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  • 14 Apr 2022 8:33 AM | Anonymous

    By: Nicole Evans-Turk, Pharm.D Candidate 2022

    Mentor: Amy Tiemeier, Pharm.D., BCPS

    With the growing medicalization of marijuana and legalization of recreational marijuana, information on the medicinal value of the plant as well as risks of using marijuana are needed. With any drug, there are risks and benefits to its use. Marijuana is the most used drug by adolescents.1 With strains of marijuana becoming more potent and with new inventive ways to consume it, risks may be more significant in adolescents and have impact into adulthood. This article will discuss the potential risks for adolescents who use marijuana, with marijuana being defined as the whole plant that is smoked or ingested.

    Adolescents have more access to marijuana now than they did even 10 years ago. While it is available for adults over 21 in some states, 11-23% of recreational outlets may sell to minors.2 Marijuana has also commercialized and is advertised in newspapers and on billboards. While more research is needed to determine whether the exposure to marijuana advertisements influences adolescents to start using marijuana before adulthood, at least one study has found a positive correlation between ad exposure and perceived ease of access for teens.3 Annual prevalence of marijuana usage among high school seniors increased from 22% to 36% over the decade from 2004 to 2014.1 In a 2020 survey, 19.8% of high school age people report using marijuana in the past month4. With the increased usage, there are effects on the brain that affect more and more people as they mature into adults. A review of adolescent brain development and marijuana is important given these facts.

    Adolescence is a critical period for neurodevelopment and it is characterized by dynamic changes in the mesolimbic dopamine pathway.5 The echocannabinoid (eCB) system reaches peak expression and activity during adolescence. The eCB system acts as a regulator in the reward pathway and also plays a role in determining vulnerability to drug addiction. The CB1 (cannabinoid 1) receptor and eCB ligand N-arachidonoylethanolamine (AEA) both have peaks in expression during adolescence as well. AEA is regulated by the enzyme fatty acid amide hydrolase (FAAH), which is expressed in brain regions that are implicated in the reward and addiction pathways. Activation of this system gives adolescents more intense effects from marijuana than adults usually experience due to the greater expression of AEA and CB1. With prolonged and repeated activation, adolescent brains have a higher risk of a psychological addiction through these pathways5. National surveys have found that youth who engaged in marijuana use in later teen years were less likely to develop substance use disorders compared with those who started earlier, which correlates with the changes in the eCB system in adolescents compared to adults.4

    Marijuana-related effects on white matter and grey matter can have widespread implications for brain development, such as impairments in daily functioning.1 White matter in the brain is the communication pathways between areas of the brain and grey matter is the structures where the processing is done. Grey matter changes for marijuana users during adolescence is still being studied, but a study in 2010 found users to have decreased right orbital prefrontal cortex volume compared to non-users. The prefrontal cortex controls the executive functioning skills such as planning and decision-making. The decreased volume of the prefrontal cortex correlates to lower executive reasoning skills and executive dysfunction. The volume reduction is positively correlated with the age in which the person started using marijuana, with the most changes being seen in those who started using at a younger age.1 Findings in white matter between adolescent marijuana users and non-users also differ. An increase in mean diffusivity in the prefrontal fiber bundles of the corpus callosum is also found in adults who use marijuana heavily and started as an adolescent. These fibers are what allows the prefrontal cortex to receive information and process it. The effects of these changes to the grey and white matter of the brain are theorized to negatively affect executive functioning skills but the full extent is still being studied.

    A common theory is that using THC (tetrahydrocannabinol) in adolescence can contribute to mental disorders in adulthood. In a study where they used a questionnaire to assess whether cannabis use was linked to increased psychiatric symptoms, respondents who met criteria for cannabis use disorder were more likely to report having experienced hallucinations or paranoia. Participants who also met criteria for depression were also more likely to experience hallucinations or paranoia with use of cannabis.6 Adolescents who use marijuana are more likely to misattribute meaning to life events, which can implicate symptoms of psychological disorders. Cannabis use is considered an environmental risk factor in the development of cognitive dysfunction and psychotic disorders.5 While psychological disorders correlate with adolescent marijuana use, there is not enough data to link the two as cause and effect. There could be another conclusion that adolescents with psychological disorders may be self-medicating with marijuana.

    The conclusions of a meta-analysis show that executive functioning seems to be more impaired in frequent users who are adolescents than in frequent users who are adults. Most age related effects seem to be prominent among heavy and dependent users compared to those who may use sporadically.  In addition, adolescents may also have more cravings after marijuana intoxication compared to adults.6 Marijuana use was associated with declines in neural connectivity over time, which correlate to adverse effects on IQ and executive function.4 Executive function refers to decision-making, planning, self-control and organization. This confirms that there are physical changes in the adolescent brain that happen with frequent marijuana usage. The full extent of how the brain and cognitive abilities are affected needs to be researched further.

    In conclusion, pharmacists should be aware of the decisions that adolescents make to use marijuana. With new data coming out that confirms there are neurodevelopmental changes that can happen with prolonged marijuana use in adolescents, children and caregivers should be educated on the potential long-term effects of using marijuana during adolescent years. A pharmacist who specializes in pediatrics or psychiatry should also continue to keep up to date on new research as it comes out about the eCB system and its mechanisms in relation to marijuana.


    1. Jacobus J, Tapert SF. Effects of cannabis on the adolescent brain. Curr Pharm Des. 2014;20(13):2186-2193. doi:10.2174/13816128113199990426
    2. Lipperman-Kreda S, Grube JW. Impacts of Marijuana Commercialization on Adolescents' Marijuana Beliefs, Use, and Co-use With Other Substances. J Adolesc Health. 2018;63(1):5-6. doi:10.1016/j.jadohealth.2018.05.003
    3. Turel O. Perceived Ease of Access and Age Attenuate the Association Between Marijuana Ad Exposure and Marijuana Use in Adolescents. Health Educ Behav. 2020;47(2):311-320. doi:10.1177/1090198119894707
    4. Dharmapuri S, Miller K, Klein JD. Marijuana and the Pediatric Population. Pediatrics. 2020;146(2):e20192629. doi:10.1542/peds.2019-2629
    5. Hurd YL, Manzoni OJ, Pletnikov MV, Lee FS, Bhattacharyya S, Melis M. Cannabis and the Developing Brain: Insights into Its Long-Lasting Effects [published correction appears in J Neurosci. 2020 Jan 8;40(2):493]. J Neurosci. 2019;39(42):8250-8258. doi:10.1523/JNEUROSCI.1165-19.2019
    6. Levy S, Weitzman ER. Acute Mental Health Symptoms in Adolescent Marijuana Users. JAMA Pediatr. 2019;173(2):185-186. doi:10.1001/jamapediatrics.2018.3811
    7. Meruelo AD, Castro N, Cota CI, Tapert SF. Cannabis and alcohol use, and the developing brain. Behav Brain Res. 2017;325(Pt A):44-50. doi:10.1016/j.bbr.2017.02.025
  • 13 Apr 2022 1:18 PM | Anonymous

    By: Avery Tolliver, PharmD; PGY1 Pharmacy Resident

    Mentor: Blake Rosenfelder, PharmD; Clinical Pharmacy Specialist
    Mercy Hospital, Springfield, MO

    Program Number:  2022-04-07
    Approved Dates:  April 1, 2022-October 1, 2022
    Pending Approval for Contact Hours:  One Hour(s) (1) CE(s) per session

    Learning Objectives:

    1. Identify similarities and differences between tenecteplase and alteplase for fibrinolysis.
    2. Identify ischemic stroke patients in which tenecteplase could be of benefit.  
    3. Discuss the most recent data surrounding the use of tenecteplase for ischemic strokes.


    Acute ischemic strokes (AIS) are one of the leading causes of death for Americans.  In the United States around 795,000 people suffer from strokes each year, leading to significant morbidity and mortality.1 The American Heart Association’s (AHA) and American Stroke Association’s (ASA) joint guidelines on the early management of AIS has for many years recommended the use of the fibrinolytic medication alteplase for select ischemic stroke patients who can be treated within 4.5 hours of symptom onset. AHA/ASA AIS guidelines prior to the 2019 revision did not recommend the use of fibrinolytics other than alteplase. In the 2019 guideline revision AHA/ASA changed their recommendations, suggesting the use of tenecteplase over alteplase could be reasonable in patients without contraindications for intravenous (IV) fibrinolysis that are also eligible to undergo mechanical thrombectomy.2 The updated recommendation was a result of newly published studies comparing tenecteplase and alteplase. Since the publication of the 2019 guidelines, additional studies have shown the efficacy of tenecteplase for ischemic strokes and have further supported its use. These studies, along with shortages of alteplase, have increased the medical community’s interest in and use of tenecteplase. The following discussion of the evidence supporting tenecteplase for AIS and comparing it to alteplase will better prepare pharmacists to treat ischemic stroke patients and answer tenecteplase related questions from their multidisciplinary teams.

    Tenecteplase vs. Alteplase

    Alteplase (brand name Activase) and tenecteplase (brand name TNKase) are thrombolytic agents that have been approved by the Food and Drug Administration (FDA) for the treatment of ST-elevation myocardial infarction (STEMI).3,4 Alteplase is also FDA approved for acute ischemic stroke and pulmonary embolism, but these are off-label uses for tenecteplase. Alteplase is one of the most used thrombolytic agents and gained FDA approval in 1989, afterwards came the approval of tenecteplase in 2000.3,4

    Tenecteplase and alteplase are in the same drug class causing them to have similarities but also to have pharmacokinetic and pharmacodynamic differences. Both agents work by binding to fibrin and converting plasminogen to plasmin initiating fibrinolysis of a thrombus.3 Alteplase, a recombinant tissue plasminogen activator (tPA), varies from tenecteplase (TNK-tPA) by modifications of three molecular sites. The three molecular modifications were engineered to give tenecteplase a longer half-life compared to alteplase.5 Tenecteplase has a biphasic initial half-life of 20 to 24 minutes and terminal half-life of 90 to 130 minutes which is longer than alteplase’s initial half-life of 5 minutes and terminal half-life of 27 to 46 minutes.3,4 Additionally, tenecteplase’s three molecular modifications allow for higher fibrinogen specificity and enhanced resistance to plasminogen activator inhibitor-1 compared to alteplase.5 Although pharmacokinetically different in some ways alteplase and tenecteplase are both hepatically metabolized.3,4

    Due to the structural and pharmacokinetic differences between tenecteplase and alteplase their dosing strategies are different from one another. For the indication of AIS, a total dose of 0.9 mg/kg of alteplase is given IV, with 10% of the dose given as a bolus over one minute followed by the remaining 90% of the dose given by continuous infusion over 60 minutes.3 The maximum dose of alteplase for AIS is 90 mg. The complex administration of bolus and continuous infusions is due to alteplase’s short half-life and is avoided with tenecteplase’s longer half-life. For tenecteplase the AHA/ASA guideline recommended AIS dosing is 0.25 mg/kg with a maximum of 25 mg given as a single IV bolus over 5 seconds.2,3 The difference in tenecteplase dosing for the FDA-approved STEMI indication and the off-label AIS indication should be noted.  The tenecteplase dosing for STEMI is based on weight ranges, and doses range from 30 to 50mg, which is approximately 0.5 mg/kg; however, the dose is still administered as a single bolus over 5 seconds. Neither tenecteplase nor alteplase require dose adjustments for renal or hepatic impairment.3

    Although these two thrombolytic agents are dosed differently, they are supplied in similar ways and are expensive. Alteplase comes in kits from the manufacturer, Genentech, with 50 mg or 100 mg vials of alteplase.3,4 The kits contain sterile water for injection and a transfer device to reconstitute the vials. Additionally, alteplase vials include a hanging loop to allow administration of the dose from the vial. The 50 mg alteplase kit costs around $5,300 and the 100 mg kits cost around $10,500 each. Tenecteplase is also supplied by Genentech, and a 50 mg kit contains a 50 mg vial of tenecteplase, sterile water for injection, and syringe for reconstituting the vial and bolus administration. The tenecteplase kit costs around $7,500. One precaution to be aware of when preparing and administering tenecteplase is that it is incompatible with dextrose solutions; lines must be flushed with saline prior to and after administration. Alteplase is compatible with 5% dextrose and 0.9% saline.3,4 Additionally, the packaging for tenecteplase kits is designed to highlight the dosing for a STEMI.  As a consequence, this could result in a substantial overdose if STEMI dosing is used when treating an AIS. 

