Granisetron: The Second Serotonin-Receptor Antagonist

1995 ◽  
Vol 29 (12) ◽  
pp. 1240-1251 ◽  
Author(s):  
Val R Adams ◽  
Amy W Valley
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Receptor Antagonist ◽  
Serotonin Receptor ◽  
English Language ◽  
Data Extraction ◽  
Optimal Dose ◽  
Nausea And Vomiting ◽  
Cost Comparison ◽  
Antiemetic Agents

Objective: To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of granisetron, focusing on critical analysis of published clinical trials and comparison with other antiemetic agents, including ondansetron. Data Sources: MEDLINE (1966–1995) and CANCERLIT (1991–1995) searches of English-language literature using the terms “granisetron” and “granisetron (m)” were performed. Study Selection And Data Extraction: All articles were considered for possible inclusion in this review. Abstracts of clinical trials were included only when they were judged to add critical information not otherwise available in the medical literature. For studies published more than once, the most recent publication was cited. Data Synthesis: Nausea and vomiting are rated by patients as the most distressing chemotherapy-related adverse effects and may produce potentially life-threatening complications. The discovery of the role of serotonin in nausea and vomiting and the development of selective serotonin3-receptor (5-HT3) antagonists has significantly diminished the incidence and consequences of chemotherapy-related nausea and vomiting. Granisetron is the second 5-HT3-receptor antagonist to be marketed in the US. Granisetron has been compared with other antiemetic agents, including ondansetron, against highly and moderately emetogenic chemotherapy. The results of these trials have shown granisetron to be superior to conventional antiemetics and as effective as ondansetron in the prevention of chemotherapy-induced nausea and vomiting. The optimal dose of granisetron has yet to be determined. Formulary decisions should be based on a cost comparison among the 5-HT3-receptor antagonists at individual institutions. Conclusions: Granisetron is a safe, effective antiemetic agent for the management of nausea and vomiting caused by cancer chemotherapy.

Tocilizumab: An lnterleukin-6 Receptor Inhibitor for the Treatment of Rheumatoid Arthritis

2008 ◽  
Vol 42 (11) ◽  
pp. 1660-1668 ◽  
Author(s):  
Susyn L Plushner
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Adverse Effects ◽  
English Language ◽  
Data Extraction ◽  
Joint Damage ◽  
Clinical Trial Data ◽  
Liver Function Tests ◽  
Biologic Agent ◽  
American College Of Rheumatology

Objective: To review the pharmacology, pharmacokinetics, clinical trial data, and safety profile of tocilizumab, a new biologic agent targeting the lnterleukin-6 cytokine receptor. Data Sources: A systematic search of MEDLINE (1998–June 2008) and International Pharmaceutical Abstracts (1970–June 2008) was performed to identify published clinical trials and review articles. Key search terms were tocilizumab, MRA, interleukin-6/receptors, interleukln-6/immunology, and rheumatoid arthritis. The search was limited to studies in humans that were published in the English language. References from articles located during this search were evaluated for other relevant citations. Abstracts from national and international rheumatology meetings (American College of Rheumatology and European League Against Rheumatism) and from unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov ) were also reviewed. Study Selection and Data Extraction: All available human studies describing the pharmacology, pharmacokinetics, efficacy, safety, and adverse effects of tocilizumab were included. Data Synthesis: At doses greater than 4 mg/kg, tocilizumab use has resulted In significant improvement in clinical outcomes, including the American College of Rheumatology parameters indicating a patient's level of improvements and disease remission. Improvements were noted when tocilizumab was used as monotherapy or in combination with methotrexate or other disease-modifying antirheumatic drugs. The most effective dose of tocilizumab appears to be 8 mg/kg, which has shown significant improvements in radiographic measures of joint damage. The most common adverse effects have included abnormal results of liver function tests, hyperlipidemia, neutropenia, infections, nasopharyngitis, gastrointestinal complaints, musculoskeletal disorders, headache, rash, and pruritus. Conclusions: Tocilizumab represents a promising new treatment for rheumatoid arthritis. Additional research is warranted to confirm its radiographic benefits, clarify its safely profile, and identify its place in rheumatoid arthritis treatment relative to current biologic agents.

