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

Abstract

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.

Optimizing the Clinical Use of Carvedilol in Liver Cirrhosis Using a Physiologically Based Pharmacokinetic Modeling Approach

“…This finding indicate that drugs that can alter UGT enzymes activity [39] will play a more significant role in cirrhotic patients when compared to healthy population where CYP metabolism predominates the overall carvedilol metabolism. This is important keeping in mind that patients with liver cirrhosis have often multiple comorbidities that require a concurrent administration of different drugs with a higher potential for DDI's and eventually, ADR's [40]. Using the developed PBPK model, clinically possible ''what if'' scenarios can be explored and DDI's between carvedilol and other co-administered drugs (e.g.…”

Review article: depression and the use of antidepressants in patients with chronic liver disease or liver transplantation

“…79 Amitriptyline interacts with a number of drugs including certain antibiotics; a recent report described cirrhotic patients developing long QT c syndrome after co-administration of amitriptyline and trimethoprim-sulfamethoxazole. 68 There are no published trials of nortriptyline, clomipramine, dibenzepin, imipramine or trimipramine use in patients with liver disease, and only occasional reports of DILI associated with their use. 95 Consensus advice is for initial doses of TCAs to not exceed 50% of standard starting doses, with subsequent titration dependent upon the balance of efficacy and adverse effects.…”

“…65 To add to the complexity, changes to pharmacodynamics are also prevalent in patients with CLD; for instance, increased sensitivity is found for the central effects of opiates and benzodiazepines. 68 Because of these effects, considerable anxiety exists amongst clinicians regarding the risk of drug-induced liver injury (DILI) and drug-related adverse effects when prescribing in patients with CLD. With regards to DILI, there is scant evidence that patients with pre-existing liver disease are at any increased risk of DILI compared to those with healthy livers following administration of medications known to be associated with idiosyncratic drug hepatotoxicity; conversely, pre-existing liver disease may potentially protect against certain DILI in particular circumstances by interrupting metabolite-generating pathways.…”

“…These are currently the most common class of antidepressants prescribed to patients with CLD. 68 Side effects of these medications are rare, but include nausea and vomiting, diarrhoea, hyponatraemia, changes in cognition, sedation, apathy and -rarely -suicidal thoughts. A further concern regarding the safety of SSRIs is their apparent association with gastrointestinal bleeding.…”

Incidence of potential drug interactions in a transplant centre setting and relevance of electronic alerts for clinical practice support

“…11,12 The most vulnerable patients are those with chronic diseases that require long-term multitherapy; patients with liver or kidney failure who are using drugs included in the group at risk of interaction, and geriatric and paediatric patients, whose metabolic activity is significantly related to age. [13][14][15][16][17][18][19] To ensure safe therapy for these patients, appropriate drug prescription is required. In the age of information technology (IT) systems, the use of electronic health records and computerised physician order entry (CPOE) can be an efficacy tool to promote patient safety.…”