Apremilast in the Management of Disseminated Granuloma Annulare.

Granuloma annulare (GA) is a common inflammatory skin condition that manifests as annular skin colored to erythematous papules and plaques. Disseminated GA is a subtype of GA that presents with diffuse cutaneous involvement. While topical and intralesional corticosteroids and phototherapy have been used as therapies for GA, there is no consensus on the best course of treatment for GA. Apremilast is a phosphodiesterase 4 (PDE4) inhibitor that has been Food and Drug Administration (FDA) approved for psoriasis, psoriatic arthritis, and oral ulcers associated with Behcet's disease; apremilast has also shown promise off-label for other inflammatory skin conditions. Here, we present the case of a woman in whom apremilast use led to an almost complete resolution of her disseminated GA. Our patient tolerated apremilast well and reported no side effects. We also review the literature on the use of apremilast in other patients with GA.

[Situation analysis of off-label drug use in China].

To introduce current literature reporting situations of the off-label drug use(OLDU) by analyzing relevant literatures published in China, this study comprehensively focused on literatures about OLDU in China in seven Chinese and English databases, then extracted and analyzed the data by different literature types. A total of 667 papers were analyzed. The number of literatures about OLDU data analyzed in hospitals was 325, and the number of clinical studies relating to OLDU was 329, in which case series and case reports were the majority(69.91%). In addition, there were 13 expert consensuses of OLDU and another 56 studies about drug use based on the real-world data characteristics and influencing factors. The number of OLDU data studies has increased year by year. Based on the existing studies, there were more western medicine reports than traditional Chinese medicines, and OLDU types were mainly for over-dosage use. The literatures from OLDU data in hospital were mostly limited to one or several tertiary hospitals in a certain area, and the OLDU types were not uniform. Clinical studies were mainly clinical control trials and case series/reports, but with contradictory reporting results. There were fewer OLDU consensus, and the recommended classification was not uniform. The characteristics and analysis of influencing factors of drug using data in real-world focused on traditional Chinese medicine injections, and the results were not the same. In the future, we shall pay more attention to and strengthen reporting and analysis of OLDU, define study objectives, and unify the content and reporting standards, so as to promote the integrated utilization of OLDU data and reflect real situations in our country.

Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals.

BACKGROUND: A previous analysis of 113 National Comprehensive Cancer Network® (NCCN®) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak. METHODS: In order to determine the strength of the evidence, we carried out an in-depth re-analysis of the 44 off-label recommendations listed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). RESULTS: Of the 44 off-label recommendations, 14 were later approved by the FDA and/or are supported by randomized controlled trial (RCT) data. In addition, 13 recommendations were either very minor extrapolations from the FDA label (n = 8) or were actually on-label (n = 5). Of the 17 remaining extrapolations, 8 were for mechanism-based agents applied in rare cancers or subsets with few available treatment options (median response rate = 43%), 7 were based on non-RCT data showing significant efficacy (>50% response rates), and 2 were later removed from the NCCN Guidelines because newer therapies with better activity and/or safety became available. CONCLUSION: Off-label drug use is a frequent component of care for patients with cancer in the United States. Our findings indicate that when the NCCN recommends beyond the FDA-approved indications, the strength of the evidence supporting such recommendations is robust, with a significant subset of these drugs later becoming FDA approved or supported by RCT. Recommendations without RCT data are often for mechanism-based drugs with high response rates in rare cancers or subsets without effective therapies.

Case report of high-dose hydroxocobalamin in the treatment of vasoplegic syndrome during liver transplantation.

A 66-year-old man with cryptogenic cirrhosis secondary to nonalcoholic steatohepatitis presented for orthotopic liver transplantation. Following organ reperfusion, the patient developed vasoplegic syndrome, with arterial blood pressures of approximately 60-70/30-40 mm Hg (mean arterial pressure [MAP] <45 mm Hg) for >90 minutes. He required high-dose norepinephrine and vasopressin infusions, as well as i.v. bolus doses of norepinephrine and vasopressin to reach a goal MAP> 60 mm Hg. There was minimal response to a 2 mg/kg i.v. bolus of methylene blue. Following the administration of 5 g of i.v.hydroxocobalamin, the patient had a profound improvement in arterial blood pressure, with subsequent discontinuation of the vasopressin infusion and rapid reduction of norepinephrine infusion from 20 to 2 µg/min. While there have been several reports of the efficacy of hydroxocobalamin for vasoplegia after cardiopulmonary bypass, there have been only limited cases of hydroxocobalamin used in liver transplantation, and none with high-dose administration. We present a case of vasoplegic syndrome during liver transplantation that was refractory to high-dose vasopressors and methylene blue but responsive to high-dose i.v. hydroxocobalamin.

