Tapentadol hydrochloride: a centrally acting oral analgesic.

BACKGROUND: Tapentadol hydrochloride is a centrally acting oral analgesic approved by the US Food and Drug Administration in November 2008 for the treatment of moderate to severe acute pain. It is available as immediate-release 50-, 75-, and 100-mg tablets. OBJECTIVE: The purpose of this article is to review animal studies, pharmacokinetic studies, drug-drug interaction studies, and Phase II/III trials of tapentadol in various conditions producing moderate to severe pain. Efficacy and tolerability data from these studies are summarized. METHODS: A search of MEDLINE and International Pharmaceutical Abstracts was conducted from January 2005 through June 30, 2009. Search terms included tapentadol, tapentadol hydrochloride, and (-)-(1R,2R)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride. Relevant information was extracted from the identified articles, and the reference lists of these articles were reviewed for additional pertinent publications. The manufacturer was contacted for clinical trials, abstracts, and poster presentations that were not identified by the literature search. ClinicalTrials.gov was searched to identify recently completed studies. RESULTS: Tapentadol produces analgesia through a dual mechanism of action: mu-opioid-receptor activation and norepinephrine reuptake inhibition. Its efficacy has been reported in a number of animal studies, as well as in Phase II/III clinical trials. Primary pain disorders in which efficacy has been reported include dental extraction pain, pain after bunionectomy surgery, osteoarthritis pain of the knee and hip, and low back pain. Major adverse effects reported in Phase II/III trials primarily involved the gastrointestinal system (2%-66% of subjects) and the central nervous system (4%-65% of subjects). The occurrence of gastrointestinal adverse effects appeared to be less frequent in tapentadol recipients than in those receiving oxycodone. CONCLUSIONS: Tapentadol appears to be a well-tolerated and effective analgesic for the treatment of moderate to severe acute pain. Although not currently approved for the management of chronic pain, tapentadol has been reported to be effective in managing pain associated with osteoarthritis and low back pain.

Comparison of estimated glomerular filtration rate with estimated creatinine clearance in the dosing of drugs requiring adjustments in elderly patients with declining renal function.

BACKGROUND: The National Kidney Foundation's practice guidelines for chronic kidney disease recommend using the Modification of Diet in Renal Disease (MDRD) equation for calculating the estimated glomerular filtration rate (GFR). OBJECTIVE: The purpose of this article was to compare the use of this estimated GFR with estimated creatinine clearance (CrCl) calculated using the Cockcroft-Gault equation (CG(CrCl)-Eq) in the dosing of drugs requiring adjustments in elderly patients with declining renal function. Existing as well as new serum creatinine assay standards were used. METHODS: A PubMed literature search for all English-language articles published before November 2007 was conducted using the terms estimated glomerular filtration, GFR, modified diet in renal disease, MDRD, creatinine clearance, CrCl, drug dosing adjustment, renal impairment, human, and elderly. Mathematical comparisons of the age, race, and sex factors for these 2 equations (CG(CrCl)-Eq and MDRD) were performed, as well as a simulation of resulting values from these equations using various combinations of age, weight, and sex factors. RESULTS: None of the articles identified found that the use of the MDRD equation in the elderly was better than the CG(CrCl)-Eq for estimating renal drug elimination. Substantial mathematical differences are inherent in these 2 prediction equations that make any clinical comparison quite difficult. Implementation of new creatinine assay standards will further confuse the use of these 2 equations for estimating GFR and for dosage adjustments in elderly patients with renal insufficiency. CONCLUSIONS: Although an MDRD equation may be useful for estimating GFR, the CG(CrCl)-Eq should still be used for drug dosage adjustments. The CG(CrCl)-Eq may require a slight "adjustment factor" to be applied using serum creatinine values measured by newly established assay procedures.

Cost-effectiveness of dalteparin versus unfractionated heparin as venous thromboembolism prophylaxis in malignant gynecologic surgery.

