Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies target the underlying cause of cystic fibrosis (CF), and are generally well-tolerated; however, real-world studies indicate the frequency of discontinuation and adverse events (AEs) may be higher than what was observed in clinical trials. The objectives of this systematic review were to summarize real-world AEs reported for market-available CFTR modulators (i.e., ivacaftor (IVA), lumacaftor/ivacaftor (LUM/IVA), tezacaftor/ivacaftor (TEZ/IVA), and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA)), and to identify ways in which the pharmacist on CF healthcare teams may contribute to mitigating and managing these AEs. The MEDLINE, EMBASE, CINAHL, and Web of Science Core Collection online databases were searched from 2012 to 1 Aug 2020. Full manuscripts or conference abstracts of observational studies, case series, and case reports were eligible for inclusion. The included full manuscripts and conference abstracts comprised of 54 observational studies, 5 case series, and 9 case reports. The types of AEs reported generally aligned with what have been observed in clinical trials. LUM/IVA was associated with a higher frequency of respiratory-related AE and discontinuation in real-world studies. A signal for mental health and neurocognitive AEs was identified with all 4 CFTR modulators. A systematic approach to monitoring for AEs in people with CF on CFTR modulators in the real-world setting is necessary to help better understand potential AEs, as well as patient characteristics that may be associated with higher risk of certain AEs. Pharmacists play a key role in the safe initiation and monitoring of people with CF on CFTR modulator therapies.

BackgroundGenetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood.ObjectivesThe objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed.MethodsMEDLINE (1946–3 May, 2017), EMBASE (1974–3 May, 2017), Pharmacogenomics Knowledge Base, and Public Health Genomics Knowledge Base online databases were searched. Studies were included if genotyping and analyses of phenytoin pharmacokinetics were performed in patients of the Middle East and North Africa region. Study quality was assessed using a National Institutes of Health assessment tool. A secondary search identified studies reporting genotypic and allelic frequencies of assessed genetic polymorphisms within the Middle East and North Africa region.ResultsFive studies met the inclusion criteria. CYP2C9, CYP2C19, and multidrug resistance protein 1 C3435T variants were evaluated. While CYP2C9*2 and *3 variants significantly reduced phenytoin metabolism, the impacts of CYP2C19*2 and *3 variants were unclear. The multidrug resistance protein 1 CC genotype was associated with drug-resistant epilepsy, but reported impacts on phenytoin pharmacokinetics were conflicting. Appreciable variability in minor allele frequencies existed both between and within countries of the Middle East and North Africa region.Conclusions CYP2C9 decrease-of-function alleles altered phenytoin pharmacokinetics in patients originating from the Middle East and North Africa region. The impacts of CYP2C19 and multidrug resistance protein 1 C3435T variants on phenytoin pharmacokinetic and clinical outcomes are unclear and require further investigation. Future research should focus on the clinical outcomes associated with phenytoin therapy.PROSPERO 2017: CRD42017057850

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Intranasal lidocaine has been studied and recommended as an alternative in the management of acute headache. The objective of this systematic review was to evaluate the efficacy and safety of intranasal lidocaine in the acute management of primary headaches. The MEDLINE (1946 to May 2018), EMBASE (1974 to May 2018), Cochrane Central Register of Controlled Trials (2008 to May 2018), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to May 2018), and ClincialTrials.gov online databases were searched. Studies conducted in patients with acute primary headache were included if lidocaine was compared with placebo or alternative treatments, lidocaine dosing was specified, and patients' pain before and after treatment were clearly reported. Six studies met the inclusion criteria. Intranasal lidocaine demonstrated potential benefit over placebo in acute pain reduction and need for rescue medication only in the four studies deemed to be of poor quality, not in the two fair-quality studies. No study reported benefit in preventing headache recurrence or repeat visits to the emergency department. Lidocaine was associated with significantly higher rates of adverse events compared with placebo and may result in lower rates of patient satisfaction. There is insufficient evidence to support the use of intranasal lidocaine in acute management of primary headaches. Further research is warranted to better elucidate whether intranasal lidocaine has a role in the management of specific primary headache subtypes and whether there is an optimal regimen.