Hydration Methods for Cisplatin Containing Chemotherapy: A Systematic Review.

INTRODUCTION: Cisplatin-induced nephrotoxicity (CIN) can be prevented by fluid hydration, electrolyte supplementation, or forced diuresis; however, the best way to prevent CIN is still unknown. The aim of this study was to provide objective evidence on the optimal design of hydration schemes to prevent CIN based on an update of the literature. METHODS: A Pubmed and Embase search were conducted in December 2021 and repeated in April 2022 and March 2023. Two independent reviewers screened the articles. The included articles were categorized and reviewed per category. RESULTS: Twenty-seven articles met the inclusion criteria. The included studies varied widely. Four out of seven studies investigating diuretics found a protective effect of adding mannitol to the hydration scheme. All six studies investigating duration and amount of volume of hydration found that a short-hydration scheme resulted in less CIN than a longer hydration scheme. Seven out of nine articles evaluating the role of electrolytes found that magnesium supplementation reduced the risk of nephrotoxicity. Three studies investigated the safety of oral hydration and concluded that nephrotoxicity did not occur more frequently after oral hydration. CONCLUSION: The hydration scheme of cisplatin should be short and consist of a relatively small amount of volume. The scheme should include mannitol and magnesium supplementation. Head-to-head studies are needed to investigate the safety of furosemide compared with mannitol and the dose of mannitol and magnesium.

Clozapine Treatment During Pregnancy and the Postpartum Period: A Systematic Literature Review.

Objective: The objective of this systematic review was to provide a critical appraisal of the evidence related to the safety of clozapine for schizophrenia during pregnancy and lactation.Data Sources: PubMed/MEDLINE, Embase, and the Cochrane Library were searched from inception through December 2020. Reference lists of included studies were hand-searched. The International Clinical Trials Registry Platform and ClinicalTrials.gov were searched for unpublished trials, and PROSPERO was searched for unpublished reviews. The current marketing authorization holder of the originator brands Clozaril and Leponex was also contacted for pharmacovigilance data.Study Selection: Original reports published in English, German, French, or Dutch containing clinical and preclinical data were included if they provided data on maternal, fetal, and neonatal outcomes after clozapine exposure during pregnancy or lactation.Data Extraction: Two reviewers independently extracted relevant data.Results: A total of 860 records were identified, and the full texts of 117 articles were reviewed. Forty-two studies met the inclusion criteria. Data on perinatal clozapine exposure are of limited quality and quantity. Although clozapine demonstrates partial placental passage, data thus far do not support that clozapine is teratogenic; that it increases the risk of stillbirth, abortion, or fetal disorders; or that it increases the risk of delivery complications or premature birth. Information about clozapine exposure through breast milk is scarce, but based on its chemical properties, it is likely that clozapine enters the breast milk of nursing mothers taking clozapine.Conclusions: When weighing the risks and benefits of clozapine continuation during pregnancy and lactation versus switching to another antipsychotic, one should include severity of illness and treatment history but also be aware of the limitations of the available safety data regarding perinatal clozapine use, including the fact that there are few studies.

Difference in decline in renal function due to cisplatin after a short or long hydration scheme in non-small-cell lung cancer: A retrospective cohort study (HYCIS-XL).

WHAT IS KNOWN AND OBJECTIVE: Nephrotoxicity is a frequently occurring side effect of cisplatin, which may be reduced by applying ample hydration. The aim of this study was to determine whether there is a difference in decline in renal function due to cisplatin between a short hydration (SH) and long hydration scheme (LH). METHODS: A retrospective, observational, cohort study was conducted in two hospitals. Patients in one hospital received an SH scheme (SH group), whereas patients in the other hospital received an LH scheme (LH group). Other aspects of treatment and hydration were comparable between both patient groups. Consecutive patients (≥18 years) treated for non-small-cell lung cancer with cisplatin-pemetrexed with ≥1 cisplatin dose were included. Patients were excluded when serum creatinine at baseline was <40 µmol/L. Primary outcome was the difference in estimated glomerular filtration rate (eGFR) between baseline and after the last cisplatin cycle for the SH and LH patients, regardless of the number of administered cisplatin courses. RESULTS: Fifty patients were included in the SH and LH group. There were no significant differences in baseline characteristics between the two groups. None of the patients had renal failure at baseline. After two cisplatin cycles, the median differences between the baseline eGFR and the eGFR after the last cisplatin dose were 1 (-6 to 5) and -9 (-22 to -2) mL/min/1.73 m2 (interquartile range) for the SH and LH group, respectively (P = .000). Less patients completed the four cycles in the LH group (16%) compared to the SH group (64%), mainly because more LH patients were switched to another treatment and due to nephrotoxicity. However, the difference in eGFR remained statistically significant (P = .027). WHAT IS NEW AND CONCLUSION: In this retrospective study, the SH scheme resulted in less decrease in renal function compared with the LH scheme, with a significant and clinically relevant difference. Additionally, more LH patients had to stop this effective treatment prematurely due to nephrotoxicity. Therefore, a short hydration scheme provides adequate and safe hydration, with a lower risk of nephrotoxic side effects and therefore better outcomes for patients and a reduction of healthcare costs.

