Applied PK Exam 1: Fong

What is a DDI?

• The process by which the pharmacokinetic (PK) or pharmacodynamic (PD) process of a drug is altered by the influence of another drug after combination.

  • PK: ______

  • PD: ______

what the body does to the drug, what the drug does to the body

PK DDI

• When one drug impacts/interferes with the ______ properties of another drug, impacting its ______

• Absorption – ______ absorption (e.g., cation binding) leading to ______

• Distribution – decreased protein binding leading to increased unbound drug. Potentially more activity but also more clearance

• Metabolism – decreased/increased metabolism which can lead to increased/decreased ______

• Excretion – decreased secretion in renal tubules leading to increased plasma levels

• Interacting drugs ______ to each other clinically (e.g., antibiotics inhibiting metabolism of an anticoagulant)

PK, clinical effect, decreased, lower plasma levels, plasma levels, may have no relationship

Enzyme Inhibition and Induction

• Most commonly impacts ______ enzyme system (______)

  • Other enzymes can be involved (e.g., UGT, MAOi’s, etc.)

CYP, CYP34, 2D6, 2C8/9

Inhibition

• Competitive/non-competitive binding of ______ to ______, leading to decreased metabolism

• Typically impacts the ______ system

  • Can be important to know which specific enzyme effected

• Inhibition typically occurs ______ and requires ______

  • Half-life of inhibitor needs to be considered

substrate, metabolizing enzyme, CYP450 enzyme, rapidly, presence of inhibiting drug

Induction

• ______ production of ______ (usually ______) leading to eventual ______ metabolism

• Induction ______ and can be ______ or ______ as ______ enzymes need to be ______. ______ of drug may not lead to ______ as enzymes need to be ______

  • Half-life of inducer needs to be considered

Increased, metabolizing enzymes, CYP, increased, timeline varies, rapid, take days, more, produced, removal, immediate reversal, downregulated

CYP Induction Example

• Most potent enzyme inducer → ______ (antibacterial)

Rifampin

Pharmacodynamic (PD) DDI

• Typically involves ______ drugs that have the ______ physiological effect and not necessarily any interaction in the PK process.

• Multiple agents that ______ (e.g., ______, ______, etc.)

• Multiple agents that ______ (e.g., ______, ______, etc.).

2 or more, same/similar, effect the clotting pathway, anticoags, antiplatelets, effect QTc, antiarrhythmics, antibiotics

DDI References

• AI, Micromedex, UpToDate (LexiComp), Specialized Sites (e.g., Liverpool), and Primary Literature

KNOW

Case Example: Posaconazole and Bictegravir

• Posaconazole: antifungal medication primarily used to treat fungal infections that occur in immunocompromised pts

  • CYP3A4 inhibitor

  • Adverse effects: liver injury, prolonged QTC (lead to Torsdades), pseudohyperaldosteronism (hypokalemia (low K)/HTN)

  • Alternatives: voriconazole, isavuconazole

• Bictegravir: newer generation HIV medication that is potent, well-tolerated and 1st line

  • Metabolized via UGT1A1 and CYP3A4

  • Adverse effects: minimal

  • Alternatives: dolutegravir

KNOW

PK vs. Clinical Consequence

• Claude prompt: Are there any reports of harm caused by the interaction between bictegravir and posaconazole? (published case reports of drug causing harm?)

• Summary:

  • No published case reports or pharmacovigilance signals specifically tying bictegravir + posaconazole to patient harm.

  • The interaction is real and predicted (increased bictegravir exposure), based on shared metabolic pathways, but it hasn't been formally studied as a pair.

  • Bictegravir's pharmacology suggests a wide margin of safety even with exposure increases seen from similar-mechanism inhibitors.

KNOW

Significance

• Unlikely harm

• Possible harm → Serious harm?

• Likely harm

  • ______

  • ______

  • ______

Intolerance, clinically relevant harm, life-threatening harm

Clinical Consequences/Interventions

• FYI and monitor

  • Inform provider and/or patient

  • Give guidance on ______

• Adjust dosing

  • Can be formally ______ or ______

  • Need to provide monitoring parameters

• Change to an alternative

  • Decide which agent ______

  • Understand ______ – ______

S/Sxs to pay attention to, recommended adjustment, clinical judgement, needs to be switched, tradeoffs, shared decision making

Assessment and Plan (ENTER AFTER EACH BULLET POINT)

• Unlikely Harm → ______

• Possible Harm → ______

• Likely Harm → ______

FYI and Monitor
FYI and Monitor, Adjust Dosing, or Change to an Alternative
Adjust Dosing or Change to an Alternative

Things to consider:

1. How serious are the potential SEs?

2. How difficult is it to monitor (e.g., self-monitor SEs vs. getting routine labs drawn)?

3. Does adjusting a dose potentially compromise efficacy of a critically important drug?

4. What are the tradeoffs of switching to an alternative?

KNOW

Drug interactions only occur when one drug alters pharmacokinetics of another drug.

False

Most pharmacokinetic drug interactions occur in the elimination phase of “ADME”.

False

CYP3A4 is the only CYP enzyme through which drug interactions occur.

False

Both enzyme inhibition and induction lead to immediate changes in the affected drugs plasma concentration.

False

UpToDate is the preferred reference for checking drug interactions.

False

For a drug interaction that is likely to cause harm, it is typically still okay to just let the provider/patient know and continue to monitor.

False

Which statement about drug interactions is TRUE?

a. Drug interactions only occur when one drug alters the pharmacokinetics of another drug.

b. Drug interactions can be pharmacokinetic or pharmacodynamic.

c. Drug interactions only occur during drug metabolism.

d. Drug interactions only occur with prescription medications.

B

Most pharmacokinetic drug interactions occur during which phase of ADME?

a. Absorption

b. Distribution

c. Metabolism

d. Elimination

C

Which statement regarding CYP enzymes is TRUE?

a. CYP3A4 is the only CYP enzyme involved in drug interactions.

b. Multiple CYP enzymes, including CYP3A4, CYP2D6, CYP2C9, CYP2C19, and CYP1A2, can be involved in drug interactions.

c. CYP2D6 is the only CYP enzyme involved in drug interactions.

d. CYP enzymes do not contribute to drug interactions.

B

Which statement best describes enzyme inhibition and enzyme induction?

a. Both cause immediate changes in drug plasma concentrations.

b. Enzyme induction causes immediate effects, while inhibition takes days.

c. Enzyme inhibition usually occurs quickly, whereas enzyme induction develops over several days to weeks.

d. Neither affects drug plasma concentrations.

C

Which resource is generally considered the preferred reference for evaluating drug interactions in clinical practice?

a. Google

b. Lexicomp only

c. UpToDate only

d. Lexicomp (or dedicated drug interaction databases) is generally preferred over UpToDate for detailed drug interaction screening.

D

A pharmacist identifies a drug interaction that is likely to cause significant patient harm. What is the most appropriate action?

a. Notify the provider and continue therapy without changes.

b. Tell the patient to monitor for symptoms only.

c. Document the interaction and take no further action.

d. Recommend an appropriate intervention rather than simply monitoring.

D