Journal of Clinical Pharmacy and Therapeutics (J Clin Pharm Therapeut)

Publications in this journal

• Article: Efficacy and safety of short-term administration of recombinant human atrial natriuretic peptide (rhANP) for congestive heart failure: a phase II, multicentre randomized controlled dose-finding study.

  P Wang, X Luan, G Wang, W Liu, J Zhang, W Li, X Gao, Y Wang, Y Mao, X Sun, Q Wang, Y Zhang, S Bai
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Although the long-term infusion of ANP has proved effective to treat heart failure, no published randomized controlled study has been reported to confirm the efficacy of the short-term ANP infusion in congestive heart failure (CHF) patients. This study was designed to assess the efficacy and safety of short-term infusion of recombinant human atrial natriuretic peptide (rhANP) in CHF patients. METHODS: A total of 48 patients with CHF were enrolled and randomized into four groups, treated with standard therapy or rhANP (0·05, 0·1 or 0·2 μg/kg/min) for 1-hour infusion in addition to standard therapy. The hemodynamics were assessed for 12 h by Swan-Ganz catheter. RESULTS AND DISCUSSION: The effect of the 0·05 μg/kg/min rhANP dose group on CO was modest and transient. The 0·2 μg/kg/min rhANP dose group tended to be associated with better effect on SV, CO and dyspnoea improvement, but modest effect on PCWP and more adverse events probably attributed to the study drug. However, the 0·1 μg/kg/min rhANP infusion was well tolerated and effective both on PCWP decrease (maximum:-9·46 ± 5·81 mmHg compared with baseline (P = 0·0002) and -6·75 mmHg compared with standard therapy, the 95% confidential interval [-13·43, -0·06 mmHg] at 1 h) and CO increase (maximum: 1·02 ± 1·43 L/min [P = 0·0308] at 1 h). WHAT IS NEW AND CONCLUSION: In this small-sample study, 1-hour infusion of rhANP produced beneficial hemodynamic effects in CHF patients compared with standard therapy, and it was well tolerated. 0·1 μg/kg/min may be the optimum dose for short-term rhANP infusion to treat CHF for the further large sample trial before clinical application.
  Journal of Clinical Pharmacy and Therapeutics 05/2013;
• Article: Fatal hypersensitivity reaction to an oral spray of flurbiprofen: a case report.

  G Calapai, S Imbesi, V Cafeo, E Ventura Spagnolo, P L Minciullo, A P Caputi, S Gangemi, L Milone
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Safety of the anti-inflammatory drug flurbiprofen is comparable with that of other non-steroidal anti-inflammatory drugs of the propionic acid class, which are commonly associated with gastrointestinal and renal side effects. Here we report a case of a fatal hypersensitivity reaction to an oral spray of flurbiprofen taken for sore throat. CASE SUMMARY: A 29-year-old man came to the emergency care unit reporting sore throat with an intense burning sensation associated with fever. Pharyngotonsillitis was diagnosed, and local treatment with oral flurbiprofen spray was prescribed. Immediately after using the spray, the patient experienced a severe reaction characterized by serious dyspnoea, followed by death. The cause of death was heart failure with acute asphyxia from oedema of the glottis. The cause of death was concluded to be hypersensitivity to flurbiprofen spray. WHAT IS NEW AND CONCLUSION: Oral propionic acid derivatives have been associated with a relatively high frequency of allergic reactions. However, allergy to flurbiprofen has rarely been documented. Scientific literature reports two relevant cases of hypersensitivity reaction to flurbiprofen: in one case, a patient presented with a maculopapular rash 48 h after having taken oral flurbiprofen followed by angio-oedema and hypotension. In another case, a single oral dose of flurbiprofen caused itching and swelling around the eyes, redness and increased lacrimation. We describe, for the first time, a fatal case of hypersensitivity reaction to flurbiprofen oral spray. Hypersensitivity reactions to flurbiprofen are infrequent; however, health professionals should be aware of potential adverse reactions, even during topical administration as oral spray.
  Journal of Clinical Pharmacy and Therapeutics 05/2013;
• Article: Cancer 'survivor-care': II. Disruption of prefrontal brain activation top-down control of working memory capacity as possible mechanism for chemo-fog/brain (chemotherapy-associated cognitive impairment).

