Nelarabine: A Nucleoside Analog with Efficacy in T-Cell and other Leukemias

2005 ◽  
Vol 39 (6) ◽  
pp. 1056-1063 ◽  
Author(s):  
David F Kisor
Keyword(s):  
T Cell ◽  
English Language ◽  
Data Extraction ◽  
Safety Information ◽  
Hematologic Malignancies ◽  
Water Soluble ◽  
Significant Activity ◽  
Study Selection ◽  
Important Addition ◽  
Key Terms

OBJECTIVE: To present the pharmacology and pharmacokinetics of nelarabine, 9-β-D-arabinofuranosylguanine (ara-G) and intraleukemic cellular pharmacokinetics of 9-β-D-arabinofuranosylguanine triphosphate (ara-GTP) generated from the administration of nelarabine, and clinical and safety information relative to nelarabine use in the treatment of hematologic malignancies. DATA SOURCES: MEDLINE (1966—December 2004) was searched using the English-language key terms 2-amino-6-methoxypurine arabinoside, 506U78, and nelarabine. Data were also obtained from published abstracts. STUDY SELECTION AND DATA EXTRACTION: Clinical studies evaluating the pharmacokinetics of nelarabine, ara-G, and cellular ara-GTP and use of nelarabine, alone or in combination with other agents for the treatment of hematologic malignancies, were included in this review. DATA SYNTHESIS: Nelarabine is the water-soluble, 6-methoxy analog of 9-β-D-ara-G. Nelarabine is readily converted to ara-G by endogenous adenosine deaminase. The half-life of nelarabine is approximately 15 minutes compared with 2–4 hours for ara-G. The clearance of ara-G is higher in children than in adults (0.312 vs 0.213 L × h−1 × kg−1). Intracellular ara-GTP elimination is slow relative to nelarabine and ara-G. In pediatric and adult patients, neurologic toxicity is dose limiting. Severe myelosuppression was not consistently observed. Major responses were seen in patients with T-cell malignancies. Patients who responded had significantly higher intracellular ara-GTP concentrations compared with those who did not respond. CONCLUSIONS: Nelarabine is an effective ara-G prodrug. Nelarabine has significant activity against malignant T-cells and appears to be an important addition to treatments of various leukemias.

Use of Fish Oil to Prevent Coronary Angioplasty Restenosis

1992 ◽  
Vol 26 (12) ◽  
pp. 1541-1545 ◽  
Author(s):  
Vincent F. Mauro ◽  
Lawrence A. Frazee
Keyword(s):  
Eicosapentaenoic Acid ◽  
Fish Oil ◽  
English Language ◽  
Data Extraction ◽  
Current Data ◽  
Study Selection ◽  
Number Of Patients ◽  
Bibliographic Search ◽  
Definition Of ◽  
Key Terms

OBJECTIVE: To review the literature investigating the use of fish oil in preventing restenosis postangioplasty (RPA). DATA SOURCES: An Index Medicus and bibliographic search of the English-language literature pertaining to the use of fish oil in preventing RPA. The key terms used were fish oil, angioplasty, and eicosapentaenoic acid. STUDY SELECTION AND DATA EXTRACTION: The results of all trials, including abstracts, that were obtained are reviewed and critiqued. DATA SYNTHESIS: Restenosis of a coronary vessel at the site of angioplasty occurs 30–40 percent of the time. Because fish oil has been theorized to prevent atherosclerosis and because atherosclerotic-like processes are theorized to be involved in RPA restenosis, fish oil has been studied to determine whether it can prevent RPA. Results of such trials have been mixed. Some have observed a reduction in the number of patients with angiographic or clinical evidence of restenosis. Two trials have failed to observe such an effect. Reasons for the differences are unknown. Possible explanations include differences in study design, endpoint parameters, definition of restenosis, and dosing methods of the fish oil. Bleeding was not of significant concern in any of the trials, even when fish oil was combined with antiplatelet therapy. CONCLUSIONS: Fish oil may be considered for use in patients to prevent RPA. It probably should be continued for only six months following the procedure. Current data suggest that at least 3 g/d of eicosapentaenoic acid and 1 g/d of docosahexaenoic acid should be used. If possible, therapy should be started as soon as it is known that angioplasty will be performed or at least as soon as possible following the procedure. Many patients may not be able to tolerate fish oil because of its gastrointestinal effects.

Rasburicase for the Treatment and Prevention of Hyperuricemia

2003 ◽  
Vol 37 (7-8) ◽  
pp. 1047-1054 ◽  
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.

