Andexanet Alfa: A Recombinant Modified Human Factor Xa Protein for Drug Reversal of Rivaroxaban and Apixaban

Objective: To review the pharmacology, safety, and efficacy of andexanet alfa (andexanet), a recombinant modified human factor Xa protein for reversal of factor Xa inhibitors. Data Sources: English-language articles were obtained from MEDLINE (1966 to February 2019) using the following key words: andexanet, andexanet alfa, AndexXa, factor Xa, antidote, and reversal. Citations from selected articles were used to identify additional sources. Study Selection and Data Extraction: Available published articles reporting results of human studies of andexanet alfa were reviewed for inclusion. Prescribing information was used to obtain additional information regarding pharmacology, adverse events, contraindications, and precautions. Data Synthesis: Andexanet is a recombinant modified human factor Xa protein indicated for reversal of rivaroxaban and apixaban in patients with life-threatening or uncontrolled bleeding. Onset of action is rapid and sustained throughout bolus and infusion administration. Medication effects subside 1 to 3 hours postadministration. Andexanet is administered as a bolus followed by a 120-minute continuous infusion. Anti-factor Xa activity was reduced by 95% and 92% in apixaban and rivaroxaban groups, respectively, on infusion completion. Thrombin regeneration occurred within 2 to 5 minutes in up to 96% of patients. Minor infusion reactions and gastrointestinal upset were reported most. A black box warning for thrombotic events, cardiac arrest, ischemia, and sudden death should be noted. Conclusions: Andexanet is effective in reversing rivaroxaban and apixaban anticoagulation due to reduction of anti-factor Xa activity in healthy patients and those with acute major bleeds. Safety concerns, including thrombotic risks, exist and should be assessed against individual patient factors.

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Recent Advances: Antiinfectives

Annals of Pharmacotherapy ◽

10.1177/106002809502901015 ◽

1995 ◽

Vol 29 (10) ◽

pp. 1035-1040 ◽

Cited By ~ 2

Author(s):

Laurie L Briceland ◽

John D Cleary ◽

Courtney V Fletcher ◽

Daniel P Healy ◽

Charles A Peloquin

Keyword(s):

Infectious Diseases ◽

English Language ◽

Data Extraction ◽

Information Service ◽

Ulcer Disease ◽

Additional Information ◽

Study Selection ◽

Enterococcus Spp ◽

Scientific Meetings ◽

Clinically Significant

Objective: To update readers on the significant changes in infectious diseases pharmacotherapy. Data Sources: An Index Medians and Iowa Drug Information Service search (1993–1994) of English-language literature pertaining to the selected topic areas was performed. Additional information from abstracts presented at scientific meetings were identified by the authors. Study Selection and Data Extraction: All identified studies were screened and those judged relevant to the update were evaluated. Data Synthesis: New or clinically significant data since 1992 that related to peptic ulcer disease, microbial resistance (e.g., Enterococcus spp., Streptococcus pneumoniae, Mycobacterium tuberculosis, Candida albicans), immunomodulators, and AIDS were evaluated and compared with previous data. Conclusions: There have been several exciting and significant changes in infectious diseases pharmacotherapy evident from this review.

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Rasburicase for the Treatment and Prevention of Hyperuricemia

Annals of Pharmacotherapy ◽

10.1345/aph.1c336 ◽

2003 ◽

Vol 37 (7-8) ◽

pp. 1047-1054 ◽

Cited By ~ 40

Author(s):

Barbara T Yim ◽

Rosalyn P Sims-McCallum ◽

Pang H Chong

Keyword(s):

