Annals of Pharmacotherapy

Insulin remains a mainstay of treating hyperglycemia in an acute setting. Insulin glargine 300 units/mL (Toujeo, iGlar300) has a different pharmacokinetic profile than 100 units/mL basal insulins, such as insulin detemir (iDet100) and iGlar100. While conversion from iGlar300 to iGlar100 requires a 20% dose decrease, there is currently no recommended interchange from iGlar300 to iDet100.

Compare the incidence of hypoglycemia in patients who received a 1:1 unit interchange from home iGlar300 or iGlar100 to iDet100 while admitted.

A retrospective study was conducted to evaluate adults within a multi-site network admitted between May and December 2019. Patients were included if they received at least one dose of iDet100 following interchange from home iGlar300 or iGlar100. The primary endpoint was the incidence of hypoglycemic events following a 1:1 interchange of iGlar300 vs. iGlar100 to inpatient iDet100. Secondary outcomes include overall hypoglycemic events, time to hypoglycemia, and doses given before hypoglycemia.

Of 615 patients, 394 received a 1:1 unit interchange to iDet100 (52 from iGlar300 and 342 from iGlar100). Incidence of hypoglycemic events was significantly higher in those with a 1:1 interchange from iGlar300 versus iGlar100 (36.5% vs. 18.7%, p = 0.007). Significant differences were observed in overall hypoglycemic events, time to hypoglycemia, and number of doses given before hypoglycemic event.

A 1:1 unit interchange from iGlar300 to iDet100 led to a higher incidence of hypoglycemic events compared to those interchanged from iGlar100. Dose reduction should be considered when transitioning from home iGlar300 to iDet100 in the inpatient setting.

Current guidelines recommend norepinephrine as the first-line vasopressor in septic shock followed by addition of vasopressin to achieve a goal mean arterial pressure. Limited evidence exists evaluating how the timing of vasopressin addition affects clinical outcomes in septic shock.

The objective of this study was to determine whether the timing of the addition of vasopressin to norepinephrine affects shock resolution.

This was a multi-site, single system, retrospective cohort, institutional review board (IRB)-approved study examining adult patients with septic shock who received norepinephrine and vasopressin. Patients were divided and statistically analyzed in two subgroups: early vasopressin addition (<3 hours) and late vasopressin addition (≥3 hours). The primary outcome was time to shock resolution, defined as vasopressor free for at least 24 hours. Secondary outcomes included norepinephrine dose at 3 hours after initiation of vasopressin, in-hospital mortality, and intensive care unit length of stay.

A total of 243 patients were included in this study. A statistically significant decrease in time to shock resolution was observed in the early vasopressin addition group compared to the late vasopressin addition group (37.6 hours vs 60.7 hours; adjusted hazard ratio [HR]: 2.07 [1.48-2.89; P = <0.001]). The early addition of vasopressin did not affect norepinephrine dose or in-hospital mortality but did lead to a decreased intensive care unit (ICU) length of stay (4.3 days vs 5.3 days, P = 0.02).

Addition of vasopressin to norepinephrine within 3 hours was associated with a faster time to shock resolution. These findings suggest a potential for improved clinical outcomes with earlier vasopressin addition.

Whether 5% lidocaine-medicated plaster (LMP) is a valuable therapeutic option for the treatment of trigeminal neuralgia (TN) is worth exploring. If LMP is proven effective for TN, positive predictors of the analgesic effects of LMP warrant further investigation.

To evaluate the efficacy and safety of LMP for the treatment of TN, and to explore the predictive factors for the treatment efficacy of LMP.

This is a retrospective and observational study. We analyzed the efficacy of LMP for the treatment of TN between March 2019 and January 2022. The follow-up time was approximately 2 weeks, 1 month, 2 months, and 3 months after LMP treatment. The LMP response was considered the Barrow Neurological Institute (BNI) score of I to III and an improvement in BNI of at least I grade from pretreatment baseline. Univariable and multivariable logistic analyses were performed to identify the predictive factors for LMP response.