Safety of clozapine use during pregnancy: Analysis of international pharmacovigilance data.

PURPOSE: Safety data on clozapine use during pregnancy are limited. The aim of this study was to determine disproportionality in case safety reports on adverse pregnancy outcomes between clozapine and other antipsychotics (OAP) used during pregnancy. METHODS: We included all reports of suspected adverse drug reactions (ADRs) to antipsychotics registered in the World Health Organization global individual case safety report (ICSR) database (VigiBase) in children younger than 2 years and women aged 12-45 years. A case/non-case approach was used to evaluate the association between several pregnancy-related ADRs and clozapine exposure during pregnancy, using 2×2 contingency tables to investigate disproportionality and Standard MedDRA Queries to select cases. Clozapine exposure was defined as all ICSR-ADR combinations with clozapine as (one of) the suspected drug(s). Non-exposure was defined as all ICSR-ADR combinations with OAP as (one of) the suspected drug(s). RESULTS: We identified 42 236 unique ICSR-ADR combinations related with clozapine exposure and 170 710 with OAP exposure. Of these, 494 and 4645 ICSR-ADR combinations involved adverse pregnancy outcomes related with clozapine exposure and OAP exposure respectively. Overall, no signal of disproportionate reporting associating clozapine with the studied adverse pregnancy outcomes was found compared with OAP exposure. CONCLUSION: Based on global pharmacovigilance data, we did not find any evidence that clozapine is less safe during pregnancy than OAP. Although this is not automatically equivalent to the relative safety of clozapine during pregnancy, these findings add to the convergence of proofs to allow final conclusions and decisions regarding the treatment of pregnant women with clozapine.

No Differences in Weight Gain Between Risperidone and Aripiprazole in Children and Adolescents After 12 Months.

BACKGROUND: Weight gain due to the use of second-generation antipsychotics is a major health care issue for adult and paediatric psychiatric patients. Little is known about long-term weight gain effects of aripiprazole compared to risperidone in children and adolescents. OBJECTIVE: The primary aim of this study is to assess whether risperidone and aripiprazole are associated with different weight changes in children and adolescents during the first 12 months of treatment. Secondary aim was to assess the influence of the covariates co-medication, gender and indication on weight change. METHODS: This study was a retrospective observational cohort study of in- and outpatients of a Dutch mental health organization aged ≤19 years on long-term treatment with risperidone or aripiprazole. Primary outcome measure was body-mass index (BMI) z-score change. Data were extracted from medical charts and analysed using linear mixed models. RESULTS: In total, 89 risperidone patients and 42 aripiprazole patients were included in the study. At baseline, the BMI z-score of aripiprazole subjects was significantly higher than risperidone subjects (p = 0.003). In both treatment groups BMI z-score significantly increased during 12 months of follow-up. This weight change was not significantly different in risperidone and aripiprazole users after 12 months (p = 0.943). Covariates did not significantly influence weight change. CONCLUSION: This study demonstrated that there was no significant difference in weight gain between risperidone and aripiprazole users during the first year of treatment. Based on this study, aripiprazole should not be favoured over risperidone in children and adolescents because of the degree of weight gain.

Predicting Unsuccessful Clozapine Treatment After First Use in Adult Patients With Psychotic Disorders.

