Intravenous versus Oral Acetaminophen for Pain: Systematic Review of Current Evidence to Support Clinical Decision-Making

Background:

Intravenous (IV) acetaminophen is increasingly used around the world for pain control for a variety of indications. However, it is unclear whether IV administration offers advantages over oral administration.

Objective:

To identify, summarize, and critically evaluate the literature comparing analgesic efficacy, safety, and pharmacokinetics for IV and oral dosage forms of acetaminophen.

Data Sources:

A literature search of the PubMed, Embase, and International Pharmaceutical Abstracts databases was supplemented with keyword searches of Science Direct, Wiley Library Online, and Springer Link databases for the period 1948 to November 2014. The reference lists of identified studies were searched manually.

Study Selection and Data Extraction:

Randomized controlled trials comparing IV and oral dosage forms of acetaminophen were included if they assessed an efficacy, safety, or pharmacokinetic outcome. For each study, 2 investigators independently extracted data (study design, population, interventions, follow-up, efficacy outcomes, safety outcomes, pharmacokinetic outcomes, and any other pertinent information) and completed risk-of-bias assessments.

Data Synthesis:

Six randomized clinical trials were included. Three of the studies reported outcomes pertaining to efficacy, 4 to safety, and 4 to pharmacokinetics. No clinically significant differences in efficacy were found between the 2 dosage forms. Safety outcomes were not reported consistently enough to allow adequate assessment. No evidence was found to suggest that increased bioavailability of the IV formulation enhances efficacy outcomes. For studies reporting clinical outcomes, the results of risk-of-bias assessments were largely unclear.

Conclusions:

For patients who can take an oral dosage form, no clear indication exists for preferential prescribing of IV acetaminophen. Decision-making must take into account the known adverse effects of each dosage form and other considerations such as convenience and cost. Future studies should assess multiple-dose regimens over longer periods for patients with common pain indications such as cancer, trauma, and surgery.     

Molecular Basis of Crystal Morphology-Dependent Adhesion Behavior of Mefenamic Acid During Tableting

Purpose

The molecular basis of crystal surface adhesion leading to sticking was investigated by exploring the correlation of crystal adhesion to oxidized iron coated atomic force microscope (AFM) tips and bulk powder sticking behavior during tableting of two morphologically different crystals of a model drug, mefenamic acid (MA), to differences in their surface functional group orientation and energy.

Methods

MA was recrystallized into two morphologies (plates and needles) of the same crystalline form. Crystal adhesion to oxidized iron coated AFM tips and bulk powder sticking to tablet punches was assessed using a direct compression formulation. Surface functional group orientation and energies on crystal faces were modeled using Accelrys Material Studio software.

Results

Needle-shaped morphology showed higher sticking tendency than plates despite similar particle size. This correlated with higher crystal surface adhesion of needle-shaped morphology to oxidized iron coated AFM probe tips, and greater surface energy and exposure of polar functional groups.

Conclusions

Higher surface exposure of polar functional groups correlates with higher tendency to stick to metal surfaces and AFM tips, indicating involvement of specific polar interactions in the adhesion behavior. In addition, an AFM method is identified to prospectively assess the risk of sticking during the early stages of drug development.     

Quality by design development of brivanib alaninate tablets: Degradant and moisture control strategy

A quality by design approach was applied to the development of brivanib alaninate tablets. Brivanib alaninate, an ester pro-drug, undergoes hydrolysis to its parent compound, BMS-540215. The shelf-life of the tablets is determined by the rate of the hydrolysis reaction. Hydrolysis kinetics in the tablets was studied to understand its dependence on temperature and humidity. The BMS-540215 amount versus time profile was simulated using a kinetic model for the formation of BMS-540215 as function of relative humidity in the environment and a sorption–desorptiom moisture transfer model for the relative humidity inside the package. The combined model was used to study the effect of initial tablet water content on the rate of degradation and to identify a limit for initial tablet water content that results in acceptable level of the degradant at the end of shelf-life. A strategy was established for the moisture and degradant control in the tablet based on the understanding of its stability behavior and mathematical models. The control strategy includes a specification limit on the tablet water content and manufacturing process controls that achieve this limit at the time of tablet release testing.     

The surgical and orthodontic management of cherubism in a growing child

Cherubism is a rare non-neoplastic disease that affects the jaws causing significant destruction and disfigurement. The disease also affects the normal eruption, occlusion and function of the dento-alveolar complex. Cherubism may radiographically and histologically resemble central giant cell granuloma, fibrous dysplasia and other giant cell lesions. The case of a 15-year 4-month-old girl with no obvious facial swelling or signs of cherubism is described in this report. The patient presented with a dental malocclusion that included the ectopic eruption and displacement of teeth caused by the lesion. The radiographic findings derived from Cone Beam Computed Tomography (CBCT) technology are described. This case report details the orthodontic and surgical diagnosis and management of a teenager during the post growth period.     

Meta-analysis of the association between progression-free survival and overall survival in metastatic colorectal cancer

Purpose  

The validity of progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in metastatic colorectal cancer (mCRC) trials has been studied, primarily in first-line treatment. The relationship between PFS and OS has not been well studied in later lines of treatment.     

Extraosseous plasmacytoma with an aggressive course occurring solely in the CNS

Extraosseous (extramedullary) plasmacytoma is a relatively indolent neoplasm that constitutes 3–5% of all plasma cell neoplasms. Rare cases have been reported to truly occur in the CNS and not as an extension from a nasal lesion. EBV expression in plasma cell neoplasms has been reported in very few cases that are mainly post‐transplant or occurring in severely immunosuppressed patients. We report a case of extraosseous plasmacytoma with an aggressive course in an HIV‐positive individual that occurred solely in the CNS, showing EBV expression by in situ hybridization, and presenting as an intraparenchymal mass as well as in the CSF.