What is the best approach for managing the interaction between pantoprazole (Proton Pump Inhibitor) and cabotegravir/rilpivirine (Antiretroviral therapy) in a patient with HIV and gastroesophageal reflux disease?

Managing Pantoprazole-Rilpivirine Interaction in Cabotegravir/Rilpivirine Therapy

Replace pantoprazole with famotidine 40mg once daily and take at the same time as oral cabotegravir and rilpivirine on an empty stomach (Option C).

Critical Drug Interaction

The FDA label for pantoprazole explicitly states that concomitant use with rilpivirine-containing products is contraindicated 1. This is because proton pump inhibitors (PPIs) like pantoprazole significantly decrease rilpivirine exposure by reducing gastric acidity, which is essential for rilpivirine absorption 1. This reduced exposure can lead to virologic failure and development of drug resistance 1.

Why the Oral Lead-In Cannot Be Skipped

• The oral lead-in phase serves as a critical safety assessment period to identify potential tolerability issues before committing to long-acting injections 2
• Skipping the oral lead-in (Option A) would expose the patient to the pantoprazole-rilpivirine interaction immediately with injectable therapy, where drug levels persist for months (rilpivirine half-life: 13-28 weeks intramuscularly) 3
• If virologic failure occurs with long-acting therapy, the prolonged drug exposure creates extended periods of subtherapeutic levels, increasing resistance risk 3

Why Dose Separation Strategies Fail

• Option B (taking medications 4 hours before or 6 hours after pantoprazole) does not overcome the interaction because PPIs cause prolonged elevation of gastric pH lasting well beyond the dosing interval 1
• The mechanism of PPI-rilpivirine interaction is sustained acid suppression, not simply concurrent administration 1

The Correct Approach: H2-Receptor Antagonist Substitution

Famotidine is the appropriate alternative because:

• H2-receptor antagonists like famotidine have a different mechanism and shorter duration of acid suppression compared to PPIs 1
• While H2RAs can affect rilpivirine absorption, the interaction is manageable with proper timing and dosing 1
• Famotidine 40mg daily provides adequate GERD symptom control while allowing safe rilpivirine administration 4
• Taking famotidine simultaneously with oral cabotegravir/rilpivirine on an empty stomach minimizes the interaction risk while maintaining GERD control 1

Why Antacids Are Inadequate

• Option D (calcium antacids) is inappropriate because antacids provide only short-term symptom relief (hours, not 24-hour control) 4
• The patient has severe GERD requiring chronic PPI therapy with documented rebound symptoms upon discontinuation 4
• Antacids would not provide adequate disease control for this patient's established GERD 4

Implementation Algorithm

1. Before starting oral lead-in:

   • Discontinue pantoprazole
   • Initiate famotidine 40mg once daily 1
   • Take famotidine with oral cabotegravir/rilpivirine on an empty stomach 1

2. During oral lead-in (4-5 weeks):

   • Monitor for GERD symptom control on famotidine 4
   • Assess HIV viral load at 4-6 weeks to confirm virologic suppression 2
   • Evaluate tolerability of oral cabotegravir/rilpivirine 2

3. Transition to injections:

   • If oral lead-in is successful, proceed to long-acting injections every 8 weeks 2
   • Continue famotidine 40mg daily throughout injectable therapy 1

Critical Monitoring Points

• Check HIV RNA at 4-6 weeks after starting oral therapy to ensure the famotidine substitution maintains adequate rilpivirine levels 2
• Monitor GERD symptoms closely during the transition from pantoprazole to famotidine 4
• If GERD symptoms are inadequately controlled on famotidine, consider increasing to famotidine 40mg twice daily rather than returning to PPI therapy 1

Important Caveats

• Never use PPIs with rilpivirine-containing regimens - this is an absolute contraindication, not just a precaution 1
• The long elimination half-life of injectable rilpivirine (13-28 weeks) means any drug interaction causing subtherapeutic levels creates prolonged vulnerability to resistance development 3
• Injectable cabotegravir/rilpivirine eliminates gastrointestinal-level drug interactions but hepatic interactions still occur, making the PPI contraindication relevant even with injectable formulations 3