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David R P Guay

Publications and source records attributed to David R P Guay.

At least 19 recordsLinked to original sources
PubMed2006

Ibandronate, an experimental intravenous bisphosphonate for osteoporosis, bone metastases, and hypercalcemia of malignancy.

Ibandronate is an experimental intravenous bisphosphonate under study for the prevention or treatment of osteoporosis and skeletal complications of bone metastases, as well as hypercalcemia of malignancy. To review the data on this drug, PubMed/MEDLINE was searched for pertinent studies in English; data from January 1986-October 2005 were reviewed. In preclinical studies, ibandronate was an extremely potent bisphosphonate compared with its predecessors and was active in all animal models of human postmenopausal and corticosteroid-associated osteoporosis. Similar to other bisphosphonates, ibandronate exhibits antitumor activity and prevents or reduces bone metastases. Forty to fifty percent of the dose is bound to bone; renal clearance of unchanged drug accounts for 70% of total body clearance. Early clinical trials demonstrated efficacy and tolerability of intravenous ibandronate in the prevention or treatment of postmenopausal and corticosteroid-associated osteoporosis when administered once every 3 months. Intravenous ibandronate also reduces skeletal complications of bone metastases, including pain, although the cumulative dose used is much higher than that used in osteoporosis, as the drug is administered every 3-4 weeks. Single doses of intravenous ibandronate are probably also effective in the treatment of hypercalcemia of malignancy. The major tolerability issue with intravenous bisphosphonates is renal safety, thus the drugs generally require infusion (e.g., 0.25 hr for zoledronic acid, 2-24 hrs for pamidronate). However, intravenous ibandronate can be administered by bolus injection over a few minutes without an elevated risk of nephrotoxicity. The experimental intravenous dosage is 2 mg every 3 months for treatment or prevention of osteoporosis, and 2-6 mg every 3-4 weeks or in a single dose for treatment of bone metastases or hypercalcemia of malignancy, respectively. Ibandronate can be used in the presence of severe renal impairment with proper dosage adjustment. The drug will be an interesting addition to the available drugs for osteoporosis, bone metastases, and hypercalcemia of malignancy. Studies of intravenous ibandronate as an adjunctive treatment for cancers that tend to metastasize to bone are under way. Whether intravenous ibandronate will be a therapeutic advance is best answered by randomized, controlled trials. These are ongoing and should provide data with which to make better-informed choices concerning intravenous bisphosphonates.

Bone Density Conservation Agents↗
PubMed2005

Duloxetine for management of stress urinary incontinence.

OBJECTIVE: The aim of this article was to review data regarding the efficacy and tolerability of duloxetine, a selective serotonin (5-HT)-norepinephrine (NE) reuptake inhibitor that has received US Food and Drug Administration marketing approval for the treatment of major depressive disorder and painful diabetic neuropathy, and that has been investigated as a treatment for stress urinary incontinence. METHODS: A MEDLINE/PubMed search was conducted to identify English-language study reports. In addition, proceedings of meetings of the International Continence Society, European Association of Urology, American Urological Association, and American College of Obstetrics and Gynecology were reviewed for relevant abstracts (search terms included duloxetine, thiophenes, serotonin uptake inhibitors, adrenergic uptake inhibitors, and stress urinary incontinence). Additional references were obtained from the bibliographies of these sources. Data for the period from 1986 through January 2005 were reviewed. RESULTS: All in vitro and in vivo studies of duloxetine were included. Because both 5-HT and NE are involved in the maintenance of urinary continence, duloxetine may have a role in the treatment of urinary incontinence. Duloxetine is primarily eliminated via metabolism, with < 1% of the parent compound excreted via urine. Duloxetine QD or BID has been found to be significantly superior to placebo in reducing incontinence episode frequency (P < 0.001 to P < 0.05), increasing the interval between micturitions (P < 0.001 to P = 0.004), and improving the condition as measured by patient self-report (P < 0.001 to P = 0.028) and incontinence quality-of-life scores (P = 0.002 to P = 0.03). The most problematic adverse events are nausea, dry mouth, constipation, dizziness, and insomnia. CONCLUSIONS: Although statistically superior to placebo in efficacy trials, the clinical effects of duloxetine therapy on incontinence are small, suggesting that any benefits to the patient would be modest and must be weighed against the drug's adverse event profile. No comparative efficacy/tolerability data with alpha-receptor agonists (eg, pseudoephedrine) are available. On the basis of available data, duloxetine is a modest, but welcome, advance in the pharmacotherapeutic management of stress urinary incontinence.

