What is the indication and dosing for Repatha (evolocumab) in patients with high cholesterol?

Repatha (Evolocumab) Indications and Dosing for High Cholesterol

Repatha (evolocumab) is indicated for adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) as an adjunct to diet, either alone or in combination with other lipid-lowering therapies, with a recommended dosage of 140 mg subcutaneously every 2 weeks OR 420 mg once monthly. 1, 2

Specific FDA-Approved Indications

Repatha is indicated for:

1. Adults with established cardiovascular disease:

   • To reduce the risk of major adverse cardiovascular events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) 1

2. Primary hyperlipidemia:

   • As an adjunct to diet, alone or in combination with other LDL-C-lowering therapies in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH) 1, 2

3. Pediatric patients with HeFH:

   • As an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged 10 years and older with HeFH 1

4. Homozygous familial hypercholesterolemia (HoFH):

   • As an adjunct to other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older with HoFH 1, 2

Dosing Regimens

Adults with Primary Hyperlipidemia or Established CVD:

• 140 mg subcutaneously every 2 weeks OR
• 420 mg subcutaneously once monthly 1, 3

Pediatric Patients (≥10 years) with HeFH:

• 140 mg subcutaneously every 2 weeks OR
• 420 mg subcutaneously once monthly 1

Adults and Pediatric Patients (≥10 years) with HoFH:

• Initial dose: 420 mg subcutaneously once monthly
• May increase to 420 mg every 2 weeks if clinically meaningful response not achieved after 12 weeks 1, 2
• For patients on lipid apheresis: May initiate with 420 mg every 2 weeks to correspond with apheresis schedule (administer after apheresis session is complete) 1

Administration Guidelines

• Administer subcutaneously in the abdomen, thigh, or upper arm 2, 1
• For the 420 mg dose: Use the prefilled single-dose on-body infuser or give 3 (140-mg) injections consecutively within 30 minutes 2
• Allow Repatha to warm to room temperature for at least 30 minutes (prefilled autoinjector/syringe) or 45 minutes (on-body infusor) if refrigerated 1
• Visually inspect before administration (should be clear to opalescent, colorless to pale yellow solution) 1

Monitoring

• LDL-C can be measured as early as 4 weeks after initiation 1, 3
• For patients receiving the monthly 420 mg dose, measure LDL-C just prior to the next scheduled dose, as levels may vary during the dosing interval 1, 3

Efficacy

• Reduces LDL-C by 50-65% from baseline when added to statins 3, 4
• In clinical trials, evolocumab reduced LDL-C by 59-75% compared to placebo 5, 6
• The FOURIER trial demonstrated that evolocumab significantly reduced the risk of cardiovascular events (hazard ratio 0.85; 95% CI, 0.79-0.92) 5

Missed Doses

If a dose is missed:

• Within 7 days: Administer and resume original schedule
• More than 7 days:
  • For every 2-week dosing: Wait until next scheduled dose
  • For monthly dosing: Administer and start a new schedule based on this date 1

Safety Considerations

• Well tolerated in clinical trials 4, 5
• Most common adverse events: Back pain, arthralgia, headache, muscle spasms, and pain in extremity (all <2%) 6
• No significant differences in adverse events compared to placebo, except for injection-site reactions (2.1% vs. 1.6%) 5

Clinical Pearls

• Consider Repatha particularly in patients unable to reach LDL-C goals despite treatment with statins with or without other lipid-lowering therapies 4, 3
• Useful option for statin-intolerant patients 4, 3
• The high cost of evolocumab may restrict its use despite its excellent efficacy and tolerability profile 7
• When switching between dosage regimens (140 mg every 2 weeks to 420 mg monthly or vice versa), administer the first dose of the new regimen on the next scheduled date of the prior regimen 1