Defining cytotoxic drugs - you know it when you see it?

Safe handling precautions are an important measure used to prevent occupational exposure to hazardous antineoplastic drugs. Historically, the terms 'antineoplastic', 'chemotherapy' and 'cytotoxic' are frequently conflated. However, many current antineoplastic drugs do not have cytotoxic mechanisms of actions, leading to confusion when developing safe handling policies. Based on the mechanistic criteria outlined in this review, we have compiled a list of the most commonly used antineoplastic drugs with their cytotoxic or non-cytotoxic designations. We propose that this list can be used when discussing drug-specific safe handling precaution measures.

Concomitant use of capecitabine and proton pump inhibitors - Is it safe?

BACKGROUND: Capecitabine is a commonly used oral chemotherapy agent. Recent data suggest that concurrent use of proton pump inhibitors may reduce the efficacy of capecitabine by decreasing its absorption through increased gastric pH. Since proton pump inhibitors are widely used, we evaluated the supportive evidence for the probability of occurrence and potential seriousness of this drug interaction. METHODS: The probability of occurrence was evaluated based on the clinical, pharmacokinetic and in vitro evidence using the Drug Interaction Probability Scale. The possibility of seriousness was assessed based on the potential impact on the therapeutic intent of capecitabine therapy. RESULTS: The probability of occurrence of the interaction is doubtful. Clinical findings from two retrospective post hoc analyses showed inconsistent trends towards reduced survival. Pharmacokinetics studies found no significant decrease in systemic capecitabine level with concurrent gastric acid suppression with antacid or food intake. In vitro data do not support the proposed mechanism of reduced capecitabine absorption due to increased gastric pH. The possibility of seriousness varies depending on the treatment intent of capecitabine therapy. The most and least serious possible outcome would be reduced possibility of cure or survival and symptom control, respectively. CONCLUSION: Although the possible outcome may be serious, the probability of interaction between capecitabine and proton pump inhibitors is doubtful. Therefore, we suggest that intervention should be limited to minimal change to existing therapy plan. This may include routinely ascertaining the need for proton pump inhibitor use. Alternate acid suppressing agents may be considered based on the therapeutic intent of capecitabine therapy.

Approach to initiating QT-prolonging oncology drugs in the ambulatory setting.

Since the introduction of regulatory drug approval guidance on the evaluation of QT interval prolongation, an increasing number of drug monographs has included cautions on the risk of QT prolongation. For example, QT prolongation is mentioned in the Canadian product monographs of 29 drugs commonly seen in oncology practice. This presents two major challenges. First, most guidelines and risk predictive tools for QT prolongation have been developed for hospitalized patients in acute care settings. In contrast, most QT-prolonging oncology drugs are used in medically stable patients in the ambulatory setting. Second, many oncology drugs are unique for their indications and non-QT prolonging alternative agents are often not available. In this review, we will outline an empiric initial approach to ambulatory cancer patients who are treated with oncology drugs which may prolong QT interval. This includes the predictive value of QT prolongation on torsades de pointes, the risk factors of the patients and the drugs, and the limitations of existing guidance in this area.

Challenges of dispensing costly tablets with short shelf-life.

Afatinib, trametinib and regorafenib are three costly oral oncology drugs with a short shelf-life after the original container has been opened. Their short shelf-lives are due to degradation on exposure to moisture. Therefore, manufacturers recommend them to be dispensed in the original packaging with the desiccant. However, the prescribed quantities do not always match the quantities in the original packaging, usually because of dose modifications for toxicities. This leads to potentially significant drug wastage and financial losses. We describe some potential approaches to this issue.

Safe handling of monoclonal antibodies: Too large to be hazardous?

It has been argued that the larger molecular weight of hazardous monoclonal antibodies may prevent their dermal absorption via occupational exposure. However, this assertion does not seem to be supported by direct evidence. Although the larger molecular weight may render monoclonal antibodies less probable to achieve therapeutic systemic level through dermal absorption, the concern in occupational health is whether these drugs can possibly attain a detectable level through repeated dermal exposure. Currently, there is no direct evidence to support a particular molecular weight above which a drug cannot achieve a detectable level following repeated occupational exposure. Therefore, the precautionary principle would dictate that repeated exposure of healthcare workers to hazardous monoclonal antibodies should be kept to a minimum.

Rationalizing the use of auxiliary label for oral oncology drugs.

Objective The objective of this study is to develop a systematic approach to standardize the use of auxiliary labels for oral oncology drugs. Design The project was multi-phased: environmental scan of auxiliary labels used at six BC Cancer Agency centre pharmacies, develop guidelines to support auxiliary labels standardization, develop inclusion criteria for common warnings and standardize warnings based on guiding principles and evidence (Canadian Compendium of Pharmaceutical Specialties, BC Cancer Agency Cancer Drug Manual, British National Formulary, literature). Results Consistent auxiliary labels use was rare (7% of drugs). No explicit methodology for determining previous auxiliary labels use was identified. Guiding principles developed include auxiliary labels supplement counselling and drug-specific patient handouts; a maximum of four auxiliary labels (limited container size and alert fatigue); identify hazardous drugs with auxiliary labels; auxiliary labels not intended for universal warnings (e.g., keep out of reach of children); warnings prioritized by impact on storage, efficacy (e.g., administration instructions), toxicity (including interactions) and other clinical issues. Inclusion criteria were developed for warnings on pregnancy, crushing/chewing, taking with plenty of water, drowsiness/dizziness, alcohol, grapefruit juice, hazardous and sunlight exposure. First list of standardized auxiliary labels was completed in June 2014. Conclusion A systematic approach was developed to determine and prioritize auxiliary labels for oral oncology drugs. This has led to a standardized and more accurate labelling throughout the six BC Cancer Agency centres' pharmacies.

Hazards in determining whether a drug is hazardous.

The US National Institute for Occupational Safety and Health list and evaluation criteria have provided an important foundation to help institutions identify and create a list of hazardous formulary drugs. However, further guiding principles were needed to make the adoption feasible at our organization. First, we developed separate directives for determining the inherent hazardous toxicity of a drug and for the requirements for safe handling based on dosage forms (exposure risks) of these drugs. Secondly, we created a systematic approach in determining the scope of the drugs reviewed by US National Institute for Occupational Safety and Health. Thirdly, we streamlined our review process by defining which drugs needed to be evaluated by our organization. Finally, we considered the pros and cons of creating a tiered system for classifying hazardous drugs beyond those recommended by US National Institute for Occupational Safety and Health.