Facts and Comparisons Drug Interactions Module

Using the Interactions Module

The Interactions module is an interaction analysis tool that is designed to identify potential drug-drug, drug-allergy, drug-pregnancy, drug-lactation, and drug-disease interactions, as well as identify possible duplicate therapy issues. Use the blue bar at the top of the screen to access the Interactions module. Begin by entering the drugs to be analyzed. "Search Drugs" allows users to enter medications (both prescription and over-the-counter), natural products, foods, and/or alcohol. "Search Allergies," allows users to enter medication names (e.g., aspirin) or pharmacologic classes (e.g., salicylates). "Search Diseases/Conditions” allows users to select a disease/condition from the search box.

To enter an item, begin typing a keyword into the "Search Drugs" box. Once you begin entering characters, suggested terms will populate the dropdown list. The choices will narrow as more characters are entered. If multiple products match your search term, a list of products will appear. To add that medication to the medication list, simply click on the drug name or the Add button. Continue this process until all items are added. To remove an item from the list, click the “X” next to the product you wish to remove. Use the same process if you wish to add/remove allergy and disease screening terms to the analysis.

Once the list is complete, click the Analyze button to perform an analysis. Duplicate drug therapy, pregnancy and lactation options are automatically checked. If you do not want duplicate drug therapy or pregnant/lactating screening to be performed, the respective boxes can be unchecked prior to clicking the "Analyze" button.

The "Interaction Analysis" tab provides a summary statement for each interaction, organized into Drug-Allergy, Drug-Drug, Drug-Food, Drug-Alcohol, Pregnancy, Lactation, Precautions (for the disease/conditions), and duplicate therapy sections. The summary statements include the search terms used, along with the corresponding class(es), if applicable. An assigned risk icon (red, yellow, or blue) appears on the Interaction Analysis screen. Each icon represents a different level of urgency in responding to the identified interactions. The risk rating scale is defined in more detail below.

You can filter the interactions that are displayed on the Interaction Analysis screen using the available drop-down menus. Use the “Jump to Section” to go directly to the section you want to review first. Use the “Filter Item” to filter by drugs, allergies, applicable age/gender categories or conditions entered. Use the “Filter Risk Ratings” to filter by various interaction levels. To remove the filters selected, simply click the Reset Filters button to return to the full, unfiltered interaction analysis results.

Drug Interaction and Allergy Analysis Scale

Risk Rating Icon: Provides an indicator to help a clinician quickly decide how to respond to the interaction data. Each drug-drug, drug-food and drug-alcohol interaction is assigned a risk rating icon. The progression from blue to red is accompanied by increased urgency for responding to the data. In general, the blue icon indicates that the interactions are of reduced clinical relevance. Monographs with a red or yellow icon indicate situations that will likely demand a clinician’s attention. The text of the “Management” section of the monographs will provide assistance regarding responses that may be generally useful for many patients. Each drug-allergy interaction is assigned a red risk rating icon.

The definition of each drug interaction risk rating is as follows:

• Risk Rating Major - Severity Major
  Documentation - Suspected, Probable, Established
  Potentially severe or life-threatening interaction; supported by primary literature that includes multiple case reports and/or controlled studies. Some contraindicated drug combinations may also be included.
• Risk Rating Moderate - Severity Moderate
  Documentation - Suspected, Probable, Established
  Interaction may cause deterioration in the patient’s clinical status; supported by primary literature that includes multiple case reports and/or controlled studies. Some contraindicated drug combinations may also be included for which supporting documentation indicates the interaction is unlikely to be life-threatening.
• Risk Rating Moderate - Severity Major
  Documentation - Possible
  Interaction may cause major effects but literature support is very limited.
• Risk Rating Minor - Severity Moderate
  Documentation - Possible
• Risk Rating Minor Suspected
  Documentation - Probably, Established
  Interaction is unlikely to be clinically relevant. Interaction is supported by limited data in the primary literature.
• Risk Rating Minor - Severity Minor
  Documentation - Possible
• Risk Rating Any Doubtful/Unknown
  Interaction is unlikely to be clinically significant. Interaction is supported by limited and/or conflicting data.

