Potential drug-drug interactions and adverse drug reactions in patients with liver cirrhosis

Patients with liver cirrhosis may be at risk for potential drug-drug interactions (pDDIs) and/or adverse drug reactions (ADRs) due to the severity of their disease and comorbidities associated with polypharmacy. We performed a cross-sectional retrospective study including 400 cirrhotic patients and assessed diagnoses, medication patterns, pDDIs, and ADRs at hospital admission. The median (range) age of the patients was 60 (21-88) years; 68.5% were male. They had a total of 2,415 diagnoses, resulting in 6 (1-10) diagnoses per patient. Frequent were diagnoses of the digestive system (28.4%), circulatory system (14.2%), blood and blood-forming organs (8.7%), and psychiatric disorders (7.5%); 60.7% of the diagnoses were not liver-associated. The median number of drugs per patient was 5 (0-18), whereof 3 (0-16) were predominantly hepatically eliminated. Drugs were primarily indicated for gastrointestinal, cardiovascular, or nervous system disorders, reflecting the prevalent diagnoses. In 112 (28%) patients, 200 ADRs were detected, mainly associated with spironolactone, torasemide, furosemide, and ibuprofen. In 86 (21.5%) patients, 132 pDDIs were detected. Seven of these pDDIs were the direct cause of 15 ADRs, whereof 3 resulted in hospital admission. Patients with ADRs were older, had more comorbidities, were treated with more drugs, and had a worse renal function and more pDDIs than patients without ADRs. Pharmacotherapy is complex in cirrhotic patients. Hepatologists should know the principles of dose adjustment in cirrhosis and renal failure, but also the most important pDDIs of the drugs used to treat liver disease and comorbidities in this population.