  R B Raffa
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Cancer chemotherapy-associated cognitive impairments (termed 'chemo-fog' or 'chemo-brain'), particularly in memory, have been self-reported or identified in cancer survivors previously treated with chemotherapy. Although a variety of deficits have been detected, a consistent theme is a detriment in visuospatial working memory. The parietal cortex, a major site of storage of such memory, is implicated in chemotherapy-induced damage. However, if the findings of two recent publications are combined, the (pre)frontal cortex might be an equally viable target. Two recent studies, one postulating a mechanism for 'top-down control' of working memory capacity and another visualizing chemotherapy-induced alterations in brain activation during working memory processing, are reviewed and integrated. COMMENT: A computational model and the proposal that the prefrontal cortex plays a role in working memory via top-down control of parietal working memory capacity is consistent with a recent demonstration of decreased frontal hyperactivation following chemotherapy. WHAT IS NEW AND CONCLUSION: Chemotherapy-associated impairment of visuospatial working memory might include the (pre)frontal cortex in addition to the parietal cortex. This provides new opportunity for basic science and clinical investigation.
  Journal of Clinical Pharmacy and Therapeutics 05/2013;
• Article: Preventing hospital admissions by reviewing medication (PHARM) in primary care: an open controlled study in an elderly population.

  A J Leendertse, G H P de Koning, A N Goudswaard, S V Belitser, M Verhoef, H J de Gier, A C G Egberts, P M L A van den Bemt
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Limited and conflicting evidence exists on the effect of a multicomponent pharmaceutical care intervention (i.e. medication review, involving collaboration between general practitioners (GPs), pharmacists and patients) on medication-related hospitalizations, survival, adverse drug events (ADEs) and quality of life. We aimed to investigate the effect of a multicomponent pharmaceutical care intervention on these outcomes. METHODS: An open controlled multicentre study was conducted within primary care settings. Patients with a high risk on medication-related hospitalizations based on old age, use of five or more medicines, non-adherence and type of medication used were included. The intervention consisted of a patient interview, a review of the pharmacotherapy and the execution and follow-up evaluation of a pharmaceutical care plan. The patient's own pharmacist and GP carried out the intervention. The control group received usual care and was cared for by a GP other than the intervention GP. The primary outcome of the study was the frequency of hospital admissions related to medication within the study period of 12 months for each patient. Secondary outcomes were survival, quality of life and ADEs. RESULTS AND DISCUSSION: 364 intervention and 310 control patients were included. Less medication-related hospital admissions were found in the intervention group (n = 6; 1·6%) than in the control group (n = 10; 3·2%) but the overall effect was not statistically significant (hazard ratio (HR) 0·50, 95% confidence interval (CI) 0·12-1·59). The secondary outcomes were not statistically significantly different either. The study was underpowered, which may explain the negative results. A post hoc analysis showed that the effect of the intervention was statistically significant for patients with five diseases or more: five diseases, HR 0·28 (95% bootstrap CI: 0·056-0·73) and eight diseases, HR 0·11 (95% CI: 0·013-0·34). WHAT IS NEW AND CONCLUSION: A multicomponent pharmaceutical care intervention does not prevent medication-related hospital admissions. Whether this is true for such interventions in general is unknown, because the PHARM study was underpowered. The intervention may significantly reduce medication-related hospitalizations in patients with five or more comorbidities, but this is only based on a post hoc analysis and thus needs confirmation in large controlled trials.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: International standards for health economic evaluation with a focus on the German approach.

  R Riedel, U Repschläger, R Griebenow, S Breitkopf, S Schmidt, A Guhl
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Health economic evaluation (HEE) is increasingly used in healthcare decision-making on the allocation of limited resources in national healthcare systems. Although the methods used for HEE vary in different countries, all economic evaluations address two questions: Are limited resources used optimally? Is value for money achieved in their use? Our objective is to explain some fundamental concepts in HEE and how these concepts are adapted in different countries, notably in Germany. METHODS: We performed a bibliographic search to identify existing methods of health economic evaluation of new drugs used by the official agencies of 11 countries (Austria, Australia, Canada, Finland, France, the Netherlands, Norway, New Zealand, Sweden, the United States and England and Wales) and compared them with that used by the German national agency IQWiG. RESULTS AND DISCUSSION: All countries considered follow internationally established standards of HEE. The majority of countries, including Germany, utilize primary outcome parameters such as disease-related morbidity and mortality for assessing relative efficacy and effectiveness. The most frequently recommended form of health economic evaluation is the cost-utility analysis (CUA). The German IQWIG is the only HTA body to use the cost-benefit concept of 'efficiency frontier' in its assessment. WHAT IS NEW AND CONCLUSION: While the core principles of HEE are the same worldwide, there is a lack of harmonization in the details. This requires resource-consuming adaptations in the analyses to meet different national requirements. We describe the core principles of HEE as a common basis for further discussions by all stakeholders.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: Therapeutic concerns when oral medications are administered nasogastrically.

