Pharmacokinetic profile of irinotecan in patients with chronic kidney disease: Two cases and literature review.

AIMS: There are limited pharmacokinetic data on the use of irinotecan in patients with reduced glomerular filtration rate (GFR) and no haemodialysis. In this case report, we present 2 cases and review the current literature. METHODS: The dose of irinotecan in both patients was reduced pre-emptively due to reduced GFR. The first patient had her irinotecan dose reduced to 50%, but was nevertheless admitted to hospital because of irinotecan-induced toxicity, including gastrointestinal toxicity and neutropenic fever. The dose was reduced further to 40% for the second cycle; however, the patient was again admitted to the hospital, and irinotecan was stopped indefinitely. The second patient also had his irinotecan dose reduced to 50% and was admitted to the emergency department for gastrointestinal toxicity after the first cycle. However, irinotecan could be administered in the same dose in later cycles. RESULTS: The area under the curve to infinity of irinotecan and SN-38 in the first patient were comparable to those of an individual receiving 100% dose intensity. The area under the curve to infinity of irinotecan and SN-38 in patient 2 in both cycles were slightly less than reference values. Furthermore, clearance values of irinotecan and SN-38 in our patients were comparable to those without renal impairment. CONCLUSION: Our case report suggests that reduced GFR may not significantly affect the clearance of irinotecan and SN-38, but can still result in clinical toxicity. Reduced initial dosing seems indicated in this patient population. Further research is needed to fully understand the relationship between reduced GFR, pharmacokinetics, and toxicity of irinotecan and SN-38.

Prevalence and recognition of highly significant medication-smoking cessation interactions in a smoke-free hospital.

BACKGROUND: Some medications are more rapidly metabolized by smokers; upon smoking cessation, medication metabolism may be significantly reduced, resulting in medication-related adverse events. Clozapine, olanzapine and theophylline have been deemed to have potentially highly significant interactions with smoking cessation, which could lead to seizures, extrapyramidal effects and tachycardia, respectively. This study examined the period prevalence and characteristics of patients at risk of highly significant medication-smoking cessation interactions when admitted to a smoke-free hospital. METHODS: A retrospective cross-sectional study was undertaken in an Australian tertiary-referral hospital with a well-established electronic prescribing system. Smokers prescribed clozapine, olanzapine or theophylline prior to and during a hospital admission in 2015 were included. Length of hospital stay, daily doses, and recognition of the potential interaction by treating clinicians were determined from medical records. RESULTS: The period prevalence of patients at risk of a potentially highly significant medication-smoking cessation interaction was 23/48 (48%), 66/256 (26%) and 1/16 (6%) amongst smokers prescribed clozapine, olanzapine or theophylline, respectively. These interactions were poorly recognized by healthcare professionals during the admission. CONCLUSIONS: Up to one in two patients receiving medications that have potentially highly significant interactions with smoking cessation may be experiencing clinically significant potential interactions. Such interactions, however, were commonly overlooked by hospital staff. Interventions to improve awareness of this issue are warranted.

Factors associated with nicotine replacement therapy use among hospitalised smokers.

INTRODUCTION AND AIMS: Nicotine replacement therapy (NRT) is recommended as a smoking cessation aid for hospitalised smokers. We examined factors associated with NRT use during hospitalisation and after discharge, and NRT uptake when systematically offered free of cost. DESIGN AND METHODS: A nested analysis was conducted using data from a clinical trial that evaluated the effectiveness of a pharmacist-led smoking cessation intervention in 600 hospitalised smokers. RESULTS: NRT was used at least once by 285 (48%) participants during hospitalisation and by 287 (48%) participants during the 12 months post-discharge. Heavy smokers and those who expressed interest in using NRT for their next quit attempt at baseline interview were more likely to use NRT during hospitalisation [odds ratio (OR) 1.94, 95% confidence interval (CI) 1.38, 2.74; OR 2.09, 95% CI 1.48, 2.95] and after discharge (OR 1.70, 95% CI 1.20, 2.41; OR 1.97, 95% CI 1.39, 2.79). Those using six or more medications were more likely to use NRT during hospitalisation (OR 1.65, 95% CI 1.05, 2.61). Post-discharge NRT users were more likely to have been initially admitted for a respiratory or cardiac problem (OR 1.51, 95% CI 1.05, 2.18). When NRT was offered free of cost to a subset of patients (n = 300), 157 (52%) used NRT during hospitalisation. Nicotine dependence and interest in using NRT predicted its use (OR 2.26, 95% CI 1.38, 3.70; OR 2.58, 95% CI 1.58, 4.20). DISCUSSION AND CONCLUSIONS: Targeting heavy smokers, those with cardio-respiratory conditions and those interested in using NRT regardless of regimen complexity could improve NRT uptake.