Venous thromboembolic events (VTEs) are serious complications that may occur in the patient undergoing surgery for gynecologic malignancies. The American College of Chest Physicians recommends unfractionated heparin or low-molecular weight heparin as prophylaxis for deep vein thrombosis and pulmonary embolism in this patient population. Cost-effectiveness analyses comparing unfractionated heparin 3 times a day versus once daily dalteparin using published efficacy and safety data demonstrate cost savings if dalteparin were routinely utilized as VTE prophylaxis. Sensitivity analyses support this finding at the upper end of the range of reported proximal DVT, nonfatal pulmonary embolism, and major bleeding incidences. These findings should be viewed as preliminary, and institutions are encouraged to perform their own cost-effectiveness studies in this patient population.

New serum creatinine assay standardization: implications for drug dosing.

OBJECTIVE: To describe the development of new serum creatinine assay standards and discuss their implications for various drug dosing scenarios. DATA SOURCES: A MEDLINE search (1990-August 2006) was performed to identify literature on newly developed serum creatinine assay standards and the impact those standards will have on drug dosing. STUDY SELECTION AND DATA EXTRACTION: Data on the development of new creatinine assay procedures and the effect that these new values will have on drug dosing were extracted from identified references. DATA SYNTHESIS: The National Kidney Foundation's current practice guidelines recommend standardization of serum creatinine assay calibration to increase assay accuracy. This will result in a lower than the current range of values being considered normal, as well as lower value patient values. These lower creatinine values will result in higher calculated glomerular filtration rates and creatinine clearance (Cl(cr)) estimates, resulting in the difficulty of clinicians applying these values to current manufacturers' recommended drug dose modification tables in patients with declining renal function. Newer creatinine values may be as much as 5-20% lower than older assay values. CONCLUSIONS: Worldwide implementation of new serum creatinine calibration standards will produce more accurate serum creatinine values. These values may be slightly lower than those obtained with older methods. This, in turn, may cause slightly higher Cl(cr) estimates that may no longer match drug manufacturers' data for dosage adjustment in renal insufficiency, given that manufacturers' dosing tables were based on older creatinine values. If this is deemed clinically significant in a specific patient, increasing the creatinine value obtained with new assay techniques by 5-20% may give the clinician a value that more closely approximates that used by the drug manufacturer in developing these tables. This revised value can then be used for dosage adjustments.

Fondaparinux sodium in the prophylaxis and treatment of deep vein thrombosis and pulmonary embolism.

Fondaparinux sodium is the first in a new class of anticoagulants that selectively inhibits Factor Xa. It produces a predictable pharmacologic response, obviating the need for coagulation monitoring. Additionally, this agent does not bind to platelet Factor 4, thereby reducing the risk of thrombocytopenia. Clinical trials have repeatedly demonstrated superior efficacy over other anticoagulants as venous thromboembolism prophylaxis and several cost-effectiveness studies have demonstrated cost savings with this drug.

Cost analysis of fondaparinux versus enoxaparin as venous thromboembolism prophylaxis in elective hip replacement surgery.

Patients undergoing hip arthroplasty are at high risk for developing venous thromboembolic events (VTE) postoperatively in the absence of prophylaxis. In this study, a cost analysis comparing efficacy and safety data from a published trial evaluating fondaparinux and enoxaparin as VTE prophylaxis in hip replacement patients was performed. Incremental cost effectiveness ratios were calculated to determine cost per VTE avoided. Additionally, cost per death averted and cost per life year gained were calculated. Fondaparinux proved to offer minor cost savings when compared with 30 mg enoxaparin every 12 h for costs per VTE avoided, costs per death averted, and costs per life year gained. Sensitivity analyses support these findings.

Cost analysis of fondaparinux versus enoxaparin as venous thromboembolism prophylaxis in hip fracture surgery.

