Drug-drug interactions with CFTR modulator therapy in cystic fibrosis: Focus on Trikafta®/Kaftrio®.

The combination of CFTR modulators ivacaftor, tezacaftor and elexacaftor (Trikafta®, Kaftrio®) significantly improve outcomes, including survival in a broad range of cystic fibrosis patients. These drugs have complicated metabolic profiles that make the potential for drug interactions an important consideration for prescribers, care providers and patients. Prolonged survival also increases risk of age-related disease and their associated pharmacotherapy, further increasing the risk of drug interactions and the need for increased vigilance amongst care providers. We systematically searched the literature for studies identifying and evaluating pharmacokinetic and pharmacodynamic drug interactions involving the components of Trikafta®/Kaftrio®. We also searched electronic databases of drugs for possible drug interactions based on metabolic profiles. We identified 86 potential drug interactions of which 13 were supported by 14 studies. There is a significant need for research to describe the likelihood, magnitude and clinical impact of the drug interactions proposed here.

Lower opioid and higher adjuvant analgesic use in patients on haemodialysis: A single-centre cross-sectional study.

WHAT IS KNOWN: Opioids are often used to treat chronic non-cancer pain (CNCP) in patients on haemodialysis. Altered pharmacokinetics in this population increases risk for opioid-related adverse events. Although useful in pain management, there is a lack of opioid prescribing guidance for end-stage kidney disease. OBJECTIVE: To characterize opioid usage for CNCP in an outpatient haemodialysis unit. METHODS: Cross-sectional, single-centre, retrospective cohort study of 272 patients receiving outpatient haemodialysis between 01 June and 31 December 2017. Prevalence of prescription or non-prescription opioids, formulation, indication, dosing, prescriber type and therapeutic effectiveness were evaluated. RESULTS: A total of 27 (10%, aged 58 + 12.1 years, 59% women) patients received opioids for CNCP during the study period. Pain aetiology was diverse; 14 (52%) patients experienced multiple concurrent chronic pain conditions. Hydromorphone (55%) and oxycodone (37%) were the most common prescriptions. A majority (85%) of patients used non-opioid analgesics as adjunct therapy, while half (48%) used benzodiazepines or zopiclone concurrently. Patients who completed a pain scale (n = 10) reported a median pain intensity of 6.8/10 ([IQR], 4.5-7.3). DISCUSSION: Opioid usage was lower than expected despite a higher prevalence of concurrent chronic pain conditions. Though this was within opioid usage guidelines, pain may not be sufficiently controlled. High concomitant use of benzodiazepines and Z-drugs introduces the potential for additive adverse effects. Judicious opioid usage can be facilitated with stewardship to effectively treat pain while avoiding associated harms and manage potential drug-drug interactions with common concomitant medications. WHAT IS NEW AND CONCLUSION: The prevalence of chronic opioid use for non-cancer pain in haemodialysis patients was lower than expected at our centre. Despite following the recommended guidelines, pain management was relatively ineffective, and concomitant use of non-opioid analgesics was widespread. Opioid stewardship is recommended to optimize pain treatment and mitigate drug interaction risks.