notes4

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Getting Started

The table at the left shows the most clinically relevant information.

To see more detailed information about any predicted interaction expand the nodes with the icon.

For explanations about information in the table click the links and buttons in the table:

Column headings explain what is in each column.
Drug name in the Affected Drug column displays all of the metabolic characteristics of the drug.
Buttons in the Change column show the same explanation as the Change column heading.
Buttons in the Evidence column show the notes and references associated with the drug and its interactions.
All links in the Mechanisms column show the same explanation as the Mechanism column heading.

Don't show "Getting Started" with each search; show Note #1 (if there is one).

Column Heading Explanation:

Affected Drug

The drug whose metabolism may be changed.

To see all of the metabolic characteristics of the drugs involved click anywhere in this column.

To see details about an interaction and to find alternative drugs click the icon.

If the interaction is predicted because the drug is in a particular class, the name of the class appears after the drug name.

have a yellow background in this column. When the level of a prodrug changes, special attention to the effect on the active form is required. An increase in the level of a prodrug means less of the active form will be available: and a reduced level of a prodrug means more of the active form will be available.

Column Heading Explanation:

Change

Possible change in patient's exposure to the drug (includes concentration, half-life etc.). The prediction is based on clinical reports if available (noted in the Evidence column) or calculated by the program's algorithm.

The stethoscope icon indicates that the change is predicted from published clinical reports whose abstracts can be accessed through the Evidence column. The calculator icon means that our algorithm was used.

When two drugs are in the same class and intensification of therapeutic or side effects is likely the word "Additive!" appears as a reminder.

Description	Percent
Extreme increase	More than 150
Substantial	+75-150
Modest	+25-75
Minimal	Less than 25
Modest	-25-60
Substantial	-60-90
Extreme decrease	-90-100

When there are clinical reports of the interaction but they do not allow a quantitative prediction, the word "Some" is shown. If the direction of change can be predicted a + or - sign is added: '+ Some'.

When the level of a Prodrug changes, special attention to the effect on the active form is required. An increase in the level of a prodrug means less active form will be available: and a reduced level of a prodrug means more of the active form will be available.

Drugs with a narrow therapeutic range which are marked with >N< are more liely to cause problems when an interaction occurs.

Mechaism-based inhibtion interactions are flagged. They require a longer time to recover than other inhibition interactions. Roll your mouse over the text in the change column to see a pop up explanation.

Column Heading Explanation:

Causative Agent

The drug, substance or genetic allele causing this interaction. There may be more than one agent involved.

To see details expand the display by clicking the at the left of the line. Alternative drugs which do not cause this interaction can be found there as well.

If the interaction is predicted because the drug is in a particular class, the name of the class appears after the drug name.

Column Heading Explanation:

Evidence

Click in this column to see the notes (if any) associated with this interaction. If the FDA approved drug package insert is available, "Pkg Insert" appears here as a link which will take you to it.

Notes most often tell about published clinical studies. The headings for notes about clinical studies look like this:

Evidence Strength: Moderate
There has been a clinical trial.

2D6 Poor Metabolizer and Atomoxetine

Notes that are based on clinical data have a box like the yellow one above which shows the confidence we place in the clinical reports. The background color of the box also shows the level of confidence.

Weak Evidence

Moderately Strong Evidence

Strongest Evidence

The title of the note has a colored background - like the red one above - which shows the intensity or clinical significance of the drug interaction it discusses. The colors and their meaning are the same as those in the Change column.

Extreme change

Substantial

Modest

Minimal

To see the references click on the References link at the bottom of the note. Most references are represented by links to PubMed abstracts or other Web resource. If the reference is not available through the Web a traditional reference is displayed.

Column Heading Explanation:

Drug Details

Details about the drug above.

Lines with light cream colored background show major metabolic pathways. Both interactions and uninvolved pathways are included.
Rows with this background are less important. Their interactions are usually - but not always - of minor importance. When there are several minor interactions with a similar effect they may become significant. An interaction is of lesser importance either because it involves a minor metabolic pathway or because the pathway is only modestly affected
Uninvolved pathways are shown. They may reduce the impact of changes in affected pathways. Previously unknown pathways for drugs are frequently being found.

