Evolocumab (Repatha) is a novel drug that has been approved in 2015. It is a human monoclonal antibody that inhibits the enzyme PCSK9. It is indicated in patients who do not achieve their target lipid goals with maximum doses of moderate to high-intensity statins and have high residual cardiovascular disease risk factors. PCSK9 inhibitors (Evolocumab) use in diabetic patients had a greater absolute cardiovascular disease risk reduction [Ref]. Unlike statins, it is not associated with an increased risk of developing Diabetes or worsens glycemic control in diabetic patients.

Evolocumab injection Uses:

• Homozygous familial hypercholesterolemia:

  • It is used as an adjunct to diet and drugs that lower LDL levels (statins, ezetimibe, LDL apheresis) for the treatment of patients with homozygous familial hypercholesterolemia who do not achieve their target LDL goals.

• Primary Hyperlipidemia:

  • It is used as an adjunct to diet for the treatment of adults with primary hyperlipidemia to reduce LDL-C levels, including patients with heterozygous familial hyperlipidemia.
  • It may be used alone or in combination with the maximum tolerated dose of statins.

• Prevention of cardiovascular events in patients with established cardiovascular disease:

  • It is used in combination with a high-intensity statin in adults with established cardiovascular disease to reduce the risk of myocardial infarction, stroke, and coronary revascularization.

Evolocumab Vs Alirocumab:

Evolocumab dose in Adults:

Note:  The AHA and ACC recommend using Evolocumab in patients who do not achieve the target lipid treatment goals with dietary modification and maximally tolerated statins with or without ezetimibe.

Evolocumab injection dosage in the treatment of Homozygous familial hypercholesterolemia:

• 420 mg subQ once monthly.

• Off-label dosing:

  • 420 mg twice monthly (once every 2 weeks).
  • The dose is then reduced to 420 mg once a month after 12 weeks in conjunction with lipid apheresis.
  • Direct administration after lipid apheresis has also been recommended by the European Atherosclerosis Society.

Evolocumab injection dose in the treatment of Primary Hyperlipidemia:

• 140 mg SubQ every 2 weeks or
• 420 mg once a month.

Evolocumab dose in the Prevention of cardiovascular events (in patients with established cardiovascular disease):

• 140 mg SubQ every 2 weeks or
• 420 mg once a month.

• Switching regimens:

  • When switching from one regimen (140 mg or 420 mg) to another, the dose of the new regimen should be given on the scheduled day of the previous dosing regimen.

• Missed dose:

  • If a dose is missed, administer as soon as possible and within 7 days from the missed dose.
  • If the two-weekly regimen is followed, and the missed dose is not administered within 7 days, wait until the next scheduled dose.
  • If the once-monthly dosing regimen is followed, and the missed dose is not administered within 7 days, administer the missed dose and start a new dosing schedule based on this date.

Evolocumab dose in Childrens

Refer to adults dosing.

Pregnancy Risk Category: C

• Animal studies have not shown any adverse fetal events.
• Exposure to the infant can be expected, as IgG antibodies cross over the placental barrier, especially during the second and third trimesters.

Use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• Neonatal exposure to IgG antibodies is possible because breastmilk contains IgG antibodies.
• Manufacturer recommends that you weigh the risks and benefits of therapy for the mother-to-be against the potential dangers to the neonate.

Dose adjustment in kidney disease:

Adjustment in the dose is not necessary.

Evolocumab dose in Liver disease:

• Mild to moderate impairment (Child-Pugh Classes A and B):

  • Adjustment in the dosage is not necessary.

• Severe impairment (Child-Pugh Class C):

  • It has not been studied in severe hepatic impairment.
  • Adjustment in the dose has not been provided by the manufacturer.

 Evolocumab Side Effects (common):

• Respiratory:

  • Nasopharyngitis

Side Effects of Evolocumab (Less Common):

• Cardiovascular:

  • Hypertension

• Central nervous system:

  • Dizziness
  • Fatigue

• Dermatologic:

  • Skin rash

• Endocrine & metabolic:

  • Diabetes mellitus

• Gastrointestinal:

  • Gastroenteritis
  • Nausea

• Genitourinary:

  • Urinary tract infection

• Hematologic & oncologic:

  • Bruise

• Infection:

  • Influenza

• Local:

  • Injection site reaction

• Neuromuscular & skeletal:

  • Myalgia

• Respiratory:

  • Upper respiratory tract infection
  • Cough
  • Sinusitis

Evolocumab Contraindications:

• Allergy reactions to evolocumab and any component of the formulation

Warnings and precautions

• Hypersensitivity reactions

  • It has been reported that hypersensitivity reactions such as angioedema, itching, and urticaria have been associated with the drug's use. This may necessitate discontinuation.
  • If a patient develops an allergic reaction, they should be closely monitored.
  • The patient should not be treated and should be supported.

Evolocumab: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitor:

• Lipid profile prior to initiating treatment.
• Recheck the lipid profile after 4 - 12 weeks of treatment initiation and 3 - 12 months thereafter.
• Monitor the patients for the clinical features of allergic reactions.

How to administer Evolocumab?

• SubQ administration.

  • The syringe should not be shaken.
  • Allow the single-use prefilled autoinjector or single-use prefilled syringe for 30 minutes and the single-use on-body infusor with the prefilled cartridge for 45 minutes at room temperature prior to use.
  • Avoid using warm water or heat application.
  • It should be administered just like insulin into the abdomen (sparing the navel area and the 2-inch area around the navel), upper arm, or thigh.
  • Do not inject into a bruised, tender, red, indurated, or infected area.
  • The site of injection should be rotated with each injection.
  • It should not be administered with other injectable drugs at the same site.

Once-monthly 240 mg subQ dose:

• It should be administered slowly over 9 minutes subQ using the single-use infusor with the prefilled cartridge.
• Three separate 140 mg injections may be given as stat doses within a 30 minutes period using the single-use prefilled autoinjector or single-use prefilled syringe.

Evolocumab mechanism of action:

• It is a monoclonal human antibody (IgG2 type) that binds with the enzyme PCSK9 (proprotein conversion subtilisin kexin 9).
• The LDL and LDL surface receptor complexes are normally stabilized by the enzyme PCSK9. 
• It prevents the endocytosed LDL-surface receptor from being released, which results in its destruction.
• The PCSK9 enzyme promotes the LDL-surface receptor degradation, thereby increasing the amount of LDL that circulates in the blood.
• Inhibition of PCSK9, on the other hand, will increase the ability for LDL receptors function and reduce LDL levels in blood.
• Evolocumab, a monoclonal human antibody, lowers LDL-C by blocking the enzyme PCSK9. SubQ administration takes approximately 3-4 days to reach the peak serum concentration.

Time to maximum inhibition of the PCSK9It takes approximately 4 hours. It takes approximately 4 hours.MetabolizedBy non-saturable proteolysis. It has been abioavailabilitySubQ administration and a half-life eliminationBetween 11 and 17 days

Evolocumab brand names (International):

• Repatha
• Repatha SC
• Repatha Pushtronex System
• Repatha SureClick

Evolocumab availability in Pakistan:

Evolocumab (Repatha) is not available in Pakistan.