Drug-Pregnancy/Lactation and Disease/Condition Risk Rating Scale

Risk Rating Icon: Provides an indicator to help a clinician quickly decide how to respond to the interaction data. Each drug-pregnancy, drug-lactation and drug-disease interaction is assigned a risk rating icon. The progression from blue to red is accompanied by increased urgency for responding to the data. In general, the blue icon indicates that the interactions are of reduced clinical relevance. Interactions with a red or yellow icon indicate situations that will likely demand a clinician’s attention.

The definition of each risk rating is as follows:

Risk Rating “Major” / Severity Level “Contraindicated”

• Pregnancy: Use of the drug during pregnancy is contraindicated in the source documentation. Source documentation may also indicate toxicity, teratogenicity, and/or increased morbidity or mortality of the fetus with drug use in pregnant women.
• Lactation: Breastfeeding is contraindicated in the source documentation. Drug is associated with severe adverse effects, toxicity, morbidity or mortality in the nursing infant. Effect of the drug in the nursing infant is unknown; however, similar drugs have been associated with severe adverse effects, toxicity, morbidity or mortality.
• Disease: This level is used when the risk from use of a drug product clearly outweighs any possible therapeutic benefit. Generally speaking, the source documentation will state the product is contraindicated for a given condition.

Risk Rating “Moderate Severity” / Severity Level “Not recommended”

• Pregnancy: Use of the drug during pregnancy is not recommended in the source documentation. Source information may also indicate toxicity, teratogenicity, and/or increased morbidity or mortality of the fetus with drug use in pregnant women.
• Lactation: Source documentation indicates breastfeeding is not recommended or should be withheld until therapy is discontinued. The drug is associated with an increased incidence of adverse events and/or toxicity in the nursing infant.
• Disease: This level is used when use of the product is presented in source documentation as “not recommended”, “avoid use”, “should not be used”, or similar phrasing in patients with a given condition.

Risk Rating “Moderate” / Severity “Extreme caution”

• Pregnancy: Should be used with caution during pregnancy.
• Lactation: Use with caution in breastfeeding women. Information regarding excretion of the drug in human breast milk and /or adverse effects or safety in the nursing infant is insufficient or unknown.
• Disease: Drug therapy should be used with extreme caution. Source information indicates the drug should be used with extreme caution in the specific disease state.

Risk Rating “Minor” / Severity “Use cautiously”

• Pregnancy: Safety and efficacy not established, consult physician regarding drug use during pregnancy, or there are no reports of fetal/newborn adverse effects when the drug is used during pregnancy.
• Lactation: Safety and efficacy not established, consult physician in breastfeeding women; a lack of human data but the drug is probably compatible with breastfeeding, or excretion into breast milk is unlikely to be of concern.
• Disease: Drug therapy should be used cautiously in a specific disease state.

Risk Rating “Minor” / Severity “Informational”

• Pregnancy: Source information indicates no evidence of fetal harm during pregnancy; the drug is compatible or probably compatible with use during pregnancy; there is no evidence of fetal/newborn risk when the drug is used during pregnancy; maternal systemic absorption is negligible or not sufficient to warrant precautions when administered to pregnant women; placental transfer is unknown or does not occur.
• Lactation: Human lactation information demonstrates no adverse effects or suggests safe use in the nursing infant; drug is compatible with breastfeeding or does not pose a hazard to the breastfeeding infant; drug is not found in human breast milk or drug factors make it unlikely to be excreted into breast milk; if excreted, drug factors make it unlikely to be absorbed by the nursing infant.
• Disease: Drug therapy has some precautionary information not precluding use in the given condition.

Viewing Interaction Details

Each interaction summary is a link to more detailed information on the interaction.

Drug-Drug/Drug-Food/Drug-Alcohol Interactions

Each monograph provides a summary of the interaction, along with information on the mechanism, effect and management, with a discussion and references available. At the top of the monograph there are indicators displaying the Severity, Documentation and Onset levels for the particular interaction. The levels are defined below as follows:

Severity: Used to qualify the medical risk of the interaction. Possible values:

• Major: The interaction may be life-threatening or cause permanent damage.
• Moderate: The patient’s condition may deteriorate due to the interaction, requiring additional care or extended hospitalization.
• Minor: An interaction that is bothersome, but otherwise not medically detrimental.