Zolpidem: Distinct from Triazolam?

1997 ◽  
Vol 31 (5) ◽  
pp. 625-632 ◽  
Author(s):  
Bob L Lobo ◽  
William L Greene
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Memory Impairment ◽  
English Language ◽  
Data Extraction ◽  
Residual Effects ◽  
Data Synthesis ◽  
Medline Search ◽  
Study Selection ◽  
Pertinent Information

OBJECTIVE: TO review the literature that compares Zolpidem with triazolam, with an emphasis on efficacy and safety in humans. DATA SOURCES: Information was retrieved from a MEDLINE search (1983–1996) of the English-language literature using the terms triazolam and zolpidem. STUDY SELECTION: Reports of clinical trials comparing the safety and efficacy of zolpidem and triazolam were included in this review. DATA EXTRACTION: Data were evaluated according to study design, efficacy, and adverse effects. Pertinent information was selected and the data synthesized into a review format. DATA SYNTHESIS: Zolpidem and triazolam have similar pharmacokinetic and pharmacodynamic effects in humans. Clinical trials have shown that usually recommended, equipotent dosages of zolpidem and triazolam do not differ with respect to pharmacokinetics, efficacy, tolerability, residual effects, memory impairment, rebound insomnia, abuse potential, or other adverse effects. CONCLUSIONS: Zolpidem offers no distinct therapeutic advantage over triazolam for the treatment of insomnia.

Transdermal Fentanyl

1992 ◽  
Vol 26 (11) ◽  
pp. 1393-1399 ◽  
Author(s):  
Lisa Y. Yee ◽  
Julio R. Lopez
Keyword(s):  
Chronic Pain ◽  
Clinical Trials ◽  
Placebo Group ◽  
Adverse Effects ◽  
English Language ◽  
Data Extraction ◽  
Opioid Analgesia ◽  
Transdermal Fentanyl ◽  
Study Selection ◽  
The Cost

OBJECTIVE: To review the use of transdermal fentanyl for the treatment of moderate to severe chronic pain. The article provides background on the pharmacology and pharmacokinetics of the drug, as well as the properties of the transdermal system. In addition, clinical trials, adverse effects, and therapeutic considerations and recommendations are presented. DATA SOURCES: Clinical trials, review articles, and reference texts. STUDY SELECTION: Comparative clinical trials involving the use of transdermal fentanyl on postoperative and chronic pain patients. DATA EXTRACTION: Data from clinical human trials published in the English language were reviewed. Trials were assessed by sample size, opioid dosage regimen, and therapeutic outcome. DATA SYNTHESIS: Transdermal fentanyl was found to be effective in the control of chronic and postoperative pain. In one trial the overall patient satisfaction with pain control was 79 percent for the transdermal fentanyl group and 44 percent for the placebo group. In another trial, the amount of additional parenteral morphine was significantly lower for the group receiving transdermal fentanyl than for the placebo group (49.9 ± 4.9 vs. 77.0 ± 6.3 mg, respectively, p<0.01). The most common adverse effects recorded were nausea (45–85 percent), pruritus (14–60 percent), and sedation (40–59 percent). The cost of analgesic therapy with this delivery system is higher than that of parenteral opioid analgesia, but less than patient-controlled analgesia. CONCLUSIONS: The transdermal fentanyl formulation offers some minor advantages over other forms of conventional pain management. Results of early clinical trials are promising, but more studies are needed to evaluate its long-term effectiveness and adverse effects. Specifically, comparisons with standard parenteral and patient-controlled opioid analgesia in chronic malignant and nonmalignant pain are necessary for adequate evaluation of transdermal fentanyl.