Adrenergic Uptake Inhibitors↗
PubMed2005

Ibandronate: a new oral bisphosphonate for postmenopausal osteoporosis.

OBJECTIVE: To review a new oral bisphosphonate, ibandronate, recently approved by the U.S. Food and Drug Administration for the treatment and prevention of postmenopausal osteoporosis. DATA SOURCE: A MEDLINE/PUBMED search was conducted to identify pertinent studies in the English language. Additional references were obtained from the bibliographies of these studies. Data over the time period of 1986 through July 2005 were reviewed. STUDY SELECTION AND DATA EXTRACTION: All studies evaluating any aspect of ibandronate in animals and humans. Studies in humans focused on the oral drug formulation. DATA SYNTHESIS: Preclinical studies established that ibandronate was an extremely potent bisphosphonate compared with its predecessors and that it was active in all animal models of human postmenopausal and corticosteroid-associated osteoporosis. Similar to other selected bisphosphonates, preclinical studies also showed that ibandronate exhibits antitumor activity and prevents and/or reduces bone metastases. As with other oral bisphosphonates, oral bioavailability is very poor (less than 1%) and substantially reduced by administration with or proximal to cations (e.g., food, antacids, mineral supplements). Clinical trials have demonstrated the efficacy and tolerability of oral ibandronate in the treatment and prevention of postmenopausal osteoporosis when administered once daily, once weekly, and even once monthly. Ibandronate also reduces the skeletal complications of bone metastases in patients with cancer, including pain, although the dosage used is much higher than that used in osteoporosis. As with other bisphosphonates, the major tolerability issue with ibandronate is upper gastrointestinal (GI) distress (dyspepsia, pain, esophagitis, esophageal and gastric ulcers). The dosage regimen for the treatment or prevention of postmenopausal osteoporosis (the only currently approved use in the United States) is 2.5 mg once a day or 150 mg once monthly (on the same date each month). Ibandronate should not be used in the presence of severe renal impairment (creatinine clearance below 30 mL/min). The usual complex administration instructions for other oral bisphosphonates apply to ibandronate as well. CONCLUSION: Oral ibandronate is an interesting addition to the therapeutic armamentarium for osteoporosis and cancer metastatic to bone. In fact, studies of ibandronate as an adjunctive treatment for cancers with a predilection to metastasize to bone are under way. Ibandronate has taken advantage of a complex pharmacodynamic profile in which its antiresorptive activity is independent of the frequency of dosing provided that a minimum dose-per-unit time is exceeded. Studies with every three-month dosing (and even less frequently) are under way. Whether or not the less frequent dosing of oral ibandronate will translate into a therapeutic advantage over older oral agents such as alendronate and risedronate is open to speculation. This is a difficult question to answer in the absence of head-to-head randomized controlled trials (RCTs). Older agents are still preferred until RCTs demonstrate that ibandronate is as safe and effective as these older agents.

Journal Article↗
PubMed2005

Darifenacin: another antimuscarinic for overactive bladder.

