Treatment of palmar-plantar erythrodysesthesia (PPE) with topical sildenafil: a pilot study.

PURPOSE: Palmar-plantar erythrodysesthesia (PPE) is a common chemotherapy and anti-VEGF multi-kinase inhibitor class-related toxicity that often results in debilitating skin changes and often limits the use of active anti-cancer regimens. Mechanistic and anecdotal clinical evidence suggested that topical application of sildenafil cream may help reduce the severity of PPE. Therefore, we conducted a randomized, double-blind, placebo-controlled pilot study to evaluate the feasibility, safety and efficacy of topical sildenafil cream for the treatment of PPE. METHODS: Eligible subjects were required to have grade 1-3 PPE associated with either capecitabine or sunitinib. Subjects were randomized to receive 1 % topical sildenafil cream to the left extremities or right extremities and placebo cream on the opposite extremity. Two times per day, 0.5 mL of cream was applied to each affected hand/foot. The primary endpoint was improvement in PPE grading at any point on study. Clinical assessments were evaluated by NCI-CTC 4.0 grading and patient self-reported pain. RESULTS: Ten subjects were enrolled, nine were evaluable for safety and efficacy. Five of nine subjects reported some improvement in foot pain and three of eight subjects for hand pain improvement. One of these subjects noted specific improvement in tactile function. No treatment-related toxicities were observed. CONCLUSIONS: In this limited, single-center study, topical cream containing 1 % sildenafil is feasible to administer, is well-tolerated, and may mitigate PPE-related symptoms due to anti-cancer therapeutic agents. Further validation is necessary.

Quality-control analytical methods: aqua pura: water purification systems and United States pharmacopeia waters for the compounding pharmacy, part 1.

The types of water used most often in a compounding pharmacy are potable water, purified water, and sterile water (water for injection or irrigation). Of those three types, purified water is most frequently used; it is essential as a clean glassware rinse and is used in the compounding and reconstitution of frequently prescribed no sterile compounds, such as antibiotic suspensions. Using the appropriate water is absolutely essential to good compounding practice. Purified water cannot be substituted for sterile water for irrigation or injection, and if the last step in washing glassware and pharmaceutical implements is not a thorough purified-water rinse, the cross-contamination of preparations with drugs or chemicals (the presence of which can be missed even during potency testing) can occur. In this first of a series of three articles, we briefly review the types of United States Pharmacopeia water used most frequently in compounding, discuss the basic types of water purification systems that can be used in a compounding, discuss the basic types of water purification systems that can be used in a compounding pharmacy, and answer questions about water purification systems that are of interest to compounding pharmacists. Part 2 will provide current information from the United States Pharmacopeia about various waters, and part 3 will present testimonials from compounders who are using an in-house water purification system and additional information about water purification systems from manufacturers or vendors of that equipment (a Table comparing various water purification systems will be included for easy reference).

Automated endotoxin testing program for high-risk-level compounded sterile preparations at an institutional compounding pharmacy.

PURPOSE: An endotoxin testing program for high-risk-level compounded sterile preparations (CSPs) was verified for compliance with finished-preparation release test requirements of United States Pharmacopeia chapter 797 and implemented at an institutional compounding pharmacy. SUMMARY: An efficient bacterial endotoxins test (BET) was sought for finished-preparation testing of high-risk-level CSPs prepared in batches of > or =25 units. An automated photometric BET was selected that utilized dried, pre-calibrated Limulus amebocyte lysate cartridges rather than liquid reagents and standards. Endotoxin testing began after verifying test conditions for each CSP and approving a standard procedure for training BET analysts and maintaining uniform methodology. A pharmacopeial endotoxin limit and limit dilution were determined for each CSP. The majority of CSPs included patient-controlled analgesia solutions, epidural analgesia solutions, and cardioplegia solutions. BET conditions were verified by measuring the recovery of endotoxin positive controls in sterile water dilutions for each CSP. Cardioplegia solutions met an endotoxin limit of 0.5 EU/mL, and epidural bags had an intrathecal endotoxin limit of 0.05 EU/mL. All other CSPs had detection limits well within compendial requirements. All test results collected during the first year of implementation were pyrogen free, which provided compelling evidence of appropriate application of aseptic technique, appropriate selection of equipment and methods, and the nonpyrogenic quality of powders used in compounding at the pharmacy. CONCLUSION: A photometric endotoxins test that met all requirements of the BET was verified and implemented for high-risk-level CSPs prepared in an institutional pharmacy.

Contract sterilization and validation companies offer new options for sterile compounded preparations.

To ensure patient safety, adhere to good compounding practices, and safeguard against professional liability, the sterility of some compounded preparations must be assured. When in-house sterilization capabilities do not suffice, the intervention of a contract sterilization and/or validation company can assist in establishing the sterility, purity, and potency of the pharmaceuticals used in compounded preparations. In this article, three contract steriliziation companies and two contract validation firms are profiled, methods that compounders can use to best interface with those companies are presented, and sterilization and validation processes are explained and compared.

Microbial air-sampling equipment, part 2: experiences of compounding pharmacists.

The most recent changes to Chapter 797 of the United States Pharmacopeia-National Formulary initiated an intense controversy about the frequency of cleanroom air sampling that is required to prevent the contamination of sterile preparations. For compounders who must purchase an air sampler to use in the cleanroom, choices abound. This article summarizes discussions from compounding pharmacists and their experiences with air sampling devices.

APS position statement on the use of placebos in pain management.

In the spring of 2003, the board of directors of the American Pain Society asked the APS Ethics Committee to formulate a position statement for the Society concerning the use of placebos in clinical practice (cf, reference ). A subset of the Ethics Committee under my direction composed such a statement based on the available scientific and ethical literature. We then sought feedback from the entire ethics committee as well as numerous prominent voices in the literature and presented the statement to the membership for discussion at the 2004 annual APS meeting in Vancouver, British Columbia, at both a symposium and an ethics special interest group meeting. The resultant document was approved by the APS Board and is published here for widespread distribution to the membership.

Meperidine: a critical review.

Meperidine was initially synthesized as an anticholinergic agent but was soon discovered to have analgesic properties. Although meperidine's anticholinergic effects were demonstrated in vivo, the anticholinergic effects on the biliary and renal tracts have not been demonstrated in vivo. Studies have clearly demonstrated that meperidine is no more efficacious in treating biliary or renal tract spasm than comparative mu opioids. The initial studies demonstrating the analgesic efficacy of meperidine were mostly case reports and not double-blind, randomized, controlled trials in specific populations. Subsequent comparative studies failed to demonstrate any advantages of meperidine over comparable doses of other analgesics. Meperidine was portrayed in practice and teaching as having unique clinical advantages. The analgesic effects of meperidine are not pronounced, and, in addition, meperidine use is complicated by unique side effects including serotonergic crisis and normeperidine toxicity. Meperidine's poor efficacy, toxicity, and multiple drug interactions have resulted in a movement to replace meperidine with more efficacious and less toxic opioid analgesics.

Extemporaneous compounding of pain and symptom control medications.

This paper introduces a new series in the Journal on extemporaneously compounded dosage forms for symptom control. Some advantages and limitations of compounded medications are described and issues that clinicians should consider are mentioned. Topics that will be discussed in future papers in this series are described. Changes of compounding-related chapters of the United States Pharmacopeia from advisory statements to enforceable standards are discussed. As an example of important formulation considerations, some physical-chemical characteristics and route of administration characteristics of opioid analgesics are discussed.