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.

Brexanolone: A Novel Drug for the Treatment of Postpartum Depression

2020 ◽  
pp. 089719002097962
Author(s):  
Edna Patatanian ◽  
David R. Nguyen
Keyword(s):  
Adverse Effects ◽  
Postpartum Depression ◽  
English Language ◽  
Neuronal Excitability ◽  
Data Extraction ◽  
Background Information ◽  
Pharmacologic Therapy ◽  
Loss Of Consciousness ◽  
Efficacy And Safety ◽  
Pubmed Search

Objectives: To review the pharmacology, efficacy, and safety of Brexanolone and define its role in the treatment of postpartum depression. Date Sources: A MEDLINE/PubMed search was conducted (1980-May 2020) using the following keywords: postpartum depression, antidepressants, pharmacologic therapy, drug therapy, and brexanolone to identify relevant articles. Study Selection/Data Extraction: Literature search was limited to human studies published in the English language. Phase I, II, and III studies evaluating the pharmacology, efficacy, safety of brexanolone for postpartum depression were included. Bibliographies of relevant articles evaluating postpartum depression and treatment were reviewed for additional citations and background information. Data Synthesis: Brexanolone is a soluble, proprietary, injectable formulation of allopregnanolone, a neuroactive steroid that modulates neuronal excitability. Allopregnanolone levels increase during pregnancy and decrease substantially after birth. These fluctuations have profound effects on anxiety and depression. Three clinical trials established the efficacy and safety of brexanolone in the treatment of postpartum depression. In all 3 trials, brexanolone had an acceptable safety profile and was well tolerated. The most common adverse effects were loss of consciousness, sedation, dry mouth, headache, dizziness, and flushing. Due to sudden loss of consciousness and excessive sedation, continuous pulse oximetry is recommended. Conclusion: Brexanolone has a novel mechanism of action and appears to be safe and effective for the treatment of moderate to severe postpartum depression. At present, high cost, serious adverse effects, and restricted access may limit its use in clinical practice.

Leukotriene-Receptor Antagonists and 5-Lipoxygenase Inhibitors in Asthma

1993 ◽  
Vol 27 (7-8) ◽  
pp. 898-903 ◽  
Author(s):  
Julie S. Larsen ◽  
Edward P. Acosta
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Data Extraction ◽  
Background Information ◽  
Receptor Antagonists ◽  
Lipoxygenase Inhibitors ◽  
Medline Search ◽  
Leukotriene Receptor Antagonists ◽  
Patient Tolerance ◽  
Leukotriene Receptor

OBJECTIVE: To familiarize readers with a potentially new class of compounds for treating asthma. Background information on leukotrienes is provided in addition to an indepth review of pertinent clinical trials. DATA SOURCES: Information was obtained from controlled clinical trials, abstracts, and review articles identified through a MEDLINE search of English-language articles. STUDY SELECTION: Emphasis was placed on early clinical trials that showed some benefit with these compounds as well as more recent studies using newer agents that produced more promising results. DATA EXTRACTION: Information regarding leukotriene biochemistry was extracted from basic science research and data from human studies were evaluated by the authors according to patient selection, study design, methodology, and therapeutic response. DATA SYNTHESIS: Leukotrienes have a pathophysiologic role in asthma. Two distinct but pharmacologically similar classes of leukotriene inhibitors are currently being clinically evaluated. These are leukotriene receptor antagonists and 5-lipoxygenase inhibitors. Early clinical trials with these agents yielded unfavorable results primarily because of lack of drug potency and selectivity, poor patient tolerance, and possibly the route of administration. Subsequent studies with more potent and selective agents have further implicated leukotrienes as biochemical mediators in asthma and, consequently, have shown promising clinical outcomes with respect to pulmonary function testing and patient tolerance. CONCLUSIONS: Advancements in the pathogenesis of asthma are beginning to define a role for the leukotrienes. Although more studies are needed to assess the efficacy of leukotriene inhibitors, recent clinical trials using leukotriene-receptor antagonists and 5-lipoxygenase inhibitors indicate a potential for the expansion of therapeutic regimens currently used in the treatment of asthma.