  L-L Zhu, Q Zhou
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Administering oral medications to patients with nasogastric tube (NGT) is a challenging patient-care issue. Inappropriate prescribing behaviour and incorrect procedure for extemporaneous preparation of oral suspensions given via NGT may result in significant harm to patients. There are many drugs which have not been tested regarding oral absorption profile and bioavailability derived from NGT dosing. Although several studies and case-reports have been reported, there is no up-to-date review of drug administration via NGT. The aim of this review is to increase awareness of rational drug administration via NGT and to encourage relevant research in this area. METHODS: Full prescribing information from each currently available oral medication was reviewed for any data indicating that the medication could not be crushed or opened. Literature was identified by searching PubMed (1988 to Aug 2012). RESULTS AND DISCUSSION: There is evidence to show that NGT dosing of some medications may bring both benefits (e.g. cost saving) and disadvantages (e.g. decrease in efficacy and/or safety). For medications with package inserts that warn that they should not be crushed or opened, alternatives are usually recommended. However, in some cases, there is evidence to support NGT dosing. Sometimes special procedures are required to avoid problems such as instability, interaction with enteral nutrition, adsorption, tube obstruction and low recovery when preparing extemporaneous oral suspensions. WHAT IS NEW AND CONCLUSION: Physicians, pharmacists and nurses should know the procedures for drug administration by NGT, as well as the latest evidence on such administrations. There may not be bioequivalence between oral and nasogastric administrations. Care must be taken to avoid compromising the physicochemical, biopharmaceutical and pharmacological properties of drugs given by NGT to ensure their safety and efficacy.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects.

  A Pathak, M Lebrin, A Vaccaro, J M Senard, F Despas
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Positive inotropic agents are frequently used in acute decompensated heart failure (ADHF) due to left ventricular systolic dysfunction. These agents are known to improve cardiac performance and peripheral perfusion in the short-term treatment. However, several preclinical and clinical studies emphasized detrimental effects of these drugs on myocardial oxygen demand and on sympathetic tone entailing arrhythmogenesis. Levosimendan is an inotropic agent with an original mechanism of action. This review focuses on major data available for levosimendan. METHODS: A literature search was conducted in the PubMed database by including studies published in English using combinations of the following key words, levosimendan, inotropic drugs and acute heart failure. Furthermore, bibliographies of selected references were also evaluated for relevant articles. The collection for this review was limited to the most recently available human and animal data. RESULTS AND DISCUSSION: Levosimendan's vasodilatory and cardioprotective effects are mediated by calcium sensitization of contractile proteins and opening of adenosine triphosphate (ATP)-dependent K+ channels in vascular smooth muscle cells and on mitochondrial ATP-sensitive potassium [mito.K(ATP)] channels. This inotropic agent has mild PDE inhibitory action. Unlike other inotropic agents, levosimendan improves cardiac performance without activating the sympathetic nervous system. Moreover, there are evidences that levosimendan has additional anti-inflammatory and anti-apoptotic properties that prevent cardiac toxicity and contributes to positive hemodynamic response of the drug. Four randomized trials evaluated the effects of levosimendan on mortality in patients with acute decompensated chronic heart failure; nevertheless, a clear benefit has not been demonstrated so far. Although levosimendan is indicated for the treatment of ADHF (class of recommendation IIa, level of evidence B), it is has not been approved in all countries. WHAT IS NEW AND CONCLUSION: This review summarizes the characteristics and the current knowledge of the literature on levosimendan and its active metabolite OR-1896.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: Ceftaroline - a cause for neutropenia.