Uric Acid ◽

English Language ◽

Data Extraction ◽

Hematologic Malignancies ◽

Rapid Onset ◽

Urate Oxidase ◽

Onset Of Action ◽

Treatment And Prevention ◽

Study Selection ◽

Pediatric Use

OBJECTIVE: To review the information currently available on rasburicase for treatment and prevention of hyperuricemia. DATA SOURCES: MEDLINE (1966–August 2002) was searched for primary and review articles. STUDY SELECTION/DATA EXTRACTION: Studies evaluating rasburicase, including abstracts and proceedings, were considered for inclusion. English-language literature was evaluated for the pharmacology, pharmacodynamics, pharmacokinetics, therapeutic use, and adverse effects of rasburicase. DATA SYNTHESIS: Rasburicase, a recombinant urate oxidase, has been shown to be effective in lowering uric acid and preventing uric acid accumulation in patients with hematologic malignancies who had hyperuricemia or who were at high risk for developing hyperuricemia. It has been approved for pediatric use in the US. CONCLUSIONS: In addition to allopurinol, hydration, and urinary alkalinization, rasburicase is a new alternative for the treatment and prevention of hyperuricemia in patients with hematologic malignancies. Its rapid onset of action and the ability to lower preexisting elevated uric acid levels are the advantages of rasburicase compared with allopurinol. It may allow the patient to receive chemotherapy treatment without delay.

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Brexanolone (Zulresso): Finally, an FDA-Approved Treatment for Postpartum Depression

Annals of Pharmacotherapy ◽

10.1177/1060028019873320 ◽

2019 ◽

Vol 54 (2) ◽

pp. 157-163 ◽

Cited By ~ 7

Author(s):

Jason G Powell ◽

Scott Garland ◽

Kayla Preston ◽

Chris Piszczatoski

Keyword(s):

Postpartum Depression ◽

English Language ◽

Data Extraction ◽

Clinical Information ◽

Rapid Onset ◽

Depression Symptoms ◽

Onset Of Action ◽

Fda Approval ◽

Study Selection

Objective: To review the safety and efficacy of brexanolone for the treatment of moderate to severe postpartum depression (PPD). Data Sources: A literature search through PubMed was conducted (January 2012 to July 2019) using the keyword brexanolone for clinical trials published in the English language. Study Selection and Data Extraction: Articles were selected if they were related to the Food and Drug Administration (FDA) approval of brexanolone or provided novel clinical information regarding this drug entity. Data Synthesis: The findings of the review show that brexanolone administered via IV infusion is both an effective and a fairly safe option for the treatment of PPD. Relevance to Patient Care and Clinical Practice: There are several antidepressants currently used to treat PPD; however, this is the first with FDA approval for this indication. The rapid onset of action of brexanolone may offer a quicker relief of these symptoms and may possibly lead to improved quality of life for both the mother and the child. Conclusion and Relevance: The recent FDA approval of brexanolone may offer an effective treatment of moderate to severe PPD and has been shown to rapidly decrease depression symptoms.

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Acute Management of Cancer-Related Hypercalcemia

Annals of Pharmacotherapy ◽

10.1177/106002809603000514 ◽

1996 ◽

Vol 30 (5) ◽

pp. 507-513 ◽

Cited By ~ 21

Author(s):

Marie A Chisholm ◽

Anthony L Mulloy ◽

A Thomas Taylor

Keyword(s):

Clinical Trials ◽

English Language ◽

Data Extraction ◽

Symptomatic Relief ◽

Gallium Nitrate ◽

Medline Search ◽

Patients With Cancer ◽

Study Selection ◽

Life Threatening ◽

Acute Hypercalcemia

OBJECTIVE: TO review the pathogenesis and pharmacologic treatment of acute hypercalcemia associated with malignancy. DATA SOURCES: A MEDLINE search (1966 to 1995) of the English-language literature pertaining to acute hypercalcemia was performed. Additional literature was obtained from reference lists of articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles discussing the etiology and medical management of cancer-related acute hypercalcemia were considered in the review. Clinical trials reporting efficacy and safety of antihypercalcemic agents were also included. Information selected in the review was based on the discretion of the authors. DATA SYNTHESIS: Hypercalcemia is a life-threatening disorder associated with malignancy. It occurs in approximately 10–20% of patients with cancer. A variety of medications have been used in the management of hypercalcemia including bisphosphonates, calcitonin, furosemide, gallium nitrate, glucocorticoids, NaCl 0.9%, and plicamycin. Each of these agents has been reviewed with consideration of pharmacologic mechanism of action, evaluation of clinical trials, recommended dosages, efficacy, safety, cost, and role in treating cancer-related acute hypercalcemia. CONCLUSIONS: Immediate management of cancer-related acute hypercalcemia to prevent death and provide symptomatic relief is warranted. Severity determined by symptoms, calcium concentrations, and the overall status of the patient are important considerations in selecting appropriate therapy. Although the specific role of individual agents may vary, hydration remains the cornerstone of therapy. NaCl 0.9%, calcitonin, and Pamidronate disodium have established roles as dominant first-line agents for the management of acute hypercalcemia associated with malignancy.