A total of 103 patients were included and analyzed in this study. LMP was effective in some TN patients, with an efficacy rate of 21.4%, 21.4%, 18.4%, and 16.5% after 2 weeks, 1 month, 2 months, and 3 months of LMP treatment, respectively. The overall adverse event rate associated with LMP was 5.8%, and the reported adverse events were all skin reactions. Facial trigger points (odds ratio [OR] = 0.25, 95% confidence interval [CI] = 0.07-0.86, P = 0.03) and a lower BNI score (OR = 0.37, 95% CI = 0.07-0.87, P = 0.01) were identified as potential predictors for initial efficacy (2-week follow-up) of LMP treatment.

LMP has been shown to provide effective and sustained analgesia in some TN patients with minimal risk of systemic adverse reactions. Patients with facial trigger points and mild to moderate pain are more likely to benefit from LMP treatment. Our data suggest that LMP may be an effective treatment option for patients with the aforementioned characteristics of TN.

Tenecteplase is a genetically engineered fibrinolytic with growing interest in the treatment of acute ischemic stroke. Compared to alteplase, tenecteplase is effective for neurologic improvement following ischemic stroke in patients with large vessel occlusions who are eligible for thrombectomy and for mild ischemic strokes with National Institutes of Health Stroke Scale of 0 to 5.

The purpose of this study is to determine if safety outcomes are different in patients receiving tenecteplase and alteplase for acute ischemic stroke.

This retrospective cohort reviewed all patients who received alteplase or tenecteplase from January 2019 to December 2020. Patients admitted before April 28, 2020, received alteplase intravenous bolus over 1 minute followed by an infusion over 1 hour, for a total of 0.9 mg/kg. Patients admitted after this date received tenecteplase 0.25 mg/kg as an intravenous bolus over 5 to 10 seconds. Any patient transferring from an outside facility was excluded. The primary outcome was major bleeding.

There was no significant difference in major bleeding between alteplase and tenecteplase (40 [18%] vs 21 [18.1%], P = 0.985). There was no significant difference in all-cause inpatient mortality for alteplase versus tenecteplase (10 [5%] vs 5 [4%], P = 0.934) or in adverse events between the groups (22 [9%] vs 14 [12%], P = 0.541) for alteplase and tenecteplase, respectively.

Tenecteplase had similar rates of major bleeding versus alteplase and may be a reasonable alternative in the treatment of acute ischemic stroke.

In patients who received a cardiac stent, practice guidelines recommend dual antiplatelet therapy (DAPT). However, an urgent procedure may be required necessitating interruption of DAPT. Intravenous cangrelor was previously shown to be an alternative due its short-half life and quick onset/offset.

To determine the safety and effectiveness of cangrelor bridging for patients undergoing invasive procedures in a veteran population.

Retrospective cohort of patients from Michael E. DeBakey VA Medical Center and the VA North Texas Health Care Systems who underwent perioperative cangrelor bridging. The primary outcome was the incidence of bleeding using the Bleeding Academic Research Consortium (BARC) criteria. The secondary outcome was a composite of nonfatal stroke, myocardial infarction (MI), mortality, and unplanned revascularization within 30 days. A narrative review was also performed to summarize cangrelor bridging for noncardiac invasive procedure.

There were 41 patients that met the eligibility criteria. Patients were predominantly Caucasian (57.5%) men with a median age of 70 years. The median duration on cangrelor bridging was 2.6 days with 11 and 30 patients undergoing cardiac and noncardiac invasive procedures, respectively. Nine patients (22%) had a bleeding event of which 8 were minor. One was severe due to significant iliopsoas hematoma following drain placement. All bleeding events occurred postoperatively except for 2 perioperative events that occurred during orthopedic procedures. Ischemic events up to 30 days occurred in 3 patients (7.3%) which consisted of 1 (2.4%) nonfatal MI requiring revascularization and 2 (4.9%) deaths, 1 of which was sudden cardiac.

This study suggests that cangrelor bridging may be a reasonable alternative to holding oral P2Y12 inhibitors in patients requiring interruption of antiplatelet therapy for an urgent surgery/invasive procedure.

Corticosteroids has been the mainstay of immunosuppression (IMS) following liver transplant (LT). With the advent of more potent IMS, complete steroid withdrawal has become possible after LT. However, there is limited data regarding the incidence and risk factors for acute cellular rejection (ACR) in LT recipients on steroid sparing regimens.

To identify the incidence and risk factors of ACR in LT recipients at an urban LT center utilizing a steroid-sparing IMS regimen.

