,106,112,115 The medication implicated in causing the drug-induced disease was permanently discontinued or not reported in 27 (93.1%) and 2 (6.9%) cases, respectively. The drug-induced disease should be managed with the appropriate supportive care and disease-state specific targeted therapies.…”

Section: Discussionmentioning

confidence: 99%

Medication‐Induced Hyperlactatemia and Lactic Acidosis: A Systematic Review of the Literature

2019

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Hyperlactatemia and lactic acidosis are two syndromes that are associated with morbidity and mortality. Medication-induced hyperlactatemia and lactic acidosis are diagnoses of exclusion and have the potential to be overlooked. The purposes of this systematic review are to identify published reports of medication-induced lactate level elevations to aid clinicians in diagnosing and comprehending the underlying mechanism of this rare adverse drug effect and to provide management strategies. The PubMed database was searched for case reports, case series, retrospective studies, and prospective studies describing cases of medication-induced lactate level elevation, including lactic acidosis and hyperlactatemia, published between January 1950 and June 2017. A standardized search strategy was used, and the articles identified underwent two rounds of independent evaluation by two reviewers to assess for inclusion. Articles were included if they described at least one patient older than 12 years with hyperlactatemia or lactic acidosis caused by a medication with United States Food and Drug Administration (FDA) approval and if alternative etiologies for an elevated lactate level were ruled out. Metformin and nucleoside/nucleotide reverse transcriptase inhibitors were excluded since the pathophysiology and incidence of lactic acidosis have been well established for these agents. Overall, 1918 articles were identified, and 101 met inclusion criteria. A total of 286 patients experienced medication-induced lactate level elevations, from which 59 unique medications were identified. The most commonly identified agents were epinephrine and albuterol. Medication-induced lactate level elevation was classified as lactic acidosis (64.0%), hyperlactatemia (31.1%), or not specified (4.9%). The doses ingested included FDA-labeled doses (86%), intentional overdoses (10.8%), or prescribed doses exceeding the FDA-labeled dose (3.1%). Medications were continued without a change (40.8%), were permanently discontinued (34.4%), were continued with a dosage reduction (11.6%), or were initially withheld then resumed after lactate level normalized (2.9%); medication management for the remaining 10.0% was not reported. Forty-six patients died (16%). Six deaths were attributed by treating clinicians to be secondary to medication-induced lactic acidosis. Management strategies were heterogeneous, and treatment included supportive care, exogenous bicarbonate therapy, medication specific antidotes, and decontamination strategies. Unexplained lactate level elevations should prompt clinicians to assess for medication-induced lactate level elevations. Pharmacists are members of the health care team that are well positioned to serve as experts in the diagnosis and management of medication-induced lactate level elevations. KEY WORDS adverse drug reactions, hyperlactatemia, systematic review, lactate, lactic acidosis. (Pharmacotherapy 2019;39(9):946-963)

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“… 17 , 18 Concomitant use of Metformin and Cimetidine decrease the excretion of Metformin, resulting in increased exposure of Metformin and elevated risk of Metformin Associated Lactic Acidosis (MALA). 19 , 20 It is recommended to reduce the dose of Metformin when Cimetidine is co-prescribed. 21 …”

Section: Interactions With Acid Suppressing Agentsmentioning

confidence: 99%

Drug Interactions of Metformin Involving Drug Transporter Proteins

Maideen¹,

Jumale²,

Balasubramaniam³

2017

Adv Pharm Bull

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Metformin is a most widely used medication all around the world to treat Type 2 diabetes mellitus. It is also found to be effective against various conditions including, Prediabetes, Gestational diabetes mellitus (GDM), Polycystic Ovarian Syndrome (PCOS), Obesity, Cancer, etc. It is a cationic drug and it depends Organic Cation Transporters (OCTs) and Multidrug and Toxin Extruders (MATEs) mostly for its pharmacokinetics movement. The probability of drug interaction increases with the number of concomitant medications. This article focuses the drug interactions of metformin and most of them are linked to the inhibition of OCTs and MATEs leading to increased plasma metformin concentrations and subsequent elevation of risk of Metformin Associated Lactic Acidosis (MALA). By identifying the drugs inhibiting OCTs and MATEs, the healthcare professionals can predict the drug interactions of metformin.

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Severe Lactic Acidosis and Acute Pancreatitis Associated with Cimetidine in a Patient with Type 2 Diabetes Mellitus Taking Metformin

Cited by 13 publications

References 13 publications

Drug induced pancreatitis: A systematic review of case reports to determine potential drug associations

Drug induced pancreatitis: A systematic review of case reports to determine potential drug associations

Medication‐Induced Hyperlactatemia and Lactic Acidosis: A Systematic Review of the Literature

Drug Interactions of Metformin Involving Drug Transporter Proteins

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