OBJECTIVE: To review darifenacin, a new anticholinergic for overactive bladder, approved in December 2004 by the U.S. Food and Drug Administration. DATA SOURCE: A MEDLINE/PUBMED search was conducted to identify pertinent studies in the English language. In addition, proceedings of meetings of the International Continence Society, European Association of Urology, American Urological Association, and American College of Obstetrics and Gynecology were reviewed for relevant abstracts. Additional references were obtained from the bibliographies of these sources. Data over the time period of 1986 through September 2004 were reviewed. STUDY SELECTION: All studies evaluating any aspect of darifenacin in vitro or in vivo in animals or humans. DATA SYNTHESIS: Preclinical studies demonstrated that darifenacin was an antagonist at muscarinic cholinergic M1, M3, and M5 receptors. On the basis of preclinical data, darifenacin was felt to be a "uroselective" antimuscarinic. Darifenacin is extensively metabolized, with urinary excretion of parent compound being less than 10%. Darifenacin, dosed as 7.5 or 15 mg once daily, is significantly superior to placebo in reducing the numbers of micturitions, urges, incontinence episodes, and urge severity and increasing the warning time and volume per micturition. No active-controlled trial data are available. The most problematic adverse effects of darifenacin are the anticholinergic effects of dry mouth and constipation. CONCLUSION: Although promising in preclinical studies, the "uroselectivity" of the anticholinergic activity of darifenacin has not been confirmed in clinical trials. No comparative data with marketed (for overactive bladder) anticholinergics are available. On the basis of available data, darifenacin does not appear to be a substantial advance upon existing anticholinergics in the management of overactive bladder.

Journal Article↗
PubMed2005

Pregabalin in neuropathic pain: a more "pharmaceutically elegant" gabapentin?

OBJECTIVE: This article reviews the available information on pregabalin, a new anticonvulsant for peripheral neuropathic pain. Pregabalin was provisionally approved by the US Food and Drug Administration in December 2004 and was granted final approval after controlled substance scheduling (Schedule V) by the US Drug Enforcement Agency in August 2005. METHODS: A MEDLINE search (1986-August 2005) was conducted to identify pertinent studies in the English language. The search terms included pregabalin, PD144723, CI-1008, gabapentin, and neuropathic pain. Additional references were obtained from the bibliographies of identified articles. All studies that evaluated any aspect of pregabalin in vitro or in vivo in animals or humans were included, with a focus on data relevant to older adults. RESULTS: In preclinical studies, pregabalin, a structural congener of gabapentin, exhibited antinociceptive activity in animal models of neuropathic and inflammatory pain. Unlike gabapentin, pregabalin was well absorbed (> 90%), and its absorption was dose independent. Like gabapentin, pregabalin was predominantly excreted unchanged in the urine (> or = 98%). Dosed at 50 to 200 mg TID, pregabalin was superior to placebo in relieving pain and improving sleep and health-related quality of life in patients with diabetic peripheral neuropathy and postherpetic neuralgia (P < 0.001-P < 0.049). No active-controlled trials were available. The most problematic adverse events associated with pregabalin were dizziness and somnolence (21%-26%). CONCLUSIONS: In the absence of active-controlled clinical trials and geriatric-specific efficacy/tolerability data, the place of pregabalin in the analgesic armamentarium for the elderly is unclear. Because pregabalin is a Schedule V controlled substance, its utility is not compromised by substantial limitation of access or the need for extra steps in prescribing. However, abuse potential is a consideration, and utilization should be carefully monitored, particularly in patients with a past or current history of substance abuse. The improved pharmacokinetic profile of pregabalin relative to gabapentin is manifested in linear and dose-independent absorption and a narrow therapeutic dosing range. However, pregabalin still requires multiple administrations per day, and daily doses > 150 mg/d require dose titration. The relatively high frequency of central nervous system adverse events, particularly dizziness and somnolence, is a concern in the elderly. Time and further experience should clarify the role of this agent.

Aged↗
PubMed2004

Extended-release alfuzosin hydrochloride: a new alpha-adrenergic receptor antagonist for symptomatic benign prostatic hyperplasia.

