Introduction: Drug–drug interactions (DDIs) arise in numerous different ways, involving pharmacokinetic or pharmacodynamic mechanisms. Adverse drug reactions are a possible consequence of DDIs and health operators are often unaware of the clinical risks of certain drug combinations. Many papers on drug interactions have been published in recent years, but most of them focused on potential DDIs while few studies have been conducted on actual interactions. Areas covered: This paper reviews the epidemiology of actual DDIs in outpatients as well as in hospital settings and in spontaneous reporting databases. The incidence of actual DDIs is consistently lower than that of potential DDIs. However, the absolute number of patients involved is high, representing a significant proportion of adverse drug reactions. The importance of risk factors such as age, polypharmacy and genetic polymorphisms is also evaluated. The relevance and efficacy of tools for recognizing and preventing DDIs are discussed. Expert opinion:...

Epidemiology and characteristics of adverse drug reactions caused by drug-drug interactions.

Objectives: Antineoplastic drugs are known reproductive and developmental toxicants. Our objective was to review the existing literature of reproductive health risks to workers who handle antineoplastic drugs. Methods: As tructured literature review of 18 peer-reviewed, English language publications of occupational exposure and reproductive outcomes was performed. Results: Although effect sizes varied with study size and population, occupational exposure to antineoplastic drugs seems to raise the risk of both congenital malformations and miscarriage. Studies of infertility and time to pregnancy also suggested an increased risk for subfertility.Conclusions: Antineoplastic drugs are highly toxic in patients receiving treatment, and adverse reproductive effects have been well documented in these patients. Health care workers with long-term, low-level occupational exposure to these drugs also seem to have an increased risk of adverse reproductive outcomes. Additional precautions to prevent exposure should be considered.

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Reproductive Health Risks Associated with Occupational Exposures to Antineoplastic Drugs in Health Care Settings: A Review of the Evidence

Drug−drug interactions (DDIs) occur when a patient's response to the drug is modified by administration or co-exposure to another drug. The main cytochrome P450 (CYP) enzyme, CYP3A4, is implicated in the metabolism of almost all of the tyrosine kinase inhibitors (TKIs). Therefore, there is a substantial potential for interaction between TKIs and other drugs that modulate the activity of this metabolic pathway. Cancer patients are susceptible to DDIs as they receive many medications, either for supportive care or for treatment of toxicity. Differences in DDI outcomes are generally negligible because of the wide therapeutic window of common drugs. However for anticancer agents, serious clinical consequences may occur from small changes in drug metabolism and pharmacokinetics. Therefore, the objective of this review is to highlight the current understanding of DDIs among TKIs, with a focus on metabolism, as well as to identify challenges in the prediction of DDIs and provide recommendations.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bcp.12496

Metabolism‐related pharmacokinetic drug−drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations

Occupational exposure to antineoplastic drugs in four Italian health care settings.

PurposeIn a follow-up to a previous study, surface contamination with the antineoplastic drug cyclophosphamide was compared in 30 US hospital pharmacies from 2004 to 2010 following preparation with...

/pdf/reduction-in-surface-contamination-with-cyclophosphamide-in-2dlvd6hyk5.pdf

Reduction in Surface Contamination With Cyclophosphamide in 30 US Hospital Pharmacies Following Implementation of a Closed-System Drug Transfer Device

Purpose
Surface contamination with the antineoplastic drugs cyclophosphamide, ifosfamide, and 5-fluorouracil was compared in 22 US hospital pharmacies following preparation with standard drug preparation techniques or the PhaSeal® closed-system drug transfer device (CSTD).

/pdf/reduction-in-surface-contamination-with-antineoplastic-drugs-3ya07u21fz.pdf

Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device

The harmful effects from occupational exposure to antineoplastic agents were first described nearly 40 years ago. When preparing and administering these hazardous drugs, staff (pharmacists, pharmacy technicians, nurses) risk exposure and consequent adverse effects such as DNA damage, infertility, birth defects and a possible risk of cancer. To limit environmental contamination and potential exposure to healthcare personnel, precautionary measures, including training in cytotoxic handling techniques, personal protective equipment, and biological safety cabinets or isolators, were introduced. Despite the use of these measures, studies continued to demonstrate occupational exposure and surface contamination. Closed system drug transfer devices (CSTDs) have been designed to be used, in conjunction with other strategies, to further reduce the potential exposure of health care workers to hazardous agents. Since their introduction, numerous published studies have shown the effectiveness of CSTDs in the reduction of surface contamination and occupational and environmental exposure. CSTDs have been defined as ‘‘a drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapour concentrations outside the system’’. Essentially, this means that, when the system is fully and correctly employed, it does not allow any bacteria or particulate matter into the system during compounding, thus maintaining sterility and also does not let any of the prepared hazardous products within the system to escape, thus protecting against harmful exposure. However, to date only the application of CSTDs in the reduction of workplace contamination has appeared in national and international guidelines. It is a third, as yet not fully recognised component, that is the topic for this paper – the potential use of closed system technology to be utilised as a cost saving initiative aimed against the high cost of cancer drugs by allowing vial sharing and extension of beyond use dating (BUD). We will not be addressing the regulatory environments across the globe governing the use of this technology as these differ from country to country and therefore may not allow all clinicians to take advantage of the information presented. The ability of CSTDs to prevent contamination of parenteral drug products has the potential to allow extended BUD, thereby reducing wastage and decreasing expenditure. Several studies have been performed to assess the feasibility of this approach. The United

https://journals.sagepub.com/doi/pdf/10.1177/1078155217753890

How can the use of closed system transfer devices to facilitate sharing of drug vials be optimised to achieve maximum cost savings

It is estimated that almost one-third of adverse reactions to pharmaceutical agents result from drug interactions. The potential for drug interactions in oncology complicates the pharmacist's role of finding a balance between efficacy and acceptable toxicity for all agents involved (anticancer agents, supportive therapies, and concomitant medications). In the realm of metastatic breast cancer, the heavily pretreated nature of many patients and the narrow therapeutic window associated with most therapies puts all patients at risk for drug interactions. In practice, co-administration of a pharmacological agent with the potential to alter the clinical profile of the patient's anticancer regimen may be unavoidable. Herein are discussed underlying molecular mechanisms that are usually responsible for drug interactions in the realm of breast oncology. Since more and more oral anticancer agents are emerging onto the market or are in late clinical development, special consideration is given to identification and management of potential interactions associated with oral anticancer therapeutics. In addition, recommendations are provided for dose reduction strategies, effective monitoring, management of drug interactions, and communication strategies with patients and other members of the clinical team.

Timothy G Tyler

Papers

Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device

How can the use of closed system transfer devices to facilitate sharing of drug vials be optimised to achieve maximum cost savings

Drug interactions in metastatic breast cancer