    Along with other commonalities, tenecteplase and alteplase have similar adverse drug reactions. The major adverse drug reactions for both agents include a variety of hemorrhagic complications. Tenecteplase has high rates of hematomas (12.3%), hemorrhage (21.8%), renal artery hemorrhage (3.7%), and gastrointestinal hemorrhage (1.9%). Alteplase has high rates of intracranial hemorrhage (within 90 days 15%), gastrointestinal hemorrhage (5%), and genitourinary tract hemorrhage (4%). Neither of the agents have black box warnings or risk evaluation and mitigation strategies (REMS) programs.3,4

    Recent Tenecteplase AIS Studies

    The 2019 revision to the AHA/ASA acute ischemic stroke guidelines stated that tenecteplase could be used over alteplase for patients without contraindications for IV fibrinolysis and who are eligible to undergo mechanical thrombectomy.2 This new recommendation was a result of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke) published in April of 2018.6 The EXTEND-IA TNK trial was a prospective, randomized, blinded outcome trial. Ischemic stroke patients included in the trial were within 4.5 hours of symptom onset and had large-vessel occlusion of the internal carotid, middle cerebral, or basilar artery. Patients also had to be eligible for IV thrombolysis and endovascular thrombectomy. Included patients were randomized to tenecteplase at a dose of 0.25 mg/kg (maximum 25 mg) or alteplase at a dose of 0.9 mg/kg (maximum 90 mg). The primary outcome investigated was substantial reperfusion, defined as the restoration of blood flow to more than 50% of the affected area or an absence of retrievable thrombus in the target vessel. The primary outcome was observed in 22 patients (22%) who received tenecteplase and 10 patients (10%) who received alteplase (P=0.002 for noninferiority). For the secondary outcome of modified Rankin scale (mRs) score at 90 days the tenecteplase group had a median score of 2 compared to the median score of 3 for the alteplase group (P=0.04). This outcome suggests a better functional outcome with tenecteplase compared to alteplase. However, there was no significant difference shown in early neurologic improvement measured by median National Institutes of Health Stroke Scale (NIHSS) scores at 24 hours. The NIHSS score at 24 hours for the tenecteplase group was 3 and NIHSS score was 6 for the alteplase group (P=0.06). The results of EXTEND-IA TNK show that tenecteplase is noninferior to alteplase in restoring perfusion for proximal cerebral artery occlusions and tenecteplase could lead to better functional outcomes for AIS patients.6

    The EXTEND-IA TNK trial showed noninferiority of the 0.25 mg/kg (25 mg maximum) dose of tenecteplase compared to alteplase for AIS. However, during the recruitment phase of the EXTEND-IA TNK trial the results of the Norwegian Tenecteplase Stroke Trial (NOR-TEST) were published and NOR-TEST used 0.4 mg/kg of tenecteplase. NOR-TEST, a phase 3, randomized, open-label, superiority trial was published in August 2017.7 Ischemic stroke patients with measurable deficits on the NIHSS, admitted within 4.5 hours of symptom onset or within 4.5 hours of awakening with symptoms, and eligible for IV thrombolysis were eligible for the NOR-TEST study. Patients were randomized to two groups, an alteplase group receiving standard dosing and a tenecteplase group receiving 0.4 mg/kg (maximum 40 mg) as a single bolus. The primary end point evaluated was excellent functional outcome at 3 months measured as a mRs score of 0 to 1. In the tenecteplase group 354 (64%) achieved the primary outcome compared to 345 (63%) in the alteplase group (P=0.52). For the secondary outcome of intracranial hemorrhage (ICH) 24 to 48 hours after thrombolytic treatment, 47 (9%) patients in the tenecteplase group suffered from ICH compared to 50 (9%) in the alteplase group (P=0.82). Death at 3 months was also reported showing 29 (5%) deaths in the tenecteplase group compared to 26 (5%) in the alteplase group (P=0.68).7 The NOR-TEST trial did not show tenecteplase to be superior to alteplase for treatment of AIS. However, the NOR-TEST trial did show that the higher tenecteplase dose of 0.4 mg/kg had a similar safety profile to alteplase.

    Following the EXTEND-IA TNK and NOR-TEST trial publications a meta-analysis of 5 randomized trials was performed to determine if evidence supported tenecteplase being noninferior to alteplase for acute ischemic stroke.8 The formal meta-analysis published in May 2019 looked at the primary efficacy end point of disability free outcome, measured as a mRs score of 0 to 1, at 3 months post stroke. All alteplase patients received the standard AIS dosing, and tenecteplase patients received one of three doses as a one-time bolus, 0.1 mg/kg (6.8%), 0.25 mg/kg (24.6%), or 0.4 mg/kg (68.6%). Data from all 5 trials contributed to the primary outcome of disability free outcomes in 57.9% of tenecteplase patients compared to 55.4% of alteplase patients. The random-effects meta-analysis showed a risk difference of 4% (95% CI, -1% to 8%) falling within the noninferiority criteria for the primary outcome. For the secondary analysis of functional independence, measured as a mRs score of 0 to 2 at 3 months, data was available from 4 of 5 trials. The data showed the rate of independence was 71.9% in the tenecteplase group compared to 70.5% in the alteplase group, with a risk difference of 8% (95% CI, -4 to 20%) showing noninferiority. For the safety outcomes of symptomatic ICH and death, data was available for all 5 trials. ICH occurred in 3% of tenecteplase patients and 3% of alteplase patients. Mortality occurred at 3 months in 7.6% of tenecteplase patients compared to 8.1% of alteplase patients. Overall, this combined clinical trial data indicates that tenecteplase given for the treatment of AIS is noninferior to alteplase when measuring disability free outcomes and poses no greater safety risk.8

    In addition, another systemic review with meta-analysis exploring the use of tenecteplase for thrombolysis in stroke patients was published in 2021.9 The meta-analysis included eight studies involving a total of 2031 patients that underwent thrombolysis for AIS. Tenecteplase showed an increase in recanalization rate (ARD =0.11, 95% CI [0.01;0.02]) and early neurological improvement (ARD=0.10, 95% CI [0.02;0.17]) compared to alteplase. Also, tenecteplase demonstrated an increase in good (mRs 0-2) and excellent (mRs 0-1) functional outcomes; however, these improvements were not statistically significant. Safety outcomes for this meta-analysis also showed no difference in ICH or mortality between tenecteplase and alteplase.9 This systemic review with meta-analysis reinforces the results of prior studies and further strengthens the AHA/ASA guideline recommendation on the use of tenecteplase.

    Earlier Tenecteplase AIS Studies

    The recent randomized controlled trials and meta-analysis are being used to support the AHA/ASA guideline changes, but they are not the only studies supporting the use of tenecteplase for AIS. There are three older randomized controlled studies that are also frequently referenced. The first being Phase IIB/III Trial of Tenecteplase in Acute Ischemic Stroke published in 2010.10 This study is a randomized, multi-center, double-blind trial comparing tenecteplase and alteplase in AIS patients within 3 hours of symptom onset. The study compared tenecteplase 0.1 mg/kg, 0.25 mg/kg, and 0.4 mg/kg to alteplase. Specifically looking into the co-primary outcomes of proportion of poor outcomes (mRs 4-6) and proportion of good outcomes (mRs 0-1). The study was terminated early, however, the results reported out showed the 0.1 mg/kg tenecteplase group to have the least poor outcomes with only 7 (22.6%) compared to 10 (32.3%) in the alteplase group. The 0.25 mg/kg tenecteplase group had the most good outcomes with 15 (48.4%), followed by the 0.1 mg/kg group with 14 (45.2%), and the alteplase group only had 13 (41.9%).10 This study continues to show the trend of tenecteplase having similar outcomes to alteplase for AIS and possibly having fewer poor outcomes.

    Another phase IIB, randomized, open-label, blinded trial that is commonly referenced is A Randomized Trial of Tenecteplase versus Alteplase for Acute Ischemic Stroke by Parsons, et al.11 The study included AIS patients within six hours of symptom onset with presence of intracranial occlusion of the anterior cerebral, middle cerebral, or posterior cerebral arteries on computed tomography (CT) angiography. Patients were randomized to one of three groups: 0.1 mg/kg (maximum 10 mg) tenecteplase, 0.25 mg/kg (maximum 25 mg) tenecteplase, or alteplase. The co-primary outcomes investigated were the percentage of the perfusion lesion that was reperfused 24 hours after treatment and clinical improvement at 24 hours measured by NIHSS scores. Reperfusion at 24 hours occurred in 79.3% ± 28.8% of the tenecteplase patients compared to 55.4% ± 38.7% of the alteplase patients (P=0.004). While the improvement in NIHSS scores between baseline and 24 hours was around 3 ± 6.3 hours in the alteplase group compared to 8.0 ± 5.5 hours in the tenecteplase group (P<0.001). This study is limited by its small enrollment of 75 patients in total, however, it shows greater reperfusion and greater clinical improvement in the tenecteplase group compared to alteplase.11

    The third trial, ATTEST (Alteplase Versus Tenecteplase for Thrombolysis After Ischemic Stroke: a phase 2, randomized, open-label, blinded endpoint study), is commonly referenced and is the foundation for a current on-going study.12 Eligible AIS patients had to have measurable deficits shown by the NIHSS score, be within 4.5 hours of symptom onset, and be eligible for IV thrombolysis. Patients were randomized to 0.25 mg/kg (maximum 25 mg) tenecteplase or standard dose alteplase. The primary outcome investigated was the percentage of hypo-perfused tissue salvaged at 24 to 48 hours post treatment. This was measured by pre and post treatment CTs. There was no significant difference in the primary outcome between tenecteplase (68%) and alteplase (68%). There were also no statistically significant secondary outcomes. However, there was a trend towards more early neurological improvement at 24 hours in the tenecteplase group with 19 (40%) compared to the alteplase group at 12 (24%), and a trend toward a higher proportion of good neurological outcomes (mRs 0-1) at 90 days in the tenecteplase group 13 (28%) compared to alteplase 10 (20%).12 The outcomes of this trial once again support previously discussed studies.

    Dosing of Tenecteplase for AIS  

    Considering the results of the NOR-TEST trial using tenecteplase doses of 0.4 mg/kg (maximum of 40mg) and the EXTEND-IA trial using 0.25 mg/kg (maximum of 25 mg), the EXTEND-IA trial researchers performed the EXTEND-IA TNK Part 2 trial to determine the optimal dosing of tenecteplase in AIS patients.13 EXTEND-IA TNK Part 2 is a randomized, open-label, blinded end point trial of AIS patients within 4.5 hours of symptom onset determined to have large vessel occlusion of the intracranial internal carotid, middle cerebral, or basilar artery. Additionally, patients had to be eligible for IV thrombolysis and endovascular thrombectomy. Eligible patients were randomized to either 0.4 mg/kg (40 mg maximum) of tenecteplase or 0.25 mg/kg (25 mg maximum) of tenecteplase. Substantial reperfusion defined as restoring blood flow to more than 50% of the involved territory or an absence of retrievable intracranial thrombus was the primary outcome investigated. The primary outcome occurred in 29 (19.3%) of the patients in the 0.4 mg/kg tenecteplase group and 29 (19.3%) of those receiving 0.25 mg/kg of tenecteplase (P=0.89). Additionally, the analysis of the secondary outcomes showed no significant differences between groups for mRs scores at 90 days and early neurological recovery. More notably the safety outcome showed no significant difference in symptomatic ICH with 7 (4.7%) of 0.4 mg/kg patients having symptomatic ICHs compared to 2(1.3%) of the 0.25 mg/kg patients (P=0.12). Also, no difference was seen in mortality with 26 deaths in the 0.4 mg/kg group and 22 deaths in the 0.25 mg/kg group (P=0.35). The EXTEND-IA TNK Part 2 trial showed no significantly improved cerebral reperfusion with 0.4 mg/kg of tenecteplase compared to 0.25 mg/kg prior to endovascular thrombectomy in patients with large vessel occlusion ischemic strokes.13 EXTEND-IA TNK Part 2 results further support the use of the 0.25 mg/kg (max 25 mg) dose recommended by the AHA/ASA guidelines.2

    In-Progress Studies

    Whether or not tenecteplase should be used in place of alteplase for AIS is still a difficult question to answer with the current data from small sample size studies. However, there are several studies currently being performed that will give more insight into this question when completed. One on-going study is the Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST2) which is looking at functional outcome at 90 days, measured by the modified Rankin Scale, to determine if tenecteplase is superior in efficacy to alteplase.14 A similar study is The Norwegian Tenecteplase Stroke Trial 2 (NOR-TEST 2) which is looking into the safety and efficacy of 0.4mg/kg of tenecteplase versus alteplase for AIS patients within 4.5 hours of symptom onset, awakening with stroke symptoms, or bridge therapy before thrombectomy. The primary endpoint is functional outcome at 90 days measured with the mRs.15 Another on-going study is the Alteplase Compared to Tenecteplase in Patients with Acute Ischemic Stroke (AcT) trial to see if 0.25 mg/kg (max 25 mg) IV tenecteplase is non-inferior to IV alteplase in patients with AIS. Like the other ongoing studies, the primary outcome is functional outcome between days 90 to 120 based on the mRs.16 These are a few of the in-progress studies looking into the efficacy and safety of tenecteplase compared to alteplase for AIS patients. These studies have the potential to further define tenecteplase’s place in therapy for AIS patients.  