  R H Rimawi, A Frenkel, P P Cook
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: The US Food and Drug Administration approved ceftaroline in 2010 for the treatment of community-acquired pneumonia and skin and soft-tissue infections. The most common adverse reactions are diarrhoea, nausea and rash. To present the first case of neutropenia directly related to ceftaroline. CASE SUMMARY: A 90-year-old female was given ceftaroline for treatment of a pneumonia complicated by methicillin-resistant Staphylococcus aureus bacteraemia and possible vertebral osteomyelitis. After 25 days of ceftaroline, she developed neutropenia. Ceftaroline was discontinued and her white blood cell count returned to normal within one week. WHAT IS NEW AND CONCLUSION: Although neutropenia is a potential cephalosporin class effect, we present the first case of neutropenia directly related to ceftaroline. Agranulocytosis and neutropenia are rare, yet potentially life-threatening adverse effects of cephalosporins. Healthcare providers should be aware of the potential for ceftaroline to cause neutropenia, particularly in patients treated for greater than two weeks.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: Direct and indirect comparison of the efficacy and safety of adalimumab, etanercept, infliximab and golimumab in psoriatic arthritis.

  S Fénix-Caballero, E J Alegre-Del Rey, R Castaño-Lara, F Puigventós-Latorre, J M Borrero-Rubio, J F López-Vallejo
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Psoriatic arthritis is an autoimmune disease characterized by chronic inflammation of the skin and joints. Anti-TNF drugs reduce the severity of the disease in the long term. This study compares the efficacy and safety of adalimumab, etanercept, infliximab and golimumab in patients with psoriatic arthritis. METHODS: Direct comparison was based on a literature search of drug comparison studies, whereas indirect treatment comparison was based on phase III clinical trials with biological agents, involving similar populations and durations, and with the same outcome. ACR50 was taken as primary outcome for comparison, whereas ACR20 and ACR70 were used as secondary outcomes. Indirect comparisons were made using infliximab as the reference drug and the Bucher method. In calculating δ (the maximum acceptable difference as a clinical criterion of equivalence), use was made of half of the absolute risk reduction obtained in the meta-analysis of the clinical trials included in the indirect comparison (ARR 32%; δ: 16%). The four anti-TNF drugs were also compared in relation to the secondary outcomes and adverse effects. RESULTS AND DISCUSSION: Reported direct and indirect comparisons of the four drugs did not include golimumab, and did not yield conclusive results. Four clinical trials - one for each drug studied - were identified. The estimated differences for the primary outcome, ACR50, between infliximab and the other drugs were adalimumab (ARR 4%, 95% CI -9·5 to 17·5), etanercept (ARR 4%, 95% CI -10·5 to 18·5) and golimumab (ARR 9%, 95% CI -5·4 to 23·4). Likewise, there were no relevant differences between the drugs in relation to the secondary efficacy outcomes, except for etanercept, which was less effective in ACR70 response. For adverse reactions, there were also no significant differences except for injection site, reactions which were more frequent with etanercept, with a mean difference of 26% relative to infliximab. WHAT IS NEW AND CONCLUSION: No significant differences were found in ACR50 responses to the four drugs after 24 weeks. Injection-site reactions were more common with etanercept, but this was insufficient to invalidate the inference that clinically the four drugs can be regarded as clinically equivalent for the treatment of psoriatic arthritis.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: Hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose adefovir dipivoxil: a case report and literature review suggesting ethnic predisposition.

  C Wu, H Zhang, Y Qian, L Wang, X Gu, Z Dai
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Adefovir dipivoxil (ADV) is one of the commonly used antiviral agents in the treatment of chronic hepatitis B (CHB) infection. Safety of a daily dose of 10 mg ADV is advocated by the registration trials. We report a case of severe hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose ADV in a CHB-related cirrhosis patient, and discuss the case through a thorough review of other cases reported in the literature. CASE SUMMARY: A 48-yr-old Chinese man with CHB-related cirrhosis developed severe progressive generalized bone pain and muscle weakness after receiving ADV 10 mg daily for 54 months. The laboratory results showed severe hypophosphatemia and features of proximal renal tubule dysfunction. Imaging studies were consistent with osteomalacia. After discontinuation of ADV, his symptoms resolved, laboratory abnormalities normalized and imaging studies showed improvement. In addition to our case, 12 other patients have been reported to have developed hypophosphatemic osteomalacia induced by low-dose ADV. Most of the reported cases were of subjects of East-Asian ethnicity. After discontinuation or reduction of ADV, serum phosphate level increased and clinical symptoms significantly improved in all cases. WHAT IS NEW AND CONCLUSION: Hypophosphatemic osteomalacia and renal Fanconi syndrome can be associated with low-dose ADV. Clinicians treating CHB patients with ADV 10 mg daily over long periods of time should be aware of this infrequent but serious complication.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: Sunitinib-induced hyperammonaemia in a patient with pancreatic neuroendocrine tumour.

