BNF for Children (BNFC) 2018-2019

Relative importance of interactions

Levels of severity:Most interactions have been assigned a

severity; this describes the likely effect of an unmanaged

interaction on the patient.

Severe—the result may be a life-threatening event or have

a permanent detrimental effect.

Moderate—the result could cause considerable distress or

partially incapacitate a patient; they are unlikely to be life-

threatening or result in long-term effects.

Mild—the result is unlikely to cause concern or

incapacitate the majority of patients.

Unknown—used for those interactions that are predicted,

but there is insufficient evidence to hazard a guess at the

outcome.

Levels of evidence:Most interactions have been assigned

a rating to indicate the weight of evidence behind the

interaction.

Study—for interactions where the information is based on

formal study including those for other drugs with same

mechanism (e.g. known inducers, inhibitors, or substrates of

cytochrome P450 isoenzymes or P-glycoprotein).

Anecdotal—interactions based on either a single case

report or a limited number of case reports.

Theoretical—interactions that are predicted based on

sound theoretical considerations. The information may have

been derived fromin vitrostudies or based on the way other

members in the same class act.

Action messages:Each interaction describes the effect

that occurs, and the action to be taken, either based on

manufacturer’s advice from the relevant Summary of

Product Characteristics or advice from a relevant authority

(e.g. MHRA). An action message is only included where the

combination is to be avoided, where a dose adjustment is

required, or where specific administration requirements (e.g

timing of doses) are recommended.Pharmacodynamic

interactions, with the exception of interactions with drugs

that may prolong the QT interval, do not have an action

message included as these will depend on individual patient

circumstances.

Appendix 1 structure

.^1 Drugs
Drugs are listed alphabetically. If a drug is a member of a
drug class, all interactions for that drug will be listed
under the drug class entry; in this case the drug entry
provides direction to the relevant drug class where its
interactions can be found.
Within a drug or drug class entry, interactions are listed
alphabetically by the interacting drug or drug class. The
interactions describe the effect that occurs, and the action
to be taken, either based on manufacturer’s advice from
the relevant Summary of Product Characteristics or advice
from a relevant authority (e.g. MHRA). An action message
is only included where the combination is to be avoided,
where a dose adjustment is required, or where specific
administration requirements (e.g. timing of doses) are
recommended. If two drugs have a pharmacodynamic
effect in addition to a pharmacokinetic interaction, a
cross-reference to the relevant pharmacodynamic effect
table is included at the end of the pharmacokinetic
message.
.^2 Drug classes
The drugs that are members of a drug class are listed
underneath the drug class entry in a blue box. Interactions
for the class are then listed alphabetically by the
interacting drug or drug class. If the interaction only
applies to certain drugs in the class, these drugs will be
shown in brackets after the drug class name.
.^3 Supplementary information
If a drug has additional important information to be
considered, this is shown in a blue box underneath the
drug or drug class entry. This information might be food
and lifestyle advice (including smoking and alcohol
consumption), relate to the pharmacology of the drug or
applicability of interactions to certain routes of
administration, or it might be advice about separating
administration times.
.^4 Pharmacodynamic effects
Tables at the beginning of Appendix 1 cover
pharmacodynamic effects. If a drug is included in one or
more of these tables, this will be indicated at the top of the
list of interactions for the drug or drug class. In addition to
the list of interactions for a drug or drug class, these
tables should always be consulted.
Each table describes the relevant pharmacodynamic
effect and lists those drugs that are commonly associated
with the effect. Concurrent use of two or more drugs from
the same table is expected to increase the risk of the
pharmacodynamic effect occurring. Please note these
tables are not exhaustive.
.^1 Drug entry
▶Details of interaction betweendrug entryand anotherdrug
ordrug class. Action statement.ZEvidence
▶Details of interaction betweendrug entryand anotherdrug
ordrug class. Action statement.ZEvidence
→Also seeTABLE 1
Drug entry→see Drug class entry
.^2 Drug class entry
Drug A.Drug B.Drug C.Drug D..
▶Details of interaction betweendrug class entryand another
drugordrug class. Action statement.ZEvidence
.^3 Drug entry or Drug class entry
Supplementary information
.^4 Drug entry or Drug class entry→seeTABLE 1

TABLE 1

Name of pharmacodynamic effect

Explanation of the effect

Drug

Drug

Drug

Drug

Drug

Drug

846 Appendix 1 Interactions BNFC 2018 – 2019

Interactions

|Appendix 1

A1