Documentation: Indicates the quality and quantity of the medical literature supporting the inclusion in the data. Possible values:

• Established: The interaction has been proven to occur in well controlled human studies in which either altered pharmacologic effects have been documented or known pharmacokinetic changes have been reported along with supporting clinical observations.
• Probable: Pharmacokinetic changes have been documented and are known to be of sufficient magnitude to alter the therapeutic response. However, well controlled human studies showing altered clinical effects are not available. Well-designed animal studies may support the interaction on rare occasions if numerous case reports or uncontrolled studies in humans exist.
• Suspected: Pharmacokinetic changes may have been documented in well-controlled studies, but the relationship between plasma concentrations and pharmacologic effect has not been confirmed. Altered pharmacologic effects reported in multiple case reports or uncontrolled studies may also be given this level of documentation. This includes drug interactions appearing in a black box warning and/or contraindications section of manufacturer’s product literature even in the absence of available published information. Such product literature shall be considered as carrying the same weight as case reports in the clinical literature.
• Possible: Pharmacokinetic data, such as small pharmacokinetic studies in healthy volunteers demonstrated pharmacologic response, or case reports suggest a possible interaction. However, the quality or quantity of supporting clinical data does not substantiate the predictability of the interaction.
• Doubtful/Unknown: The bulk of the clinical documentation is of poor quality, or well-controlled studies refute case reports of an interaction. Also included in this group are those interactions for which some kind of pharmacokinetic change has been reported, but the effect of this change is clinically insignificant.

Onset: Indicates how quickly the interaction may occur.

• Rapid: The clinical manifestation of the interaction may occur within 24 hours of the patient receiving the potentially interacting combination. Generally, rapid onset interactions may require immediate attention by the clinician.
• Delayed: Interactions requiring more than 24 hours from the time of administration for a problem to become clinically evident. Delayed onset interactions may be as severe as rapid onset interactions, but the clinician usually has more time to consider specific, practical options.

Drug-Allergy

To view more detail about a particular drug-allergy interaction, click on a hyperlinked term to review information on:

• Reactions reported as well as other relevant information for the clinician
• Fully referenced discussion of the available literature
• References

Drug-Pregnancy

Additional information on the severity level and placental transfer are available via the hyperlinked interaction. Severity levels are described previously in the Drug-Pregnancy/Lactation and Disease/Condition Risk Rating Scale table. Placental Transfer identifies whether the drug can transfer across the placental barrier in pregnant women. Possible settings are listed below:

Option / Description

• Yes - Does transfer across placental barrier
• No - Does not transfer across placental barrier
• Maybe - May transfer across placental barrier
• Unknown - Either source documentation states transfer across placenta unknown or no information on placental transfer is provided.

Drug-Lactation

The detail information for the Drug-Lactation interaction provides information on the severity levels (described previously in the Drug-Pregnancy/Lactation and Disease/Condition Risk Rating Scale table) and breast milk excretion. The Breast Feeding Excreted scale indicates whether a drug is excreted in breast milk based upon information in the product labeling or other source documentation. The options are as follows:

Breast Feeding Excreted Description

• Yes - Excreted in breast milk
• No - Not excreted in breast milk
• Maybe - May be excreted in breast milk
• Unknown - Either source documentation states excretion unknown or no information available on excretion.

Drug-Disease

Severity levels include Contraindicated, Not recommended, Extreme Caution, Use Cautiously and Informational (described previously in the Drug-Pregnancy/Lactation and Disease/Condition Risk Rating Scale table). There may be additional information available in the Comments section on the use of the drug and the condition together.

To return to the Interaction Analysis summary page, click on the "Interaction Analysis" tab at the top of the content panel. To return to the initial search screen to enter an additional item, click on the "Search" tab at the top of the content panel.

The Clear button will clear all items from the list and allow the user to start a new regimen.