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The Role of Pharmacists in Managing Adverse Events Related to Immune Checkpoint Inhibitor Therapy

Journal of Pharmacy Practice ◽

10.1177/0897190019885230 ◽

2019 ◽

Vol 33 (3) ◽

pp. 338-349 ◽

Cited By ~ 2

Author(s):

Patrick Medina ◽

Kate D. Jeffers ◽

Van A. Trinh ◽

R. Donald Harvey

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

English Language ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Data Extraction ◽

Single Agent ◽

Language Studies ◽

Study Selection ◽

Life Threatening

Objective: To provide an overview of immune checkpoint inhibitor (ICI) therapy-associated immune-related adverse events (irAEs) and their management, focusing on the key responsibilities for pharmacists in recognizing, distinguishing, and treating irAEs and in educating patients about irAEs and their management. Data Sources: Literature published from January 2000 to March 2018 available from online sources. Study Selection and Data Extraction: Relevant English-language studies, guidelines, and articles. Data Synthesis: ICI therapies have been approved for the treatment of several cancers as single-agent therapies, combined ICI therapies, or in combination with other agents. ICI therapies increase the activity of the immune system and consequently can have autoimmune-like adverse effects that are often termed irAEs. irAE management can be challenging as irAEs can vary in their frequency and severity among patients, according to the specific agent, and can occur at any time during treatment or after therapy discontinuation. Additionally, for patients treated with ICI therapies in combination with other therapies, ICI-associated irAEs must be distinguished from adverse events associated with chemotherapy or targeted therapies, which often require different management. Pharmacists can provide essential support to diagnose and manage irAEs. Relevance to Patient Care and Clinical Practice: Early and accurate diagnosis and prompt management of irAEs by pharmacists are critical to reduce the risk of severe or life-threatening complications and prevent premature ICI discontinuation. Conclusions: Pharmacists have a key role in the recognition, monitoring, and management of irAEs and in educating patients about irAEs associated with ICI therapies and the agents used to manage them.

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Lead in Mineral or Multivitamin-Multimineral Products

Annals of Pharmacotherapy ◽

10.1177/10600280211023328 ◽

2021 ◽

pp. 106002802110233

Author(s):

C. Michael White

Keyword(s):

English Language ◽

Data Extraction ◽

The United States ◽

Third Party ◽

Reference Level ◽

Study Selection ◽

Pubmed Search ◽

Zinc Supplements ◽

Average Lead ◽

Year 2000

Objective Assess the current daily interim reference level of lead and the amount contained in current mineral and multivitamin-multimineral (MVM) products. Data Sources PubMed search from 1980 to May 15, 2021, limited to the English language, via the search strategy ((mineral OR multivitamin OR calcium OR iron OR magnesium OR copper OR zinc OR chromium OR selenium) AND (heavy metals OR Pb OR lead)). Study Selection and Data Extraction Narrative review of studies assessing lead content in mineral or MVM products. Data Synthesis Products containing different calcium forms (dolomite, bone meal, natural carbonate) have historically had higher lead levels than others (refined carbonate, lactate, gluconate, acetate, sevelamer), but the gap has closed considerably since the year 2000. Although only limited assessments of magnesium and zinc supplements have been conducted, no alarming average lead amounts were found. MVM products assessed since 2007 had low median or mean lead concentrations. However, large interproduct differences exist, with many products having very little lead and some products having concerning amounts. Relevance to Patient Care and Clinical Practice It is difficult for pharmacists and consumers to know the amount of lead in an actual product unless it is tested in an independent third-party lab. The United States Pharmacopeia and NSF International will provide a seal on the products stating that the products have a low level of lead, but even so, children could receive more lead than the Food and Drug Administration’s Interim Reference Level. Conclusions The threat from lead exposure in mineral and MVM products have diminsihed considerably over time but some products can still have excessive amounts. Without third-party testing, it is difficult for clinicians and consumers to know which outlier products to avoid.

