Supplement 4: Ownership, Classification of Severity and Classification of Level of Evidence

Supplement 4: Ownership, classification of severity and classification of level of evidence of the databases.

Database / Owership and funding / Classification of severity / Classification of level of evidence
DrugBank / Supported by:
-The Canadian Institute of Health Research, the Canadian Government’s health research investment agency.
-Alberta Innovates – Health Solutions who delivers funding and supports health research.
-The Metabolic Centre, a research centre studying metabolomics and funded by the Canadian Government. / -Possible target-based interaction
-Possible enzyme-based interaction
-Possible transporter-based interaction / None
Drugs.com / Owned and operated by the Drugsite Trust. A privately held trust administered by two pharmacists.
Supported by advertisements and has an advertising policy. / -Major: Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
-Moderate: Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
-Minor: Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. / None
Epocrates / Owned by Athenahealth which is a listed company delivering cloud-based services for the health care industry.
Supported by third-party sponsors and have an advertising policy. / -Contraindicated: The combination should not be used under all but the most dire of circumstances.
-Avoid/Use Alternative: The combination is best avoided and/or alternative therapy should be considered.
-Monitor/Modify Therapy: An objective laboratory value or test must be followed and/or an adjustment to the dose must be made.
-Therapeutic Advantage: The combination is commonly used for the express purpose of generating the drug interaction, which results in a beneficial effect.
-Caution Advised: If an equally efficacious alternative without the interaction exists, it should be considered; otherwise, the clinician should use caution and the patient should be monitored subjectively and/or instructed to watch for the symptoms of the interaction. / None
Medscape / Owned by WebMD, a listed corporation that delivers health information services.
Supported by third-party sponsors, advertisements and have an advertising policy. / None / None
RxList / Owned by WebMD, a listed corporation that delivers health information services.
Supported by third-party sponsors, advertisements and have an advertising policy. / -Contraindicated: Never use this combination of drugs because of high risk for dangerous interaction.
-Serious: Potential for serious interaction; regular monitoring by your doctor required or alternate medication may be needed.
-Significant: Potential for significant interaction (monitoring by your is likely required).
-Minor: Interaction is unlikely, minor or non-significant. / None
Lexicomp / Provided by Wolthers Kluwer Health which is a listed information service company. / -Major: Effects may result in death, hospitalization, permanent injury or therapeutic failure.
-Moderate: Medical intervention needed to treat effects; effects do not meet criteria for Major.
-Minor: Effects would be considered tolerable in most cases no need for medical intervention. / -Excellent: Multiple randomized, controlled clinical trials or controlled, multi-patient pharmacokinetic studies (RCTs); OR single RCT plus >2 case reports.
-Good: Single RCT plus <2 case reports.
-Fair: >2 case reports; OR <2 case reports plus other supporting data; OR a theoretical interaction based on known pharmacology.
-Poor: <2 case reports with no other supporting data.
Micromedex / Micromedex solutions is owned by Truven Health Analytics, a listed company which provide solutions for the health care industry. / -Contraindicated: The drugs are contraindicated for concurrent use.
-Major: The interaction may be life-threatening and/or require medical intervention to minimize or prevent serious adverse effects.
-Moderate: The interaction may result in an exacerbation of the patient’s conditions and/or require an alteration in therapy.
-Minor: The interaction would have limited clinical effects. Manifestations may include an increase in the frequency or severity of side effects but generally would not require a major alteration in therapy.
-Unknown: Unknown. / -Excellent: Controlled studies have clearly established the existence of the interaction.
-Good: Documentation strongly suggests the interaction exists, but well-controlled studies are lacking.
-Fair: Available documentation is poor, but pharmacologic considerations lead clinicians to suspect the interaction exists; or, documentation is good for a pharmacologically similar drug.
-Unknown: Unknown.
Stockley’s / Published by the publishing division of the Royal Pharmaceutical Society, Pharmaceutical Press. The Royal Pharmaceutical Society is the membership body for pharmacy in Great Britain and founded to protect the profession’s interests and to advance scientific knowledge. / -Red: A life-threatening or contraindicated combinations.
-Yellow: Dosage adjustments or close monitoring is needed.
-Blue: Give guidance about possible adverse effects and/or consider some monitoring.
-Green: No interaction, or none interaction of clinical significance. / -Extensive: For interactions where the information given is based on numerous small or medium size studies or several large studies. The information is usually supported by case reports.
-Study: For interactions where the information given is
based on formal study. This may be one small or medium size study, or several small studies. The studies may or may not be supported by case reports.
-Case: For interactions where the information given is based either on a single report or a limited number of case reports. No trials appear to have been conducted.
-Theoretical: For interactions where the information given is based on a theoretical interaction or lack of interaction. This information may have been derived either from in vitro studies involving the drug in question or based on the way other members of the same group act.