Hip fracture patients are at high risk of developing venous thromboembolic events (VTEs) postoperatively. Efficacy and safety data from a clinical trial comparing fondaparinux and enoxaparin as VTE prophylaxis were used to perform a cost assessment of these 2 agents. Incremental cost calculations demonstrate that enoxaparin offers advantages over fondaparinux when dosed for 7 days postoperatively in this patient population. Sensitivity analyses support this finding at the lower extreme; however, fondaparinux provides cost savings at the upper extreme. Cost per death averted and cost per life year gained are similar for these 2 agents in these patients.

A cost analysis of fondaparinux versus enoxaparin in total knee arthroplasty.

Several hundred thousand total knee replacement (TKR) surgeries are performed in the United States each year. The American College of Chest Physicians has classified TKR patients in the "highest-risk" category for developing venous thromboembolic events. Recommended prophylactic agents following TKR surgery include unfractionated heparin and low-molecular weight heparins. Fondaparinux is a selective inhibitor of factor Xa and has recently received approval for the prophylaxis of venous thromboembolism in TKR patients. In November 2001, an efficacy study comparing fondaparinux with enoxaparin as deep vein thrombosis prophylaxis in TKR surgery was published by Bauer et al. The purpose of the current study was to perform an incremental cost analysis for fondaparinux versus enoxaparin using the efficacy and safety data of the Bauer et al study. Specific comparisons evaluated included cost per venous thromboembolic event avoided, cost per death averted, and cost per life-year gained with fondaparinux and enoxaparin. All analyses were performed from an institutional perspective and projected to 1000 patients. The incremental cost analysis indicates an USD $1081.33 cost savings with fondaparinux over enoxaparin per venous thromboembolic event avoided. Cost per death averted in the enoxaparin group is USD $88,943.54; cost per death averted in the fondaparinux groups is USD $81,157.94. Cost per life-year gained of USD $5437 for enoxaparin and USD $4925 for fondaparinux.

Determining institution-specific costs of thromboembolic events with an algorithm and spreadsheet.

A systematic process whereby an institution may perform a pharmacoeconomic analysis of all direct medical costs associated with the diagnosis and treatment of venous thromboembolic events (VTEs) that reflects both institution-specific costs and clinical practice patterns is described. Current Content, International Pharmaceutical Abstracts, and MEDLINE were searched to identify English-language articles addressing procedures for diagnosing and treating symptomatic deep-vein thrombosis and pulmonary embolism. From the information gathered, a diagnostic algorithm and a resource spreadsheet were developed. The diagnostic procedures were classified as standard, alternative, confirmatory, or supplemental. The spreadsheet resources were assigned priorities based on practice standards and quantified on the basis of units typically used in the clinical setting. Three major categories of resources were identified: diagnostic, treatment, and laboratory test monitoring. Diagnostic procedures consisted of five subcategories containing 31 cost resources, treatments consisted of nine subcategories with 26 cost resources, and laboratory monitoring tests consisted of 9 cost resources. Units of use for all resources identified were also noted. A systematic process utilizing a diagnostic algorithm and a spreadsheet was developed to facilitate the determination of institution-specific costs associated with the diagnosis, treatment, and laboratory test monitoring of VTEs.

Cost analysis: fondaparinux versus preoperative and postoperative enoxaparin as venous thromboembolic event prophylaxis in elective hip arthroplasty.

Patients undergoing hip arthroplasty in the absence of prophylaxis for venous thromboembolic events (VTEs) are at high risk for experiencing postoperative VTEs. In the study reported here, we performed cost analyses involving efficacy and safety data from clinical trials evaluating fondaparinux and enoxaparin as VTE prophylaxis. Incremental cost-effectiveness ratios were calculated to determine cost per VTE avoided. In addition, cost per death averted and cost per life-year gained were calculated. Once-daily fondaparinux proved to be more cost-effective than once-daily enoxaparin 40 mg but less cost-effective than twice-daily enoxaparin 30 mg.