PCSK9 inhibitors: Uses, common brands, and safety info

Having high cholesterol (hyperlipidemia) is a risk factor for cardiovascular disease. Many people with hyperlipidemia take a type of medication called a statin, such as Lipitor (atorvastatin). For some, a statin is well-tolerated and effective in lowering cholesterol (lipid) levels. Others may take a high dose of a statin and still develop cardiovascular disease—or may not be able to tolerate a statin medication at all. 

In 2015, the U.S. Food and Drug Administration (FDA) approved two injectable prescription drugs that lower LDL cholesterol and prevent cardiovascular events. The drugs—Repatha and Praluent—are classified as PCSK9 inhibitors. PCSK9 inhibitors work differently than statins. They can be used alone or in combination with a statin. Amgen, Inc. makes Repatha and Regeneron Pharmaceuticals, Inc. makes Praluent. 

This article will discuss the uses, side effects, and safety information of PCSK9 inhibitors. The table below lists the two currently available PCSK9 inhibitors.

What are PCSK9 inhibitors?

PCSK9 inhibitors are prescription medications that are injected under the skin (subcutaneously), used to lower low-density lipoprotein cholesterol levels (LDL-C levels) and lower the risk of cardiovascular events. A PCSK9 inhibitor may be prescribed to patients who have genetic hyperlipidemia or who are at very high risk for cardiovascular disease (heart disease) and cannot tolerate statins, or when high-dose statins are not effective enough.

How do PCSK9 inhibitors work?

PCSK9 inhibitors are monoclonal antibodies. A monoclonal antibody is made in a lab and can bind to a substance. 

PCSK9 inhibitors bind to proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 binds to low-density lipoprotein receptors (LDL receptors, or LDLR) on the surface of liver cells (hepatocytes). This PCSK9 inhibition increases the number of LDLRs that can clear LDL and thereby lowers LDL cholesterol (LDL-C) levels.

Praluent was studied in the ODYSSEY OUTCOMES trial. This trial studied the safety and efficacy of Praluent compared with placebo in patients with recent acute coronary syndrome (ACS) who were already on high-dose/maximum-tolerated statin therapy. 

The trial showed that Praluent, taken every other week, significantly decreased ischemic events, including heart attack (myocardial infarction) and death, compared with placebo, in patients with a recent (past 1-12 months) acute coronary syndrome event. Praluent also reduced first events and total nonfatal events.

Repatha was studied in the FOURIER trial. This trial studied the safety and efficacy of Repatha in high-risk patients taking statins. The study concluded that Repatha was effective, compared to placebo, at reducing cardiovascular events. Repatha significantly lowered LDL cholesterol levels. This study did not find a benefit in regards to mortality. 

What are PCSK9 inhibitors used for?

PCSK9 inhibitors are injectable medications indicated:

• To lower LDL cholesterol (along with diet, alone or combined with other LDL cholesterol-lowering medications) in adults with primary hyperlipidemia (high cholesterol caused by genetics), including heterozygous familial hypercholesterolemia.

• To lower LDL cholesterol (along with other LDL cholesterol-lowering medications) in patients with homozygous familial hypercholesterolemia.

• In adults with cardiovascular disease to lower the risk of cardiovascular events such as heart attack and stroke.

Who can take PCSK9 inhibitors?

Before taking a PCSK9 inhibitor, tell your doctor about all of your medical conditions and medical history. Tell your doctor about all of the medications you take, including prescription drugs, over-the-counter (OTC) medicines, and vitamins or supplements. 

Men

Men can take a PCSK9 inhibitor, provided they fit into one of the indications, and the doctor determines a PCSK9 inhibitor will be safe and appropriate. 

Women

Women who are not pregnant or breastfeeding can take a PCSK9 inhibitor, provided they fit into one of the indications and prescribed by their doctor. 

Pregnancy and breastfeeding

Praluent and Repatha have not been studied enough to determine safety in pregnancy. However, they have the potential to be transmitted to the developing unborn baby. There is no information regarding PCSK9 inhibitors and breastfeeding. 

Consult your healthcare professional for medical advice on PCSK9 inhibitors and pregnancy and/or breastfeeding. 

Children

Praluent has not been studied for safety and efficacy in children.

Repatha may be used in patients ages 13 years and older, along with diet and other LDL lowering medication to treat homozygous familial hypercholesterolemia.

Older adults

Clinical trials for both Praluent and Repatha did not find a difference in safety or efficacy based on age. However, the prescribing information for both PCSK9 inhibitors states that “greater sensitivity of some older individuals cannot be ruled out.” Consult your healthcare provider for medical advice. 

Are PCSK9 inhibitors safe?

Recalls

No recalls were found on PCSK9 inhibitors. You can search the FDA database to find updates on recalls. 

Restrictions and warnings

Do not take a PCSK9 inhibitor if you are allergic to any component of the drug. 

Caution should be used with Repatha in people who are allergic to latex.

Before using a PCSK9 inhibitor, your healthcare provider will instruct you on administration. Follow your healthcare provider’s instructions and consult them with any questions or concerns. Also, be sure to follow storage requirements as described in the product labeling. 

Are PCSK9 inhibitors controlled substances?

No, PCSK9 inhibitors are not controlled substances.

Common PCSK9 inhibitors side effects

Common adverse effects of the PCSK9 inhibitors Praluent and Repatha include:

• Common cold

• Cough 

• Upper respiratory infection

• Sinus infection

• Bronchitis 

• Influenza 

• Diabetes mellitus (when used for cardiovascular prevention)

• Back pain 

• Allergic reaction 

• Injection site reaction

• Urinary tract infection 

• Headache 

• Muscle spasms

• Muscle and/or bone pain 

• Dizziness 

• Increased blood pressure

• Diarrhea 

• Stomach virus 

• Confusion 

• Abnormal liver function tests

Serious side effects may include:

• Allergic reaction (can be common and/or severe)

• Swelling beneath the skin (angioedema)

• Severe skin reaction with inflamed blood vessels (hypersensitivity vasculitis)

If you are taking a PCSK9 inhibitor and experience symptoms of an allergic reaction, such as hives, rash, skin sores, blisters, difficulty breathing, or swelling of the lips, tongue, or face, seek emergency medical treatment right away.

Other adverse events may occur. Consult your healthcare professional about what side effects to expect and how to address them. You can report side effects to your doctor. You can also report side effects to the FDA by calling 1-800-FDA-1088.

How much do PCSK9 inhibitors cost?

Because PCSK9 inhibitors are currently only available in brand-name form, they can be quite expensive. Insurance and Medicare prescription coverage vary by plan. Contact your insurance provider for up-to-date coverage information. You can also check the manufacturer websites for Repatha or Praluent, as both manufacturers offer copay assistance programs to people who fit certain eligibility requirements.

You can always use our free discount cards and coupons when filling and refilling your PCSK9 inhibitor prescription. Using a SingleCare card can save up to 80% on prescription prices. Ask your pharmacist to compare costs and see how you can save on your prescriptions.