Shortened interval between tetanus vaccines.

OBJECTIVE: To identify the minimum safe interval between tetanus-diphtheria (Td) and tetanus-diphtheria-acellular pertussis (Tdap) vaccines. DATA SOURCES: Literature was retrieved through a review of ImmunoFacts, the Centers for Disease Control and Prevention (CDC) Web site, MEDLINE (1966-February 2012) and International Pharmaceutical Abstracts (1970-February 2012) using the terms Tdap, Td, and interval. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. Studies addressing an interval of 2 years or less between Td and Tdap vaccines were included. DATA SYNTHESIS: Two observational noninferiority studies have evaluated the safety of an interval of 2 years or less. The first involved a school-based immunization program to compare the safety of a single dose of Tdap given 18 months to 9 years after a tetanus and diphtheria toxoid-containing vaccine versus an interval of 10 or more years. Injection site erythema and swelling were increased among participants with shortened intervals between vaccines; however, no serious adverse events, entire limb swelling, or Arthus-like reactions were reported. The second study involved health care workers who received Tdap during a pertussis outbreak with the objective to compare safety of intervals less than 2 years between prior tetanus vaccination and Tdap with intervals 2 years or more. Criteria for noninferiority were met overall between the 2 intervals in terms of moderate and severe injection site reactions. Fever was more common with the shortened interval, as was any redness or any swelling. No serious adverse events were reported among the group with an interval of less than 2 years between vaccine administration. CONCLUSIONS: Although well-designed randomized controlled trials are lacking, the current observational evidence and CDC provisional recommendations support a shortened interval between Td and Tdap vaccines to protect health care workers from pertussis. Intervals less than 2 years may be associated with an increased incidence of local injection site reactions.

Principles of conservative prescribing.

Judicious prescribing is a prerequisite for safe and appropriate medication use. Based on evidence and lessons from recent studies demonstrating problems with widely prescribed medications, we offer a series of principles as a prescription for more cautious and conservative prescribing. These principles urge clinicians to (1) think beyond drugs (consider nondrug therapy, treatable underlying causes, and prevention); (2) practice more strategic prescribing (defer nonurgent drug treatment; avoid unwarranted drug switching; be circumspect about unproven drug uses; and start treatment with only 1 new drug at a time); (3) maintain heightened vigilance regarding adverse effects (suspect drug reactions; be aware of withdrawal syndromes; and educate patients to anticipate reactions); (4) exercise caution and skepticism regarding new drugs (seek out unbiased information; wait until drugs have sufficient time on the market; be skeptical about surrogate rather than true clinical outcomes; avoid stretching indications; avoid seduction by elegant molecular pharmacology; beware of selective drug trial reporting); (5) work with patients for a shared agenda (do not automatically accede to drug requests; consider nonadherence before adding drugs to regimen; avoid restarting previously unsuccessful drug treatment; discontinue treatment with unneeded medications; and respect patients' reservations about drugs); and (6) consider long-term, broader impacts (weigh long-term outcomes, and recognize that improved systems may outweigh marginal benefits of new drugs).

Efficacy of agents to prevent and treat enteral feeding tube clogs.

OBJECTIVE: To review the efficacy and safety of agents used to prevent and treat clog formation in enteral feeding tubes. DATA SOURCES: A literature search was conducted through MEDLINE (1948-February 2011) and International Pharmaceutical Abstracts (1970-February 2011) using the search terms enteral feeding tube and occlusion. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language publications were reviewed for applicability. DATA SYNTHESIS: Occlusion is a common complication of enteral tube feeding. With Food and Drug Administration regulations, pancreatic enzymes have recently been reformulated and previously published reports can no longer be applied to currently available agents. This has led to concern over what available products have been shown to be efficacious. Three in vitro studies, 1 randomized in vivo trial, and 1 descriptive report were reviewed. In the prevention of tube clogging, it was concluded that water was comparable in efficacy, while being more readily available and cost effective, when compared to Coca-Cola, and both were superior to cranberry juice. For resolution of an existing clog, evidence of the efficacy of any individual agents is limited and has not been reproducible. New formulations of pancreatic enzymes, a new delivery system for enzymes, and products to mechanically dismantle clogs have become commercially available, but no studies have been completed to evaluate safety and efficacy. Comparative in vivo studies of currently available products are needed to evaluate possible methods for resolving an occlusion. CONCLUSIONS: Water flushes have shown to be the most effective method in preventing enteral feeding tube clogging. Well-designed trials are needed to establish the proper place in therapy of new commercially available agents marketed for resolving clogs. In addition, well-designed in vivo trials are needed to establish the role, dosage, and extemporaneous formulation of extended-release pancreatic enzymes in treating such clogs.