Metabolites The metabolites shown are pharmacologically active except in rare instances where 'inactive' is added after the name.

Alternative Drugs Click the to search for alternative drugs which are not substrates of the same CYP as this drug.

Expanded Display:

Interaction Details

You can open the interaction details for individual drugs by clicking the

icons in the column below the question mark you just clicked. If there are no icons it is because no interactions are predicted for that drug.

Lines with light cream colored background show major metabolic pathways.

Rows with this background are of less importance. Their interactions are usually - but not always - of minor importance. When there are several minor interactions with a similar effect they may become significant. An interaction is of lesser importance either because it involves a minor metabolic pathway or because the pathway is only modestly affected. You can change whether minor interactions are included by setting it in the Preferences page.

Uninvolved pathways are shown. They may reduce the impact of changes in affected pathways. Previously unknown pathways for drugs are frequently being found.

Column Heading Explanation:

Will go . . .

The direction of change in the drug's concentration. Not quantitative

When a prodrug is given, the available active form of the drug will change in the opposite direction from that of the prodrug. The change shown here is for the prodrug.

Column Heading Explanation:

Because of . . .

The drug, substance or genetic allele causing this interaction. There may be more than one agent involved.

Alternative Drugs Click the to search for alternative drugs which are not inhibitors or inducers (as appropriate) of the same CYP as this drug.

Column Heading Explanation:

Mechanisms

1. Metabolic Pathway:

Appearance	Pathway Importance
	The red is roughly the proportion of the affected drug metabolized by this route.

2. Inhibition:(Jersey barriers*)

Appearance	Affect	Ki
	Major	Ki <2
	Moderate	Ki 2-5
	Small	Ki >5

3. Induction:(Fans)

Appearance	Intensity
	Strong
	Unknown
	Weak

"Undisturbed Route" means that the metabolic route is not affected by any interaction and therefore will be normally available as a metabolic route.

(seesaw) = Reminder: What lowers the parent compound raises the level of its active metabolites.

* History of the origin of the New Jersey barrier: http://www.roadstothefuture.com/Jersey_Barrier.html

Affected Drugs This table shows only drugs which are predicted to experience significant change as a result of the drug you are starting or stopping.

Change The bar graph shows the drug's predicted level before and after the change you are making. Sometimes the drug's level is higher or lower than normal before the change because of interactions already present. The percentages on the left indicate the amount of change from a 'normal' - no interaction - level.

Speed Interactions which raise a drug's level through inhibition occur quickly because the barrier to metabolism is already in place; those that occur as a result of induction of an enzyme occur slowly because the induced enzymes are produced slowly. When a drug causing an interaction by inhibition is stopped levels drop quickly because the inhibiting drug is removed quickly; but if the cause was increased enzyme then it drops slowly because enzymes are replaced slowly.

Reason for Change To get an explanation of this column open the details section of the main results table and see the column explanations there.

Help

Interactions Report Help

Interaction predictions are based on published clinical reports and on an algorithm which incorporates knowledge about the metabolism of individual drugs. The algorithm permits predicting potential interactions even when there are no clinical studies. The notes about interactions contain links to the original research.

The first thing to note in the search results is what background color the top rows of drugs have. Red indicates possible severe interaction and often means the combination is contraindicated. Green background means no expected interaction. The two shades of yellow are for intermediate levels of risk. Results are organized in descending order of importance of the possible interactions. Click on the column headings to see explanations about each column.

For any interaction predicted you can expand its row by clicking on the icon to see the details about the prediction. Clicking the column headings in the details section also shows more explanations.

Often the key question about potential drug interactions is what may happen if a drug is started or stopped while the patient is taking several other drugs. The "Starting-Stopping" page makes the dynamics of the changing medication set clearer. The column heading in its table also help to explain.

The print button allows printing of the potential drug interaction report. There are options to include as much or as little detail as you need in the printed version.