Investigation of Off-label Drug Use of Pregnant and Parturient Women in Obstetrics Ward / 医药导报

Objective To investigate the off-label use status in obstetrics ward so as to provide references for carrying out obstetrics pharmaceutical care and promoting safe medication use in pregnant and parturient women. Methods The prescriptions for pregnant and parturient women from January to June, 2015 in obstetrics ward were investigated. According to drug instructions, the off-label drug use of prescriptions of all selected patients was analyzed in the following aspects:the category of off-label drug use, and drugs use information. In addition, a logistic regression was conducted that modeled the odds of receiving an off-label prescription as a function of the following possible risk factors:pregnant, parturient women and the rank of doctors. The clinical results including the unreasonable drug application, abortion rate and birth defect were compared between the off-label drug use and on-label drug use groups. Results Total of 384 patients were selected, and 5330 prescriptions involving 50 drugs were analyzed. The rate of off-label drug use was 68. 5%, 27. 7% and 24. 0% in patients, prescriptions and drug categories, respectively. The main categories of off-label drug use were super solvent use ( 76. 6%) and indication (14. 3%). The top 3 drugs of off-label use were those for urinary and reproductive (56. 2%), alimentary tract (46. 9%) and traditional Chinese medicine (43. 4%). In addition, there was no significant correlation between the risk of off-label drug use and maternal status and the level of doctors. And no significant difference between the two groups in the unreasonable drug application, abortion rate and birth defect was detected. Conclusion The off-label drug use in obstetrics ward is common in this hospital and most of them are supported by clinical evidence. Due to the lack of more authoritative evidence-based medication, the doctors are suggested to use the drug according to provisions of the drug instructions. When off-label drug use is really needed, it should be based on the surpport of evidence basde medicine,so as to ensure the drug safety for pregnant and parturient women and avoid professional risks.

Improving Good Practice: A Survey of Unlicensed and Off-Label Drug Use in a General Hospital in China.

BACKGROUND: Off-label and unlicensed drug use is common in Europe and the US; however, information about this issue in China is limited. OBJECTIVE: To determine the scope and scale of off-label and unlicensed drug use in general hospitals in Shanghai, China, and to evaluate the varying levels of supporting evidence. METHODS: A total of 493 cases of discharge history were randomly sampled. Off-label uses were defined according to package inserts, the China Pharmacopeia Clinical Medication Notice (2010), and New Pharmacology (16th edition). All drugs administered were assessed to determine whether their use was unlicensed and off-label. RESULTS: There were 459 cases (93.10%) of off-label drug use, and 47.64% of total therapeutic drugs prescribed were off-label. Of these cases, 8.72% of patients received 1 off-label drug, and 9.94% of patients received 2 off-label drugs. Use of multiple off-label medications per patient was also common, and the percentage of patients receiving 3, 4, 5, 6, 7, 8, 9, and ≥10 medications was 9.74%, 9.74%, 8.72%, 7.91%, 12.58%, 7.10%, 5.88%, and 12.78%, respectively. Categories of off-label drugs used most frequently were vitamins, cardiovascular drugs, and gastroenteric drugs. The most common off-label use was that the indication for which a drug was prescribed was not approved (83.49%); other off-label uses involved disregard for contraindications and drug incompatibility (6.37%), dose exceeding approved amount (4.76%), unapproved route of administration (4.65%), and unapproved dosing intervals (0.73%). Vitamins and nutritional supplements are the drugs most frequently prescribed off-label, while off-label use of vasodilators, lipid-lowering drugs, and adjuvant therapy medications for cardiovascular and cerebrovascular conditions is also common. CONCLUSION: Unlicensed and off-label prescribing of drugs may be common in China.