    Tenecteplase has many positive attributes making it a more ideal choice than alteplase for thrombolysis in AIS patients. Its molecular modifications allow higher fibrinogen specificity, enhanced resistance to plasminogen activator inhibitor 1, and a longer half-life compared to alteplase. These qualities allow bolus administration of tenecteplase which is faster and less error prone than the bolus and infusion administration of alteplase. The bolus administration of tenecteplase also allows non-thrombectomy hospitals faster door-in to door-out times for those patients that require thrombolysis followed by thrombectomy at a qualified institution. Finally, in addition to faster administration, tenecteplase is less costly than alteplase by approximately $3,000 dollars per dose.

    Tenecteplase’s pharmacokinetic profile is ideal for AIS patients, and study results are starting to reinforce that fact. The studies reviewed show tenecteplase has comparable efficacy to alteplase in AIS patients with large vessel occlusions and could lead to better functional outcomes. Tenecteplase, compared to alteplase in one meta-analysis, also showed non-inferiority in disability free outcomes and increased functional independence. Another meta-analysis reported increased recanalization rates and early neurological improvement with tenecteplase compared to alteplase. All of these studies are showing positive results in favor of using tenecteplase for patients who are candidates for IV thrombolysis and mechanical thrombectomy. In addition to positive outcomes, the studies also indicate that tenecteplase’s safety profile is similar to alteplase’s profile in regard to adverse drug reactions. Although currently reported studies already illustrate promising results in favor of tenecteplase, the results of on-going studies will further define tenecteplase efficacy and place in therapy for AIS.

    Take the CE Quiz


    1. Centers for Disease Control and Prevention. Stroke Facts. Centers for Disease Control and Prevention website. May 25, 2021. Accessed January 20, 2022. https://www.cdc.gov/stroke/facts.htm.
    2. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344-e418. doi: 10.1161/STR.0000000000000211.
    3. Lexi-Drugs. Lexicomp Online. Wolters Kluwer Health, Inc. Accessed January 7, 2021. http://online.lexi.com
    4. In: IBM Micromedex® DRUGDEX® (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Accessed January 7, 2021. https://www.micromedexsolutions.com.
    5. Tanswell P, Modi N, Combs D, Danays T. Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction. Clin Pharmacokinet. 2002;41(15):1229-45. doi: 10.2165/00003088-200241150-00001.
    6. Campbell B, Mitchell P, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2018 Apr 26;378(17):1573-1582. doi: 10.1056/NEJMoa1716405.
    7. Logallo N, Novotny V, Assmus J, et al. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): A phase 3, randomized, open-label, blinded endpoint trial. Lancet Neurol. 2017 Oct;16(10):781-788. doi: 10.1016/S1474-4422(17)30253-3.
    8. Burgos AM, Saver JL. Evidence that tenecteplase is noninferior to alteplase for acute ischemic stroke: Meta-analysis of 5 randomized trials. Stroke. 2019 Aug;50(8):2156-2162. doi: 10.1161/STROKEAHA.119.025080.
    9. Oliveira M, Fidalgo M, Fontao L, et al. Tenecteplase for thrombolysis in stroke patients: Systematic review with meta-analysis. Am J Emerg Med. 2021 Apr;42:31-37. doi: 10.1016/j.ajem.2020.12.026.
    10. Haley E, Thompson J, Grotta J, et al. Phase IIB/III trial of tenecteplase in acute ischemic stroke: Results of a prematurely terminated randomized clinical trial. Stroke. 2010 Apr;41(4): 707-11.doi: 10.1161/STROKEAHA.109.572040.
    11. Parsons M, Spratt N, Bivard A, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med. 2012 Mar 22;366(12):1099-107. doi: 10.1056/NEJMoa1109842.
    12. Huang X, Cheripelli B, Lloyd S, et al. Alteplase versus tenecteplase for thrombolysis after ischemic stroke (ATTEST): A phase 2, randomized, open-label, blinded endpoint study. Lancet Neurol. 2015 Apr;14(4):368-76. doi: 10.1016/S1474-4422(15)70017-7.
    13. Campbell B, Mitchell PJ, Churilov L, et al. Effect of intravenous tenecteplase dose on cerebral reperfusion before thrombectomy in patients with large vessel occlusion ischemic stroke: The EXTEND-IA TNK Part 2 randomized clinical trial. JAMA. 2020 Apr 7;323(13):1257-1265. doi: 10.1001/jama.2020.1511.
    14. U.S. National Library of Medicine. Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST2). ClinicalTrials.gov. June 27, 2016. Updated March 29, 2018. Accessed January 20, 2022.https://clinicaltrials.gov/ct2/show/NCT02814409.
    15. U.S. National Library of Medicine. The Norwegian Tenecteplase Stroke Trial 2 (NOR-TEST 2). ClinicalTrials.gov. February 26, 2019. Updated November 8, 2021. Accessed January 20, 2022. https://clinicaltrials.gov/ct2/show/NCT03854500.
    16. U.S. National Library of Medicine. Alteplase Compared to Tenecteplase in Patients with Acute Ischemic Stroke (AcT). ClinicalTrials.gov. March 26, 2019. Updated December 16, 2021. Accessed January 20, 2022. https://clinicaltrials.gov/ct2/show/NCT03889249 ?term=Tenecteplase&cond=Stroke&draw=2&rank=17.
  • 13 Apr 2022 12:45 PM | Anonymous

    Authors: Lauren McCulley, PharmD, Center for Behavioral Medicine - Kansas City, MO And Mary Beth Dameron, PharmD, BCACP, University Health - Kansas City, MO

    Program Number: 2022-02-02
    Approved Dates:   April 1, 2022-October 1, 2022
    Approved Contact Hours:  One Hour(s) (1) CE(s) per session

    Learning Objectives:

    • Identify the pathophysiology for migraines
    • Describe the role of CGRP inhibitors in migraine therapy
    • Differentiate dosing and mechanism of action between the different CGRP inhibitors
    • Analyze the relevant studies looking at the safety and efficacy of CGRP inhibitors in migraine treatment
    • Determine the place in therapy for CGRP inhibitors


    Migraine is a chronic neurologic disease that affects more than 10% of the population worldwide.1 It is often associated with significant distress in a person’s life, which can lead to an inability to perform daily tasks, financial burden, and an increased risk for comorbid mental health diagnoses (such as anxiety and depression).2 The prevalence of migraine and severe headache in the US adult population is 9.7% in males and 20.7% in females.3 According to the National Institutes of Health, migraine-associated pain involves an intense pulsing or throbbing pain in one area of the head. It is often accompanied by nausea, vomiting, phonophobia, and/or photophobia. Common migraine triggers include stress, anxiety, hormonal changes, weather changes, bright or flashing lights, lack of food or sleep, and dietary substances.1 Identification and avoidance of patient-specific triggers may reduce or prevent migraine attacks.

    There are many proposed mechanisms that likely play a pivotal role in the pathophysiology of migraines. Migraine pain is thought to happen after stimulation of the trigeminal sensory nervous pain pathways from vasodilation of local intracranial blood vessels.4 As the trigeminovascular pain pathway is stimulated, vasoactive peptides such as substance P and calcitonin gene-related peptide (CGRP) are released. This leads to an exacerbation of vasodilation, which results in inflammation and pain.5 Due to knowledge regarding the role of CGRP in migraine pathophysiology, new medications specifically targeting CGRP or its receptor have been developed. CGRP antagonists are thought to alleviate migraines through the following processes6:

    • Blocking neurogenic inflammation: CGRP antagonists bind to CGRP receptors present on mast cells, which inhibits inflammation caused by the trigeminal nerve release of CGRP onto mast cells within the meninges of the brain
    • Decreasing artery dilation: CGRP antagonists inhibit dilation of intracranial arteries by blocking CGRP receptors present in smooth muscle cells
    • Inhibiting pain transmission: CGRP antagonists bind to CGRP or its receptors, which results in suppression of pain through inhibition of the central relay of pain signals

    According to the International Classification of Headache Disorders (ICHD-3), a diagnosis of migraine is based on the frequency of monthly migraine days (MMDs), monthly headache days (MHDs), duration of headache attack, and symptom presentation.7 Migraines can be categorized as episodic or chronic and can be treated with preventive and abortive therapies. There are many preventive and abortive treatments approved for migraine. Preventative treatments are used to reduce attack frequency, severity, duration, and disability. Based on patient preference, use of prophylactic therapy is indicated in patients whose migraine attacks interfere with their daily routines despite abortive treatment, have frequent attacks, and have contraindications to or fail abortive treatments.2 Before CGRP inhibitors were studied and approved for preventative treatment, people with migraines were trialed on many oral medications including beta blockers, tricyclic antidepressants, and antiepileptics.  According to the consensus statement in 2021 from the American Headache Society, CGRP inhibitors are indicated for preventative treatment in migraines when persons with migraines have an intolerance or an inadequate response to an 8-week trial of two or more oral preventative treatment options.2

    With CGRP inhibitors playing a larger role in treatment for preventative migraines, this article will discuss CGRP inhibitors and the evidence behind each agent.

    CGRP inhibitors:

    Four CGRP monoclonal antibodies (mAbs) have been approved by the U.S. Food and Drug Administration (FDA) for migraine prophylaxis: eptinezumab, erenumab, fremanezumab, and galcanezumab. Erenumab is the only CGRP mAb that targets the CGRP receptor, whereas the others target the CGRP ligand. Small molecule CGRP antagonists are oral options approved for the preventive treatment of episodic migraine and include atogepant and rimegepant. Additional details outlining medication-specific characteristics can be found in Table 1 below.

    Literature Review:

    Several efficacy and safety trials have been performed to investigate CGRP agents for episodic and chronic migraines and for abortive and preventative treatment. There are no head-to-head trials of CRGP inhibitors in patients with migraines but most of these trials had similar designs and primary endpoints. Each of these trials will be discussed below.

    Erenumab (Aimovig)

    Erenumab has been studied for preventative treatment for both episodic and chronic migraines. There were 2 trials performed for efficacy and safety in episodic migraines. Study 1, known as the STRIVE trial, included 955 patients who were randomized to a subcutaneous injection of erenumab 70mg, 140mg, or placebo once monthly for 6 months. Individuals were included in the trial if they had a history of migraine (with or without aura) for at least 12 months and had at least 4 but no more than 15 migraine days a month across the 3 months prior to screening and during baseline. The primary endpoint was to assess the change from baseline in mean monthly migraine days over months 4 to 6. Researchers found that both erenumab 70mg and 140mg significantly reduced monthly migraine days and use of acute migraine-specific medications when compared to placebo, as outlined in table 2 below.8

    Like the STRIVE trial, study 2 aimed to assess efficacy and safety in episodic migraine preventative treatment. The trial included 546 patients randomized to either erenumab 70mg or placebo subcutaneously once monthly for 3 months. The inclusion criteria was the same as the STRIVE trial. The primary endpoint was the change from baseline in monthly migraine days at month 3. Similar to the STRIVE trial discussed above, this trial found that erenumab 70mg once monthly significantly reduced monthly migraine days and use of acute migraine-specific medications when compared to placebo. Additional details regarding results of efficacy endpoints can be found in table 3.8

    The last trial assessed erenumab for prevention of chronic migraines. This was a 3 month trial with 667 patients randomized to erenumab 70mg, 140mg or placebo given as a subcutaneous injection once monthly. This trial included those with a history of at least 5 attacks of migraine without aura or migraine with visual sensory, speech, language, retinal, or brainstem aura. Participants had to have at least 15 headache days and a minimum of 8 migraine days per month as reported by the participant. The primary endpoint was similar to trials 1 and 2, change from baseline in monthly migraine days at month 3. Consistent with previous studies discussed, both erenumab 70mg and 140mg demonstrated statistically significant improvements in monthly migraine days compared to placebo. A summary of key efficacy endpoints can be found in table 4.8

    Galcanezumab (Emgality)

    Trials for galcanezumab have been performed to assess safety and efficacy in episodic and chronic migraines. Study 1 (EVOLVE-1) and Study 2 (EVOLVE-2) had similar trial designs and included adults with a history of episodic migraine (4 to 14 migraine days per month). The primary endpoint for both studies was the mean change from baseline in the number of monthly migraine headache days over a 6 month treatment period. Patients in EVOLVE-1 and EVOLVE-2 were randomized to receive once monthly injections of galcanezumab 120mg, 240mg, or placebo. Those randomized to the 120mg group received a 240mg galcanezumab loading dose as well. EVOLVE-1 had a total of 858 patients randomized and EVOLVE-2 had a total of 915 patients randomized all 18 to 65 years of age. Overall, these trials demonstrated statistically significant improvements in monthly migraine days with galcanezumab 120mg once monthly dose. The 240mg once monthly dose showed no additional benefit over the 120mg dose. Results of the primary efficacy endpoint are summarized in table 5.9