  Y-F Shea, W-Y J Chiu, M-Y M Mok, I F-N Hung, C-C T Yau
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Sunitinib can improve progression-free survival and overall survival in patients with advanced pancreatic neuroendocrine tumor (PNET). From clinical trial, most commonly reported adverse events of sunitinib were neutropenia (12%), diarrhea (10%), asthenia (7%), erythrodysesthesia (7%), hypertension (7%) and thrombocytopenia (6%). CASE SUMMARY: We report a patient with PNET with liver metastases who developed hyperammonemia with a low dosage of sunitinib probably contributed by the presence of liver metastases. WHAT IS NEW AND CONCLUSIONS: We would like to draw attention to the potential risk of sunitinib induced hyperammonemic encephalopathy even with a low dosage of sunitinib. The absence of sunitinib-induced hyperammonemia during its initial course does not rule out this possibility if there is increased in liver metastases. We suggest checking the ammonia level if patient on sunitinib presented with altered sensorium even if the liver function is normal.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: Analysis of new drugs whose clinical development and regulatory approval were hampered during their introduction in Japan.

  R Asada, S Shimizu, S Ono, T Ito, A Shimizu, T Yamaguchi
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Many drugs fail during development. However, detailed reasons for failure during drug development are almost never disclosed. We focused on the drugs whose clinical development and registration were initially hampered, but which were finally approved to identify reasons that delayed their marketing approval in Japan. METHODS: We analysed 727 new drug applications (NDAs) approved in Japan between 2001 and 2011. RESULTS AND DISCUSSION: Fifty-three NDAs had serious and identifiable problems during drug development. Of these, 43 NDAs had 'problem related to clinical data'. We found that the problems for withdrawal of these NDAs could be ascribed largely to inappropriate clinical data package and study design for supporting the intended indications and usage and to unclear clinical results for defining dosage regimen or efficacy of the drugs. WHAT IS NEW AND CONCLUSION: Our results indicate the importance of careful determination of the optimal dosage regimen and the choice of objective endpoints in clinical trials. Further, it is important to establish a clear strategy for generating the clinical data package, to include careful design of clinical trials on the basis of the nature of the target disease and target population. For drugs marketed in Japan, there is a need to include sufficient numbers of Japanese patients in the trials.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: Severe acute nephrotoxicity in a kidney transplant patient despite low tacrolimus levels: a possible interaction between donor and recipient genetic polymorphisms.

  M Quaglia, S Terrazzino, R Boldorini, P Stratta, A A Genazzani
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Tacrolimus has a narrow therapeutic index and shows large interindividual variations in pharmacokinetics, which may be partly explained by genetic variability in metabolic enzymes of the cytochrome P450 (mainly CYP3A4 and CYP3A5) and transport P-glycoprotein (encoded by the ABCB1 gene). Genetic variability in the expression of biotransformation enzymes and drug transporters may also predispose individuals to tacrolimus-induced nephrotoxicity. CASE SUMMARY: We report a case of severe biopsy-proven Tacrolimus (TAC) nephrotoxicity that occurred 1 month after renal transplantation despite persistently low TAC levels. The donor genotype was CYP3A5*3/*3 (loss-of-function genotype), whereas that of the recipient was CYP3A5*1/*3. The donor and recipient genotypes did not differ with respect to either CYP3A4 rs35599367C>T (both were CC homozygotes) or ABCB1 gene polymorphisms (both TT homozygotes for the 1236C>T polymorphism and CT heterozygotes for the 3435C>T polymorphism). WHAT IS NEW AND CONCLUSION: This case study suggests that donor/recipient genetic mismatch in metabolic enzymes may have an important role in modulating tacrolimus nephrotoxicity. It provides a possible explanation for the intriguing observation that for a subset of patients, cumulative TAC doses appear to correlate better with nephrotoxicity than trough levels.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: Efficacy and cost of single-dose rasburicase in prevention and treatment of adult tumour lysis syndrome: a meta-analysis.