Ticlopidine and Antiplatelet Therapy

1993 ◽  
Vol 27 (9) ◽  
pp. 1090-1098 ◽  
Author(s):  
Patricia Flores-Runk ◽  
Ralph H. Raasch
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Data Extraction ◽  
Artery Bypass ◽  
Antiplatelet Agent ◽  
Antiplatelet Agents ◽  
Graft Patency ◽  
Diabetic Microangiopathy ◽  
Severe Reaction ◽  
English Language Journal

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and toxicity of ticlopidine. Comparisons with other antiplatelet agents are presented, with an emphasis on efficacy, and a recommendation is provided regarding ticlopidine's place in therapy. DATA SOURCES: A MEDLINE literature retrieval of English-language journal articles from 1987 to January 1993 and references identified from bibliographies of review articles and clinical trials. STUDY SELECTION: Randomized, blind, controlled studies of ticlopidine and other antiplatelet agents were preferentially selected. DATA EXTRACTION: Clinical trials were reviewed in terms of study design, efficacy results, and toxicity. DATA SYNTHESIS: Ticlopidine is a new antiplatelet agent with a distinct mechanism of action. In the largest trial of the drug for the prevention of stroke, it was found to be more effective than aspirin in reducing the risk of stroke or death. Clinical trials have also shown ticlopidine to decrease the rate of vascular death and myocardial infarction in patients with unstable angina, and to maintain venous graft patency after coronary artery bypass grafting. The use of ticlopidine in diabetic microangiopathy and peripheral vascular disease appears promising, but further studies are needed. Adverse reactions most commonly reported with ticlopidine are gastrointestinal complaints; the most severe reaction is transient neutropenia, which is seen in approximately 2.3 percent of patients and is severe in nearly 1 percent. CONCLUSIONS: Ticlopidine is a reasonable alternative for use in preventing stroke among patients unable to take aspirin or those who do not benefit from aspirin therapy. Its use as first-line therapy is limited by its high cost and the occurrence of hematologic adverse effects.

Lactulose in the Management of Constipation: A Current Review

1992 ◽  
Vol 26 (10) ◽  
pp. 1277-1282 ◽  
Author(s):  
Theresa V. Kot ◽  
Ngaire A. Pettit-Young
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Clinical Studies ◽  
Data Extraction ◽  
Point Of View ◽  
Data Synthesis ◽  
Study Selection ◽  
Beneficial Response ◽  
A Current

OBJECTIVE: To review the current published clinical studies evaluating the clinical efficacy and safety of lactulose compared with other laxatives or placebo. Adverse effects associated with lactulose are also reported. DATA SOURCES: Information was retrieved by searching the MEDLINE and EMBASE databases for clinical trials, abstracts, conference proceedings, and review articles dealing with lactulose. STUDY SELECTION: Emphasis was placed on clinical trials where lactulose was compared with other laxatives or placebo in patient populations where the diagnosis of constipation was reasonably established. DATA EXTRACTION: The methodology and results from clinical studies were evaluated. Assessment of the studies was made based on diagnosis of constipation, prior management of patients, follow-up of patients, dosage, and adverse effects. DATA SYNTHESIS: Clinical trials in geriatric patients, terminally ill patients, children, and normal and constipated subjects were reviewed. In most instances, lactulose was compared with a placebo, without incorporating the current education on dietary techniques for improving defecation. CONCLUSIONS: Generally, clinical trials have demonstrated a beneficial response compared with placebo, although sometimes that response has been only marginally better, from a clinical point of view.

