Usage
Evolocumab is prescribed to reduce low-density lipoprotein cholesterol (LDL-C) levels (“bad” cholesterol) and thereby decrease the risk of cardiovascular events like heart attack and stroke. It’s specifically indicated for:
- Primary Hyperlipidemia (including Heterozygous Familial Hypercholesterolemia (HeFH)): As an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), to lower LDL-C.
- Homozygous Familial Hypercholesterolemia (HoFH): As an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) when additional LDL-C lowering is required.
- Established Cardiovascular Disease: To reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults.
Pharmacological Classification: Evolocumab is a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor.
Mechanism of Action: Evolocumab is a fully human monoclonal antibody that binds to PCSK9 and inhibits its interaction with the LDL receptor. This inhibition prevents PCSK9 from degrading LDL receptors, increasing the number of LDL receptors available on liver cells to clear LDL-C from the blood, resulting in lower LDL-C levels.
Alternate Names
International Nonproprietary Name (INN): Evolocumab
Brand Name: Repatha
How It Works
Pharmacodynamics: Evolocumab significantly lowers LDL-C levels by increasing the number of LDL receptors available to clear LDL-C from circulation. This reduces the risk of cardiovascular events.
Pharmacokinetics:
- Absorption: Evolocumab is administered subcutaneously and is absorbed with an absolute bioavailability of 72%. Maximum plasma concentration is reached in 3 to 4 days.
- Metabolism: As a monoclonal antibody, evolocumab is primarily catabolized like endogenous IgG antibodies, through intracellular catabolism to small peptides and amino acids, rather than by specific metabolic pathways.
- Elimination: Evolocumab has a half-life of 11 to 17 days. It is eliminated via non-renal routes, primarily catabolism into amino acids and peptides which are subsequently re-utilized.
Mode of Action: Evolocumab acts by binding to circulating PCSK9. PCSK9 typically binds to LDL receptors, which leads to their degradation. By preventing PCSK9 from binding to LDL receptors, evolocumab increases the recycling of LDL receptors to the hepatocyte cell surface, resulting in increased LDL-C uptake and clearance from circulation.
Receptor Binding: Binds to PCSK9, preventing PCSK9 from binding to and degrading LDL receptors.
Enzyme Inhibition: Inhibits the activity of PCSK9.
Elimination Pathways: Primarily non-renal, by intracellular catabolism like endogenous IgGs.
Dosage
Standard Dosage
Adults:
- Primary Hyperlipidemia/Established Cardiovascular Disease: 140 mg subcutaneously every 2 weeks or 420 mg subcutaneously once monthly. Both doses are clinically equivalent.
- Homozygous Familial Hypercholesterolemia: Initial dose of 420 mg subcutaneously once monthly. May be increased to 420 mg every 2 weeks if LDL-C reduction is inadequate after 12 weeks. Patients undergoing LDL apheresis may start with 420 mg every 2 weeks to coordinate with their apheresis schedule; administer evolocumab after completing an apheresis session.
Children:
- Primary Hyperlipidemia/Homozygous Familial Hypercholesterolemia (10 years and older): Same dosage as adults.
- Children younger than 10 years: Safety and efficacy have not been established. Use and dose must be determined by a doctor.
Special Cases:
- Elderly Patients: No dose adjustment is necessary.
- Patients with Renal Impairment: No dose adjustment is necessary.
- Patients with Hepatic Dysfunction: No dose adjustment necessary for mild or moderate impairment. Evolocumab should be used with caution in patients with severe hepatic impairment, with close monitoring, as reduced exposure has been observed.
- Patients with Comorbid Conditions: Dosage adjustments are generally not recommended for specific comorbidities. However, careful monitoring is advised, especially in patients with diabetes, as evolocumab may slightly increase blood glucose levels.
Clinical Use Cases
Evolocumab’s dosing does not change for clinical use cases such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. The standard dosing guidelines based on the indication should be followed.
Dosage Adjustments
Dosage adjustments are generally not necessary based on age, gender, race, or body weight. However, monitoring of LDL-C levels is recommended to assess treatment response and adjust dosage frequency for HoFH patients if necessary.
Side Effects
Common Side Effects:
- Nasopharyngitis
- Upper respiratory tract infection
- Back pain
- Arthralgia
- Influenza
- Nausea
- Injection site reactions (pain, redness, bruising, swelling)
- Hyperglycemia
Rare but Serious Side Effects:
- Allergic reactions, including angioedema, urticaria, and hypersensitivity
Long-Term Effects:
Limited data are available on truly long-term side effects beyond several years. However, ongoing monitoring for potential adverse events is recommended.