  X Feng, K Dong, D Pham, S Pence, J Inciardi, N S Bhutada
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Single-dose rasburicase for the treatment and prevention of hyperuricaemia in adult and paediatric patients with cancer at high risk of tumour lysis syndrome (TLS) has been widely adopted in pharmacy practice as unlabelled use with limited clinical evidence. This meta-analysis study evaluated the efficacy and cost savings of a single-dose rasburicase (SDR) regimen compared with the Food and Drug Administration-approved daily dosing of rasburicase (DDR) for 5 days or the traditional treatment with allopurinol in adult cancer patients with hyperuricaemia or at high risk for TLS. METHODS: Prospective and retrospective studies were retrieved from a systemic search of major electronic data sources. Studies included in the meta-analysis were those with SDR for the prophylaxis of high-risk TLS or treatment of hyperuricaemia in adult patients with cancer. The results of response rate and controlling of time-dependent plasma uric acid (UA) reduction were pooled and compared with the results from patients treated with DDR for 5 days or patients treated with allopurinol. A cost analysis was performed to analyse the treatment costs for adults with hyperuricaemia or at high risk for TLS. RESULTS AND DISCUSSION: Ten studies (eight retrospective and two prospective) evaluated the SDR response rate and plasma UA level reduction over time. The pooled total number of patients treated with SDR (from 0·05 mg/kg to 0·20 mg/kg) was 269. The pooled response rate of the SDR arm was not significantly different than that of DDR (0·2 mg/kg) arm (88·15% vs. 90·18%, P = 0·542), but significantly stronger than that of allopurinol (300 mg/day orally days 1 to 5) arm (response rate: 88·15% vs. 66%, P < 0·0005). Pooled SDR group efficiently controlled the plasma uric acid (UA) level below 4·5 mg/dL over 24 h, 48 h and 72 h, whereas DDR reduced plasma UA levels to hypouricaemia level (<2 mg/dl). In addition, cost analysis demonstrated that standard-dose SDR (≥6 mg) has non-inferior clinical benefit and significant cost savings compared with the DDR regimen. WHAT IS NEW AND CONCLUSION: Single-dose rasburicase (SDR) for adult cancer patients with hyperuricaemia or at high risk for TLS demonstrated better response rate and stronger control of uric acid level compared with allopurinol. SDR response rate was not inferior to that of DDR, and the standard-dose SDR generates more cost savings compared with the DDR. It suggests that the single-dose rasburicase is clinically effective and cost efficient for the prophylaxis of high-risk TLS and the treatment of hyperuricaemia in adult patients with cancer. Additional randomized control studies are needed to confirm the findings of this meta-analysis study.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: A severe case of haemodynamic instability during anidulafungin administration.

  M Fink, U Zerlauth, C Kaulfersch, A Rab, D Alberer, P Preiss, K Sternad-Klobschauer, E Habernig, W Wandschneider, G Grimm
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Anidulafugin is an echinocandin used for the treatment of candida infections in non-neutropenic adults. Echinocandins show few drug-drug interactions and are usually well tolerated. We report a case of acute hypotension, bradycardia and haemodynamic instability with consecutive cardiopulmonary resuscitation during anidulafungin administration. CASE SUMMARY: A 41-year-old man ICU patient received anidulafungin for a suspected Candida glabrata infection. During the first administration of the drug, he developed acute haemodynamic instability with hypotension and bradycardia. The infusion was discontinued immediately and cardiopulmonary resuscitation was performed successfully. The patient regained haemodynamic stability. WHAT IS NEW AND CONCLUSION: To the authors' knowledge, this is the first report of a life-threatening adverse event due to haemodynamic instability during anidulafungin administration. Cardiac toxicity associated with echinocandins has been described. Further studies seem to be mandatory to investigate this potential risk.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: Ulipristal acetate - safety and pharmacokinetics following multiple doses of 10-50 mg per day.

