Neonatal Abstinence Syndrome and Corresponding Pharmacotherapy Approaches from 2 University-affiliated Neonatal Intensive Care Units in Puerto Rico (2018-2020).

OBJECTIVE: Neonatal abstinence syndrome (NAS) is a set of drug withdrawal symptoms suffered by neonates exposed to drugs in utero. Several studies have widely described NAS incidence and treatment approach; however, little is known regarding the incidence and manifestations of this disease in Puerto Rico (PR). The principal aim of this study was to describe NAS incidence in the neonatal units of hospitals affiliated with the University of PR in terms of occurrence, clinical manifestations, and treatment approaches. METHODS: Our study evaluated the medical records of NAS babies diagnosed from 2018 through 2020 at 2 hospitals affiliated with the University of PR Medical Sciences Campus. Descriptive and inferential statistics were employed to analyze trends. RESULTS: We identified 12 neonates diagnosed with NAS, 5 with low birthweights (<2500 g); for a NAS incidence of 2 cases per 1000 admitted for the 3 years of recollected data. The urine toxicology results revealed that 9 had experienced intrauterine polydrug exposure. Phenobarbital loading dose were determined on the day of diagnosis (indicated by Finnegan score). The first manifestation of NAS symptoms varied: 8 neonates showed symptoms within 48 hours after birth, whereas 4 had withdrawal symptoms within 72-120 hours of their births. Differences between dosing practices and guidelines were observed, ranging from a 0.69% to a 25% difference during treatment initiation. CONCLUSION: Further research on the incidence of NAS in PR (national level) is needed for a deeper understanding that we hope will lead to the development of enhanced treatment protocols in PR.

Experiences and Preferences of Opioid-Use-Disorder Patients Who Switched from Brand to Generic Buprenorphine/Naloxone Films: A Case Series.

PURPOSE: Differences in the suppression of withdrawal symptoms have been observed in opioid-use-disorder (OUD) patients who were switched from Suboxone (the brand name of buprenorphine/naloxone sublingual films) to either 1 of 2 generic versions. These descriptive observations evidence the need to further assess the use of these generics and its impact on the adherence to and outcomes of OUD treatments. The objective of this case series was to describe patient and provider experiences, perceptions, and preferences when said patients were abruptly switched from Suboxone to one of the generic versions manufactured by Sandoz or Alvogen. PATIENTS AND METHODS: A retrospective chart review of 24 Suboxone-maintained OUD patients from a single clinic who were forced to switch to a generic was performed to collect withdrawal and craving symptoms that occurred after the switch, as well as toxicology results and changes in dose (documented by the provider). RESULTS: The medical records of 9 (37.5%) of the 24 patients showed that they were suffering from withdrawal symptoms and/or cravings, had had their doses adjusted, and/or had had a positive urine toxicology screen. All 9 subjects communicated a preference for the brand formulation over that of either of the generic versions; few expressed a preference for one generic formulation over the other. None of patients were able to switch back to the brand formulation, nor were any of them able to choose the generic that worked best for them. Insomnia, muscle pain, and gooseflesh skin were the most common withdrawal symptoms reported by the patients using the generics. Better outcomes were observed in patients who received a buprenorphine dose increase (2 mg) to suppress the withdrawal symptoms experienced while using the generics. CONCLUSION: Our study serves as a reference to prescribers regarding approaches (eg, a small dose adjustment) that may potentially encourage OUD treatment adherence and even improve outcomes in patients who appear to be decompensating after the brand-to-generic switch.

Brand-to-Generic Substitution of Buprenorphine/Naloxone Sublingual Film in Puerto Rico: A Case Study.

A 56-year-old patient with a 1-year history of stable maintenance treatment with Suboxone for opioid use disorder (OUD) was switched to a generic formulation in May of 2019. The patient reported experiencing-over the course of the following 3 months-withdrawal symptoms when switched to the Alvogen-produced generic formulation in May of 2019 and then to the Sandoz-produced version in July of that same year, she also was positive for fentanyl during that time. As a result, the buprenorphine dose was increased, and the patient was stable at this new dose using the generic versions. Blood levels pre- and post-change (not reported in previous case reports) showed maximum buprenorphine concentration being reached more quickly when the brand-name drug was used. Additionally, the area under the curve (AUC) values indicate that the generic formulation had higher exposures than the brand-name drug. Based on the clinical impact of the brand-to generic switch in this patient, further research in this area is warranted. In the meantime, clinicians should carefully monitor their patients so that, if warranted, dose adjustments can be made quickly and safely to minimize negatively impacting the OUD therapy outcomes of patients.

Characterization of amorphous celecoxib mixed with plasticizing (TPGS) and anti-plasticizing (PVP) ingredients using Hot Melt Extrusion.