BACKGROUND: Extended-release (ER) alfuzosin hydrochloride is the most recently approved alpha-adrenergic receptor antagonist (AARA) for the management of symptomatic benign prostatic hyperplasia (BPH). Although new to the United States, alfuzosin has been available in immediate-release (IR) and sustained-release (SR) formulations in other countries for many years. OBJECTIVE: This article reviews data on the pharmacodynamics, pharmacokinetics, efficacy, tolerability, drug-interaction potential, and dosing of alfuzosin ER. METHODS: Relevant articles were identified through MEDLINE, EMBASE, and International Pharmaceutical Abstracts searches of the English-language literature published between 1986 and September 2003 using the terms alfuzosin, alpha-adrenergic receptor antagonists, and quinazolines. The reference lists of identified articles were also searched, as were abstracts from annual meetings of the American Urological Association for the past 5 years. Data regarding the ER formulation were emphasized, and data involving the IR/SR formulations were included only when data for the ER formulation were not available or as needed for clarification. RESULTS: In comparative trials with its IR counterpart (alfuzosin ER 10 mg QD vs alfuzosin IR 2.5 mg TID), alfuzosin ER was an equieffective once-daily AARA. No comparative trials of alfuzosin ER with the SR (BID) formulation or with other AARAs were identified. Food has been found to exert a clinically important effect by enhancing the bioavailability of the ER formulation; thus, the drug should be taken on a full stomach. Hepatic impairment has been found to significantly delay the elimination of alfuzosin IF, which constitutes a contraindication to use of the ER formulation. Renal impairment does not appear to exert clinically important effects on the pharmacokinetics of alfuzosin ER. Adverse events with alfuzosin ER include dizziness, upper respiratory tract infection, headache, and fatigue, with hypotension and syncope reported rarely. Concurrent use of inhibitors of the cytochrome P450 3A4 isozyme (eg, ketoconazole, diltiazem, cimetidine, atenolol) can significantly elevate serum concentrations of alfuzosin and enhance its pharmacodynamic effects. CONCLUSIONS: In the absence of direct head-to-head comparative trials, the role of alfuzosin ER in the management of symptomatic BPH relative to that of other AARAs is unclear. Because the effect size (drug response minus placebo response) of alfuzosin ER is comparable to that of other AARAs, marked differences in efficacy are unlikely. Extrapolating from direct comparative trials between these agents and alfuzosin IR/SR, alfuzosin ER would be expected to have better cardiovascular tolerability (eg, in terms of dizziness and orthostasis) than prazosin, terazosin, or doxazosin, and to have similar tolerability to tamsulosin. However, the existing data do not suggest that alfuzosin ER is likely to represent a significant advance over tamsulosin.

Adrenergic alpha-Antagonists↗
PubMed2004

Dalbavancin: an investigational glycopeptide.

Glycopeptide antimicrobials have been a component of our therapeutic armamentarium for nearly 50 years. Although vancomycin, and more recently teicoplanin, have performed yeoman service over the years, the specter of bacterial resistance among Gram-positive aerobes has created doubts concerning how long they will continue to be useful antimicrobial agents. In an attempt to prolong the utility of the glycopeptides, efforts are underway to create new derivatives with improved pharmacologic and pharmacokinetic properties. One example of an improved glycopeptide from the pharmacokinetic perspective is dalbavancin (BI397)--a teicoplanin analog currently undergoing human testing. Elimination of this compound from the body occurs extremely slowly, with terminal disposition half-lifes of up to 200 h in healthy volunteers, thus allowing once-weekly dosing. Although not generally considered to be a potential alternative for the treatment of infections due to glycopeptide-resistant Gram-positive pathogens, dalbavancin may still be considered an advance on existing agents based on its patient-convenient once-weekly dosing regimen.

Animals↗
PubMed2004

Oritavancin and tigecycline: investigational antimicrobials for multidrug-resistant bacteria.

