Drug tolerability versus drug safety

Introduction

While dermatology treatments continue to advance and offer dermatologists and patients an assortment of safe drugs to manage cutaneous conditions, they often come with negative side effects, contributing to poor adherence and treatment interruptions. It is essential to understand the differences to effectively communicate this with patients and recommend the appropriate dermatological treatment considering drugs’ safety and tolerability, to optimize disease clearance and adherence. Drug tolerability and drug safety are sometimes used interchangeably, but they represent somewhat different concepts. While drug tolerability is based on the patient’s subjective experience, drug safety is based on an objective assessment of the drug’s side effects. This editorial aims to characterize the differences between drug tolerability and safety.

What is drug tolerability?

The United States Food and Drug Administration (FDA) defines drug tolerability as the degree to which the drug’s adverse effects can be tolerated by the subject (1). Drug tolerability is determined by the patient’s subjective experience and how it affects their quality of life while taking the drug. For example, fatigue and nausea are subjective drug tolerability issues, as opposed to dangerous objective health risk issues (2). Apremilast, an oral phosphodiesterase 4 inhibitor approved to treat psoriasis and psoriatic arthritis in the United States, has tolerability issues such as nausea, and headaches but is still safe, given the lack of common serious adverse effects associated with it (3). A drug’s tolerability is an important outcome directly and indirectly because of its potential effects on patient adherence. If the drug is intolerable, the patient may stop taking it entirely.

What is drug safety?

The FDA defines drug safety as the medical risk to the subject, analyzed by laboratory tests, vital signs, clinical adverse events, and other special safety tests in clinical trials (1). Drug safety is determined by objective criteria such as drug pharmacokinetics and metabolism, which may cause adverse effects in susceptible patient populations and in interaction with other drugs. Drug safety is a multifaceted concept based on factors such as patient age, health, and use of other medications. Vulnerable populations such as the elderly, children and pregnant women are at greater safety risks than the general population. Geriatric patients often have several chronic conditions requiring multiple medications, which increases the potential for harmful drug-drug interactions. Depending on the age of the pediatric patients, many of their organs have not fully developed resulting in varying metabolisms, which may increase toxic levels of a drug. In pregnant females, medication use can deleteriously affect the growing fetus.

How do we measure drug safety?

Drug safety is measured using objective methods in a series of clinical trials the FDA oversees. In phase 1 studies, toxicity parameters, pharmacokinetic, and pharmacodynamic data are obtained. In phase 2 studies, therapeutic effectiveness and common adverse effects are examined. In phase 3 studies, clinical safety is determined based on what adverse events occur. Phase 4 studies consists of postmarketing surveillance of patients after the drug is approved to detect potential long-term or rare side effects (4).

How do we measure drug safety?

Drug safety is measured using objective methods in a series of clinical trials the FDA oversees. In phase 1 studies, toxicity parameters, pharmacokinetic, and pharmacodynamic data are obtained. In phase 2 studies, therapeutic effectiveness and common adverse effects are examined. In phase 3 studies, clinical safety is determined based on what adverse events occur. Phase 4 studies consists of postmarketing surveillance of patients after the drug is approved to detect potential long-term or rare side effects (4).

Conclusion

Drug tolerability, the extent to which a drug’s adverse effects can be subjectively tolerated by patients, is somewhat distinct from drug safety, which measures objective adverse effects of a drug.

Disclosure statement

He is founder and part owner of Causa Research and holds stock in Sensal Health. Prajapati and Tao have no conflicts to disclose. No potential conflict of interest was reported by the author(s).

Additional information

Funding

Feldman has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Ortho Dermatology, Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, BMS, Ono, Micreos, Eurofins, Informa, UpToDate and the National Psoriasis Foundation.