Introduction
Buprenorphine in the treatment of opioid use disorder (OUD) has several benefits including better long-term treatment adherence (1) and is a safer option for many patients due to buprenorphine’s limited potential to cause respiratory depression (4). In comparison to standard buprenorphine induction, induction via micro-dosing does not require a period of withdrawal and dramatically shortens the time required to complete induction. Prior micro-dosing protocols using sublingual (SL) (7-10) and transdermal forms (11) have been reported. We present a case of buprenorphine induction using a novel inpatient intravenous micro-dosing 4-day protocol in a patient on methadone.
Case Presentation
A 62-year-old man with chronic obstructive pulmonary disease (COPD) on chronic methadone 80mg daily for OUD presented with respiratory failure and was diagnosed with opioid overdose. He was transitioned from a naloxone infusion to intravenous micro-doses of buprenorphine and low dose methadone without experiencing significant withdrawal, and he was discharged on buprenorphine/naloxone SL.
Discussion
This case demonstrates a successful and well tolerated buprenorphine induction without interruption of methadone treatment or precipitation of significant opioid withdrawal. To the best of our knowledge, this is the first report describing micro-induction with intravenous buprenorphine.
Purpose
Properly charged particles can be used for effective lung targeting of pharmaceutical aerosols. The objective of this study was to characterize the performance of a new induction charger that operates with a mesh nebulizer for the production of highly charged submicrometer aerosols to bypass the mouth-throat and deliver clinically relevant doses of medications to the lungs.
Methods
Variables of interest included combinations of model drug (i.e. albuterol sulfate) and charging excipient (NaCl) as well as strength of the charging field (1–5 kV/cm). Aerosol charge and size were measured using a modified electrical low pressure impactor system combined with high performance liquid chromatography.
Results
At the approximate mass median aerodynamic diameter (MMAD) of the aerosol (~ 0.4 μm), the induction charge on the particles was an order of magnitude above the field and diffusion charge limit. The nebulization rate was 439.3 ± 42.9 μl/min, which with a 0.1 % w/v solution delivered 419.5 ± 34.2 μg of medication per minute. A new correlation was developed to predict particle charge produced by the induction charger.
Conclusions
The combination of the aerosol induction charger and predictive correlations will allow for the practical generation and control of charged submicrometer aerosols for targeting deposition within the lungs.
however dose reductions (DR) secondary to adverse effects (AE) are often required. The outcomes of MMF DR in OHT recipients have not yet been examined. We sought to determine the frequency of MMF DR within the first year post-OHT, and evaluate incidence of AE and biopsy-proven acute rejection (BPAR) in patients receiving full versus reduced dose MMF. Methods: Patients transplanted between May 2009 and October 2014 were retrospectively reviewed. MMF dose, rationale for dose change, and white blood cell counts (WBC) were recorded at time of hospital discharge, 3, 6, and 12 months post-OHT. Incidences of infection requiring treatment, leukopenia (WBC less than 3 cells/mm 3), gastrointestinal (GI) complaints (nausea, vomiting, diarrhea) and BPAR (≥ grade 2R/3A) were then correlated with MMF dose. Standard immunosuppression included tacrolimus and prednisone as well. Results: 86 patients were included in this study. The mean age at time of OHT was 56 ± 12 years; 76% of the patients were male. The mean MMF dose and WBC at discharge was 2470 ± 666 mg/day and 11 ± 4.3 cells/mm 3 , respectively. The mean MMF doses at month 3, 6, and 12 post-OHT were 1928 ± 920 mg/day, 1560 ± 984 mg/day, and 1560 ± 890 mg/day, respectively. At least one or more MMF DR occurred in 75/86 (87%) patients, with the highest percent DR between months 0 and 3. The primary indication for DR was leukopenia (60%). At 12 months, patients with persistent leukopenia required significantly lower mean MMF doses than those with transient leukopenia (467 ± 372 mg vs. 975 ± 325 mg, p= 0.0001). MMF DR occurred in 2 patients for GI complaints and in 11 patients due to infection. There were 6 incidences of ≥ 2R/3A rejection; 4 patients were on MMF 3 grams/day, 1 patient was on 2grams/day, and 1 patient was off MMF. Conclusion: Conventional MMF dosing of 3grams/day was poorly tolerated in our patients. When utilized as part of a standard immunosuppression regimen, a lower initial MMF dose may limit AE and decrease pill burden while still maintaining acceptable patient and graft outcomes. Further prospective studies are needed.
The overall adherence rate to the 2013 ACC/AHA cholesterol guideline from this nonteaching outpatient clinic was significantly lower than that previously observed in a teaching outpatient clinic. The single pharmacist-led seminar did not significantly affect prescribers' adherence rate to the guideline.
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