The advent of multidrug-resistant gram-positive aerobes such as Staphylococcus aureus, Streptococcus pneumoniae, and the enterococci, which are resistant to beta-lactams, vancomycin, and a host of other commonly used antimicrobials, has complicated our approach to antibiotic therapy. Despite marketing of the first oxazolidinone, linezolid, and the streptogramin combination, quinupristin-dalfopristin, an urgent need exists for more agents to combat these pathogens. Two such agents, the glycopeptide oritavancin (LY333328) and the glycylcycline tigecycline (GAR-936), are in phase III clinical trials. These agents, which require parenteral administration, exhibit substantial in vitro activity against a variety of gram-positive aerobes and anaerobes, including the multidrug-resistant organisms listed previously. Only tigecycline demonstrates useful activity against gram-negative organisms. Combination therapy of these agents with ampicillin or aminoglycosides frequently leads to synergistic in vitro activity against multidrug-resistant staphylococci and streptococci. These agents are also active in a variety of animal models of systemic and localized infections. Few published efficacy and tolerability data are available in humans. If controlled clinical trial data verify these agents' efficacy and tolerability, both drugs should become welcome additions to the available antimicrobials. However, restricting their use to the treatment of infections caused by bacteria resistant to other antimicrobials, especially multidrug-resistant staphylococci and streptococci, may prolong their clinical utility by retarding the development of resistance. Careful surveillance of bacterial sensitivity to these agents should be undertaken to assist clinicians in the decision whether or not to use these agents empirically to treat infections caused by suspected multidrug-resistant gram-positive pathogens.

Animals↗
PubMed2004

The scourge of sarcoptes: oral ivermectin for scabies.

OBJECTIVE: To review the use of the oral antiparasitic ivermectin in the treatment of scabies, with an emphasis on its use in the elderly and in long-term care settings. DATA SOURCE: A MEDLINE/PUBMED search was conducted to identify pertinent studies, case reports, letters, and reviews in the English language. All articles published from 1980 to October 2003 were reviewed. Additional references were obtained from the bibliographies of these articles. STUDY SELECTION: All studies evaluating ivermectin in the context of scabies mite infestation. DATA SYNTHESIS: The semisynthetic macrocyclic lactone ivermectin has been available since the early 1980s as a broad-spectrum antiparasitic agent in animals and humans. This agent, which works by suppressing motor nerve conduction leading to parasite paralysis and death, was first used in ectoparasitic diseases (i.e., those caused by lice and mites) shortly after commercial introduction. A large body of literature, mainly uncontrolled case reports and series, has since evolved. However, these reports and results of the small number of placebo- and/or active-controlled studies have demonstrated the favorable response of both classic and crusted scabies to single- and multiple-dose oral ivermectin. Adverse reactions to the drug are uncommon, with the exception of a transient, new onset, or mild increase in existing pruritus soon after drug ingestion, which is thought to be a hypersensitivity reaction to dead mites and/or their products. CONCLUSION: Oral ivermectin may prove to be a time- and labor-saving alternative to topical scabicide treatments, especially in the institutional setting where labor shortages make the management of scabies outbreaks a true challenge. However, the use of this agent does not change the need to decontaminate the environment (clothing, bedding, bed clothes, and, in selected cases, floors and walls) in order to truncate an outbreak and prevent reinfestation.

Journal Article↗
PubMed2004

Drug forecast--solifenacin: an investigational anticholinergic for overactive bladder.