Romiplostim management of immune thrombocytopenic purpura.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of romiplostim, the first drug approved for use in patients with immune thrombocytopenic purpura (ITP). DATA SOURCES: Articles were identified through searches of MEDLINE (1966-January 2009) and International Pharmaceutical Abstracts (1970-January 2009) using the key words romiplostim and AMG 531. Searches were limited to articles published in English. The manufacturer was contacted for additional data. STUDY SELECTION AND DATA EXTRACTION: Clinical trials and pharmacokinetic data were selected for review. DATA SYNTHESIS: Romiplostim is a second-generation thrombopoietic receptor agonist that exerts its therapeutic effect by stimulating megakaryopoiesis. Subcutaneous therapy results in a dose-dependent increase in platelets; however, interindividual variability exists. Time to peak concentration is approximately 14 hours, and the elimination half-life is approximately 3.5 days (range 1-34). Romiplostim undergoes endothelial recirculation and is eliminated by the reticuloendothelial system. The results of 2 Phase 3, randomized, double-blind, placebo-controlled trials have demonstrated the efficacy of romiplostim for increasing platelet counts in patients with ITP refractory to other therapies, including splenectomy. Effects on platelets were transient and decreased within 2 weeks of discontinuing the drug. Interim results of an open-label extension study revealed that romiplostim has sustained efficacy and tolerability for up to 156 weeks at a dosage range of 1-17 microg/kg/wk (mean 5.9 +/- 3.9). The most common adverse effects include headache, fatigue, epistaxis, and contusion. Romiplostim is also under investigation for treatment of thrombocytopenia associated with myelodysplastic syndrome. The drug must be ordered directly from the manufacturer through a limited access program, and weekly subcutaneous injections are given in the clinic setting. CONCLUSIONS: Romiplostim is effective for the management of ITP in adults refractory to other therapies, including splenectomy.

Bisphosphonate-induced osteonecrosis of the jaw.

OBJECTIVE: To review the risk of osteonecrosis of the jaw associated with bisphosphonates. DATA SOURCES: A MEDLINE search (1966-January 2007) and a search of International Pharmaceutical Abstracts (1970-January 2007) were conducted to identify relevant literature. Additional references were reviewed from selected articles. STUDY SELECTION AND DATA EXTRACTION: Articles related to bisphosphonate-induced osteonecrosis of the jaw were reviewed and summarized. Inclusion criteria required that articles be either case studies or case series that were reporting actual cases linking osteonecrosis of the jaw with bisphosphonate use. Articles that addressed sites of osteonecrosis not involving the jaw, teaching cases (fictitious patients), and a retrospective claims analysis paper were excluded from consideration. DATA SYNTHESIS: Bisphosphonates have recently been linked to osteonecrosis of the jaw, with the greatest incidence seen with the intravenous preparations zoledronic acid and pamidronate. Osteonecrosis refers to death of a part of the bone, resulting in decreased bone density. Although the majority of occurrences have been associated with the intravenous bisphosphonates, oral bisphosphonates have also been implicated. Other risk factors noted from reported cases include dental extraction or trauma to the jaw exposing part of the bone. It is difficult to determine an exact incidence of osteonecrosis of the jaw in the general population of patients prescribed bisphosphonates; however, the incidence in cancer patients is approximately 6-7%. CONCLUSIONS: Although discontinuation of intravenous bisphosphonates in cancer patients has been recommended, stopping oral bisphosphonates prior to dental work cannot be universally endorsed at this time, since it is unknown whether this is effective in reducing the risk of osteonecrosis of the jaw. Treatment of this condition is not well established; therefore, efforts should be directed toward prevention. Pharmacists may further counsel patients to practice good oral hygiene and regularly follow up with their dentist during therapy. Current evidence suggests limited surgical debridement with systemic and local antibiotics as treatments.