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Pegfilgrastim-Induced Bone Pain: A Review on Incidence, Risk Factors, and Evidence-Based Management

Annals of Pharmacotherapy ◽

10.1177/1060028017706373 ◽

2017 ◽

Vol 51 (9) ◽

pp. 797-803 ◽

Cited By ~ 7

Author(s):

Donald C. Moore ◽

Annie E. Pellegrino

Keyword(s):

Risk Factors ◽

Bone Pain ◽

English Language ◽

Data Extraction ◽

Treatment Modalities ◽

Management Options ◽

Data Synthesis ◽

Pharmacological Management ◽

Study Selection ◽

Incidence Risk

Objective: To review the incidence, risk factors, and management of pegfilgrastim-induced bone pain (PIBP). Data Sources: PubMed was searched from 1980 to March 31, 2017, using the terms pegfilgrastim and bone pain. Study Selection and Data Extraction: English-language, human studies and reviews assessing the incidence, risk factors, and management of PIBP were incorporated. Data Synthesis: A total of 3 randomized, prospective studies and 2 retrospective studies evaluated pharmacological management of PIBP. Naproxen compared with placebo demonstrated a reduction in the degree, incidence, and duration of bone pain secondary to pegfilgrastim. Loratadine was not effective in reducing the incidence of bone pain prophylactically, but a retrospective study evaluating dual antihistamine blockade with loratadine and famotidine demonstrated a decreased incidence in bone pain when administered before pegfilgrastim. Conclusion: Naproxen is effective at managing PIBP. Although commonly used, antihistamines have a paucity of data supporting their use. Dose reductions of pegfilgrastim and opioids may also be potential management options; however, data supporting these treatment modalities are scarce.

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Role of Topical Oxymetazoline for Management of Erythematotelangiectatic Rosacea

Annals of Pharmacotherapy ◽

10.1177/1060028017740139 ◽

2017 ◽

Vol 52 (3) ◽

pp. 263-267 ◽

Cited By ~ 5

Author(s):

Rebecca M. Hoover ◽

John Erramouspe

Keyword(s):

English Language ◽

Human Subjects ◽

Data Extraction ◽

Drug Approval ◽

Current Data ◽

Patient Response ◽

Study Selection ◽

Cochrane Database ◽

Drug Approval Process ◽

Individual Patient Response

Objective: To review and summarize topical oxymetazoline’s pharmacology, pharmacokinetics, efficacy, safety, cost, and place in therapy for persistent redness associated with erythematotelangiectatic rosacea. Data Sources: Literature searches of MEDLINE (1975 to September 2017), International Pharmaceutical Abstracts (1975 to September 2017), and Cochrane Database (publications through September 2017) using the terms rosacea, persistent redness, α -agonist, and oxymetazoline. Study Selection and Data Extraction: Results were limited to studies of human subjects, English-language publications, and topical use of oxymetazoline. Relevant materials from government sources, industry, and reviews were also included. Data Synthesis: Data support the efficacy of oxymetazoline for persistent facial redness. Little study beyond clinical trials cited in the drug approval process has been conducted. Current data suggest that oxymetazoline is similar in safety and efficacy to brimonidine. Head-to-head comparisons of topical α-agonists for erythema caused by rosacea are needed. Conclusion: The topical α-agonist, oxymetazoline, is safe and effective for reducing persistent facial redness associated with erythematotelangiectatic subtype of rosacea. Health care practitioners selecting among treatments should consider not only the subtype of rosacea but also individual patient response, preference, and cost.