OBJECTIVE: To review a new anticholinergic for overactive bladder undergoing review by the U.S. Food and Drug Administration, solifenacin. DATA SOURCE: A MEDLINE/PUBMED search was conducted to identify pertinent studies in the English language. In addition, proceedings of meetings of the Incontinence Society, European Association of Urology, American Urological Association, and American College of Obstetrics and Gynecology were reviewed for relevant abstracts. Additional references were obtained from the bibliographies of these sources. Data over the time period of 1986 through October 2003 were reviewed. STUDY SELECTION: All studies evaluating any aspect of solifenacin in animals and humans. DATA SYNTHESIS: Preclinical studies demonstrated that solifenacin was an antagonist at muscarinic cholinergic M1, M2, and M3 receptors. On the basis of comparative preclinical studies evaluating the effects of solifenacin and oxybutynin on guinea pig detrusor muscle cells, mouse submandibular gland cells, and the intact rat, solifenacin was felt to be a "uroselective" antimuscarinic. Solifenacin is predominantly eliminated via metabolism, with urinary excretion of parent compound being less than 10%. Solifenacin, dosed once daily, is significantly superior to placebo in reducing the number of micturitions, urge episodes, and urge incontinence episodes per day and increasing the volume voided per micturition. In two active-controlled trials, solifenacin was at least equivalent to tolterodine in efficacy and tolerability. The most problematic adverse effects of solifenacin are the anticholinergic effects of dry mouth, blurred vision, and constipation. CONCLUSION: Although promising in preclinical studies, the uroselectivity of the anticholinergic activity of solifenacin has not been validated in clinical trials. No comparative efficacy/tolerability data with oxybutynin are available. On the basis of available data, solifenacin does not appear to be a substantial advance upon existing anticholinergics in the management of overactive bladder.

Journal Article↗
PubMed2004

Daptomycin: the first approved lipopeptide antimicrobial.

OBJECTIVE: To review the literature concerning the first Food and Drug Administration-approved lipopeptide antimicrobial, daptomycin. DATA SOURCES: A PUBMED search was conducted to identify pertinent English-language journal articles between 1985 and November 2003, and additional references were obtained from the bibliographies of these articles. Abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy meetings from 1985 through 2003 also were reviewed. STUDY SELECTION: All studies evaluating any aspect of daptomycin. DATA SYNTHESIS: Daptomycin is a semisynthetic lipopeptide, the first such antimicrobial agent to reach the marketplace. Its mechanism of action differs from that of the related agent vancomycin in that much of its effect is not because of inhibition of peptidoglycan biosynthesis, but instead is a result of alterations in cell-membrane electrical charge and transport. It exhibits a broad spectrum of activity against gram-positive aerobes and anaerobes, including methicillin-, penicillin-, aminoglycoside-, and vancomycin-resistant strains. In subjects with normal renal function, the terminal disposition half-life is about 7 to 10 hours. It is principally eliminated as unchanged drug in the urine. Available clinical trial data demonstrate efficacy in complicated skin and skin-structure infections resulting from susceptible gram-positive pathogens, but not in pneumonia. The principal adverse event of concern, although rare, is myotoxicity, manifested by muscle pain and/or weakness and elevated serum creatine phosphokinase (CPK) concentrations. The approved dosage regimen is 4 mg/kg intravenously over 30 minutes once daily for 7 days to 14 days. Studies are underway evaluating doses of up to 8 mg/kg once daily. CONCLUSIONS: Daptomycin, the first lipopeptide antimicrobial to be marketed, exhibits activity against multiresistant gram-positive pathogens, including linezolid- and quinupristindalfopristin-resistant strains. As such, it is a potentially valuable agent to treat infections resulting from such pathogens. To preserve its utility, it should not be used indiscriminately for infections resulting from pathogens sensitive to other antimicrobials. It is probably best used with restricted access and used only for multiresistant gram-positive pathogens where alternative agents cannot be employed. If used, careful monitoring for the signs and symptoms of myotoxicity, including obtaining weekly serum CPK levels, is mandatory. In addition, bacterial sensitivities to this agent should be prospectively monitored by national antimicrobial surveillance programs like SENTRY, TRUST, and LIBRA.

Journal Article↗
PubMed2003

Trandolapril: a newer angiotensin-converting enzyme inhibitor.