  O Pohl, I Osterloh, J-P Gotteland
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Ulipristal acetate (UPA) is a novel selective progesterone receptor modulator for benign gynaecological conditions such as uterine myoma. The safety and pharmacokinetics of multiple-dose UPA and its N-mono-demethylated metabolite, PGL4002, were investigated in women. METHODS: The double-blind, placebo-controlled study randomized 32 healthy women of reproductive age to receive 10 consecutive daily doses of placebo, 10, 20 or 50 mg UPA. Safety assessments included vital signs, physical examination, ECG, clinical laboratory tests and reporting of adverse events. Blood samples for pharmacokinetic analysis were collected on Days 1 and 10 at intervals until 168 h after multiple dosing. RESULTS: UPA was well tolerated at all doses. Mild or moderate adverse events occurred with similar frequency in UPA and placebo groups. UPA median tmax was 0·75 and 0·89 h, and mean plasma half-life was between 38 and 49 h. Cmax values (Day 1) were 42·2, 130·9 and 354·8 ng/mL for the UPA 10, 20 and 50 mg treatment groups, respectively. Corresponding Cmax values for Day 10 were 63·7, 169·8 and 454·9 ng/mL. AUCSS values on Day 10 were 216·6, 602·8 and 1655·7 ng h/mL after 10, 20 and 50 mg UPA, respectively. For the principal metabolite PGL4002, tmax and plasma elimination half-life values were similar to those of UPA. PGL4002 AUCSS Day 10 values were 84·7, 203·6 and 452·1 ng h/mL for 10, 20 and 50 mg groups, respectively. WHAT IS NEW AND CONCLUSION: Daily administration of UPA at therapeutic and supratherapeutic doses was well tolerated by women of reproductive age. UPA exposure increases with dose. Exposure to PGL4002 is approximately one-third that of UPA.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: A search for interaction among combinations of drugs of abuse and the use of isobolographic analysis.

  R J Tallarida, U Midic, N S Lamarre, Z Obradovic
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Individuals who abuse drugs usually use more than one substance. Toxic consequences of single and multi-drug use are well documented in the Treatment Episodes Data Set that lists drug combinations that result in hospital admissions. Using this list as a guide, we focused our attention on combinations that result in the most hospital admissions and searched the PubMed database with the objective of determining the number of such publications and, in particular, those that used the term synergism in their titles or abstracts. COMMENT: Using the search criteria produced an extensive list of published articles. However, a further intersection of the search terms with the term isobole revealed a surprisingly small number of literature reports. WHAT IS NEW AND CONCLUSION: Because the method of isoboles is the most common quantitative method for distinguishing between drug synergism and simple additivity, the small number of investigations that actually employed this quantification suggests that the term synergism is not properly documented in describing the toxicity among abused substances. The possible reasons for this lack of quantification may be related to a misunderstanding of the modelling equations. To help rectify this possible hurdle to understanding and clinical utility, the theory and modelling are discussed here.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: Application of the STOPP/START criteria: a systematic review of the prevalence of potentially inappropriate prescribing in older adults, and evidence of clinical, humanistic and economic impact.

  B Hill-Taylor, I Sketris, J Hayden, S Byrne, D O'Sullivan, R Christie
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVE: Potentially inappropriate prescribing (PIP) has significant clinical, humanistic and economic impacts. Identifying PIP in older adults may reduce their burden of adverse drug events. Tools with explicit criteria are being developed to screen for PIP in this population. These tools vary in their ability to identify PIP in specific care settings and jurisdictions due to such factors as local prescribing practices and formularies. One promising set of screening tools are the STOPP (Screening Tool of Older Person's potentially inappropriate Prescriptions) and START (Screening Tool of Alert doctors to the Right Treatment) criteria. We conducted a systematic review of research studies that describe the application of the STOPP/START criteria and examined the evidence of the impact of STOPP/START on clinical, humanistic and economic outcomes in older adults. METHODS: We performed a systematic review of studies from relevant biomedical databases and grey literature sources published from January 2007 to January 2012. We searched citation and reference lists and contacted content experts to identify additional studies. Two authors independently selected studies using a predefined protocol. We did not restrict selection to particular study designs; however, non-English studies were excluded during the selection process. Independent extraction of articles by two authors used predefined data fields. For randomized controlled trials and observational studies comparing STOPP/START to other explicit criteria, we assessed risk of bias using an adapted tool. RESULTS AND DISCUSSION: We included 13 studies: a single randomized controlled trial and 12 observational studies. We performed a descriptive analysis as heterogeneity of study populations, interventions and study design precluded meta-analysis. All observational studies reported the prevalence of PIP; however, the application of the criteria was not consistent across all studies. Seven of the observational studies compared STOPP/START with other explicit criteria. The STOPP/START criteria were reported to be more sensitive than the more-frequently-cited Beers criteria in six studies, but less sensitive than a set of criteria developed in Australia. The STOPP criteria identified more medications associated with adverse drug events than the 2002 version of the Beers criteria. Patients with PIP, as identified by STOPP, had an 85% increased risk of adverse drug events in one study (OR = 1·85, 95% CI: 1·51-2·26; P < 0·001). There was limited evidence that the application of STOPP/START criteria optimized prescribing. Research involving the application of STOPP/START on the impact on the quality of life was not found. The direct costs of PIP were documented in three studies from Ireland, but more extensive analyses on the economic impact or studies from other jurisdictions were not found. WHAT IS NEW AND CONCLUSION: The STOPP/START criteria have been used to review the medication profiles of community-dwelling, acute care and long-term care older patients in Europe, Asia and North America. Observational studies have reported the prevalence and predictors of PIP. The STOPP/START criteria appear to be more sensitive than the 2002 version of the Beers criteria. Limited evidence was found related to the clinical and economic impact of the STOPP/START criteria.
  Journal of Clinical Pharmacy and Therapeutics 04/2013;
• Article: The potential role of newer gram-positive antibiotics in the setting of osteomyelitis of adults.