Nilutamide: An Antiandrogen for the Treatment of Prostate Cancer

1997 ◽  
Vol 31 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Ernest J Dole ◽  
Mark T Holdsworth
Keyword(s):  
Prostate Cancer ◽  
Adverse Effects ◽  
Advanced Prostate Cancer ◽  
English Language ◽  
Data Extraction ◽  
Performance Status ◽  
Major Advance ◽  
Improved Performance ◽  
The Impact ◽  
Nonsteroidal Antiandrogens

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of nilutamide and to compare this agent with the currently marketed nonsteroidal antiandrogens (i.e., bicalutamide, flutamide) by critically analyzing the published literature. DATA SOURCES: MEDLINE (1980–1995) and CANCERLIT (1991–1995) were searched for English-language publications using the terms nilutamide, bicalutamide, and flutamide alone, and either nilutamide or androgen antagonists in combination with prostatic neoplasms. STUDY SELECTION AND DATA EXTRACTION: All articles with subject matter on nilutamide, bicalutamide, and flutamide were considered for inclusion. For studies published in more than one journal, the first publication was used unless a subsequent publication included additional or follow-up data, in which case the latter publication was cited instead. DATA SYNTHESIS: Nilutamide was effective in combination with orchiectomy in improving responses in patients with advanced prostate cancer. However, patient survival was not improved in these trials, and improvements in bone pain did not usually result in improved performance status in these patients. The few trials of nilutamide monotherapy or nilutamide in combination with a luteinizing hormone-releasing hormone analog are too small to draw meaningful conclusions regarding its efficacy or its role in the treatment of advanced prostate cancer. No comparative trials of nilutamide with other antiandrogens and no analysis of the impact of nilutamide on patient quality of life are currently available. Nilutamide appears to produce a higher frequency of adverse effects than the other currently marketed nonsteroidal antiandrogens, bicalutamide and flutamide. CONCLUSIONS: Nilutamide does not appear to represent a major advance in the treatment of advanced prostate cancer and appears to be somewhat inferior to both flutamide and bicalutamide with regard to adverse effects. Nilutamide should not be considered the antiandrogen of choice in the treatment of advanced prostate cancer.

Direct Oral Anticoagulants in Chronic Liver Disease

2019 ◽  
Vol 53 (10) ◽  
pp. 1042-1049 ◽  
Author(s):  
Taylor D. Steuber ◽  
Meredith L. Howard ◽  
Sarah A. Nisly
Keyword(s):  
Clinical Trials ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
English Language ◽  
Data Extraction ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Chronic Liver ◽  
Venous Thromboembolic ◽  
The Individual

Objective: To review the use of direct oral anticoagulants (DOACs) in patients with chronic liver disease (CLD). Data Sources: A MEDLINE literature search was performed from 1964 through February 2019 using the following search terms: cirrhosis, chronic liver disease, direct oral anticoagulant, and the individual DOACs. Study Selection and Data Extraction: All English-language human trials and reports that examined DOACs for treatment or prevention of venous thromboembolic (VTE) events in patients with CLD were included. Data Synthesis: A total of 6 clinical trials examining the use of DOACs in patients with CLD were identified. All DOACs have been utilized in patients with CLD, with the exception of betrixaban, for prevention of stroke in atrial fibrillation or treatment of VTE (except for treatment of pulmonary embolism). The studies primarily evaluated patients with mild to moderate liver disease (Child-Turcotte-Pugh class A and B). The DOACs had similar rates of bleeding compared with traditional anticoagulants. Relevance to Patient Care and Clinical Practice: This review evaluates and summarizes the available evidence on DOACs in the setting of CLD. These agents may be more appealing in this population because monitoring or administration may be difficult with traditional anticoagulants (warfarin or low-molecular-weight heparins). Conclusion: Early data suggest that DOACs may be safe in patients with mild to moderate CLD. Should a DOAC be selected as an alternative to traditional anticoagulants, more frequent monitoring should be used because hepatotoxicity may be a concern. Larger clinical trials are needed to address efficacy outcomes as well as differences among individual DOACs in this population.

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