Interaction between warfarin and cranberry juice.

Warfarin is extensively used for anticoagulation to a target international normalized ratio of 2.0-3.0 for most indications or 2.5-3.5 for high-risk indications; however, many drugs and dietary supplements induce fluctuations in the international normalized ratio. Such fluctuations may lead to therapeutic failure or bleeding complications. Cranberry juice is increasingly used for the prevention and adjunctive treatment of urinary tract infections. The United Kingdom's Committee on Safety of Medicines has alerted clinicians to a potential interaction between warfarin and cranberry juice and has advised that patients avoid their concurrent use. Review and analysis of the literature revealed that ingestion of large volumes of cranberry juice destabilize warfarin therapy. Small amounts of juice are not expected to cause such an interaction. Clinicians should be aware of this potential interaction and monitor and counsel patients accordingly.

Use of failure mode and effects analysis in improving the safety of i.v. drug administration.

PURPOSE: Failure mode and effects analysis (FMEA) was used to identify dosing and administration errors associated with i.v. medications and evaluate the effectiveness of subsequent system improvements. SUMMARY: A multidisciplinary medication safety team conducted an FMEA to identify and reduce common medication errors and selected wrong-dose errors for process improvement. In 2002, wrong-dose errors comprised 17% of all medication errors at the hospital (59 of 347 errors). The most common reason for administering the wrong dose was error in programming the i.v. infusion pump (41%). Potential errors (i.e., failures) identified were misinterpretation of the order, removing the wrong medication or wrong concentration of the correct medication, using the wrong diluent or drug to prepare the drip, and entering the wrong concentration or infusion rate on the pump. Errors in programming the i.v. infusion pump was the step in the medication-use process associated with the highest criticality index. Based on the results of the FMEA, two main interventions were performed. First, standard order sets were revised after streamlining the formulary and eliminating the use of unapproved abbreviations. Second, an i.v. pump with enhanced safety features was implemented. One-year follow-up data revealed that the number of medication errors related to dosing (wrong dose or incorrect infusion rate) had decreased slightly (from 59 in 2002 to 46 in 2003); however, a dramatic reduction was noted in the percentage of pump-related errors. In 2003, pump-related errors accounted for 22% of dosing errors, compared with 41% in 2002. CONCLUSION: Medication errors related to i.v. infusion pumps were reduced by conducting an FMEA and implementing the process changes needed.

High- versus low-dose oxytocin for augmentation or induction of labor.

OBJECTIVE: To compare the use of high- and low-dose oxytocin for augmentation or induction of labor. DATA SOURCES: Clinical trials were accessed through MEDLINE (1966-November 2003). Published literature relevant to the use of oxytocin for augmentation or induction of labor was evaluated. STUDY SELECTION AND DATA EXTRACTION: Articles identified from the data sources were evaluated and included if they were clinical trials comparing high-versus low-dose oxytocin for augmentation or induction of labor. DATA SYNTHESIS: Oxytocin is a treatment of choice for augmentation and induction of labor; however, no consensus exists regarding optimal dosing. Relevant studies comparing high-dose (2-6 mU/min) and low-dose (1-2 mU/min) therapy for labor augmentation and induction were evaluated. CONCLUSIONS: High-dose oxytocin decreases the time from admission to vaginal delivery, but does not appear to decrease the incidence of cesarean sections when compared with low-dose therapy.