Related Experiment Video
Updated: Jun 17, 2026
12:08
Diagonal Method to Measure Synergy Among Any Number of Drugs
Published on: June 21, 2018
Black box warning contraindicated comedications: concordance among three major drug interaction screening programs
Lorraine M Wang1, Maple Wong, James M Lightwood
1San Francisco Veterans Administration Medical Center, San Francisco, CA, USA.
The Annals of Pharmacotherapy
|December 31, 2009
Summary
Major drug interaction programs show significant discrepancies in identifying and rating contraindicated drug combinations found in black box warnings. Clinicians should use multiple resources to ensure patient safety and detect potential drug interactions.
Area of Science:
- Pharmacovigilance
- Drug Safety
- Clinical Pharmacology
Background:
- Black box warnings are the FDA's strongest safety alerts for prescription drugs.
- Some warnings identify drug combinations with increased risks of severe or life-threatening effects.
Purpose of the Study:
- To assess agreement among three leading drug interaction screening programs.
- Evaluate discrepancies in identifying, rating severity, and documenting contraindicated drug combinations from black box warnings.
Main Methods:
- Reviewed prescribing information for drugs with black box warnings mentioning contraindicated combinations.
- Assessed interactions using Facts & Comparisons 4.0, MICROMEDEX DRUG-REAX, and Lexi-Comp Lexi-Interact databases.
- Analyzed discrepancies in inclusion, severity scores, and documentation ratings.
Main Results:
- Identified 59 unique contraindicated drug combinations across 11 drugs; only 68% were covered by any program.
- Lexi-Comp detected the most interactions (29), DRUG-REAX the fewest (18).
- Only 3 combinations were consistently identified and rated as critical across all three programs; severity and documentation varied widely.
Conclusions:
- Significant discrepancies exist among drug interaction screening programs regarding black box warning contraindications.
- These inconsistencies may impact clinical practice and patient safety.
- Clinicians are advised to consult multiple drug interaction resources to mitigate risks.
Related Concept Videos
01:30Drug toxicity: Drug–Drug Interaction
Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...
01:25Pharmacokinetics: Drug–Drug Interactions
Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
01:30Combined Effects of Drugs: Antagonism
The combined effects of drugs can result in various interactions, of which an important type is antagonism. Antagonism is a mechanism where one drug inhibits or counteracts the effects of another drug. Antagonism can occur through various means, including receptor binding, allosteric modulation, functional interaction, chemical reactions, and pharmacokinetic processes.
The most common type is receptor antagonism, where one drug acts as an antagonist to block the effects of another drug by...
The most common type is receptor antagonism, where one drug acts as an antagonist to block the effects of another drug by...
01:26Pharmacokinetics: Drug–Food and Drug–Viral Interactions
A drug interaction occurs when the concurrent use of another drug, food, or an external substance alters the pharmacological activity of a drug. This interaction can modify the action of the original drug, affecting its effectiveness and safety.Drug–food interactions are significant as they impact drug absorption, metabolism, and excretion. For example, grapefruit juice is a well-known disruptor of drug metabolism. It inhibits the cytochrome P450 3A4 enzyme, crucial for the metabolism of many...
01:27Combined Effects of Drugs: Synergism
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
01:29Therapeutic Drug Monitoring: Affecting Factors
Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.