Lumateperone: A Novel Antipsychotic for Schizophrenia

2020 ◽  
Vol 55 (1) ◽  
pp. 98-104
Author(s):  
Jessica Greenwood ◽  
Rucha B. Acharya ◽  
Valerie Marcellus ◽  
Jose A. Rey
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
English Language ◽  
Partial Agonist ◽  
Data Extraction ◽  
Double Blind ◽  
Study Selection ◽  
Syndrome Scale ◽  
Negative Syndrome ◽  
Key Terms

Objective: To provide a concise review of the new Food and Drug Administration (FDA)-approved antipsychotic, lumateperone, for use in schizophrenia. Data Sources: A literature search of PubMed was performed (January 2000 to May 2020) using the following key terms: lumateperone, Caplyta, and ITI-007. Abstracts from conferences, review articles, clinical trials, and drug monographs were reviewed. Study Selection and Data Extraction: Relevant English-language monographs and studies conducted in humans were considered. Data Synthesis: Lumateperone was FDA approved for the treatment of schizophrenia in December 2019 based on 2 published randomized, double-blind, placebo-controlled trials. Lumateperone’s pharmacology is consistent with that of other second-generation antipsychotics in that it has a higher affinity for the serotonin (5-HT2A) receptors compared with dopamine (D2) receptors but with lower affinities for α-1 and histaminergic receptors. In addition, it serves as a presynaptic dopamine partial agonist, serotonin reuptake inhibitor, and an indirect modulator of glutamatergic systems. Based on the 4-week clinical trials, lumateperone was well tolerated. Most common treatment-emergent adverse events were headache, somnolence, and dizziness. Relevance to Patient Care and Clinical Practice: At this time, lumateperone had a statistically significant reduction in Positive and Negative Syndrome Scale when compared with placebo and was not significantly associated with the extrapyramidal symptoms (EPS) and metabolic adverse effects commonly seen with other antipsychotics. Conclusions: Lumateperone has the potential to benefit individuals with schizophrenia who are intolerant to the EPSs or metabolic adverse effects of other antipsychotics. However, further head-to-head trials with commercially available antipsychotics are still required to assist in establishing its role in treatment.

Lead in Mineral or Multivitamin-Multimineral Products

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.

Recent Advances: Antiinfectives

1995 ◽  
Vol 29 (10) ◽  
pp. 1035-1040 ◽  
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.

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

2017 ◽  
Vol 51 (9) ◽  
pp. 797-803 ◽  
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.

Role of Topical Oxymetazoline for Management of Erythematotelangiectatic Rosacea

2017 ◽  
Vol 52 (3) ◽  
pp. 263-267 ◽  
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.

Drug-Induced Restless Legs Syndrome

2018 ◽  
Vol 52 (7) ◽  
pp. 662-672 ◽  
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.

Role of Ambrisentan in the Management of Pulmonary Hypertension

2008 ◽  
Vol 42 (11) ◽  
pp. 1653-1659 ◽  
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.

Meropenem/Vaborbactam, the First Carbapenem/β-Lactamase Inhibitor Combination

2018 ◽  
Vol 52 (8) ◽  
pp. 769-779 ◽  
Author(s):  
Jonathan C. Cho ◽  
Monika T. Zmarlicka ◽  
Kristy M. Shaeer ◽  
Joe Pardo
Keyword(s):  
English Language ◽  
Clinical Success ◽  
Data Extraction ◽  
Phase Iii ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Preclinical Phase ◽  
Study Selection ◽  
Tract Infections ◽  
Lactamase Inhibitor

Objective: To review the pharmacology, spectrum of activity, pharmacokinetics, pharmacodynamics, safety, efficacy, administration, and considerations for clinical use of meropenem/vaborbactam (M/V). Data Sources: A literature search using PubMed and clinicaltrials.gov (June 2013 to December 2017) was conducted using the search terms meropenem, vaborbactam, RPX7009, biapenem, RPX2003, and carbavance. References from relevant articles and conference abstracts were also reviewed. Study Selection and Data Extraction: Preclinical, phase I studies, and phase III studies written in the English language were evaluated. Data Synthesis: M/V is a novel carbapenem/β-lactamase inhibitor antimicrobial with in vitro activity against nearly 99% of Klebsiella pneumoniae carbapenemase–producing Enterobacteriaceae. M/V is approved for the treatment of adults with complicated urinary tract infections (cUTIs), including pyelonephritis. In a phase III cUTI trial (TANGO I), 98.4% of patients treated with M/V experienced overall clinical success compared with 94% of patients treated with piperacillin/tazobactam (95% CI = 0.7 to 9.1). When compared with best available therapy for carbapenem-resistant Enterobacteriaceae (CRE) infections in TANGO II, patients receiving M/V were more likely to achieve clinical cure at both the end of therapy (64.3% vs 33.3%, P = 0.04) as well as at the test of cure (57.1% vs 26.7%, P = 0.04). The most common adverse effects associated with M/V were headache, infusion-site reactions, and diarrhea. Conclusion: M/V has a valuable role in the treatment of CRE and should be used judiciously to preserve its use for resistant infections.

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