    The third trial, REGAIN, included adults ages 18 to 65 years old who had a history of chronic migraines (≥15 headache days per month with ≥8 migraine days per month). Patients were randomized to the same doses as trialed in the EVOLVE studies over a 3 month treatment period. The primary endpoint was the mean change from baseline in the number of monthly migraine headache days over the 3 month treatment period. REGAIN had a total of 1113 patients randomized and 1037 individuals completed the 3-month study. Galcanezumab 120mg demonstrated statistically significant improvement in mean change from baseline in the monthly migraine headache days, which is consistent with findings of the EVOLVE trials as discussed above. Galcanezumab 240mg once monthly showed no additional benefit compared to galcanezumab 120mg once monthly. See table 6 for additional details.9

    Fremanezumab (Ajovy)

    The efficacy of fremanezumab was demonstrated in 2 randomized, 3 month, placebo-controlled studies. Study 1 included adults with a history of episodic migraine (<15 headache days per month) who were randomized to receive subcutaneous injections of fremanezumab 675mg every 3 months, fremanezumab 225mg once monthly, or placebo once monthly. Additionally, patients had to have 85% compliance with a headache e-diary and a total body weight between 99 and 265 pounds for study inclusion. The primary endpoint was the mean change from baseline in the monthly average number of migraine days during the 3 month treatment period. A total of 791 patients completed the trial and the trial found that the quarterly (every 3 month) injection and the monthly injection demonstrated statistically significant improvements in migraine days compared to placebo. Results of the primary efficacy endpoint are summarized in table 7.10

    Much like the other trials involving CGRP inhibitors, fremanezumab was also studied in those with chronic migraines (at least 15 headache days per month). In study 2, patients were randomized to fremanezumab 675mg initially, followed by 225 mg once monthly, 675 mg every 3 month, or placebo once monthly for a 3 month treatment period. This study had the same inclusion criteria as study 1 with the exception of the number of headache days per month. A total of 1034 patients completed the trial, and the primary efficacy endpoint was the mean change from baseline in the monthly average number of headache days of at least moderate severity during the 3-month treatment period. Both the monthly and quarterly dosing provided statistically significant improvement in migraine days compared to placebo as outlined in table 8 below.10

    Eptinezumab (Vyepti)

    Eptinezumab has been evaluated for efficacy in two randomized placebo-controlled trials. Study 1 included adults with a history of episodic migraines, which was defined as 4 to 14 headache days with at least 4 migraine days per month. A total of 665 patients were randomized to receive eptinezumab 100mg, 300mg, or placebo every 3 months for 12 months. The primary endpoint was change from baseline in mean monthly migraine days over months 1 through 3. Treatment with eptinezumab 100mg and 300mg demonstrated statistically significant improvements in migraine days compared to placebo. Refer to table 9 for results of the primary efficacy endpoint.11

    The second eptinezumab study included patients with a history of chronic migraine defined as 15 to 26 headache days per month of which at least 8 were migraine days. A total of 1073 patients were randomized to receive eptinezumab 100mg, 300mg, or placebo every 3 months for 6 months total. This study also included those who had a diagnosis of chronic migraine and medication overuse headache. The primary endpoint was the same as study 1 and eptinezumab 100mg and 300mg demonstrated statistically significant improvements in monthly migraine days compared to placebo. Table 10 includes details of the primary efficacy endpoint for this trial.11

    Rimegepant (Nurtec ODT)

    The efficacy of rimegepant was evaluated for the preventive treatment of episodic migraine in adults in a randomized, double-blind, placebo-controlled trial. Individuals with at least a 1-year history of migraine (with or without aura) were randomized to receive every other day dosing of rimegepant 75mg or placebo for 12 weeks. Trial participants had a history of 4 to 18 moderate or severe monthly migraine attacks. Those who experienced ≥6 migraine days and ≤18 headache days during the observation phase were eligible for the study. The primary efficacy endpoint was change from baseline in the mean number of monthly migraine days during weeks 9-12. Results of the trial showed statistically significant improvements for the primary efficacy endpoint in those given rimegepant 75mg every other day compared to placebo, as further described in table 11.12

    Atogepant (Qulipta)

    The efficacy of atogepant was evaluated for the preventive treatment of episodic migraine in adults in two randomized, multicenter, double-blind, placebo-controlled studies. In study 1, 910 participants were randomized to atogepant 10mg, 30mg, 60mg, or placebo once daily for 12 weeks. The primary efficacy endpoint was the change from baseline in mean monthly migraine days across the 12-week treatment period. A total of 805 (88%) of individuals completed the study and atogepant showed statistically significant improvements for the primary efficacy endpoint in those receiving atogepant at any dose when compared to placebo. Key results are included in Table 12.13

    In study 2, 652 participants were randomized to receive atogepant 10mg, 30mg, 60mg, or placebo once daily for 12 weeks. The primary efficacy endpoint evaluated was the same as study 1 and as demonstrated in study 1, there was a significantly larger reduction in mean monthly migraine days across the 12-week treatment period in those receiving atogepant at any dose compared to placebo. Refer to Table 13 for additional details regarding results of the primary efficacy endpoint.13


    Migraines can be extremely disabling and may lead to significant distress regarding ability to function or complete daily activities. Preventative migraine treatment is indicated when someone experiences frequent and prolonged severe attacks. Many oral options are available for patients for preventative treatment. However, the emergence of CGRP inhibitors have allowed for yet another treatment option for people who suffer from migraines. Guidelines suggest CGRP inhibitors are indicated after failure of at least two oral preventative treatments. The choice of which CGRP inhibitor to use in a patient is dependent on several factors such as insurance status, patient preference, and tolerability.

    Take the CE Quiz


    1. Migraine Information Page. National Institute of Neurological Disorders and Stroke. U.S. Dep. Health Hum. Serv. Updated online December 31, 2019. Accessed January 9, 2021. https://www.ninds.nih.gov/Disorders/All-Disorders/Migraine-Information-Page
    2. Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021 Jul;61(7):1021-1039. doi: 10.1111/head.14153. Epub 2021 Jun 23. PMID: 34160823.
    3. Burch R, Rizzoli P, Loder E. The Prevalence and Impact of Migraine and Severe Headache in the United States: Figures and Trends From Government Health Studies. Headache. 2018 Apr;58(4):496-505. doi: 10.1111/head.13281. Epub 2018 Mar 12. PMID: 29527677.
    4. Hargreaves RJ, Shepheard SL. Pathophysiology of migraine--new insights. Can J Neurol Sci. 1999 Nov;26 Suppl 3:S12-9. doi: 10.1017/s0317167100000147. PMID: 10563228.
    5. Durham P. Calcitonin Gene-Related Peptide (CGRP) and Migraine. Headache. 2006 June;46 Suppl 1:S3-S8.
    6. Durham PL. CGRP-receptor antagonists--a fresh approach to migraine therapy? N. Engl. J. Med. 2004;350(11):1073-1075. doi:10.1056/NEJMp048016.
    7. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018; 38(1):1-211.
    8. Aimovig [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019.
    9. Emgality [package insert]. Indianapolis, IN: Eli Lilly and Company; 2018.
    10. Ajovy [package insert]. North Wales, PA: Teva Pharmaceuticals Inc.;2020.
    11. Vyepti [package insert]. Bothell, WA: Lundbeck Seattle BioPharmaceuticals; 2021.
    12. Nurtec [package insert]. New Haven, CT: Biohaven Pharmaceuticals, Inc.; 2020.
    13. Qulipta [package insert]. Dublin, Ireland: Forest Laboratories Ireland Ltd.;2021.
  • 13 Apr 2022 10:15 AM | Anonymous

    By: Brittany Heuay, PharmD Candidate 2022; St. Louis College of Pharmacy at University of Health Sciences and Pharmacy in St. Louis

    Mentor: Kara Berges, PharmD; Mercy Pharmacy Wentzville

    The COVID-19 pandemic has had far-reaching effects beyond the illness caused by the novel virus. The disruption and isolation brought on by the pandemic has increased the demand for mental health services as feelings of loneliness, loss, grief, and anxiety overwhelm those with and without pre-existing mental health illness1. In September of 2021, authors from The Journal of the American Medical Association (JAMA) reported a startling increase of cannabis use in pregnant women during the COVID-19 pandemic. Women report using cannabis as a way to relieve stress and anxiety brought on by both general stressors of pregnancy and those related to COVID, such as social isolation, financial and psychosocial distress, increased burden of childcare, changes in accessing prenatal care, and concerns about heightened risk of COVID-19 for both mother and baby2.

    Data from Kaiser Permanente Northern California was pulled to test the hypothesis that prenatal cannabis use was increasing during the COVID-19 pandemic. Urine samples were screened using universal toxicology from January 1, 2019 through December 21, 2020 during standard prenatal care (approximately 8 weeks gestation). The pre-pandemic period was defined as tests conducted from January 2019 to March 2020, while the pandemic period included tests taken from April through December 2020. Urine samples from 100,005 pregnancies in 95,412 women with a mean age of 31 years were tested. Before the pandemic, prenatal cannabis use was reported in 6.75% of pregnancies; during the pandemic, the rate of prenatal cannabis use increased to 8.14% (95% CI, 7.85 – 8.43%), a 25% increase (95% CI, 12 – 40%)2.

    The American College of Obstetricians and Gynecologists (ACOG), the American Academy of Pediatrics (AAP), and the Academy of Breastfeeding Medicine (ABM) all advise against the use of cannabis during pregnancy and breastfeeding4-6. Cannabis use during pregnancy can lead to a multitude of adverse effects including low birth weight, disruption of normal brain development in the fetus, increased risk of stillbirth, and increased risk of preterm birth3. There was a significantly increased risk of adverse effects such as low birth weight (OR 1.27, 95% CI, 1.05 – 1.54) and small for gestational age (OR 2.14, 95% CI, 1.38 – 3.30) among cannabis users, but not preterm birth. Additionally, a dose-related effect was noted – heavy cannabis users, defined as weekly use or more, had twice the risk of delivering a low birth weight or small for gestational age baby compared to non-cannabis users7. Due to the risk of adverse effects to the fetus, pregnant women who are currently using cannabis to treat anxiety caused or exacerbated by the COVID-19 pandemic should be counselled by their pharmacists and physicians to quit and seek alternative treatment methods that are safer for both mother and baby.

    However, weighing the benefits and risks of taking medication during pregnancy is an age-old conundrum that patients, pharmacists, and physicians have to continually battle. Treating medical conditions during pregnancy involves the patient’s healthcare team taking multiple factors into account, such as the severity of the condition and the risks to mother and baby if the condition goes untreated. Furthermore, health professionals must look at both pharmacologic and non-pharmacologic treatment options and whether there is evidence of detrimental fetal effects of any chosen medication. With rising anxiety levels fueled by the COVID-19 pandemic, it is important for clinicians to have recommendations ready for pregnant women that are safer than cannabis, which has not been extensively studied for safety or efficacy.

    For mild anxiety, non-pharmacologic options may be sufficient for treatment and can ease a pregnant patient’s fear about potential risks medication may have on their unborn baby. Counselling, cognitive behavioral therapy, exercise, and meditation may be appropriate non-pharmacologic strategies to help pregnant women manage their anxiety over cannabis use9. For generalized anxiety disorder, the 2016 Psychopharmacology Algorithm Project at the Harvard South Shore Program recommended selective serotonin reuptake inhibitors (SSRIs) as first line treatment. Various research studies have identified potential areas of concern in the use of SSRIs during pregnancy including a small increase in birth defects such as congenital heart defects, neonatal abstinence syndrome, low birth weight, and preterm delivery9. Other medications such as buspirone and bupropion in particular seem to pose very low risks to the fetus when used for the treatment of anxiety in pregnant women based on current studies9. Since the potential for risk is still present when utilizing medication to treat anxiety during pregnancy, pharmacists and other clinicians must make sure pregnant women have all the facts made available to them. Leaving anxiety untreated also poses its own set of risks, as anxiety can interfere with the woman’s sleep and diet, can negatively impact her relationships with friends and family, or push them to use substances known to be harmful to both mother and baby, such as alcohol, tobacco, or illicit drugs to manage their anxiety8. In studies, moderate to severe maternal anxiety and depression have been linked to adverse effects such as miscarriage, preeclampsia, preterm delivery, and low birthweight.
    This generation’s pregnant women are facing a unique challenge in managing their mental health during the COVID-19 pandemic, and pharmacists play a key role in helping pregnant women make safe, data-driven recommendations when it comes to treating anxiety. Staying up to date on the most current information is vital, and most data points to cannabis being an inappropriate treatment option for pregnant women experiencing anxiety. Non-pharmacologic treatment options remain the safest options for those patients whose symptoms are mild, while patients with more moderate to severe anxiety may find the benefits of medication such as SSRIs, bupropion, or buspirone may outweigh the rare fetal risk.