This was a single center retrospective study evaluating incidence of ACR in adults (>18 years) who received a LT between 01/01/2008 and 6/30/2019 at a steroid-sparing liver transplant center. Data between patients who had ACR and patients who did not were compared and risk factors were identified by multivariate logistic linear regression.

A total of 266 patients were included in this analysis, of which 18.4% experienced ACR within the first year of LT. Median time to first ACR was 134 (interquartile range [IQR]: 34-246) days. Black race (odds ratio [OR]: 4.39, P < 0.001), continued need for prednisone (OR: 2.80, P = 0.015) and cytomegalovirus (CMV) viremia (OR: 6.27, P < 0.001)) were independent risk factors for ACR. Tacrolimus use was associated with less ACR (OR: 0.33, P = 0.013).

Steroid sparing regimens for IMS post-LT were not associated with an increased incidence of ACR when compared to reported ACR rates in literature. Potential risk factors for ACR include Black race, the use of prednisone maintenance IMS therapy, and CMV viremia.

Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) can be detected using nasal swab polymerase chain reaction (PCR) assay and is associated with clinical MRSA infection. The MRSA nasal PCR has a rapid turnaround time and a negative predictive value for MRSA pneumonia of >98%; however, data are limited in critically ill patients.

The purpose of this study is to determine the impact of a pharmacist-driven algorithm, utilizing MRSA PCR nasal screening on duration of anti-MRSA therapy in patients admitted to the intensive care unit (ICU) with suspected pneumonia.

A single-center pre/post study was conducted in 4 ICUs at a large tertiary care community hospital. Adult patients admitted to the ICU initiated on vancomycin or linezolid for pneumonia managed using a pharmacist-driven MRSA PCR algorithm were included in the algorithm cohort. A historical cohort with standard management was matched 1:1 by age, type of pneumonia, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The primary outcome was duration of anti-MRSA therapy. Secondary outcomes included MRSA rates, number of vancomycin levels, new onset of acute kidney injury (AKI), ICU length of stay (LOS), hospital LOS, and mortality.

Of the 245 patients screened, 50 patients met inclusion criteria for the algorithm cohort and were matched to 50 patients in the historical cohort. The duration of anti-MRSA therapy was significantly lower compared with the historical cohort (47 vs 95 hours; P < 0.001). Secondary outcomes were similar between groups for MRSA rates, new onset of AKI, LOS, and mortality. There were less vancomycin levels ordered in the algorithm cohort (2 vs 3, P = 0.026).

A pharmacist-driven MRSA PCR algorithm significantly reduced anti-MRSA duration of therapy in critically ill patients with pneumonia. Future studies should validate these results in critically ill populations and in settings where MRSA pneumonia is more prevalent.

To review the pharmacology, efficacy, and safety of intranasal olopatadine hydrochloride-mometasone furoate (OM) combination in the treatment of seasonal allergic rhinitis (SAR).

The PubMed database and ClinicalTrials.gov were searched using the following terms: mometasone + olopatadine, GSP301, mometasone furoate, and olopatadine hydrochloride.

Articles published in English between January 1987 and August 2022 related to pharmacology, safety, and clinical trials were assessed.

In 2 phase II clinical trials, twice-daily (BID) and once-daily (QDay) intranasal OM demonstrated significant improvements in reflective total nasal symptom score (rTNSS) (BID P < 0.001 and QDay P < 0.001) and instantaneous total nasal symptom score (iTNSS) (BID P < 0.001 and P < 0.0001; QDay P < 0.001 and P < 0.0001). In 2 phase III clinical trials, BID OM showed significant improvements in rTNSS vs. placebo (P < 0.001), olopatadine monotherapy (P = 0.03 and P = 0.003), and mometasone monotherapy (P = 0.02 and P = 0.059).

OM is indicated for treatment of SAR symptoms. Caution with use must be considered for certain high-risk patients, existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. Due to its quick and sustained onset of action, OM may be an ideal agent for initial treatment of moderate-severe SAR for patients 12 years and older.

OM significantly improves SAR symptoms and is a viable treatment option in short-term SAR.

To review the pharmacologic and clinical profile of risankizumab-rzaa in the treatment of Crohn’s disease (CD).

A PubMed search was performed from inception to August 2022 using keywords risankizumab, risankizumab-rzaa, interleukin-23 inhibitor, and Crohn’s disease. Information was obtained from package inserts as well as published abstracts.