Adverse Drug Reactions (ADR):
Serious hypersensitivity reactions, requiring immediate discontinuation of treatment and supportive care.
Contraindications
- History of serious hypersensitivity reaction to evolocumab or any of its excipients.
Drug Interactions
No clinically significant drug interactions have been identified. Evolocumab is not metabolized by CYP450 enzymes, reducing the likelihood of metabolic drug interactions. Concomitant use with statins is common and often recommended.
Pregnancy and Breastfeeding
- Pregnancy: Limited data are available. Evolocumab should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Monoclonal antibodies are less likely to cross the placenta in the first trimester but can cross in increasing amounts in the second and third trimesters. A pregnancy exposure registry exists to monitor outcomes.
- Breastfeeding: It is unknown whether evolocumab is present in human milk. Because it is a large protein molecule, the amount in milk is likely to be low. Due to the potential for minimal absorption in the infant’s gastrointestinal tract, the risk is thought to be minimal. However, use with caution, especially in nursing newborns or premature infants.
Drug Profile Summary
- Mechanism of Action: Inhibits PCSK9 binding to LDL receptors, increasing LDL receptor recycling and LDL-C clearance.
- Side Effects: Nasopharyngitis, upper respiratory tract infections, back pain, injection site reactions, hyperglycemia. Rare but serious hypersensitivity reactions possible.
- Contraindications: Serious hypersensitivity to evolocumab or any of its components.
- Drug Interactions: No clinically significant drug interactions.
- Pregnancy & Breastfeeding: Limited data. Use with caution during pregnancy only if the potential benefit outweighs the potential risk. Minimal risk anticipated during breastfeeding but use with caution.
- Dosage: Adults/Children ≥10 years: 140 mg SC q2weeks or 420 mg SC monthly (Primary Hyperlipidemia/Established Cardiovascular Disease); 420 mg SC monthly (HoFH, initial dose). Adjustments may be needed for HoFH.
- Monitoring Parameters: LDL-C levels, blood glucose, signs of hypersensitivity reactions.
Popular Combinations
Evolocumab is commonly combined with statins (e.g., atorvastatin, rosuvastatin) and/or ezetimibe for synergistic LDL-C lowering effects in patients with primary hyperlipidemia or established cardiovascular disease.
Precautions
- General Precautions: Evaluate for pre-existing hypersensitivity reactions, moderate/severe hepatic impairment. Exclude secondary causes of hyperlipidemia before initiating therapy.
- Specific Populations: See Pregnancy and Breastfeeding section above.
- Lifestyle Considerations: Counsel patients on maintaining a healthy diet and lifestyle alongside evolocumab therapy for optimal cardiovascular risk reduction. No driving or operating machinery restrictions are associated with evolocumab.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Evolocumab?
A: For adults and children 10 years and older with primary hyperlipidemia or established cardiovascular disease, the dose is either 140 mg subcutaneously every 2 weeks or 420 mg subcutaneously once monthly. For HoFH, the initial dose is 420 mg subcutaneously once a month, possibly increasing to every 2 weeks. Dosage for children under 10 with HoFH or primary hyperlipidemia is determined by a doctor.
Q2: How is Evolocumab administered?
A: Evolocumab is administered subcutaneously into the abdomen, thigh, or upper arm. Rotate injection sites and avoid areas that are tender, bruised, red, or hard.
Q3: What is the mechanism of action of Evolocumab?
A: Evolocumab is a monoclonal antibody that inhibits PCSK9, preventing LDL receptor degradation and increasing LDL-C clearance from the bloodstream.
Q4: What are the common side effects of Evolocumab?
A: Common side effects include nasopharyngitis, upper respiratory tract infections, back pain, injection site reactions, and hyperglycemia.
Q5: Are there any contraindications to Evolocumab use?
A: A history of serious hypersensitivity to evolocumab or its components is a contraindication.
Q6: Can Evolocumab be used during pregnancy and breastfeeding?
A: Limited data are available for pregnancy. Use only if the benefit outweighs the risk. It is unknown if evolocumab is present in breast milk, but the risk to the infant is thought to be minimal. Use with caution, especially when breastfeeding newborns or premature infants.
Q7: Does Evolocumab interact with other medications?
A: No clinically significant drug interactions have been identified.
Q8: How effective is Evolocumab at lowering LDL-C?
A: Evolocumab can lower LDL-C by approximately 55% to 75%.
Q9: How long does it take to see the maximum effect of Evolocumab?
A: The maximum response is generally achieved within 1 to 2 weeks of the first dose.
Q10: What monitoring parameters are important for patients on Evolocumab?
A: Monitor LDL-C levels, blood glucose, and be vigilant for any signs of hypersensitivity reactions.
