Glossary

The following are explanations for the content on RxISK as well as resources to explore further adverse drug effects.

Anticholinergic drug burden (ACB)

Adverse effects of anticholinergic medications may contribute to events such as fall, delirium, and cognitive impairment in older patients. If an older adult is taking one medication with an ACB score greater than 2 or having a total ACB score of 3 or more for all medications, consider reducing or changing medications. Where this is not possible, reduce doses as much as possible.

RxISK provides the ACB score for each drug where applicable.

Anatomical therapeutic chemical (ATC) classification system

The World Health Organization’s Centre for Drug Statistics Methodology has developed the ATC system to provide a global system for classifying medications. It is used around the world, but not in the United States. Under the ATC, active substances are divided into different groups according to the organ or system on which they act and their therapeutic, pharmacological, and chemical properties. Drugs are divided into 14 groups (at the first classification level). There are four sub-level classifications that result in an alphanumeric code representing a medication.

RxISK provides ATC codes for the medications in our system to make it easier to filter for drugs by organ or system and their therapeutic class. Most drugs have one ATC code but some have two or more codes.

Level 1  groups:

A — Alimentary tract and metabolism

B — Blood and blood forming organs

C — Cardiovascular system

D — Dermatologicals

G — Genito-urinary system and sex hormones

H — Systemic hormonal preparations, excluding sex hormones and insulins

J — Antiinfectives for systemic use

L — Antineoplastic and immunomodulating agents

M — Musculo-skeletal system

N — Nervous system

P — Antiparasitic products, insecticides and repellents

R — Respiratory system

S — Sensory organs

V — Various

Beers criteria for older adults

The American Geriatrics Society publishes the Beers criteria, which enumerate potentially inappropriate medications that continue to be prescribed and used as first-line treatment for older adults, despite evidence of poor outcomes. The criteria were last updated in late 2015.

There are three lists carried forward and updated in the 2015 version:

1. Medicines to avoid.
2. Medicines to avoid with specified diseases or syndromes.
3. Medicines to use with caution.

There are two new lists:

1. Medication-medication interaction criteria (non-anti-infective medications).
2. Medicines to avoided or reduce dosage with kidney function (non-anti-infective medications).

RxISK flags medications on the Beers criteria lists and provides details of Beers recommendations and rationale.

The Beers criteria includes both a Quality of Evidence (QE) and Strength of Recommendation (SR) label.

Quality of Evidence (QE)

High — Evidence includes consistent results from well designed, well-conducted studies in representative populations that directly assess effects on health outcomes (≥2 consistent, higher-quality randomized controlled trials or multiple, consistent observational studies with no significant methodological flaws showing large effects)

Moderate — Evidence is sufficient to determine risks of adverse outcomes, but the number, quality, size, or consistency of included studies; generalizability to routine practice; or indirect nature of the evidence on health outcomes (≥1 higher-quality trial with >100 participants; ≥2 higher-quality trials with some inconsistency; ≥2 consistent, lower-quality trials; or multiple, consistent observational studies with no significant methodological flaws showing at least moderate effects) limits the strength of the evidence

Low — Evidence is insufficient to assess harms or risks in health outcomes because of limited number or power of studies, large and unexplained inconsistency between higher-quality studies, important flaws in study design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes

Strength of Recommendation (SR)

Strong — Benefits clearly outweigh harms, adverse events, and risks, or harms, adverse events, and risks clearly outweigh benefits

Weak — Benefits may not outweigh harms, adverse events, and risks

Insufficient Evidence — inadequate to determine net harms, adverse events, and risks

More information on the Beers list can be found on the American Geriatrics Society site.

Black box warning

This type of Food and Drug Administration (FDA) warning appears on a prescription drug’s label and is designed to call attention to serious or life-threatening risks.

If a medication has a black box warning, RxISK provides a quick summary of the warning. However, for full details users must refer to the product data sheet.

Drug – generic name

A medication that is comparable to a brand/trade name in dosage form, strength, route of administration, quality and performance characteristics, and intended use. Most of the generic drugs listed are available in the United States. However, some are available only in other countries.

Drug – trade/brand name

This is the trademark or brand name given by the manufacturer to its drug product. These names often vary by country.

Drug – chemical name

A drug’s chemical name is the scientific name based on the molecular structure of the drug. RxISK does not display chemical names.

Forms of this drug

Drugs are administered via various “routes” or forms — for example, topical, inhalation, oral, intravenous, intramuscular, etc.

Interaction checker

The interaction checker provides information on possible interactions between medications with three levels of severity. This tool only covers medications marketed in North America. For other medications be sure to check local sources.

Medication guides

Medication guides are paper handouts/pamphlets that are required to be distributed to patients by the pharmacist for certain medications. Medication guides convey risk information that is specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

FDA requires that medication guides be issued with certain prescribed drugs and biological products when it determines that:

• certain information is necessary to prevent serious adverse effects,
• patient decision-making should be informed by information about a known serious side effect with a product, or
• patient adherence to directions for the use of a product is essential to its effectiveness.

Medication guides are included as part of a drug’s professional product monograph (PPM).

RxISK provides links to PDF versions of FDA-approved medication guides for those drugs that require one.

