Evolocumab (Repatha) 140 mg & 420 mg – a PCSK9 Inhibitor

Evolocumab (Repatha)

Evolocumab is a monoclonal antibody directed against a circulating protein called PCSK9. It is available as 140 mg and 420 mg injection that is administered twice a month or once monthly respectively subcutaneously.

It is available by the brand name of Repatha and is used in the treatment of dyslipidemias that are resistant to statins.

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Mechanism of action of Evolocumab (Repatha)?

Evolocumab lowers LDL in the blood (low-density lipoproteins) by inhibiting PCSK9.

What is PCSK9? How does evolocumab lower LDL? 

PCSK9 is the abbreviation for “Proprotein Convertase Subtilisin/Kexin type 9. It is a protein that circulates in the plasma. PCSK9 protein deficiency was found to be associated with low levels of plasma LDL levels.

PCSK9 modulates the LDL receptors in the liver cells. PCSK9 inhibitors, like evolocumab, are drugs that inhibit the action of PCSK9 proteins on liver cells. This results in an increased expression of LDL receptors on the liver cells.

Evolocumab (Repatha) increases the LDL receptors in the liver by inhibiting PCSK9. Increasing the LDL receptors causes the internalization of LDL proteins that are circulating in the plasma.

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What are the Indications of PCSK9 Inhibitors (Evolocumab)?

Evolocumab is used to lower LDL (low-density lipoproteins) in the following group of patients:

  • In adults and children who are 10 years of age or older with homozygous familial hypercholesterolemia (HoFH).
  • In adults with heterozygous familial hypercholesterolemia (HeFH).

Evolocumab (Repatha) is used as an adjunct to diet, exercise, and statins to lower the risk of stroke, myocardial infarction, and coronary revascularization in adults with established CVD (cardiovascular disease).

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Evolocumab Dosage and administration:

Evolocumab is available in the following dosage strengths:

  • Evolocumab 140 mg/ml single-dose prefilled syringe (autoinjector)
  • Evolocumab 420 mg/3.5 ml single-dose single-push Pushtronex system with a prefilled cartridge.

It is administered as a subcutaneous injection into the anterior abdomen twice a month or once a month depending on the underlying condition.

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Dose in different situations is given here:

Adults with primary hyperlipidemia and established cardiovascular diseases:

  • The manufacturer recommends a dose of either:
    • 140 mg subcutaneous once every two weeks, OR
    • 420 mg subcutaneous once every month

Children who are ten years of age or older with HeFH (heterozygous familial hyperlipidemia):

  • The manufacturer recommends a dose of either:
    • 140 mg subQ every two weekly, OR
    • 420 mg subQ once a month

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Homozygous Familial Hyperlipidemia in adults or children aged 10 years or more:

  • The manufacturer recommends an initial Repatha dose of 420 mg subQ once a month.
  • If there is an inadequate response to treatment, the dose may be increased to 420 mg subQ twice a month (or every two weeks).
  • The 420 mg dose may be administered over 9 minutes by using the single-use-on-body-infusor. The dose may also be administered as three injections of 140 mg over thirty minutes.
  • An initial high dose of 420 mg subQ every two weeks is recommended in patients who are on lipid apheresis. The dose is synchronized with the apheresis schedule and is administered after the apheresis session is over.

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What should you do if you miss the Repatha dose?

If you miss the 140 mg dose that had to be administered after an interval of two weeks and 7 days have passed, you can wait for the next scheduled dose.

However, if you missed the 420 mg dose that is administered once a month, administer the missed dose and start the new dosing schedule from the new date.

Dose adjustment in Liver or kidney diseases:

No adjustment in the dose is needed in either liver or kidney disease.

What are the side effects of Evolocumab?

Side effects of the drug are not very common and usually mild in nature. Most patients have mild upper respiratory tract symptoms such as rhinitis and nasopharyngitis.

In clinical trials, adverse reactions that occurred in more than 3% of the individuals are mentioned in the table below and compared with placebo [Ref]:

Adverse reaction

Repatha (Evolocumab) Side effects (Percentage)


Upper respiratory tract infection9.36.3
Back pain6.25.6
Injection site reactions5.75.0
Urinary tract infection4.53.6
Musculoskeletal pain3.33.0

Who should not receive Evolocumab?

Individuals who are allergic to the drug and have a history of serious hypersensitivity reactions to the drug should avoid using it.

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What do you think?

Written by Dr. Ahmed

I am Dr. Ahmed (MBBS; FCPS Medicine), an Internist and a practicing physician. I am in the medical field for over fifteen years working in one of the busiest hospitals and writing medical posts for over 5 years.

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