New Antimycotics in the Pipeline – For Ophthalmology Too?

Seven new antimycotics are presented that are at different points of development or approval. These substances are mainly first-in-class drugs. They are primarily developed for systemic administration. However, with the support of a pharmacist, the intravenous formulation may be used as eyedrops. In this short review, the activities of the substances against various fungal infections are described. After unsuccessful conventional therapy of fungal eye infections, one of these new substances might be suitable to cure the mycosis.

Subcutaneous daratumumab and hyaluronidase-fihj in newly diagnosed or relapsed/refractory multiple myeloma

Daratumumab, a human immunoglobulin G1 kappa monoclonal antibody that targets CD38, is currently approved as monotherapy and in varying combinations with approved anti-myeloma regimens in both newly diagnosed multiple myeloma and relapsed refractory multiple myeloma. Originally developed for intravenous administration, the subcutaneous formulation of daratumumab (daratumumab and hyaluronidase-fihj) was recently approved by the US Federal Drug Administration and European Commission in 2020. In clinical trials, compared with the intravenous formulation, subcutaneous daratumumab (Dara-SC) has significantly shorter administration time (median first dose 7 h versus 3–5 min, respectively), lower rates of infusion-related reactions (median first dose 50% versus less than 10%, respectively), and lower volume of infusion (median 500–1000 ml versus 15 ml, respectively). Otherwise, the pharmacokinetics, safety profile, and efficacy are comparable. This review summarizes the pivotal trials that led to the approval of Dara-SC, highlights important clinical considerations for the use of Dara-SC, and provides practical guidelines for the administration of Dara-SC in the clinic.

Pharmacology, Dosing, and Side Effects of Rifabutin as a Possible Therapy for Antibiotic-Resistant Acinetobacter Infections

Acinetobacter baumannii has among the highest rates of antibiotic resistance encountered in hospitals. New therapies are critically needed. We found that rifabutin has previously unrecognized hyperactivity against most strains of A. baumannii. Here we review the pharmacology and adverse effects of rifabutin to inform potential oral dosing strategies in patients with A. baumannii infections. Rifabutin demonstrates dose-dependent increases in blood levels up to 900 mg per day, but plateaus thereafter. Furthermore, rifabutin induces its own metabolism after prolonged dosing, lowering its blood levels. Pending future development of an intravenous formulation, a rifabutin oral dose of 900–1200 mg per day for 1 week is a rational choice for adjunctive therapy of A. baumannii infections. This dosage maximizes AUC24 to drive efficacy while simultaneously minimizing toxicity. Randomized controlled trials will be needed to definitively establish the safety and efficacy of rifabutin to treat A. baumannii infections.

Intravenous Zanamivir: A Viable Option for Critically Ill Patients With Influenza

Objective: To review the pharmacology, clinical trial data, and clinical implications for the intravenous formulation of zanamivir. Data Sources: MEDLINE, PubMed, EMBASE, and Google Scholar were searched during November 2019 to July 2020. Search terms zanamivir and neuraminidase inhibitor were used. Study Selection and Data Extraction: All human trials and major reports from compassionate use programs with the intravenous zanamivir (IVZ) formulation were assessed and reviewed here. Data Synthesis: IVZ was found to be similar but not superior to oral oseltamivir in hospitalized patients when studied in populations with very low baseline oseltamivir resistance. IVZ provides an effective alternative for critically ill patients when oral antiviral therapy is not preferred or when oseltamivir resistance is increased. Relevance to Patient Care and Clinical Practice: IVZ was recently authorized for use by the European Medicines Agency, and it is eligible for consideration in emergency use protocols and US stockpile inclusion. It will be of particular interest in critically ill patients especially during influenza seasons with appreciable oseltamivir and peramivir resistance. Conclusions: The available information suggests that the intravenous formulation of zanamivir offers a viable alternative treatment for critically ill patients with influenza, especially when resistance to other agents is present.

Misuse of Tramadol in the United States: An Analysis of the National Survey of Drug Use and Health 2002-2017

Objective: To analyze the rates of misuse - that is, use in any way not directed by a doctor - of products containing oral tramadol, a Schedule IV opioid, from the National Survey of Drug Use and Health (NSDUH), as compared to comparator Schedule II opioids (morphine, oxycodone, and hydrocodone) and alprazolam, a commonly prescribed Schedule IV controlled substance in the U.S. Methods: The NSDUH is a congressionally mandated household survey that collects information on tobacco, alcohol, and drug use, mental health and other health-related issues in the US. A cross-sectional surveillance study design was used to examine lifetime and past year misuse of oral tramadol and comparators of interest among NSHUH respondents aged 12 years or older. Based on when particular data were available, the past-year misuse analysis includes NSDUH data from 2015 to 2017, and the lifetime misuse analysis includes NSDUH data from 2002 to 2014. Results: In 2015 to 2017, past-year misuse of oral tramadol was approximately 4% of the total number of prescriptions, versus 7% to 8% for all of the comparators when adjusted for drug availability. In 2002 to 2014, lifetime misuse of oral tramadol remained at 1.5% or less over the 13-year period, and was lower than reported for hydrocodone (6%) and oxycodone (4%), respectively. Comparison of oral tramadol and alprazolam showed misuse of tramadol was also much lower than alprazolam. Too few reports of tramadol misuse by injection (n = 7) were reported, versus 570, 1096, and 32 reports of injection of morphine, oxycodone, and hydrocodone, respectively, during the 16-year analysis period to allow for any population-based estimation. Only morphine has an intravenous formulation available and tramadol was not available as an intravenous formulation in the U.S. during that time period. Conclusions: This analysis shows a low prevalence of oral tramadol misuse, relative to other commonly prescribed opioids, in a nationally representative sample of noninstitutionalized US residents. Estimates of reported oral tramadol misuse have remained relatively stable over time and are substantially lower than those reported for comparators when adjusted for prescription volume. Reports of oral tramadol misuse are also much less than alprazolam, another Schedule IV drug.