PMID- 36893722 OWN - NLM STAT- MEDLINE DCOM- 20230406 LR - 20230406 IS - 1525-5069 (Electronic) IS - 1525-5050 (Linking) VI - 141 DP - 2023 Apr TI - Real-world, long-term evaluation of the tolerability and therapy retention of Epidiolex(R) (cannabidiol) in patients with refractory epilepsy. PG - 109159 LID - S1525-5050(23)00078-1 [pii] LID - 10.1016/j.yebeh.2023.109159 [doi] AB - OBJECTIVE: Epidiolex(R) (CBD) is FDA-approved for seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC). Phase III studies suggest that certain adverse effects (AEs), possibly linked to pharmacokinetic/pharmacodynamic (PK/PD) interactions may be therapy-limiting. We sought to identify these factors that contribute to treatment success and retention of therapy. METHODS: A single-center, retrospective review of patients with refractory epilepsy taking Epidiolex(R) was performed. Kaplan-Meier analysis was performed to describe Epidiolex(R) retention, as a measure of overall effectiveness. RESULTS: One hundred and twelve patients were screened; 4 were excluded due to loss to follow-up or never starting Epidiolex(R). Of 108 patients, mean age was 20.3 years (13.1, range 2 to 63), and 52.8% were female. Mean initial and maintenance doses were 5.3 mg/kg/day (1.3) and 15.3 mg/kg/day (5.8), respectively. At the final evaluation, 75% of patients remained on Epidiolex(R). The 25th percentile for discontinuation was 19 months. 46.3% of patients experienced at least one treatment-emergent adverse effect (TEAE) with 14.5% d/c Epidiolex(R) due to treatment emerging adverse effects (TEAE). The most common reasons for discontinuation were lack of efficacy (37%), increased seizure activity (22%), worsened behavior (22%), and sedation (22%). One out of 27 discontinuations was due to liver function test (LFT) elevations (3.7%). At initiation, 47.2% were concurrently taking clobazam, and 39.2% of those patients had an initial clobazam dose decrease. 53% of patients were able to either discontinue or lower the dose of at least one other antiseizure medication. SIGNIFICANCE: Epidiolex(R) is generally well-tolerated and the majority continued long-term treatment. Patterns of adverse effects were similar to clinical trials, however gastrointestinal complaints, and significant LFT elevations were less common. Our data suggest most patients discontinue within the first several months of treatment and suggest that further studies designed to evaluate early identification and potential mitigation of adverse effects and including drug interactions are warranted. CI - Copyright (c) 2023. Published by Elsevier Inc. FAU - Georgieva, Darina AU - Georgieva D AD - University of Wisconsin-Madison School of Pharmacy, USA; UW Health Pharmacy, USA. Electronic address: dgeorgieva@wisc.edu. FAU - Langley, James AU - Langley J AD - UW Health Pharmacy, USA. Electronic address: jlangley2@uwhealth.org. FAU - Hartkopf, Katherine AU - Hartkopf K AD - UW Health Pharmacy, USA. Electronic address: khartkopf@uwhealth.org. FAU - Hawk, Lisa AU - Hawk L AD - UW Health Pharmacy, USA. Electronic address: lhawk@uwhealth.org. FAU - Margolis, Amanda AU - Margolis A AD - University of Wisconsin-Madison School of Pharmacy, USA. Electronic address: amanda.margolis@wisc.edu. FAU - Struck, Aaron AU - Struck A AD - University of Wisconsin-Madison, Department of Neurology, USA. Electronic address: struck@neurology.wisc.edu. FAU - Felton, Elizabeth AU - Felton E AD - University of Wisconsin-Madison, Department of Neurology, USA. Electronic address: felton@neurology.wisc.edu. FAU - Hsu, David AU - Hsu D AD - University of Wisconsin-Madison, Department of Neurology, USA. Electronic address: hsu@neurology.wisc.edu. FAU - Gidal, Barry E AU - Gidal BE AD - University of Wisconsin-Madison School of Pharmacy, USA. LA - eng PT - Clinical Trial PT - Journal Article DEP - 20230307 PL - United States TA - Epilepsy Behav JT - Epilepsy & behavior : E&B JID - 100892858 RN - 0 (Anticonvulsants) RN - 19GBJ60SN5 (Cannabidiol) RN - 2MRO291B4U (Clobazam) SB - IM MH - Adolescent MH - Adult MH - Child MH - Child, Preschool MH - Female MH - Humans MH - Male MH - Middle Aged MH - Young Adult MH - Anticonvulsants/adverse effects MH - *Cannabidiol/adverse effects MH - Clobazam/therapeutic use MH - *Drug Resistant Epilepsy/drug therapy/chemically induced MH - *Drug-Related Side Effects and Adverse Reactions/drug therapy MH - *Lennox Gastaut Syndrome/drug therapy MH - Seizures/drug therapy/chemically induced OTO - NOTNLM OT - Adverse effects OT - Antiseizure medication OT - Cannabidiol OT - Drug interactions OT - Epilepsy COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Georgieva, Langley, Hartkopf, Hawk, Hsu - no conflicts or disclosures to report; Margolis- Research funding from UCB; Struck- Research funding from Ceribell, and NIH RO1NS111022; Felton- Consultant Abbott, Vitalfo; Gidal- Consultant- Eisai, SK-Life Science, Aquestive, UCB. Speaking honoraria- Eisai, SK Life Science, Jazz; All authors confirm that they have read the journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Gidal - Honoraria from Greenwich, Eisai, Aquestive, SK Life Science, UCB; Felton- Honoraria from Abbott labs, Vitaflo; All other authors report none. EDAT- 2023/03/10 06:00 MHDA- 2023/04/04 06:42 CRDT- 2023/03/09 18:21 PHST- 2022/12/27 00:00 [received] PHST- 2023/02/23 00:00 [revised] PHST- 2023/02/24 00:00 [accepted] PHST- 2023/04/04 06:42 [medline] PHST- 2023/03/10 06:00 [pubmed] PHST- 2023/03/09 18:21 [entrez] AID - S1525-5050(23)00078-1 [pii] AID - 10.1016/j.yebeh.2023.109159 [doi] PST - ppublish SO - Epilepsy Behav. 2023 Apr;141:109159. doi: 10.1016/j.yebeh.2023.109159. Epub 2023 Mar 7.