Supplement 4: Ownership, classification of severity and classification of level of evidence of the databases.
Database
Owership and funding
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.
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Owned and operated by the Drugsite
Trust. A privately held trust
administered by two pharmacists.
Supported by advertisements and has
an advertising policy.
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Drugs.com
Classification of severity
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Classification of level of evidence
Possible target-based
interaction
Possible enzyme-based
interaction
Possible transporter-based
interaction
None
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.
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Medscape
Owned by WebMD, a listed
corporation that delivers health
information services.
Supported by third-party sponsors,
advertisements 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
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.
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Lexicomp
Provided by Wolthers Kluwer Health
which is a listed information service
company.
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None
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.
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.
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Minor: Effects would be
considered tolerable in most
cases no need for medical
intervention.
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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.
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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.
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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.
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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.
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Excellent: Controlled studies
have clearly established the
existence of the interaction.
Good: Documentation
strongly suggests the
interaction exists, but wellcontrolled 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.
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.
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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.