    1. Covid-19 disrupting mental health services in most countries, WHO survey. WHO. 5 Oct 2020. <https://www.who.int/news/item/05-10-2020-covid-19-disrupting-mental-health-services-in-most-countries-who-survey>
    2. Young-Wolff KC, Ray GT, Alexeeff SE, et al. Rates of prenatal cannabis use among pregnant women before and during the Covid-19 pandemic. JAMA. 2021;326(17):1745-1747.
    3. Cannabis and pregnancy. ACOG. Feb 2021. <https://www.acog.org/womens-health/faqs/cannabis-and-pregnancy?utm_source=redirect&utm_medium=web&utm_campaign=int>
    4. Committee Opinion No. 722: Cannabis use during pregnancy and lactation. Obstet Gynecol. Oct 2017;130(4):e205-e209.
    5. Ryan SA, Ammerman SD, O'Connor ME. Cannabis use during pregnancy and breastfeeding: Implications for neonatal and childhood outcomes. Pediatrics. Sep 2018;142(3):e20181889.
    6. Reece-Stremtan S, Marinelli KA. ABM clinical protocol #21: guidelines for breastfeeding and substance use or substance use disorder, revised 2015. Breastfeed Med. Apr 2015;10(3):135-41.
    7. Nguyen VH, Harley KG. Prenatal cannabis use and infant birth outcomes in the Pregnancy Risk Assessment Monitoring System. J Pediatr. Jan 2022;240:87-93.
    8. Conover EH, Forinash AB. How do I weigh the risks and benefits of taking an antidepressant medication during pregnancy? Teratology Primer. Jan 2018. <https://birthdefectsresearch.org/primer/antidepresant-risk.asp>
    9. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists. Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol. Apr 2008;111:1001-20 
  • 06 Apr 2022 5:21 PM | Anonymous

    Lumateperone for Treatment of Schizophrenia

    By: Hae Shim, PharmD Candidate 2022, St. Louis College of Pharmacy

    Mentor: Danielle Moses, PharmD, BCPP, SSM Health DePaul Hospital


    Schizophrenia is a chronic psychological disorder that affects 1% of the general population1 and is considered one of the top 15 leading causes of disability worldwide.2 Schizophrenia is characterized by having two symptoms present for a significant portion of one month (less if treated). Symptoms may include delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms. At least one presenting symptom must be a positive symptom of schizophrenia- delusions, hallucinations, or disorganized speech.3 Although the progression of schizophrenia may differ among individuals, it can affect the quality of life if not managed properly.4

    Treatment for schizophrenia requires pharmacological and psychosocial interventions. Pharmacological treatments include first-generation or second-generation antipsychotics. Second-generation antipsychotics are typically preferred due to the lower dopamine-mediated adverse effects.4 Current antipsychotic treatments are effective in reducing symptoms, but many medications are associated with adverse effects such as metabolic disturbances, cardiovascular risks, and hyperprolactinemia.1

    Lumateperone (Caplyta)

    On December 23, 2019, the Food and Drug Administration (FDA) approved lumateperone (Caplyta) for the treatment of schizophrenia.5 Lumateperone has shown to only need 40% striatal D2 receptor occupancy for treatment improvement in schizophrenia compared to other available antipsychotics that need 60-80% occupancy.1 The approved dose of lumateperone is 42 mg by mouth once daily with food. Although lumateperone is a once-daily administered oral medication due to its half-life of 13 to 21 hours, there are strict caloric requirements (at least 350 calories) during administration for its absorption.5

    Efficacy and Safety of Lumateperone for Treatment of Schizophrenia: A Randomized Clinical Trial

    Lumateperone was  studied in a 4 week randomized, double-blinded, phase 3, placebo- controlled study conducted at 12 clinical sites from November 13, 2014, to July 20, 2015.1 Patients experiencing an acute exacerbation of psychosis were eligible to participate in the inpatient study, and were randomized in a 1:1:1 ratio to 42 mg lumateperone, 28 mg lumateperone, or placebo.1 All three groups were given once-daily oral administration in the morning. The study revealed significant improvement in symptoms of schizophrenia beginning at the first week and maintained throughout the 28 day treatment period.1 The study completion rates were 85.3% in the 42 mg lumateperone group, 80.0% in the 28 mg lumateperone group, and 74.0% in the placebo group.1 Overall, 20 participants in the 42 mg lumateperone group, 28 participants in the 28 mg lumateperone group, and 38 participants in the placebo group discontinued the study.1

    Participants treated with 42 mg of lumateperone displayed a statistically significant improvement in the PANSS total score from baseline compared to placebo or treatment with lumateperone 28 mg (Table 1). Common adverse events observed were somnolence, sedation, fatigue, and constipation (Table 2). There was no increase in suicidal ideation or behavior as measured by Columbia Suicide Severity Rating Scale. No extrapyramidal symptoms related to treatment-emergent adverse events occurred in ≥ 5% of any treatment arm. There were no significant mean changes in metabolic parameters (cholesterol, glucose, triglycerides, prolactin, and insulin levels) from baseline to 28 days, and no QTc > 500 milliseconds or a change in QTc > 60 milliseconds from baseline.1


    Lumateperone 42 mg demonstrated efficacy and safety for treatment of schizophrenia.1 Lumateperone may represent a preferred option for those who desire treatment with minimal cardiac, metabolic, and motor adverse events, though longer-term studies and head-to-head comparison trials are warranted to recommend its use over widely used agents with similar adverse effect profiles (e.g., aripiprazole).


    1. Correll CU, Davis RE, Weingart M, et al. Efficacy and safety of lumateperone for treatment of schizophrenia: a randomized clinical Trial. JAMA Psychiatry. 2020;77(4):349-358.
    2. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet. 2017;390(10100):1211-1259.
    3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington D.C.: 2013.
    4. Keepers GA, Fochtmann LJ, Anzia JM, et al. The american psychiatric association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020;177(9):868-872.
    5. Lumateperone. In: Lexi-Drugs. Lexi-Comp, Inc. Updated September 30,2021. Accessed October 19, 2021.
  • 06 Apr 2022 5:08 PM | Anonymous

    Magnesium for the Treatment of Postoperative Pain

    Author: Brittany Bush, PharmD Candidate 2022, Xavier University of Louisiana College of Pharmacy

    Mentor: Rachel C. Wolfe, PharmD, MHA, BCCCP, Barnes-Jewish Hospital – Saint Louis, Missouri

    Acute postoperative pain often occurs after surgery with the most severe pain noted within the first 72 hours after intervention.1,2 Systemic opioids are routinely employed to manage postoperative pain. However, they can be associated with significant side effects, including

    long-term use and dependence.3-5 The challenge to reduce reliance on opioids for the treatment of postoperative pain has resulted in a growing interest in utilizing non-opioid analgesics. These medications help achieve pain control, while minimizing adverse effects. Since the perception of pain is a complex phenomenon, a multimodal analgesia approach may be utilized to enhance effectiveness.6 This care model lessens opioid use and drug related adverse effects by capitalizing on mechanistic differences between various analgesic medications, such as acetaminophen,

    non-steroidal anti-inflammatory drugs, dexamethasone, gabapentinoids, local anesthetics, and NMDA antagonists.6

    Literature findings indicate n-methyl-d-aspartate (NMDA) receptor activation is directly associated with pain sensory reception from peripheral tissue and nerve injury. The NMDA receptor is widely located throughout the central nervous system and regulates influx of sodium and calcium and outflow of potassium.7,8 Upon activation, the increased intracellular calcium levels seem to play a role in initiating central sensitization. This is a phenomenon by which repetitive nociceptive inputs eventually results in a prolonged decrease in the pain threshold, leading to hyperalgesia.8 The use of a NMDA receptor antagonist has been shown to significantly decrease pain.7 Magnesium, as an NMDA receptor antagonist, is a pain adjuvant that controls the excitability of the NMDA receptor.8,9

    Although there has been recent interest in preoperative oral magnesium as a pre-emptive analgesic agent, the primary perioperative dosing strategies studied utilize intravenous (IV) magnesium sulfate. Studied doses are typically administered by the way of a bolus dose, continuous infusion, or bolus plus infusion. The bolus dose, infusion rates, and infusion durations have also been variable. At this time, most of the literature supports an intraoperative IV bolus dose followed by a continuous infusion.6,8,9,11,12 The most common and well-studied dose of magnesium sulfate for perioperative pain includes an intraoperative IV loading dose of 30-50 mg/kg administered over 15 to 30 minutes at the start of the surgery followed by a continuous infusion at 6-15 mg/kg/hour until surgery completion.6,8,9,11

    The effectiveness of magnesium in reducing postoperative pain and opioid consumption has been evaluated in several surgical procedure types such as spine, thoracic, major abdominal, and hysterectomy.8-10 A systematic review performed by Albrecht and colleagues included 25 randomized trials, consisting of a total of 1,461 patients, that received perioperative magnesium for the reduction of postoperative pain. Within this review, the primary endpoint assessed was cumulative IV morphine consumption at 24 hours postoperatively. Statistically significant heterogeneity existed in the wide variety of dosing regimens chosen by various trials analyzed. Despite this limitation, magnesium significantly reduced the 24-hour cumulative consumption of IV morphine by 24.4%. A reduction in the amount of analgesics used was observed regardless of the type of surgery performed. For example, morphine consumption decreased by 12.7% in

    gynecological surgery, 37.9% in orthopedic surgeries, and 15% in gastrointestinal surgeries. Time to first analgesic request from patients, however, was not significantly changed with the incorporation of magnesium into the pain regimen. 11

    A more recent systematic review performed by Morel and colleagues provided an in-depth analysis of the literature related to magnesium for pain management. This review

    contained 81 randomized controlled trials, consisting of 5,447 patients, that explored the efficacy of magnesium for the reduction of pain and/or analgesic consumption, 49 of which focused on postoperative pain. Overall, 29 of 44 studies observed a significant decrease in pain as assessed by the visual analog scale. Contrarily, 16 randomized controlled trials displayed no efficacy in pain reduction. An important limitation among the randomized controlled trials in this review is the heterogeneity in dosing strategies. The most commonly studied method of dosing, seen in 33 of the trials reviewed, was the use of an IV bolus followed by a continuous infusion. Thirty-six of the 45 post-operative randomized controlled trials that analyzed analgesia requirements showed a significant decrease in consumption of analgesic agents such as morphine, tramadol, diclofenac, and fentanyl. Contrarily, 11 randomized controlled trials showed no significant different in analgesic consumption in patients.13

    The safety of magnesium in the management of postoperative pain has not been thoroughly evaluated in clinical trials. Side effects of magnesium can be dose or rate related and can present as flushing or hypotension, respectively.14 Monitoring of blood pressure is a useful method to ensure the safety of therapy. 15 Lastly, hypermagnesemia is uncommon in patients with normal renal function; however, due to its significant renal elimination, magnesium doses should be reduced by 50% in patients with renal impairment.12,14

    In conclusion, magnesium may play an important role in the evolution of postoperative pain and therefore could be a valuable analgesic adjunct when incorporated into a multimodal regimen within the perioperative arena. Further research is needed to determine the most effective magnesium regimen that reduces pain and opioid consumption in the immediate postoperative period. Furthermore, it is imperative that we gain insight into the patient populations and procedure types that benefit the most from perioperative NMDA antagonism provided by magnesium.


    1. Lynch EP, Lazor MA, Gellis JE, et al. Patient experience of pain after elective noncardiac surgery. Anesth Analg 1997;85(1):117-23.
    2. Svensson I, Sjostrom B, Haljamae H. Assessment of pain experiences after elective surgery. J Pain Symptom Manage 2000;20(3):193-201.
    3. Kessler ER, Shah M, Gruschkus SK, et al. Cost and quality implications of opioid-based postsurgical pain control using administrative claims data from a large health system: opioid-related adverse events and their impact on clinical and economic outcomes. Pharmacotherapy 2013;33(4):383-91.
    4. Hill MV, McMahon ML, Stucke RS, et al. Wide variation and excessive dosage of opioid prescriptions for common general surgical procedures. Ann Surg 2017;265(4):709-14.
    5. Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. J Pain Res 2017;10:2287-98.
    6. Beckham, T. Perioperative use of intravenous magnesium sulfate to decrease postoperative pain. J Anest & Inten Care Med. 2020; 10(2): 555788.
    7. Petrenko AB, Yamakura T, Baba H, Shimoji K. The role of n-methyl-d-aspartate (NMDA) receptors in pain: a review. Anesth Analg. 2003;97(4):1108-1116.
    8. Shin HJ, Na HS, Do SH. Magnesium and Pain. Nutrients. 2020;12(8):2184.
    9. Na HS, Ryu JH, Do SH. The role of magnesium in pain. Adelaide (AU): University of Adelaide Press; 2011.
    10. De Oliveira GS, Jr., Castro-Alves LJ, Khan JH, McCarthy RJ. Perioperative systemic magnesium to minimize postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology 2013;119(1):178-90.
    11. Albrecht E, Kirkham KR, Liu SS, Brull R. Peri-operative intravenous administration of magnesium sulphate and postoperative pain: a meta-analysis. Anaesthesia. 2013 Jan;68(1):79-90.
    12. Do SH. Magnesium: a versatile drug for anesthesiologists. Korean J Anesthesiol. 2013;65(1):4-8.
    13. Morel, Véronique et al. “Magnesium for Pain Treatment in 2021? State of the Art.” Nutrients vol. 13,5 1397. 21 Apr. 2021
    14. Magnesium Sulfate. Lexicomp Online. Hudson, OH: Lexi-Comp.
    15. Cascella M, Vaqar S. Hypermagnesemia. StatPearls Publishing; 2021 Jan.
  • 06 Apr 2022 5:02 PM | Anonymous

    Opioid Use Disorder: Identification and Management in the Acute Setting

    Madeline Taylor, BS, PharmD 2022 Candidate & Julianne Yeary, PharmD, BCCCP


    Opioid overdose deaths continue to increase in both urban and rural areas of Missouri, accounting for 1 out of every 56 deaths in 2018.1 The rise in patients suffering from opioid use disorder (OUD) is placing a great burden on the healthcare system. Establishing preventative measures and providing timely recognition and initiation of treatment for patients suffering from OUD is crucial.


