What are the potential interactions between Mavyret (glecaprevir/pibrentasvir) and Linzess (linaclotide) in a patient taking both medications?

No Clinically Significant Interaction Between Mavyret and Linzess

There is no clinically significant drug interaction expected between Mavyret (glecaprevir/pibrentasvir) and Linzess (linaclotide), so patients can safely take both medications together without dose adjustments or special timing considerations.

Understanding the Medications

Mavyret (glecaprevir/pibrentasvir)

• Direct-acting antiviral (DAA) combination for hepatitis C virus (HCV) treatment
• Glecaprevir is an NS3/4A protease inhibitor
• Pibrentasvir is an NS5A inhibitor
• Metabolic pathway: Glecaprevir is primarily metabolized by CYP3A4 and is a substrate of P-glycoprotein (P-gp) and OATP1B1, while pibrentasvir is primarily eliminated via biliary excretion 1

Linzess (linaclotide)

• Guanylate cyclase-C agonist used for irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation
• Acts locally in the intestinal tract
• Minimal systemic absorption
• Not metabolized through cytochrome P450 pathways

Drug Interaction Analysis

According to the European Association for the Study of the Liver (EASL) recommendations on treatment of hepatitis C, Mavyret has several important drug interactions to consider 1, but Linzess is not listed among medications that interact with Mavyret. The EASL guidelines provide comprehensive tables of drug interactions with hepatitis C medications, and Linzess is not mentioned as having any interaction with glecaprevir/pibrentasvir.

The primary concerns for Mavyret drug interactions include:

• Strong P-gp inducers (e.g., rifampin, carbamazepine, St. John's wort)
• Strong CYP3A inhibitors (e.g., certain HIV protease inhibitors)
• OATP1B inhibitors (e.g., cyclosporine)
• Ethinylestradiol-containing contraceptives

Linzess works locally in the intestine with minimal systemic absorption, so it does not affect the metabolic pathways of Mavyret.

Patient Counseling Points

When counseling patients taking both Mavyret and Linzess, focus on:

1. Administration instructions:

   • Mavyret: Take three tablets (total dose 300mg/120mg) once daily with food 1
   • Linzess: Take on an empty stomach at least 30 minutes before the first meal of the day

2. Expected side effects:

   • Mavyret: Headache, fatigue, and nausea are most common 1
   • Linzess: Diarrhea, abdominal pain, flatulence, and abdominal distension

3. Monitoring parameters:

   • Liver function tests should be monitored regularly during Mavyret treatment 1
   • No specific additional monitoring is required due to the combination

4. Importance of adherence:

   • Emphasize completing the full course of Mavyret (typically 8-12 weeks depending on HCV genotype, treatment history, and cirrhosis status)
   • Missing doses could reduce treatment effectiveness

Special Considerations

While there is no direct interaction between these medications, patients should be aware that:

1. Both medications may cause gastrointestinal symptoms, though through different mechanisms
2. Patients should report any unusual or severe symptoms
3. No dose adjustments are needed for either medication when used together

Conclusion

Patients can safely take Mavyret and Linzess concurrently without concern for drug interactions. The medications work through different mechanisms and pathways, with Linzess having minimal systemic absorption and therefore not affecting the metabolism or efficacy of Mavyret.