How do I look up potential interactions between my medications, including prescription drugs, over-the-counter (OTC) medications, and supplements?

How to Look Up Drug Interactions

Use the University of Liverpool's interactive web-based resource (www.hep-druginteractions.org) as your primary tool for checking interactions between prescription drugs, over-the-counter medications, and supplements, as this database is specifically recommended by multiple medical societies and provides regularly updated, comprehensive interaction data. 1

Essential Information to Gather Before Checking

Before using any interaction checker, compile a complete medication list including:

• All prescription medications (brand and generic names) 1
• Over-the-counter drugs (pain relievers, antacids, allergy medications) 2
• Vitamins and minerals 1
• Herbal supplements and botanical products 2, 3
• Recreational or party drugs 2
• Products purchased via the internet 2

Primary Resources for Interaction Checking

The most reliable interaction databases recommended by clinical guidelines include:

• www.hep-druginteractions.org - University of Liverpool's database covering over 800 co-medications with regularly updated recommendations 2, 1
• Drugs.com drug interaction checker - Free online tool that categorizes interactions by severity 2
• Medscape.com drug interaction checker - Another validated free resource 2
• Manufacturer drug labels (FDA-approved) - Always check these for specific contraindications 1

How to Interpret Interaction Severity

Interaction checkers typically classify findings into three categories that require different actions 2:

• Severe/Major interactions: These drug combinations should not be co-administered and require immediate intervention 2
• Moderate interactions: May require dosage adjustments, altered timing of administration, or additional monitoring 2
• Minor interactions: No clinically significant interaction expected, but awareness is still important 2

Critical Information Each Interaction Report Should Provide

When reviewing interaction results, look for these specific details 2:

• The exact drug pair causing the interaction - Both generic and brand names should be clearly identified 2
• Clinical consequences - What adverse outcome could occur (e.g., hyperkalemia, QT prolongation, bleeding, reduced drug efficacy) 2
• Mechanism of interaction - How the drugs interact (e.g., CYP3A4 inhibition, P-glycoprotein induction) 2
• Frequency or incidence - How often the adverse event occurs when drugs are combined 2

Common Pitfalls and Important Caveats

Be aware that different interaction databases often provide inconsistent information about the same drug pairs. Studies show poor inter-source reliability (kappa < 0.20) among major drug information resources for severity ratings, clinical effects, and management recommendations 4. When databases disagree:

• Prioritize FDA drug labels and manufacturer prescribing information 1
• Use multiple reputable sources to cross-reference findings 2
• Consult the most recently updated resource, as interaction data evolves 2

Patients frequently fail to disclose supplement use. Between 31-68% of patients taking supplements do not inform their physicians 5. To improve disclosure:

• Ask specifically about "vitamins, herbs, teas, or natural products" rather than just "medications" 5
• Document supplement use at every clinical encounter 5
• Remember that herbal products lack standardization and vary widely in active ingredient content 5

High-Risk Medications Requiring Extra Vigilance

Certain drugs are more likely to be involved in serious interactions and require careful checking 6:

• Warfarin - Interacts with numerous drugs, supplements, and foods; requires frequent INR monitoring when any medication is started or stopped 3
• Drugs with narrow therapeutic ranges - Antiepileptic drugs, immunosuppressants (tacrolimus, cyclosporin), digoxin 2, 6
• Statins - Particularly when combined with CYP3A4 inhibitors or cyclosporin 2
• Antiretroviral medications - Have extensive interaction profiles requiring specialized checking 2
• Direct oral anticoagulants - Interact with P-glycoprotein and CYP3A4 inhibitors/inducers 7

Supplements That Commonly Cause Serious Interactions

St. John's wort must be discontinued at least 2 weeks before starting medications metabolized by CYP3A4, as it induces this enzyme and markedly reduces plasma concentrations of affected drugs. 2, 5 This includes:

• Immunosuppressants (cyclosporin, tacrolimus) 2
• Antiretrovirals 2
• Oral contraceptives 2
• Many cardiovascular medications 5

Grapefruit juice inhibits CYP3A4 and increases blood levels of ciclosporin and most statins unpredictably. Patients on affected medications should avoid grapefruit completely, not just separate timing of ingestion 5.

Supplements affecting bleeding risk that should be checked against anticoagulants and antiplatelet agents include garlic, ginkgo biloba, ginger, turmeric, vitamin E, saw palmetto, horse chestnut, dong quai, danshen, and cranberry products 5, 3.

When to Recheck for Interactions

Perform a new interaction check whenever 2, 3:

• Starting any new medication (prescription or OTC) 2
• Discontinuing a medication 3
• A patient takes medications irregularly 3
• Transitioning care settings (hospital discharge, nursing home admission) 2
• A patient reports new symptoms that could represent drug toxicity 2

What to Do When Interactions Are Identified

Follow this hierarchy of management strategies 1:

1. Discontinue the interacting medication if it is not essential during the treatment period 1
2. Substitute with an alternative in the same therapeutic class that has lower interaction potential 1
3. Adjust the dose of one or both medications based on interaction severity 1
4. Establish a clear monitoring plan with appropriate laboratory tests (drug levels, INR, renal function, liver function) when the interaction cannot be avoided 2, 1
5. Separate timing of administration for absorption-related interactions (e.g., calcium and fluoroquinolones should be separated by several hours) 8

Special Populations Requiring Enhanced Interaction Screening

Polypharmacy patients (typically defined as taking 5 or more medications) have exponentially higher interaction risk. Studies show strong correlation between number of drugs and number of interactions (Rho 0.744, p<0.001) 9. These patients require:

• Systematic medication reconciliation at every encounter 2
• Regular deprescribing assessments to eliminate unnecessary medications 2
• More frequent monitoring for adverse effects 2

HIV-HCV coinfected patients require particularly close attention to antiretroviral-drug interactions, as many antiretrovirals are contraindicated or require dose adjustment with hepatitis C direct-acting antivirals 2.