PURPOSE: Hot melt extrusion (HME) has demonstrated to be an adequate compounding method for poorly-soluble pharmaceutical drugs, as it increases its solubility by fixing its amorphous solid-state using polymers (plasticizing) and other ingredients (non- plasticizing). However, it's amorphous state of the drug and the stability of the amorphous state will greatly depend on its interactions with these (plasticizing or not). METHODS: In this study, we aimed at characterizing the impact of the combination of plasticizing (TPGS) and anti-plasticizing (PVP) ingredients in amorphous celecoxib prepared using HME in terms of chemical interactions between the components (FTIR, Raman and NMR), viscoelasticity (loss and storage modulus) and required energy for flow (activation energy). Different celecoxib/PVP/TPGS ratios were studied to understand the synergistic effect of PVP and TPGS in inhibiting the crystallization of celecoxib when preparing amorphous dispersions using HME. We aimed at linking the viscoelastic properties of the melt with the resulting amorphous state described by the chemical interactions upon extrusion. RESULTS: The amorphous state of celecoxib was evidenced by strengthening of H-bonding between celecoxib and PVP, lack of characteristic crystalline peaks of celecoxib, and deshielding of aromatic protons. The melt was also characterized in terms of viscoelastic temperature dependent behavior (liquid G"; elastic G'), where increasing amounts of TPGS and PVP showed opposites effects; TPGS reduced the viscoelastic response whereas PVP increased it. Calculated melt activation energies (Ea) from the temperature dependent viscosity revealed a threshold of TPGS concentration where samples with 1% w/w of TPGS showed higher flow activation energies (higher Ea) independent of the drug/polymer ratios, compared to samples with higher amounts of TPGS. CONCLUSIONS: Low drug content combined with anti-plasticizing (PVP) amounts and relatively low plasticizing (TPGS) amounts yields an amorphous dispersion that is characterized with strong H-bonding due to efficient mixing using HME.

Pharmacokinetic Characterization and External Evaluation of a Quantitative Framework of Sublingual Buprenorphine in Patients with an Opioid Disorder in Puerto Rico.

BACKGROUND: The aim of this analysis was to characterize the pharmacokinetics (PK) of sublingual buprenorphine (BUP) and its metabolites (buprenorphine glucuronide; BUP-g, norbuprenorphine; Nor-BUP, and norbuprenorphine glucuronide; Nor-BUP-g) in opioid use disorder (OUD) patients in Puerto Rico (PR) as a first step of evidence-based BUP dosing strategies in this population. METHODS: BUP and metabolites concentrations were measured from 0 to 8 h after the administration of sublingual buprenorphine/naloxone films in 12 stable OUD subjects. RESULTS: PK non-compartmental characteristics showed considerable variability in parameters between the subjects over the 8-h sampling time (tmax = 1.5 ± 0.7 h, Co = 1.6 ± 1.4 ng/mL, Cmax= 7.1 ± 6 ng/mL, and AUC0-8h = 26.8 ± 17.8 h·ng/mL). Subjects had a significantly higher tendency towards CYP-mediated N-demethylation, with the AUC0-8h ratios of the molar concentrations of [Nor-BUP + Nor-BUP-g] to BUP being (3.4 ± 1.9) significantly higher compared with BUP-g to BUP (0.19 ± 0.2). A two-compartment population-PK model with linear absorption (ka = 2.54 h-1), distribution (k12= 2.34 h-1, k14 = 1.29 h-1), metabolism (k24 = 1.28 × 10-1 h-1, k23 = 6.43 × 10-2 h-1, k35 = 1.23 × 10-1 h-1, k45 = 8.73 × 10-1 h-1), and elimination (k30 = 3.81 × 10-3 h-1, k50 = 1.27 × 10-1 h-1) adequately described the time-course of BUP and its metabolites, which has been externally validated using published data. CONCLUSIONS: Although limited in sampling time and number of recruited subjects, this study presents specific BUP PK characteristics that evidenced the need for additional PK studies and subsequent modeling of the data for the development of evidence-based dosing approaches in Puerto Rico.

Readiness to provide pharmaceutical care to transgender patients: Perspectives from pharmacists and transgender individuals.

OBJECTIVES: The objectives of this study were (1) to assess pharmacist readiness to provide pharmaceutical care for transgender patients through measuring both pharmacists' knowledge and attitudes towards transgender patients, (2) to assess transgender patients' perception of pharmacist readiness to provide them pharmaceutical care through measuring both pharmacists' knowledge and attitudes toward them, and (3) to compare pharmacist readiness to provide pharmaceutical care for transgender patients and patient perception of this readiness. DESIGN: The study used a descriptive, cross-sectional design. The pharmacist's readiness and the transgender patient's perception of their readiness, defined as a combination of knowledge and attitude, were evaluated. Two separate, validated questionnaires with dichotomous, multiple choice, and open-ended questions were used to measure both constructs among both populations. SETTING: Community-based research. PARTICIPANTS: Pharmacists practicing in Puerto Rico were provided the questionnaire by e-mail or in person. Transgender participants in Puerto Rico were recruited through health clinics and community partners and were surveyed in person. The analysis included responses from 96 pharmacists and 31 transgender participants. RESULTS: The majority of the pharmacists' knowledge scores (90%) were found in the low (0-5) and moderate (6-10) ranges, with a mean score of 7.23 out of a total possible score of 16 (SD ±2.36). For the attitude construct, most of the scores (81%) were found in the high (18-26) range, with a mean score of 19.63 out of a total possible score of 26 (SD ±3.65). For both constructs, transgender patient perceptions echoed the results of the pharmacists, indicating several perceived knowledge deficits in combination with mostly positive attitudes. CONCLUSION: The majority of pharmacists demonstrated positive attitudes toward caring for transgender patients, and transgender patients also perceived these positive attitudes from pharmacists. However, the measured and perceived knowledge deficits observed in this study suggest the need for educational interventions to improve pharmacist readiness to provide care for transgender patients.