Prescrire drugs to avoid

Prescire International is based in France and provides independent information on medications. Prescrire is financed by its subscribers and not by grants, advertising, shareholders, or sponsors. Prescrire publishes an annual list of “drugs to avoid.”

RxISK flags those drugs that are on the Prescrire list and provides the Prescrire notes on reasons and suggested alternatives. RxISK also adds editorial notes to clarify some entries. These editorial notes are in [notes] brackets.

For more information visit the Prescrire in English website.

Product data sheet

Drug labeling — commonly called the package insert, prescribing information, the professional product monograph (PPM), or the product data sheet — provides information to the physician about what a prescription medication is supposed to do, who should and should not take it, and how to use it. Labeling also includes information on a drug’s side effects and warnings, and information from the clinical trials of the drug. Some prescription drug labeling also includes a part that describes the prescribing information in words that consumers will understand — this part is called a medication guide.

RxISK provides access to a growing set of FDA-approved PPMs. Each packager of a drug provides its own PPM. The PPMs are usually all or substantially all the same, but our goal is to provide access to all versions so that you can match your particular drug to the PPM of the packager for that drug.

We would like to provide access to Canadian PPMs, but so far the Health Canada says it cannot bulk release them to us in electronic form.

Proportional reporting ratio (PRR)

PRR is a statistic that is used to summarize the extent to which a side effect is observed for individuals taking a drug, compared to the frequency at which the same side effect occurs for individuals taking another drug (or any drug in a specified class of drugs).

A PRR greater than 1 suggests that the side effect is more commonly observed for individuals taking the drug of interest, relative to the comparison drugs. This could indicate that the side effect is caused by the drug of interest, although it could also reflect sampling variation in the data, reporting errors, biased reporting, or a number of other causes.

The higher the PRR, the more likely it is that the drug is causing the side effect. A PRR greater than 3 supports causality.

PRR is defined as the ratio between the frequency with which a specific side effect occurs for the drug of interest (relative to all side effects reported for the drug) and the frequency with which the same side effect occurs for all drugs in the comparison group (relative to all side effects for drugs in the comparison group).

For example, suppose that nausea was reported 83 times for a given drug of interest, out of 1,356 side effects reported for the drug. Thus, the proportion of side effects for this drug that are due to nausea is:

83/1,356 = 0.061

Suppose that we wish to compare the drug of interest to a class of drugs, for which nausea was reported as a side effect 1,489 times, out of 53,789 total side effects reported for drugs in the class. Thus, nausea was reported with the following proportion for this class of drugs:

1,489/53,789 = 0.028

The PRR in this case is:

0.061/0.028 = 2.18

This tells us that nausea has been reported more than twice as frequently (among all side effects) for the drug of interest compared to drugs in the comparison group.

QT interval

Some drugs prolong the QT interval on a patient’s electrocardiogram and thereby increase the risk of torsades de pointes (TdP), a heart arrhythmia that can cause sudden cardiac death. We licence and use the list provided and maintained by CredibleMeds, an independent non-profit organization based in Arizona. The CredibleMeds website provides detailed information on long QT syndrome and TdP and how to interpret the information provided in the lists.

See the CredibleMeds website for detailed information on these drugs as well as explanation of potential risks.

Search by side effect

This search tool uses the database of FDA and reports to find out which drugs could be linked to a particular side effect.

Side effects reported (top 100)

RxISK presents the top 100 reported side effects from the FDA Adverse Event Reporting System (FAERS) database, which contains more than 7 million adverse event and medication error reports submitted to the FDA from 2004–2016. We use the OpenFDA web service to retrieve the side effects.

Users of Open FDA are cautioned:

“Adverse event reports submitted to FDA do not undergo extensive validation or verification. Therefore, a causal relationship cannot be established between product and reactions listed in a report. While a suspected relationship may exist, it is not medically validated and should not be the sole source of information for clinical decision making or other assumptions about the safety or efficacy of a product. Additionally, it is important to remember that adverse event reports represent a small percentage of total usage numbers of a product. Common products may have a higher number of adverse events due to the higher total number of people using the product. In recent years the FDA has undertaken efforts to increase collection of adverse events. Increases in the total number of adverse events is likely caused by improved reporting.”

Screening tool of older people’s prescriptions (STOPP)

STOPP is a framework to support appropriate prescribing for the elderly with a European focus.

The essential differences between STOPP criteria and Beers criteria are as follows:

• STOPP criteria are organized according to physiological systems, whereas Beers criteria are not.
• STOPP criteria deal with drugs that are currently in widespread use; Beers criteria include several drugs that are no longer available in most European countries (e.g., trimethobenzamide, carisoprodol, clidinium-chlordiazepoxide, guanadrel, oxaprozin, and ethacrynic acid).
• STOPP criteria place special emphasis on potential adverse drug-drug interactions and duplicate-drug-class prescription, whereas Beers criteria do not.
• STOPP criteria contain several common instances of potentially inappropriate prescribing that are not mentioned in Beers criteria.

Serotonin syndrome

Serotonin syndrome is a predictable consequence of excess serotonin on the CNS and/or peripheral nervous system. Symptoms include cognitive, autonomic, and somatic effects and may range from barely perceptible to fatal.

See Drug-induced Serotonin Syndrome published by the US Pharmacist for more on serotonin syndrome and a list of drugs commonly associated with serotonin syndrome which we use.