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Drug-Induced Restless Legs Syndrome

Annals of Pharmacotherapy ◽

10.1177/1060028018760296 ◽

2018 ◽

Vol 52 (7) ◽

pp. 662-672 ◽

Cited By ~ 9

Author(s):

Edna Patatanian ◽

Melanie K. Claborn

Keyword(s):

Restless Legs Syndrome ◽

English Language ◽

Case Reports ◽

Data Extraction ◽

Case Series ◽

Predisposing Factors ◽

Drug Induced ◽

Restless Legs ◽

Drug Classes ◽

Study Selection

Objective: To review the literature on drug-induced restless legs syndrome (DI-RLS). Data Sources: The review included a search for English-language literature from 1966 to December 2017 in the MEDLINE, PubMed, and Ovid databases using the following search terms: restless legs syndrome (RLS), periodic limb movement, adverse effects, and drug-induced. In addition, background articles on the pathophysiology, etiology, and epidemiology of RLS were retrieved. Bibliographies of relevant articles were reviewed for additional citations. Study Selection and Data Extraction: All case reports, case series, and review articles of DI-RLS were identified and analyzed. There were only a small number of controlled clinical trials, and most data were from case reports and case series. Results: Several drugs and drug classes have been implicated in DI-RLS, with antidepressants, antipsychotics, and antiepileptics having the most evidence. In addition, RLS may be linked with a number of disorders or underlying predisposing factors as well. Conclusions: The prevalence of RLS is variable and ranges from 3% to 19% in the general population. There are many predisposing factors to RLS, but an emerging body of evidence suggests that there is an association between numerous drugs and RLS.

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Role of Ambrisentan in the Management of Pulmonary Hypertension

Annals of Pharmacotherapy ◽

10.1345/aph.1l014 ◽

2008 ◽

Vol 42 (11) ◽

pp. 1653-1659 ◽

Cited By ~ 15

Author(s):

Sandra L Hrometz ◽

Kelly M Shields

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

English Language ◽

Data Extraction ◽

Information Service ◽

Study Selection ◽

Pulmonary Arterial ◽

Improve Exercise Capacity

Objective: To review the role of ambrisentan in the treatment of pulmonary arterial hypertension (PAH). Data Sources: Literature was accessed through MEDLINE (1950-June 2008), Iowa Drug Information Service (1966–March 2008), EMBASE (1966-June 2008), bibliographies of pertinent articles, and unpublished data provided by the manufacturer and the Food and Drug Administration (FDA). Search terms included ambrisentan, endothelin antagonist, pulmonary hypertension, and pulmonary arterial hypertension. Due to limited literature available, additional criteria to limit searches were not used. Study Selection and Data Extraction: Abstracts and original preclinical and clinical research reports available in the English language were Identified for review. All manufacturer-provided data were also evaluated. Literature related to ambrisentan, endothelin antagonists, pulmonary hypertension, and pulmonary arterial hypertension were included. Four clinical trials evaluated the efficacy of ambrisentan in adults with symptomatic PAH. Data Synthesis: Ambrisentan is the latest endothelin-receptor antagonist (ERA) to obtain FDA approval for the treatment of PAH. It joins the first FDA-approved ERA, bosentan. Like bosentan, ambrisentan is available orally (with once-daily dosing compared with bosentan's twice-daily dosing) and has been shown to improve exercise capacity and delay clinical worsening. As with bosentan, the most significant safety concerns with ambrisentan relate to potential liver injury and a contraindication in pregnancy. Although ambrisentan has higher affinity for the endothelin type A receptor than for the endothelin type B receptor, specific advantages of this selectivity, in terms of efficacy compared with bosentan, a nonselective agent, have not been demonstrated. Conclusions: Ambrisentan has been shown to be an effective ERA in patients with PAH. A significant advantage of ambrisentan is the lack of any clinically important drug interactions with warfarin and sildenafil, which are frequently used by patients being treated for PAH.

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