Prue Anderson

and 5 more

The emerging issue of rising gabapentinoid misuse is being recognised alongside the lack of current evidence supporting the safe and effective deprescribing of gabapentinoids. This scoping review aimed to assess the extent and nature of gabapentinoid deprescribing interventions in adults, either in reducing dosages, or prescribing of, gabapentinoids. Electronic databases were searched on 23rd February 2022 without restrictions. Eligible studies included randomised, non-randomised and observational studies that assessed an intervention aimed at reducing/ceasing the prescription/use of a gabapentinoid in adults for any indication in a clinical setting. The research outcomes investigated type of intervention, prescribing rates, cessations, patient outcomes, and adverse events. Extracted outcome data was categorised as either short (≤ 3 months), intermediate (>3 but <12 months) or long (≥ 12 months) term. A narrative synthesis was conducted. The four included studies were conducted in primary and acute care settings. Intervention were of dose reducing protocols, education and/or pharmacological-based approaches. In the randomised trials, gabapentinoid use could be ceased in at least one-third of participants. In the two observational trials, gabapentinoid prescribing rates decreased by 9%. Serious adverse events and adverse events specifically related to gabapentinoids were reported in one trial. No study included patient-focussed psychological interventions in the deprescribing process, nor provided any long-term follow-up. This review highlights the lack of existing evidence in this area. Due to limited available data, our review was unable to make any firm judgements on the most effective gabapentinoid deprescribing interventions in adults, highlighting the need for more research in this area.

Josephine Adattini

and 3 more

Background: Tyrosine kinase inhibitors (TKI) have revolutionised the treatment of chronic myeloid leukaemia (CML), but patients still experience treatment-limiting toxicities or therapeutic failure. Aims: To investigate real-world use and outcomes of imatinib in patients with CML in Australia. Methods: A retrospective cohort study of patients with CML commencing imatinib (2001-2018) was conducted across two sites. Prescribing patterns, tolerability outcomes, survival and molecular response were evaluated. Results: 86 patients received 89 imatinib treatments. Dose modifications were frequently observed (12-month rate of 58%). At last follow-up, 62 patients (5-year rate of 55%) had permanently discontinued imatinib treatment, of which 44 switched to another TKI (5-year rate of 46%). Within 3 months of starting imatinib, 43% (95% CI, 32–53%) of patients experienced imatinib-related grade ≥3 adverse drug reactions (ADRs). Higher comorbidity score, lower body weight, higher imatinib starting dose, and Middle Eastern or North African ancestry were associated with a higher risk of grade ≥ 3 ADR occurrence on multivariable analysis (MVA). Estimated overall survival and event-free survival rates at 3 years were 97% (95% CI, 92–100%) and 81% (95% CI, 72–92%), respectively. Cumulative incidence of major molecular response (MMR) at 3 years was 63% (95% CI, 50–73%). On MVA, imatinib starting dose, ELTS score, BCR-ABL1 transcript type, pre-existing pulmonary disease, and potential drug-drug interactions were predictive of MMR. Conclusion: Imatinib induced deep molecular responses that translated to good survival outcomes in a real-world setting, but was associated with a higher incidence of ADRs, dose modifications and treatment discontinuations than in clinical trials.

Adele Hosseini

and 2 more

Aims: This study investigated the safety, tolerability, and PK after administration of a specific Cannabis sativa cultivar extract, standardised to CBD content as sublingual wafer or oil formulation compared to nabiximols oromucosal spray. Methods: For the single-dose study, the design was an open-label, four-way crossover in 12 healthy volunteers randomised to receive a sequence of four different single doses of CBD as a sublingual wafer (25 or 50 mg CBD), oil solution (50 mg CBD), or nabiximols oromucosal spray (20 mg CBD, 21.6 mg THC). For the multiple-dose study, sublingual wafer (50 mg CBD) was administered twice a day for five days. Results: The extract was generally well tolerated by participants when administered in either wafer or oil form, with some adverse events, including mild or moderate somnolence, sedation and altered mood. The relative bioavailability of CBD after administration as a sublingual wafer was comparable with that of oil solution with 90% confidence interval of 83–131%. The median maximum concentrations of CBD after administration of oil solution and wafer was 9.4 and 11.9 ng mL-1, respectively. Maximum concentrations of CBD occurred 4 hours after administration, with an estimated terminal elimination half-life of 6 hours. There was no statistically significant difference between the AUC0-t of CBD after administration of oil solution or wafer compared with nabiximols oromucosal spray. Conclusion: Oil solution and sublingual wafer formulations of the extract standardised with CBD were well tolerated and demonstrated safe and achieved equivalent concentrations of CBD when compared to an available commercial formulation.

Stephen Clarke

and 6 more

AIM: This study aimed to assess the pharmacokinetics, tolerability, safety and exploratory analgesic efficacy of a novel water-soluble oro-buccal nanoparticle spray of a cannabis-based medicine in advanced cancer patients with unrelieved pain. METHODS: The study was a non-blinded single arm, single escalating dose (n=5) [2.5 mg Δ9-THC and 2.5 mg CBD) and multiple escalating doses (up to 5.5 doses)] of a two-stage pilot study in patients diagnosed with advanced cancers and intractable pain (n=25). RESULTS: As the cannabis-based medicine dose increased, maximum plasma concentrations of all analytes were approximately proportional to dose. The bioavailability of Δ9-THC and CBD in this water-soluble nanoparticle formulation was approximately twice the bioavailability reported for Δ9-THC/CBD formulation with ethanol. The water-soluble formulation in the current study resulted in a higher median (min, max) bioavailability of Δ9-THC than CBD (AUC from 2.5 mg each of Δ9-THC and CBD was 1.71 ng mL.h-1 (1.1, 6.6) and 0.65 ng mL.h-1 (0.49. 4.1), respectively). Analyte accumulation was not observed. In a subgroup of patients diagnosed with breast and prostate cancer with bone metastases, mean pain scores improvement from baseline was 40% (unadjusted) and 33% adjusted for rescue medication use. For all patients the most commonly reported adverse events were mild or moderate drowsiness affecting 11 (44%) and 4 (6%) patients, respectively and nausea and vomiting that affected 18 (72%) patients. CONCLUSIONS: The water-soluble cannabis-based medicine (NanaBisTM) provided acceptable bioavailability for Δ9-THC and CBD, appeared safe and tolerable in cancer with uncontrolled pain with preliminary evidence of analgesic efficacy.