What is the guidance for managing missed doses of inclisiran (Leqvio)?

Managing Missed Doses of Inclisiran (Leqvio)

If a planned dose of inclisiran is missed by less than 3 months, administer the dose and maintain the patient's original dosing schedule. If a planned dose is missed by more than 3 months, restart with a new dosing schedule - administer initially, again at 3 months, and then every 6 months. 1

Dosing Schedule and Administration Guidelines

Inclisiran (Leqvio) follows a specific administration schedule:

• Initial dose: 284 mg administered as a single subcutaneous injection
• Second dose: 3 months after initial dose
• Maintenance doses: Every 6 months thereafter 1

Management of Missed Doses

The FDA-approved guidance for missed doses is clear and straightforward:

1. Missed by <3 months:

   • Administer the missed dose immediately
   • Continue with the original dosing schedule
   • No need to adjust future dosing dates 1

2. Missed by >3 months:

   • Restart the entire dosing schedule
   • Administer the dose immediately (consider this a new initial dose)
   • Schedule the next dose at 3 months
   • Resume every 6 months dosing thereafter 1

Clinical Considerations

Administration Requirements

• Inclisiran must be administered by a healthcare professional
• Injection sites include the abdomen, upper arm, or thigh
• Avoid injecting in areas with active skin disease or injury 1

Monitoring After Missed Doses

• LDL-C can be measured as early as 30 days after administration
• Assessment of LDL-C should be performed when clinically indicated
• No special monitoring is required after administering a missed dose 1

Advantages of Inclisiran's Dosing Schedule

The twice-yearly maintenance dosing of inclisiran (after initial doses) offers significant advantages:

• Improves adherence compared to more frequently dosed medications 2, 3
• Administration by healthcare professionals ensures proper delivery 4
• Less frequent dosing compared to PCSK9 monoclonal antibodies (twice yearly vs. biweekly/monthly) 4, 5

Practical Implementation

When a patient misses an inclisiran dose:

1. Calculate the time elapsed since the scheduled dose
2. Determine whether it's been less or more than 3 months
3. Apply the appropriate protocol based on timing
4. Document the new schedule in the patient's record
5. Educate the patient about their updated dosing schedule

Efficacy Considerations

Even with occasional missed doses, inclisiran maintains effectiveness:

• Provides approximately 50% LDL-C reduction with twice-yearly dosing 5, 6
• Maintains LDL-C reduction through extended treatment periods 4
• Demonstrates consistent effects across different patient categories 2

Key Points to Remember

• The 3-month threshold is the critical decision point for managing missed doses
• Restarting the dosing schedule when missed by >3 months ensures optimal therapeutic effect
• The unique pharmacokinetics of inclisiran allows for this flexible approach to missed doses 7
• Healthcare provider administration helps ensure proper dosing and reduces the impact of potential missed self-administered doses 1, 3