    Identification of Patients

    In patients presenting with risk factors for OUD (e.g., personal or family history of OUD, related mental health or personality disorder, or a positive urine drug screen), clinicians should keep OUD on their differential diagnosis when particular signs and symptoms are present.2 Signs and symptoms can frequently involve the following domains: mood, physical, psychological, and behavior.2 The DSM-5 criteria should be used to make an official diagnosis in patients suspected to have OUD. Patients must meet at least two of the criteria to be eligible for pharmacological treatment.3

    Acute withdrawal is seen when rebound hyperexcitability occurs after abrupt opioid cessation in opioid dependent patients.2 Opioid withdrawal symptoms (OWS) include anxiety or restlessness, diarrhea, fever, diaphoresis, nausea, vomiting, dilated pupils, tachycardia, and hypertension.4 Onset of withdrawal is dependent on the type of substance being used.5 For example, discontinuation of heroin, a short-acting opioid, will produce OWS in 8-12 hours. Alternatively, methadone, a long-acting opioid, may take up to 36 hours before OWS are apparent.5,6 The Clinical Opioid Withdrawal Scale (COWS) is a scale used in the inpatient setting to score the level of withdrawal as mild, moderate, moderately severe, or severe.5,7 The severity of OWS determined by COWS score guides treatment decisions.


    Managing Opioid Use Disorder

    The current Food and Drug Administration approved medications for OUD include methadone, buprenorphine, and naltrexone.2 Methadone and buprenorphine are agents commonly used in the inpatient setting. Naltrexone cannot be initiated until at least seven days since last opioid usage and is therefore not commonly used for the acute management of OUD.2 There are factors that should be considered when selecting optimal pharmacologic intervention for OUD in the hospital including any previous outpatient medication for addiction treatment (MAT), co-morbid conditions, current withdrawal symptoms, willingness to receive OUD treatment, and concomitant medications.

    Opioid Withdrawal Symptom Management

     The opioid agonists buprenorphine and methadone are the primary treatment agents in OUD, while several non-opioid medications focus on OWS. Clonidine, an alpha-2 agonist, is the mainstay of non-opioid treatments for OWS, and is used off-label to manage specific symptoms, such as tachycardia, anxiety, and hypertension.4 Oral hydration, antiemetics, and antidiarrheals are also used for supportive care in OWS.4,5


    Buprenorphine is a partial agonist at the mu opioid receptor which allows for maximal opioid effect with less risk of severe adverse reactions, such as respiratory depression, compared to full opioid agonists.2,5 Sublingual administration is preferred over the oral route to avoid first-pass effect and loss of bioavailability due to intestinal absorption. Peak effect occurs three to four hours after sublingual administration. Buprenorphine is metabolized by the liver, primarily via the cytochrome P450 (CYP) CYP3A4 enzyme, which can lead to drug interactions. Buprenorphine has an extremely high binding affinity and slowly dissociates from the mu opioid receptor providing the sublingual formulation with a long half-life of 38 hours. The only contraindication to its use is a known hypersensitivity to buprenorphine.2,5 Buprenorphine is typically initiated when a patient is in moderate withdrawal or COWS > 11 to avoid precipitating severe OWS (Table 1).2,5 New approaches are emerging to explore buprenorphine initiation strategies prior to OWS, however to date evidence is limited to case reports.15 The drug’s long half-life allows for a “self-taper” effect as it slowly dissociates from the opioid receptors.10,11,12 In two systematic reviews buprenorphine was more effective than clonidine for the management of opioid withdrawal and appeared to be equally effective to methadone.13,14 One systematic review found that buprenorphine may offer advantages over methadone in the inpatient setting for resolution of withdrawal symptoms; however more research is warranted for verification.14

    Buprenorphine is often given in combination with naloxone, a full opioid receptor antagonist. This combination works to reduce adulteration and abuse rates when used for long term management in the outpatient setting and may be restarted when patients present to the acute care setting. Buprenorphine is a Schedule III medication, and prescribers need a waiver to prescribe this medication. Prescribing abilities for a 30-day prescription have also been extended to nurse practitioners and physician assistants, so long as their collaborative practice is with a physician who is waiver certified.16


    Methadone, a long-acting full agonist at the mu opioid receptor, works by dampening the rewarding effects of other opioids through its long-acting effect on the opioid receptors while preventing withdrawal symptoms.2,5 Methadone, which is metabolized in the liver primarily via the CYP2B6 enzyme, carries the risk for drug interactions as well as hypokalemia and QTc interval prolongation.5 Contraindications include current respiratory depression, severe bronchial asthma or hypercapnia, and paralytic ileus.2 A patient with lower opioid tolerance (e.g. re-initiating treatment after relapse) may require a lower initiation dose (Table 1).


    Clonidine stimulates alpha-2 adrenoceptors in the brain, activating an inhibitory neuron, which results in reduced central nervous system (CNS) sympathetic outflow and ultimately decreases heart rate and blood pressure.8 In a systematic review, clonidine was superior to placebo in reducing withdrawal symptoms.9 Clonidine is metabolized in the liver, however, it does not carry the risk of CYP drug interactions. Patients using clonidine may experience hypotension and bradycardia.2,10 The only contraindication to its use is a known hypersensitivity to clonidine.

    Outpatient MAT

    Both behavioral and medical screening is necessary to determine which patients would be good candidates for MAT at time of discharge. Goals of initial screening include access for crisis intervention, federal and state eligibility requirements, a patient’s ability to understand and accept program responsibilities including benefits and drawbacks of MAT, and recognition of barriers that might hamper a patient’s ability to meet treatment requirements (e.g. lack of transportation, other substance abuse, and commitment concerns).



    The focus of caring for patients with OUD in the inpatient setting should be on both acute treatment as well as prevention. Patients initiated on MAT while inpatient will require follow-up post discharge in the outpatient setting for continued management. Educating clinicians on symptoms of OUD, the importance of providing MAT, and evidence-based treatment options employed to alleviate OWS may improve timely diagnosis and treatment.


    1. Missouri Department of Health and Senior Services. Missouri Opioids Information. https://health.mo.gov/data/opioids/ (accessed 2021 June 20).
    2. 2020 Focused Update Guideline Committee. The ASAM national practice guideline for the treatment of opioid use disorder: 2020 focused update. J Addict Med. 2020; 14(2S Suppl1):1-91.
    3. American Psychiatric Association. Opioid Use Disorder. https://www.psychiatry.org/patients-families/addiction/opioid-use-disorder (accessed 2021 July 15).
    4. Kosten TR, Baxter LE. Review article: effective management of opioid withdrawal symptoms: a gateway to opioid dependence treatment. Am J Addict. 2019; 28:55-62.
    5. Koehl JL, Zimmerman DE, Bridgeman PJ. Medications for the management of opioid use disorder. Am J Health-Syst Pharm. 2019; 76:1097-1104.
    6. American Addiction Centers. Opiate withdrawal timeline, symptoms, and treatment. (2021). https://americanaddictioncenters.org/withdrawal-timelines-treatments/opiate (accessed 2021 July 16).
    7. Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003; 35:253-259.
    8. Catapres (clonidine hydrochloride) package insert. Ridgefield, CT: Boehringer Ingelheim Corporation; 2009 Oct.
    9. Gowing L, Farrell MF, Ali R, White JM. Alpha2-adrenergic agonists for the management of opioid withdrawal. Cochrane Database Syst Rev. 2016; 3:CD002024.
    10. Toce MS, Chai PR, Burns MM, Boyer EW. Pharmacological treatment of opioid use disorder: a review of pharmacotherapy, adjuncts, and toxicity. J Med Toxicol. 2018; 14:306-322.
    11. Sigmon SC, Bisaga A, Nunes EV et al., Opioid detoxification and naltrexone induction strategies: recommendations for clinical practice. Am J Drug Alcohol Abuse. 2012; 38:187-99.
    12. Fishbain DA. Opioid tapering/detoxification protocols, a compendium: narrative review. Pain Med. 2021; 22(7):1676-1697.
    13. Gowing L, Ali R, White JM, Mbewe D. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst Rev. 2017; 2:CD002025.
    14. Gowing L, Ali R, White JM. Buprenorphine for the management of opioid withdrawal. Cochrane Database Syst Rev. 2009; 3:CD002025.
    15. Adams KK, Machnicz M, Sobieraj DM. Initiating buprenorphine to treat opioid use disorder without prerequisite withdrawal: a systematic review. Addict Sci Clin Pract. 2021;16(1):36. Published 2021 Jun 8. doi:10.1186/s13722-021-00244-8
    16. State of Missouri. 630.875 Citation of Law. Missouri Revisor of Statutes - Revised Statutes of Missouri, RSMo, Missouri Law, MO Law, Joint Committee on Legislative Research. https://revisor.mo.gov/main/OneSection.aspx?section=630.875&amp;bid=47957&amp;hl=buprenorphine%25u2044. Accessed March 19, 2022.
  • 06 Apr 2022 11:17 AM | Anonymous

    Authors: Stephanie Chau PharmD and Sarah Billings PharmD, BCACP, CDCES

    Program Number: 2202-02-03
    Approved Dates:  April 1, 2022 - October 1, 2022
    Approved Contact Hours:  One Hour(s) (1) CE(s) per session


    1. Compare the difference between the nonsteroidal mineralcorticoid receptor antagonist finerenone to steroidal mineralocorticoid receptor antagonists
    2. Assess literature on cardiovascular and renal effects of finerenone in type 2 diabetics with diabetic kidney disease
    3. Review other medications with cardiovascular and renal benefits used in type 2 diabetics


    Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) and is associated with an increase in mortality in diabetics1. Chronic kidney disease (CKD) and diabetes mellitus lead to an additive effect that increases the cardiovascular mortality rate. The current mainstay of therapy used to reduce the progression of DKD are angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Sodium-glucose co-transporter-2 (SGLT2) inhibitors further decrease the progression of DKD, incidence of major adverse cardiovascular events, and heart failure hospitalizations.

    Mineralocorticoid receptor antagonists (MRA) have been shown to reduce albuminuria in patients with CKD when given alone or with renin-angiotensin system (RAS) blockers and reduce overall mortality in patients with heart failure. Albuminuria reduction is a main factor of improving renal outcomes in patients with CKD. A 30% or greater reduction in albumin that is sustained for at least 2 years is considered to be a validated surrogate for slowing down CKD progression1. The addition of spironolactone or eplerenone to RAS blockers to improve renal outcomes is unclear in patients with DKD since there is limited renal outcome data. An issue with steroidal MRAs such as spironolactone and eplerenone is they are associated with an increase in serum potassium. The potential benefits and adverse events of steroidal and non-steroidal MRAs in DKD patients will be compared.

    Non-steroidal vs Steroidal Mineralocorticoid Receptor Antagonists

    While both non-steroidal and steroidal MRAs block aldosterone activity, the effects on potassium levels are different. Spironolactone is a potent steroidal MRA, has a long half-life, and relatively low selectivity since it also acts on progesterone and androgen receptors as well. One of the most important side effects of spironolactone is hyperkalemia. Eplerenone is another steroidal MRA with higher receptor specificity, but is still associated with hyperkalemia especially at a higher dose of 200 mg1. Both spironolactone and eplerenone are associated with a three-to-eight-fold increased risk of hyperkalemia in stage 3 CKD or higher patients1.

