Pharmacokinetic drug-drug interactions in the intensive care unit ― single-centre experience and literature review

 

BACKGROUND: Drug-drug interactions constitute a serious health hazard in everyday clinical practice in critically ill patients. Drug-drug interactions may be pharmacokinetic or pharmacodynamic in their nature. We aimed to investigate the quantity and quality of possible drug-drug interactions, and their possible side effects in intensive care unit patients in a 12-month period.

METHODS: This retrospective study covered data on pharmacological treatment of 43 consecutive patients (11 females, 32 males) aged 62 ± 15 years, hospitalized between January 2015 and February 2016. Pharmacokinetic DDIs were identified and graded. Only severe and clinically important drug-drug interactions were subjected for further analysis.

Results. Median baseline SAPS III was 53 (IQR 38–67) points. Median intensive care unit stay was 12 (6–25) days. Subjects were treated with a median number of 22 (12–27) drugs. We identified 27 (16–41) possible drug-drug interactions per patient, including 3 (1–7) drug-drug interactions of a severe grade. The total number of severe and clinically important drug-drug interactions was 253 of which 227 were analyzed in detail. No possible side-effects of drug-drug interactions were identified.

CONCLUSIONS: DDIs as well as their side-effects are challenging regarding their precise evaluation, especially due to the need for multidrug treatment in critically ill patients. Concentration-controlled therapy should be recommended, especially for treatment with vancomycin, digoxin and valproate. Pantoprazole should be a proton pump-inhibitor of choice. Drug dose modification is necessary in combined treatment with fluconazole and amiodarone or rifampicin. From a clinical point of view, the most important impact of drug-drug interactions is on antibiotic treatment effectiveness, especially with meropenem when valproate is also prescribed.

 

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