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).
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.
| Prodrugs 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. |
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.
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.
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.
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.
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.
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.
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.
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 |
4. Pharmacokinetic Interactions
| Interaction Type | Description |
| Absorption | One drug interferes with the absorption of the other in the gut. |
| Renal Excretion | One drug interferes with the excretion of the other. |
| Plasma Proteins | |
| Unknown | The mechanism is not known. |
"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.
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.
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