    Non-steroidal MRAs include the agents apararenone, esaxerenone, and finerenone. Finerenone has a high potency and selectivity for mineralocorticoid receptors and acts as an inverse agonist. It has a greater receptor selectivity compared to spironolactone. Finerenone has stronger mineralocorticoid receptor binding affinity compared to eplerenone and a lower affinity for androgen, progesterone, and glucocorticoid receptors similar to eplerenone. Compared to steroidal MRAs, finerenone has a reduced blood pressure lowering effect since it is unable to cross the blood-brain barrier and does not inhibit central mineralocorticoid receptors. However, finerenone is expected to have a lower risk of hyperkalemia compared to steroidal MRAs. This is thought to be due to a balanced kidney and heart distribution of finerenone while spironolactone and eplerenone are mostly distributed in the kidney compared to the heart. Also finerenone has no active metabolites and a shorter half-life of 2 hours compared to spironolactone which has a half-life of 14-16 hours with active metabolites. Eplerenone has no active metabolites, but has a slightly longer half-life of 4-6 hours2. However, finerenone is still dosed based potassium levels, which requires routine monitoring.

    Table Finerenone vs Traditional Steroidal Mineralocorticoid Receptors Antagonists1

    Table 2 Dosing of Finerenone3

    Finerenone Tolerability

    The ARTS studies looked at the tolerability of MRAs in heart failure in DKD. The study included patients with chronic systolic heart failure and stage 3 CKD who received finerenone, placebo, or open-label spironolactone. Finerenone was associated with smaller increases in serum potassium levels compared to spironolactone and a reduced incidence of hyperkalemia. The ARTS-DN trial and ARTS-HF trial looked at tolerability of finerenone in DKD and heart failure, which showed that finerenone was safe and efficacious.

    The ARTS-DN study was a randomized, double-blind, parallel-group placebo-controlled trial that compared efficacy and safety of different once-daily doses of finerenone compared to placebo for 90 days in patients with type 2 diabetes who had high or very high albuminuria. High albuminuria is defined as a urine to albumin creatinine ratio (UACR) 30 mg/g and very high albuminuria is defined as UACR 300 mg/g. This study had all patients receive an ACE inhibitor or ARB, have albuminuria (UACR 30 mg/g), have an estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73 m2 with serum potassium levels less than or equal to 4.8 mmol/L. The doses of finerenone varied from 1.25, 2.5, 5, 7.5, 10, 15, and 20 mg daily. The primary outcome of the study was the ratio of UACR at day 90 vs at baseline. Finerenone doses of 7.5-20 mg daily showed a dose-dependent reduction in the UACR with the largest reduction in the 20 mg daily group at day 904. The study observed a mean change in serum potassium of 0.2-0.25 mmol/L in the 20 mg daily finerenone group4. Hyperkalemia and discontinuation of finerenone was observed in 1.8% of patients who received 7.5-20 mg daily compared to zero patients in the placebo group4. There were two cases of serum potassium levels greater than 6 mmol/L in the finerenone 1.25 mg group, and 1 in the 15 mg group only4. There was not a difference in the incidence of an eGFR decrease of at least 30% between finerenone and placebo4. There was also no difference in the overall difference in the incidence of adverse events between both groups4.

    The ARTS-HF study evaluated the effectiveness and safety of finerenone in heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes and/or CKD stage 3 or higher patients compared to eplerenone. The patients also had to require hospitalization and treatment with emergency intravenous diuretics. In this study patients received finerenone 2.5 to 20 mg daily and eplerenone 25 to 50 mg daily. The primary outcome of this study was the percent of patients who had a decrease in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of >30% from baseline to day 90. About 30.9% to 38.8% of patients in the finerenone group compared to 37.2% of patients in the eplerenone group had a >30% decrease in NT-proBNP levels from baseline to day 905. Finerenone had a greater benefit in the composite endpoint of cardiovascular hospitalization, death from any cause, and emergency presentation for worsening heart failure at day 90. The most benefit was seen with a finerenone dose of 10-20 mg daily (HR: 0.56, 95% CI: 0.35-0.90, P=0.02) mostly due to a reduction in cardiovascular hospitalization5. Overall there were a total of 44 patients with hyperkalemia ( 5.6 mmol/L) and these were balanced between the finerenone and eplerenone group5. There were 5 patients in the eplerenone group and 4 in the finerenone group who had potassium concentrations >6.0 mmol/L at any point after baseline. The mean change in potassium from baseline to day 90 was greater in the epelerenone group (0.262 mmol/L) compared to the finerenone groups (0.119-0.202 mmol/L)5.

    Finerenone Trials on Progression of Diabetic Kidney Disease

    The FIDELIO-DKD trial evaluated the efficacy and safety of finerenone, in addition to the standard of care, on the progression of CKD in type 2 diabetics and advanced CKD. The study included patients who were at least 18 years old or older with type 2 diabetes with an established clinical diagnosis of CKD who were already being treated with maximally tolerated RAS blocker therapy. Patients with heart failure with reduced ejection fraction were excluded. Patients received finerenone 10 mg daily if they had an eGFR of 25-59 mL/min/1.73 m2 and 20 mg daily for an eGFR greater or equal to 60 mL/min/1.73 m2 or placebo. Patients had a serum potassium of 4.8 mmol/L or less upon study entry. Either finerenone or placebo were held if potassium concentration exceeded 5.5 mmol/L. Finerenone or placebo were restarted when potassium levels fell to 5.0 mmol/L or less. The average dose of finerenone was 15.1 mg daily. The primary composite outcome was kidney failure, a sustained decrease of at least 40% in the eGFR from baseline over at least 4 weeks, or death from renal causes. The main secondary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The median follow-up time was 2.6 years and the primary outcome event occurred in 504 (17.8%) patients in the finerenone group and 600 (21.1%) in the placebo group (HR: 0.82; 95% CI: 0.73-0.93; P=0.001)6. This benefit was mostly due to a reduction in the sustained decrease of at least 40% in eGFR from baseline (HR: 0.81, 95% CI: 0.72-0.92). There was not a statistically significant difference in the incidence of kidney failure or death from renal causes. However a total of 4.6% of patients were on a SGLT2 inhibitor, which have been shown to have renal benefits as well. The secondary outcome occurred in 367 (13.0%) patients in the finerenone group and 420 (14.8%) in the placebo group (HR: 0.86; 95% CI: 0.75-0.99; P=0.03)6. Finerenone was associated with a 31% greater reduction in the UACR from baseline to month four compared to placebo (ratio of least-squares mean change from baseline: 0.69; 95% CI: 0.66-0.71)6. A total of 252 (8.9%) of finerenone patients compared to 326 (11.5%) of placebo patients had a secondary composite kidney outcome event which included kidney failure, a sustained decrease of 57% or greater in the eGFR from baseline, or death from renal causes (HR: 0.76; 95% CI: 0.65-0.90)6. The incidence of hyperkalemia-related adverse events was more frequent in the finerenone group compared to placebo (18.3% and 9.0% respectively)6. The incidence of hyperkalemia-related discontinuation was higher in the finerenone group compared to placebo (2.3% and 0.9% respectively), but no fatal hyperkalemia adverse events were reported6. This study showed a statistically significant benefit in kidney outcomes and cardiovascular benefit with finerenone with the main adverse event being hyperkalemia.

    The FIGARO-DKD trial evaluated the effectiveness of finerenone in reducing major cardiovascular event and death from cardiovascular cause in type 2 diabetics with CKD. The study included patients who were at least 18 years old or older with type 2 diabetes and CKD stage 2 to 4 with moderately elevated albuminuria or stage 1 or 2 CKD with severely elevated albuminuria who were receiving a RAS inhibitor. Patients with symptomatic chronic heart failure with reduced ejection fraction and patients highly represented in the FIDELIO-DKD trial (UACR of 300-5000 mcg/mg and eGFR of 25 to less than 60 mL/min/1.73 m2) were excluded. Patients received finerenone 10 mg once daily if eGFR was 25 to less than 60 mL/min/1.73 m2 and 20 mg once daily if eGFR was at least 60 mL/min/1.73 m2 or placebo. Patients had a serum potassium of 4.8 mmol/L or less upon study entry and finerenone or placebo were held if potassium concentration exceeded 5.5 mmol/L. Finerenone or placebo were restarted when potassium levels fell to 5.0 mmol/L or less. The average dose of finerenone received was 17.5 mg daily. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The main secondary outcome was a composite of the first occurrence of kidney failure, a sustained decrease from baseline of at least 40% in the eGFR for a period of at least 4 weeks, or death from renal causes. The median follow up time was 3.4 years and the primary outcome event occurred in 458 (12.4%) in the finerenone group compared to 519 (14.2%) in the placebo group (HR: 0.87; 95% CI: 0.76-0.98; P=0.03)7. The number needed to treat to prevent one primary outcome event was 47 based on a between group difference of 2.1% after 3.5 years7. More specifically, there was a lower incidence of hospitalization for heart failure in the finerenone group compared to placebo (HR: 0.71; 95% CI: 0.56-0.90)7. However 8.4% of patients were also on SGLT2 inhibitors, which have also been shown to have cardiovascular and heart failure benefits. The secondary composite outcome occurred in 350 (9.5%) in the finerenone group compared to 395 (10.8%) in the placebo group (HR: 0.87; 95% CI: 0.76-1.01)7. The reduction in the UACR from baseline to month 4 was 32% greater in the finerenone group compared to the placebo group (ratio of the least-squares mean change from baseline: 0.68; 95% CI: 0.65-0.70)7. The incidence of hyperkalemia was higher in the finerenone group compared to placebo (10.8% and 5.3%), but no adverse events resulted in death7. Hyperkalemia led to discontinuation in 1.2% in the finerenone group compared to 0.4% of placebo patients7. The incidence the composite outcome of kidney failure occurred in 108 (2.9%) patients in the finerenone group compared to 139 (3.8%) in the placebo group (HR: 0.77; 95% CI: 0.60-0.99)7. This study showed a statistically significant benefit in cardiovascular events mostly due to a reduction in heart failure hospitalizations, but the benefit in kidney outcomes was not statistically significant. 

    Table 3 FIDELIO-DKD vs FIGARO-DKD Trials6,7

    Esaxerenone Trial on the Progression Diabetic Kidney Disease

    The ESAX-DN investigated the effects of esaxerenone on microalbuminuria defined as a UACR 45 to <300 mg/g creatinine in type 2 diabetes patients receiving RAS inhibitors. The primary outcome was UACR remission defined as a <30 mg/g creatinine and a  30% reduction from baseline on two consecutive occasions. The study included 455 type 2 diabetes patients with microalbuminuria who received esaxerenone 1.25 mg and titrated to 2.5 mg daily or placebo. After 52 weeks, the esaxerenone showed a significantly increased incidence of UACR remission (22%) compared to the placebo group (4%) with an absolute difference of 18% (95% CI: 12%-25%; P<0.001)8. The change in UACR from baseline was a 58% decrease in the esaxerenone group compared to 8% in the placebo group8. Furthermore there was a significant improvement in time to first remission and time to first UACR 300 mg/g creatinine. Hyperkalemia was observed in 9% in the esaxerenone group compared to 2% in the placebo group, but the events were asymptomatic8. Hyperkalemia was resolved after dosage reduction or treatment discontinuation. Esaxerenone in addition to a RAS inhibitor in patients with type 2 diabetes and microalbuminuria increased the incidence albuminuria returning to normal and reduced the progression of albuminuria to higher levels. However, esaxerenone has only been approved in Japan for the treatment of hypertension since January 2019.

    Other Agents with Cardiorenal Benefits

    Newer antihyperglycemic agents, which include SGLT2 inhibitors and GLP-1 receptor agonists have also been shown to have cardiorenal benefits. The SGLT-2 inhibitors that have shown cardiovascular benfit include empagliflozin and canagliflozin9. In addition, dapagliflozin and empagliflozin have shown a benefit in heart failure as well9. The SGLT-2 inhibitors that have shown renal benefits as the primary outcome include dapagliflozin and canagliflozin9. The GLP-1 receptor agonists that have shown cardiovascular benefit include albiglutide, dulaglutide, liraglutide and semaglutide (injection)9. The cardiovascular and renal benefits of these SGLT-2 inhibitors and GLP-1 receptor agonists have become the preferred agents used in type 2 diabetics.