Phase 2 and 3 studies plus relevant literature on risankizumab-rzaa pharmacologic and clinical profile were reviewed.

Risankizumab-rzaa approval was based on ADVANCE, MOTIVATE, and FORTIFY. In these 3 phase 3 studies involving patients with moderate to severe CD, risankizumab-rzaa, when compared with placebo, resulted in clinical remission and endoscopic response in a significantly higher proportion of patients in both the induction and maintenance phase. In addition, risankizumab-rzaa met the secondary endpoints of clinical response, endoscopic improvement, corticosteroid-free remission, and mucosal healing. Common adverse events noted include nasopharyngitis, arthralgia, headache, abdominal pain, and nausea.

Risankizumab-rzaa is the first selective IL-23 inhibitor approved for CD and provides an additional therapeutic option for patients, particularly those who have been previously treated with other advanced inflammatory bowel disease therapies. Additional studies are required to determine how to best position risankizumab-rzaa in both bio-naïve and bio-experienced patients with CD.

Risankizumab-rzaa is the most recent therapeutic advance for CD. It has a selective mechanism of action with a similar safety profile comparable with other currently approved advanced therapies.

To evaluate the safety and efficacy of tisotumab vedotin-tftv (TV), a first-in-class vectorized anti-tissue factor (TF) antibody-drug conjugate (ADC), for the treatment of recurrent or metastatic cervical cancer.

A literature search of ClinicalTrials.gov, Embase, and PubMed was conducted using the terms tisotumab vedotin AND cervical cancer from inception to June 30, 2022.

All applicable publications, package inserts, meeting abstracts, and clinical trials involving TV in the treatment of cervical cancer were reviewed.

TV is a fully human TF-specific monoclonal antibody conjugated to monomethyl auristatin E, which serves as a highly potent cytotoxic payload. In the pivotal phase II InnovaTV 204 clinical trial, TV demonstrated an objective response rate of 24% (95% confidence interval [CI], 16%-33%). The mean duration of response was 8.3 months. Common toxicities included abdominal pain, alopecia, conjunctivitis, constipation, decreased appetite, diarrhea, dry eye, epistaxis, nausea/vomiting, and peripheral neuropathy. Unique and/or serious adverse events warranting careful monitoring include ocular complications, hemorrhaging, peripheral neuropathies, fetal-embryo toxicity, pneumonitis, and immunogenicity.

Recurrent or metastatic cervical cancer remains a high-risk disease with limited treatment options. Using ADCs to target tumors with aberrant expression of TF appears to be a viable treatment strategy.

TV is the first Food and Drug Administration–approved TF-directed ADC. With a manageable safety profile and promising anticancer activity, TV warrants consideration as a novel targeted agent for the treatment of recurrent or metastatic cervical cancer. Further studies are required to determine the optimal place in therapy for TV.

To review the efficacy and safety of maribavir for management of cytomegalovirus (CMV) in solid organ transplant recipients.

A literature search of PubMed and the Cochrane Controlled Trials Register (1960 to early July 2022) was performed using the following search terms: maribavir, 1263W94, and cytomegalovirus.

All relevant English-language studies were reviewed and considered, with a focus on phase 3 trials.

Maribavir, an orally available benzimidazole riboside with minimal adverse effects, was originally studied for universal prophylaxis in phase 3 trials but failed to demonstrate noninferiority over placebo and oral ganciclovir. It was effective for preemptive treatment in a dose-finding Phase 2 study. Maribavir is FDA approved for treatment of refractory/resistant CMV infection based on improved response rate at 8 weeks compared with investigator-assigned therapy (IAT) when initiated at median viral loads less than approximately 10 000 IU/mL (55.7% vs 23.9%, P < 0.001). Recurrence after 8-week treatment for refractory/resistant CMV was high (maribavir 50% vs IAT 39%). Significant drug interactions exist and must be managed by a pharmacotherapy expert to prevent harm.

The addition of maribavir to the antiviral armamentarium should improve the management of refractory/resistant CMV, allowing early transition from toxic, high-cost, intravenous agents such as foscarnet and outpatient management. Optimal timing of initiation, duration, and potential alternative uses are unclear.

Future studies are needed to fully elucidate the role of maribavir in the management of CMV after transplant.