BACKGROUND: Trandolapril is a newer angiotensin-converting enzyme (ACE) inhibitor that is approved by the US Food and Drug Administration for the treatment of hypertension and for use in stable patients who have evidence of left ventricular (LV) systolic dysfunction or symptoms of chronic heart failure within the first 2 days after an acute myocardial infarction (AMI). The fixed-dose combination of trandolapril and verapamil extended release (ER) is approved for the treatment of hypertension only. OBJECTIVE: The purpose of this article was to review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of trandolapril as monotherapy and in fixed-dose combination with verapamil ER. METHODS: Relevant studies were identified through a MEDLINE/PubMed search of the English-language literature published between January 1983 and August 2002 and a review of the bibliographies of identified articles. RESULTS: Trandolapril has a sufficient duration of inhibition of plasma ACE activity to allow once-daily dosing. It is converted by esterases to the active trandolaprilat metabolite, with mean terminal disposition half-lives of < 1 and approximately 75 hours for the prodrug and metabolite, respectively. In comparative trials in the management of hypertension, trandolapril 1 to 4 mg/d was statistically indistinguishable from or superior to captopril 100 mg/d, enalapril 10 or 20 mg/d, hydrochlorothiazide (HCTZ) 25 mg/d, nifedipine ER 30 or 40 mg/d, nitrendipine 20 mg/d, perindopril 4 mg/d, and verapamil ER 120 to 240 mg/d. In the Trandolapril Cardiac Evaluation, trandolapril also significantly reduced all-cause mortality, cardiovascular mortality, sudden death, and progression to severe chronic heart failure in patients with evidence of LV systolic dysfunction after AMI. In comparative trials in the management of hypertension, the combination of trandolapril 1 or 2 mg/d and verapamil ER 180 mg/d was statistically indistinguishable from or superior to the combinations of atenolol 50 or 100 mg/d plus chlorthalidone 12.5 or 25 mg/d, captopril 50 mg/d plus HCTZ 25 mg/d, lisinopril 20 mg/d plus HCTZ 12.5 mg/d, and metoprolol 100 mg/d plus HCTZ 12.5 mg/d. The most common adverse effects of trandolapril monotherapy in clinical trials of < or = 1 year's duration included cough, dizziness, and diarrhea (frequency < or = 1.9%). The most common adverse effects of trandolapril/verapamil ER therapy in clinical trials of < or = 1 year's duration included first-degree atrioventricular block, bradycardia, constipation, cough, diarrhea, dizziness, fatigue, and dyspnea (frequency < or = 4.6%). Based on the literature search, there are no published pharmacoeconomic evaluations of trandolapril alone or combined with verapamil ER in the US health care setting. CONCLUSIONS: Based on the literature, trandolapril is a well-tolerated and effective antihypertensive agent, whether used alone or in combination with verapamil ER. These products may be valuable in patients with LV systolic dysfunction after AMI, although the combination product is approved for the management of hypertension only.

Acute Disease↗
PubMed2003

Oxcarbazepine, topiramate, zonisamide, and levetiracetam: potential use in neuropathic pain.