    Table 4 Agents with Cardiorenal Benefits in Type 2 Diabetics

    Application to Practice

    The FIDELIO-DKD study showed renal benefits and the FIGARO-DKD study showed cardiovascular benefits with finerenone in type 2 diabetics with CKD in addition to guideline recommended RAS blockers, cardiovascular medications, and well-controlled hemoglobin A1c levels and blood pressure levels. In addition, both trials covered a wide spectrum of CKD stage 2 to stage 4 with moderately elevated albuminuria or stage 1 to stage 4 CKD with severely elevated albuminuria. The FIDELIO-DKD trial showed a statistically significant decrease from baseline of at least 40% in the eGFR, but the FIGARO-DKD trial showed a decrease that was not statistically significant difference as a secondary outcome. The FIGARO-DKD did show a significant cardiovascular benefit, but it was mostly due to a reduction in heart failure hospitalizations. There is a need for more data to determine whether combination therapy with finerenone will result in greater cardiorenal protection in patients with DKD. In addition, the ESAX-DN trial also showed that esaxerenone is beneficial in returning albuminuria to normal and reducing the progression of albuminuria in type 2 diabetes patients with microalbuminuria. However esaxerenone is not available in the United States. One of the major concerns with use of MRAs is the increase serum potassium, but finerenone has been showed to have a lower incidence of hyperkalemia compared to spironolactone making it a better option for patients with DKD. Dosing for finerenone is adjusted based on serum potassium levels which requires frequent potassium monitoring especially during initaition. Currently finerenone is only available under the brand name Kerendia with an estimated cash price of $680 for a 30 day supply. There are savings programs available for patients who qualify, but cost is still a major concern for this medication. Overall, finerenone is another agent that provides cardiorenal benefits for patients with DKD.

    Take the CE Exam


    1. Al Dhaybi O, Bakris GL. Non-steroidal mineralocorticoid antagonists: Prospects for renoprotection in diabetic kidney disease. Diabetes Obes Metab. 2020;22(Suppl.1):69-76. doi:10.1111/dom.13983
    2. Kawanami D, Takashi Y, Muta Y, et al. Mineralocorticoid receptor antagonists in diabetic kidney disease. Front Pharmacol. 2021;12. doi:10.3389/fphar.2021.754239
    3. AHFS DI. Lexicomp. UpToDate, Inc,; 2021. Updated periodically. Accessed December 2021. http://online.lexi.com
    4. Bakris GL, Agarwal R, Chan JC, et al. Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial. JAMA. 2015;314(9):884–894. doi:10.1001/jama.2015.10081
    5. Filippatos G, Anker SD, Böhm M, et al. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. Eur Heart J. 2016;37(27):2105-2114. doi:10.1093/eurheartj/ehw132
    6. Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219-2229. doi:10.1056/nejmoa2025845
    7. Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. August 2021. doi:10.1056/nejmoa2110956
    8. Ito S, Kashihara N, Shikata K, et al. Esaxerenone (CS-3150) in Patients with Type 2 Diabetes and Microalbuminuria (ESAX-DN): Phase 3 Randomized Controlled Clinical Trial. Clin J Am Soc Nephrol. 2020;15(12):1715-1727. doi:10.2215/CJN.06870520
    9. Rangaswami J, Bhalla V, de Boer IH, Staruschenko A, Sharp JA, Singh RR, Lo KB, Tuttle K, Vaduganathan M, Ventura H, McCullough PA; on behalf of the American Heart Association Council on the Kidney in Cardiovascular Disease; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Council on Lifestyle and Cardiometabolic Health. Cardiorenal protection with the newer antidiabetic agents in patients with diabetes and chronic kidney disease: a scientific statement from the American Heart Association. Circulation. 2020;142:e265–e286. doi:10.1161/CIR.0000000000000920
  • 06 Apr 2022 11:03 AM | Anonymous

    By: Jordan Welch, Pharm.D. Candidate 2022

    Mentor: Sara Lingow, Pharm.D., BCACP

    What is a preceptor? Pharmacy preceptors are mentors and educators to pharmacy students and residents. They facilitate approximately 30% of the Doctor of Pharmacy curriculum for student pharmacists via practice-based learning.1 The Accreditation Council for Pharmacy Education (ACPE) states that preceptor development is mandatory, but currently does not outline a specific set of requirements for the “optimal” preceptor.2 The council encourages pharmacy schools to recruit preceptors who excel in the areas of collaboration and professionalism, as well as strategic plan development.These qualities are vital when teaching students how to behave and interact with an interprofessional team, while also sharpening the student’s focus to achieve both personal and professional deadlines. In order to ensure a successful experiential education program, preceptor development, education, and engagement should not only be emphasized, but prioritized. 3

    There are many challenges that experiential education offices face while implementing effective preceptor development.3 Content preparation and development poses a great obstacle to overcome with regard to the time it takes to create and deliver a program. Geographic location can become an issue if the content is being delivered in-person. The cost for continuing education (CE) accreditation can also serve as a drawback to preceptor development, as well as locating pharmacists that are interested in becoming a preceptor.3Additionally, it may be challenging for preceptors to dedicate time for additional development while also working full-time at their practice sites. This article aims to identify and provide potential solutions to the challenges of preceptor development through implementation of strategic, evidence-based programs.

    A 2015 qualitative analysis discovered that pharmacy schools continue to face challenges creating and implementing developmental programs for preceptors.4 Preceptor development varies amongst pharmacy schools, with many taking an individualized approach to address the topic. Preferences for learning and teaching styles when designing and implementing a preceptor development program can vary by generations.3 Therefore, it may be optimal to offer more than one learning approach, such as online modules and in-person training sessions. It is also important to consider preceptor background, certification(s), and experience when designing a program.5 By taking these factors into account, the method of preceptor development should be approached as multifaceted.

    A 2021 survey from the American Society of Health-System Pharmacists (ASHP) was conducted to identify the needs of a preceptor based on his or her background and previous experience.5 Of the 272 respondents, a majority of the preceptors reported the highest need for skill development in precepting, leadership, and communication. For precepting skills needed, preceptors requested specific skill development in setting expectations, assessing performance, developing rotation activities, and managing generational differences. For teaching skills needed, effective didactic education strategies and patient counseling were most requested. For communication skills needed, promoting critical thinking was the most requested, followed by resolving conflicts, communicating feedback, and presentation skills. For leadership skills needed, implementing quality improvement projects, general leadership skills, and time management were similarly requested.Results were independent of years spent precepting and did not favor one skill over another.5

    The survey found on-demand web-based programs for education delivery to be the preferred method amongst the preceptors. A high percentage of the survey respondents also appreciated a “tip of the week” email. Finally, the survey reported that 81% of preceptors prefer to use a survey as a tool to identify areas of self-improvement, followed by the strength’s finder. The learning styles inventory for preceptors and students’ assessment tool, student self-evaluation templates, and grading rubrics were also helpful instruments to utilize when identifying areas for improvement.5

    The Canadian Experiential Education Project for Pharmacy published articles in a three-part series to determine best practice recommendations for the Canadian colleges of pharmacy experiential education program.6,7,8 The project aimed to streamline a national preceptor development program (PDP) that could be adopted by pharmacy schools in Canada, which has not been achieved elsewhere. Twelve recommendations were constructed to guide successful development and implementation of a PDP.6 The national PDP focused on the primary principles: preceptor performance and competency indicators, preceptor engagement strategies, and quality improvement/assurance measures to ensure ongoing feedback.8

    The project proposes developing a web-based platform that allows rotation-specific training alongside continuous professional development for the preceptor.8 It is hypothesized that preceptors can interact with the online modules, once constructed, based on the twelve core recommendations.6,8 The electronic delivery platform will allow flexibility, sharing of resources and social networking between institutions and preceptors, and virtual collection of data that would provide insight for continuous adaptation. The final installation of the series was published in 2021, however, the website has yet to set a launch date.8

    Preceptor development is a complex topic that requires a multi-level approach. Though a national program may be helpful, the limitations such as increased workload, insufficient time, and accessibility may support college- or site-specific programs. These could be spearheaded by experiential education offices and/or compensating the cost of pre-made preceptor development modules by national pharmacy organizations. Development strategies would ideally be no-cost to preceptors, and CE credit could be offered as an incentive to complete the additional training. Many pharmacy schools across the nation offer free CE to their preceptors.10-12 The American Pharmacist Association (APhA) and ASHP also offer continuing education credit for a fee. Pharmacy schools have the opportunity to develop modules or offer CE certified modules as an incentive to become a preceptor for their students.13-14 Based on feedback form the ASHP survey, a web-based, asynchronous program would allow for virtual delivery at a time that is most convenient for the preceptor.5

    Approaching preceptor development from multiple angles by offering courses that encompass many skills is instrumental to both the program and preceptor success. Above all, it is important to assess the preceptor needs of each institution. Developing and adapting the training modules to fit the preferences of the preceptors is crucial for a successful experiential education program.9 Investment in educating the preceptors will not only be beneficial for the precepting pharmacist, but also ensure achievement of the ultimate goal – properly training students, the future of pharmacy.

    Preceptor Development Opportunities for Missouri Pharmacists:

    MSHP Preceptor Development Series: http://www.moshp.org/Professional-Development

    UHSP Preceptor Development: https://www.uhsp.edu/experiential/preceptors/development.html


    1. Vos SS, Trewet CB. A comprehensive approach to preceptor development. Am J Pharm Educ. 2012;76(3):47.
    2. Accreditation Standards and Guidelines for the Professional Program in Pharmacy Leading to the Doctor of Pharmacy Degree. Chicago, IL: Accreditation Council for Pharmacy Education;  http://www.acpe-accredit.org/standards/default.asp. Accessed February 12, 2022.
    3. Howard ML, Yuet WC, Isaacs AN. A Review of Development Initiatives for Pharmacy Student and Resident Preceptors. Am J Pharm Educ. 2020;84(10):ajpe7991.
    4. Danielson J, Craddick K, Eccles D, Kwasnik A, O'Sullivan TA. A qualitative analysis of common concerns about challenges facing pharmacy experiential education programs. Am J Pharm Educ. 2015;79(1):06.
    5. Enderby CY, Davis S, Sincak CA, Shaw B. Health-system pharmacist preceptor development and educational needs for accessible resources. Curr Pharm Teach Learn. 2021;13(9):1110-1120.
    6. Mulherin K, Walter S, Cox CD. National preceptor development program (PDP): Influential evidence and theory. The first of a 3-part series. Curr Pharm Teach Learn. 2018;10(3):255-266.
    7. Walter S, Mulherin K, Cox CD. A Preceptor competency framework for pharmacists. Part 2 of a 3-part series. Curr Pharm Teach Learn. 2018;10(3):402-410.
    8. Cox CD, Mulherin K, Walter S. National preceptor development program (PDP) prototype. The third of a 3-part series. Curr Pharm Teach Learn. 2018;10(3):298-306.
    9. Williams CR, Wolcott MD, Minshew LM, Bentley A, Bell L. A Qualitative Preceptor Development Needs Assessment to Inform Program Design and Effectiveness. Am J Pharm Educ. 2021;85(10):8450.
    10. Preceptors' corner. Purdue University College of Pharmacy Office of Continuing Education. https://ce.pharmacy.purdue.edu/preceptors-corner. Published 2022. Accessed February 18, 2022. 
    11. Online preceptor development modules. https://www.pharmacy.umaryland.edu/about/offices/elp/online-preceptor-development modules/. Published 2022. Accessed February 18, 2022. 
    12. Preceptors. https://www.uhsp.edu/experiential/preceptors/index.html. Accessed February 22, 2022. 
    13. Preceptor toolkit. ASHP. https://www.ashp.org/pharmacy-practice/resource-centers/preceptor-toolkit?loginreturnUrl=SSOCheckOnly. Published 2022. Accessed February 18, 2022. 
    14. APhA advanced preceptor training. American Pharmacists Association. https://www.pharmacist.com/Education/eLearning/Advanced-Training/Advanced-Preceptor. Published 2021. Accessed February 18, 2022. 
  • 06 Apr 2022 10:51 AM | Anonymous

    The MSHP R&E Foundation continues to offer our new Resident Ground Rounds series and our Preceptor Development Series. 

    Information for the Resident Ground Rounds Series can be found here:


    This series is expected to run routinely (approximately every other week) for the next several months.  We are excited to bring this offering forward to provide a vehicle for residents within the state to continue to hone their presentations skills as well as share new information with other pharmacy practitioners (pharmacists, technicians, and students) throughout the state.  These sessions are available for CE through the Missouri State Board of Pharmacy.

    The latest session of our Preceptor Development Series took place on March 3rd titled Enhancing Layered Learning Experiences for Preceptors and Learners.  This event was well attended and sparked excellent discussion amongst the panel and participants.

    Spring Meeting poster and award submissions have been received and are being reviewed.  All submitted posters were accepted for presentation.  Award winners will be announced in the coming weeks.

    Regarding the Spring Meeting if you, your organization, or other colleagues want to assist in the R&E Foundation fundraising efforts, we will once again be hosting a virtual auction and will be accepting donations of gift baskets from groups across the state.  Of course, if you cannot sponsor a basket, we encourage you to bid on the baskets throughout the meeting later in the year!

    Please check out the recently updated R&E Website at https://www.moshp.org/foundation which includes the R&E Board, updated award winners, and award archives!

    Have a great spring and see you virtually during the spring meeting.

    Respectfully submitted,

    Tony Huke, Pharm.D., BCPS

    MSHP R&E Executive Director

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