  Ryan P Moenster, Travis W Linneman, William B Call, Chad L Kay, Theresa A McEvoy, Jamie L Sanders
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  ABSTRACT: To summarize available literature regarding the potential role of linezolid, daptomycin, telavancin, tigecycline and ceftaroline for the treatment of osteomyelitis caused by resistant gram-positive organisms. Literature was obtained through PubMed searches from January 1980 to October 2011 using the terms osteomyelitis, bone, linezolid, daptomycin, telavancin, tigecycline and ceftaroline. Results were limited to those published in English. All articles identified from the PubMed searches were evaluated. Any published data related to bone penetration (animal or human) or clinical outcomes in adult osteomyelitis of these agents were included in the review. Animal models report bone concentrations of 2·3 mcg/dL (vertebral) for linezolid, 0·45 mcg/mL (tibiae) for daptomycin, 0·78 mcg/mL (tibiae) for tigecycline and 0·27 mcg/mL (tibiae) for telavancin; no data are available for ceftaroline. Human studies demonstrate bone concentrations of 4·6, 17·0 and 3·9 mcg/mL (sternal, metatarsal and cancellous bone respectively) for linezolid, 4·7 mcg/mL (metatarsal) for daptomycin and 0·078 mcg/mL (unspecified) for tigecycline; no data are available for telavancin and ceftaroline. Retrospective cohort data, and prospective/retrospective case series support the use of linezolid in this setting; however, side-effects may limit use. Retrospective and prospective cohort data support daptomycin use. A retrospective case series is available supporting the use of telavancin. No data are available supporting clinical effectiveness for ceftaroline or tigecycline in the setting of osteomyelitis. Limited data are available evaluating the safety and efficacy of these agents in osteomyelitis in adults. Daptomycin and telavancin may be potential alternatives or second-line agents to vancomycin in selected patients. Linezolid, because of an increase in clinically important ADRs with prolonged use, should be reserved as a second- or third-line agent. Due to a lack of clinical data and poor bone penetration, along with concerns regarding outcomes in severe infections, tigecycline's potential is limited. Little data exist regarding ceftaroline use in osteomyelitis.
  Journal of Clinical Pharmacy and Therapeutics 04/2013; 38(2):89-96.
• Article: Polymorphisms of the HTR3B gene are associated with post-surgery emesis in a Chinese Han population.

  Xiao-Xu Ma, Qi-Xing Chen, Shui-Jing Wu, Yan Hu, Xiang-Ming Fang
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  ABSTRACT: WHAT IS KNOWN AND OBJECTIVES: The serotoninergic receptor 5-hydroxytryptamine (serotonin) receptor 3 (HTR3) is instrumental in the regulation of nausea and emesis (vomiting).This study investigated whether common genomic variations of the A and B subunits of HTR3 (HTR3A, HTR3B) are associated with the incidence of post-operative vomiting in a Chinese Han population. Two hundred and thirty-one female Chinese Han patients undergoing gynaecological surgery with standardized general anaesthesia were recruited for the study. Clinical symptoms after surgery were recorded and direct DNA sequencing was performed to detect polymorphisms of HTR3A and HTR3B. Five single nucleotide polymorphisms (SNPs) in HTR3A and HTR3B were found, with R > 0·8 and minor allele frequency > 10%. One of these (rs3758987 in HTR3B) was statistically associated with vomiting, after adjusting for body weight, body mass index and duration of general anaesthesia in dominant and additive models (P = 0·047 and P = 0·034). The HTR3B rs3758987 SNP might serve as a predictor of post-operative vomiting in Chinese Han patients undergoing gynaecological laparoscopic surgery.
  Journal of Clinical Pharmacy and Therapeutics 04/2013; 38(2):150-5.