PURPOSE/BACKGROUND: Cessation of clozapine therapy and insufficient response may result in relapse of psychotic symptoms and in clinical admissions. However, discontinuation rates are high. Identifying patients at risk for unsuccessful clozapine use might enable clinicians to direct specific attention to them. METHODS/PROCEDURES: Routinely collected data from a large insurance company were used to develop a simple prediction model for unsuccessful clozapine treatment in psychiatric patients 1 year after clozapine was first dispensed by a community pharmacy in the Netherlands. Multivariate logistic regression analyses were performed with the Nagelkerke R statistic as a measure of the predictive value of the model. FINDINGS/RESULTS: A total of 937 patients were dispensed clozapine for the first time by their community pharmacy between January 1, 2011, and December 31, 2015 (index date). Of these, 741 patients had started their clozapine treatment in hospital before the index date (inpatient starters); the remaining 196 patients started clozapine as outpatients on the index date (outpatient starters). In 191 patients (20.4%), clozapine treatment was unsuccessful 1 year after the index date. Unsuccessful treatment was more common among outpatient starters than among inpatient starters (32.1% vs 17.3%). Using backward selection of the variables, a model consisting of 61 variables had the best predictive value overall (Nagelkerke R = 0.301), whereas a model consisting of 52 variables had the best predictive value in outpatient starters (Nagelkerke R = 0.676). IMPLICATIONS/CONCLUSIONS: The likelihood of unsuccessful clozapine treatment after 1 year was higher among patients who started clozapine as outpatients. Despite the use of a diversity of variables and different statistical approaches, it was not possible to make a simple prediction model for unsuccessful clozapine treatment using relatively easily accessible data.

Successful clozapine continuation during chemotherapy for the treatment of malignancy: a case report.

CASE: The need for chemotherapy treatment in a cancer patient who uses clozapine raises a clinical dilemma because both therapies can cause agranulocytosis. A 45-year-old male diagnosed with schizophrenia used clozapine together with zuclopenthixol for more than 15 years. Non-Hodgkin's lymphoma was treated with chemotherapy twice, and clozapine was continued during both courses of chemotherapy. Agranulocytosis did not occur during the first treatment. During the second treatment, agranulocytosis occurred, but was attributed to chemotherapy, and blood counts recovered spontaneously. Successful concomitant use of clozapine and cancer chemotherapy is based on a limited number of case reports. However, two case reports describe persistent neutropenia or agranulocytosis, possibly related to this combination. CONCLUSION: Clozapine should only be continued during cancer chemotherapy if favoured by the risk-to-benefit ratio.

Detection and correct handling of prescribing errors in Dutch hospital pharmacies using test patients.

BACKGROUND: Hospital pharmacists and pharmacy technicians play a major role in detecting prescribing errors by medication surveillance. At present the frequency of detected and correctly handled prescribing errors is unclear, as are factors associated with correct handling. OBJECTIVE: To examine the frequency of detection of prescribing errors and the frequency of correct handling, as well as factors associated with correct handling of prescribing errors by hospital pharmacists and pharmacy technicians. SETTING: This study was conducted in 57 Dutch hospital pharmacies. METHOD: Prospective observational study with test patients, using a case-control design to identify factors associated with correct handling. A questionnaire was used to collect the potential factors. Test patients containing prescribing errors were developed by an expert panel of hospital pharmacists (a total of 40 errors in nine medication records divided among three test patients; each test patient was used in 3 rounds; on average 4.5 prescribing error per patient per round). Prescribing errors were defined as dosing errors or therapeutic errors (contra-indication, drug-drug interaction, (pseudo)duplicate medication). The errors were selected on relevance and unequivocalness. The panel also defined how the errors should be handled in practice using national guidelines and this was defined as 'correct handling'. The test patients had to be treated as real patients while conducting medication surveillance. The pharmacists and technicians were asked to report detected errors to the investigator. MAIN OUTCOME MEASURE: The percentages of detected and correctly handled prescribing errors were the main outcome measures. Factors associated with correct handling were determined, using multivariate logistic regression analysis. RESULTS: Fifty-nine percent of the total number of intentionally added prescribing errors were detected and 57 % were handled correctly by the hospital pharmacists and technicians. The use of a computer system for medication surveillance compared to no computer system was independently associated with correct handling [odds ratio (OR) 15.39 (95 % confidence interval (CI) 3.62-65.50] for computerized physician order entry system; OR 15.40 (95 % CI 3.61-65.70) for order entry by pharmacy technicians), but because the reference category contained only one hospital these results can't be interpreted. Furthermore, manual screening of dosages in children with or without computerized surveillance compared to no dosage checks for children [OR 2.02 (95 % CI 1.06-3.84)], qualified pharmacy technicians compared to no qualified pharmacy technicians [OR 1.32 (95 % CI 1.03-1.67)] and pharmacy technicians using protocols compared to ones not using protocols [OR 1.30 (95 % CI 1.04-1.61)] were independently associated with correct handling. CONCLUSION: This study showed that the quality of medication surveillance in Dutch hospital pharmacies can be subject to improvement and the identified factors may give direction to such improvements.