BACKGROUND: Oxcarbazepine, topiramate, zonisamide, and levetiracetam are the antiepileptic drugs (AEDs) most recently approved by the US Food and Drug Administration. Based on the experience with carbamazepine, gabapentin, and lamotrigine, these newer AEDs are being investigated for the management of neuropathic pain. OBJECTIVE: This article reviews preclinical and clinical data on the efficacy and tolerability of these 4 AEDs in the management of neuropathic pain, as well as the pharmacokinetics, drug-interaction potential, adverse effects, and dosing of these agents, with an emphasis on their use in older individuals. METHODS: Relevant studies were identified through a MEDLINE search of the Englidh-language literature published between 1986 and May 2003, a review of the reference lists of identified articles, and abstracts from the annual meetings of the American Academy of Neurology (1986-2002) and the 2003 Annual Meeting of the American Pain Society. Search terms were oxcarbazepine, topiramate, zonisamide, and levetiracetam. RESULTS: Oxcarbazepine and topiramate have been effective in animal models of neuropathic pain. Thirty-four publications on the efficacy and tolerability of the 4 agents were identified (25 case reports/case series, 6 randomized parallel-group studies, and 3 randomized crossover studies). The 9 randomized studies were restricted to oxcarbazepine and topiramate, and 23 (68%) publications were available in abstract form only. These preliminary data suggest that the 4 newer AEDs may be useful in a wide variety of neuropathic pain syndromes; however, additional data, including full-length peer-reviewed reports, are necessary before their true analgesic potential in neuropathic pain can be determined. All 4 agents have pharmacodynamic interactions with other psychotherapeutic drugs, potentiating adverse central nervous system events such as sedation. With the exception of levetiracetam, these drugs also have pharmacokinetic interactions with other drugs, although to a somewhat lesser extent than carbamazepine. These agents have some unique adverse effects not frequently monitored by clinicians, such as hyponatremia, nephrolithiasis, acute myopia with secondary angle-closure glaucoma, and weight loss. CONCLUSIONS: Based on preliminary data, oxcarbazepine, topiramate, zonisamide, and levetiracetam may be useful in the treatment of a wide variety of neuropathic pain syndromes, although full publication of the results of controlled trials is awaited. These agents are associated with specific adverse effects not commonly monitored by clinicians. Of the 4, levetiracetam appears to be easiest to use (ie, no need for dose adjustment in organ dysfunction, no need for laboratory monitoring) and best tolerated, and has not been associated with the unique toxicities seen with oxcarbazepine, topiramate, and zonisamide. The ultimate role of these agents in the therapeutic armamentarium against pain requires further research and experience. In the interim, these 4 agents should be used to treat neuropathic pain in the elderly only when carbamazepine, gabapentin, or lamotrigine cannot be used or when the response to the aforementioned agents is suboptimal.

Aged↗
PubMed2003

Pneumococcal polysaccharide revaccination: immunoglobulin g seroconversion, persistence, and safety in frail, chronically ill older subjects.

OBJECTIVES: To determine the 1-month postpneumococcal polysaccharide-revaccination immunoglobulin G (IgG) antibody response, its persistence at 1 year, and tolerability of revaccination in frail, chronically ill older nursing facility residents. DESIGN: Prospective study conducted between December 1998 and July 2000. SETTING: Six skilled nursing facilities in the Minneapolis-St. Paul, Minnesota, metropolitan area. PARTICIPANTS: Sixty-seven subjects aged 65 and older having received primary vaccination with pneumococcal polysaccharide vaccine (PPV) at least 5 years before enrollment. INTERVENTION: Revaccination with one dose of 23-valent PPV. MEASUREMENTS: Adverse events and concentrations of seven individual pneumococcal polysaccharide type-specific IgG antibodies (against serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) and their aggregate before and 1 and 12 months after revaccination. RESULTS: A significant increase in all individual and aggregate median antibody concentrations over baseline was observed 1 month after revaccination. However, after 1 year, the increase remained significant only for serotypes 6B and 18C and the aggregate parameter. One month after revaccination, the mean increase in antibody concentration over baseline was significantly greater than 1.4-fold for six of the seven serotypes and the aggregate. However, the increase was not significantly greater than 1.4 at 1 year for any of the serotypes or the aggregate. Minor, self-limited localized adverse reactions and systemic reactions occurred in 11.3% of the subjects. CONCLUSIONS: In frail, chronically ill older nursing facility residents, revaccination with 23-valent PPV at least 5 years after primary vaccination (whether primary vaccination occurred before or after age 65) is associated with a significant, albeit brief, immunological response for most of the serotypes tested. Revaccination was well tolerated.

Aged↗