Leqvio

• The recommended dosage of LEQVIO is 284 mg administered as a single subcutaneous injection initially, again at 3 months, and then every 6 months. (
  2.1     Recommended Dosage

  • The recommended dosage of LEQVIO is 284 mg administered as a single subcutaneous injection initially, again at 3 months, and then every 6 months.
  • If a planned dose is missed by less than 3 months, administer LEQVIO and maintain dosing according to the patient’s original schedule.
  • If a planned dose is missed by more than 3 months, restart with a new dosing schedule - administer LEQVIO initially, again at 3 months, and then every 6 months.
  • Assess LDL-C when clinically indicated. The LDL-lowering effect of LEQVIO may be measured as early as 30 days after initiation and anytime thereafter without regard to timing of the dose.
  )
• LEQVIO should be administered by a healthcare professional. (
  2.2     Important Administration Instructions

  • LEQVIO should be administered by a healthcare professional.
  • Inject LEQVIO subcutaneously into the abdomen, upper arm, or thigh. Do not inject in areas of active skin disease or injury, such as sunburns, skin rashes, inflammation, or skin infections.
  • Inspect LEQVIO visually before use. It should appear clear and colorless to pale yellow. Do not use if particulate matter or discoloration is seen.

  For more detailed instruction on administration of the prefilled syringe, see Instructions for Use.
  )
  
• Inject LEQVIO subcutaneously into the abdomen, upper arm, or thigh. (
  2.2     Important Administration Instructions

  • LEQVIO should be administered by a healthcare professional.
  • Inject LEQVIO subcutaneously into the abdomen, upper arm, or thigh. Do not inject in areas of active skin disease or injury, such as sunburns, skin rashes, inflammation, or skin infections.
  • Inspect LEQVIO visually before use. It should appear clear and colorless to pale yellow. Do not use if particulate matter or discoloration is seen.

  For more detailed instruction on administration of the prefilled syringe, see Instructions for Use.
  )
  

Injection: 284 mg/1.5 mL (189 mg/mL) of inclisiran as a clear, and colorless to pale yellow solution in a single-dose prefilled syringe.

Discontinue LEQVIO when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Inclisiran increases LDL-C uptake and lowers LDL-C levels in the circulation, thus decreasing cholesterol and possibly other biologically active substances derived from cholesterol; therefore, LEQVIO may cause fetal harm when administered to pregnant patients based on the mechanism of action

There are no available data on the use of LEQVIO in pregnant patients to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

In animal reproduction studies, no adverse developmental effects were observed in rats and rabbits with subcutaneous administration of inclisiran during organogenesis at doses up to 5 to 10 times the maximum recommended human dose (MRHD) based on body surface area (BSA) comparison (

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively.

In embryo-fetal development studies conducted in Sprague-Dawley rats and New Zealand White rabbits, inclisiran was administered by subcutaneous injection at dose levels of 50, 100, and 150 mg/kg once daily during organogenesis (rats: Gestation Days 6 to 17; rabbits: Gestation Days 7 to 19). There was no evidence of embryo-fetal toxicity or teratogenicity at doses up to 5 and 10 times, respectively, the MRHD based on BSA comparison/dose. Inclisiran crosses the placenta and was detected in rat fetal plasma at concentrations that were 65 to 154 times lower than maternal levels.

In a pre- and postnatal development study conducted in Sprague-Dawley rats, inclisiran was administered once daily by subcutaneous injection at levels of 50, 100, and 150 mg/kg from Gestation Day 6 through Lactation Day 20. Inclisiran was well-tolerated in maternal rats, with no evidence of maternal toxicity and no effects on maternal performance. There were no effects on the development of the F1 generation, including survival, growth, physical and reflexological development, behavior, and reproductive performance at doses up to 5 times the MRHD, based on BSA comparison/dose.