Basic Information About Kynamro (Mipomersen)

injectable drug
urfinguss, istockphoto

Kynamro (mipomersen) is a medication that is taken in conjunction with other cholesterol-lowering drugs and a healthy diet to lower:

Kynamro is indicated in individuals who have been diagnosed with homozygous familial hypercholesterolemia, which is a rare, inherited, medical condition that is associated with very high LDL levels and premature cardiovascular disease.

Kynamro was approved for use in the United States by the Food and Drug Administration (FDA) in January 2013.

There are a few studies examining the effectiveness and safety of Kynamro, however most those studies only included individuals diagnosed with homozygous familial hypercholesterolemia. In these studies, LDL cholesterol was lowered by an average of 25%, apo B levels were lowered down to 36%, and total cholesterol levels decreased by an average of 21% after 26 weeks of treatment. The dose of Kynamro administered was 200 mg per week, and roughly three-fourths of individuals given Kynamro were also taking other cholesterol-lowering medications.

Although these studies show that Kynamro has the ability to significantly lower cholesterol in these patients, they also revealed that Kynamro can cause some significant side effects, such as severe liver disease.

Kynamro has also been studied in other severe lipid disorders – besides homozygous familial hypercholesterolemia - with similar safety and efficacy results, such as:

  • Heterozygous familial hypercholesterolemia
  • Severe hypercholesterolemia in individuals at high risk for cardiovascular disease who have maxed out on their current lipid-lowering medications or are statin-intolerant

 

How Does Kynamro Work?

Kynamro is classified as an antisense inhibitor. The drug works by preventing apolipoprotein B-100 (apo B-100) from being made in the body.

Apo B-100 is the protein portion of some lipoproteins, such as LDL or VLDL – both of which can contribute to heart disease in high levels. To make apo B-100 proteins for use in lipoproteins, messenger RNA converts the particular region of DNA coding for apo B-100 into the protein, apo B-100. Kynamro binds complementary to this section of messenger RNA, reducing the amount of apo B-100 from being made. This, in turn, lowers the amount of VLDL and LDL in the body.

 

How Should I Take This Medication?

Kynamro is an injectable medication and should be stored in the refrigerator or otherwise according to the manufacturer’s instructions. When you are ready to administer the drug, you should allow the medication to come to room temperature for about 30 minutes. The recommended dose of Kynamro is 200 mg once a week. It should be injected subcutaneously as directed by your healthcare provider.

 

What Side Effects Should I Expect While Taking Kynamro?

There is a strong association between taking Kynamro and the accumulation of fat in the liver and elevated liver enzymes, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Due to these side effects, the FDA has issued a strong warning – referred to as a “black box warning” - regarding the hepatotoxicity associated with Kynamro.  Because of the potentially harmful effects on the liver, Kynamro is only available under a restricted program referred to as the Kynamro REMS program. Under this program, only healthcare providers and pharmacies that have been specifically trained on the medication and its risks can prescribe and distribute Kynamro. If your physician decides to prescribe Kynamro for you, he or she will direct you on how to enroll in this program.

The most common side effects experienced when taking Kynamro include swelling, redness, and warmth at the injection site. These side effects occurred within 48 hours after injection. Fatigue, headache and flu-like symptoms have also been reported by individuals taking Kynamro.

 

Who Should Not Take This Medication?

Kynamro is only indicated only for individuals who have been diagnosed with homozygous familial hypercholesterolemia. It is not fully known if Kynamro would be effective or safe in individuals who have high lipid levels caused by other medical conditions. Your healthcare provider will run a series of tests on you to determine whether or not Kynamro is right for you. These tests will include a lipid profile, liver enzyme measurements, and a pregnancy test if you are female. Kynamro may not be taken if you have one of the following conditions:

  • Individuals who have liver disease – Kynamro can increase fat in your liver and cause an elevation in liver enzymes, including transaminases.
  • Individuals with kidney disease – Kynamro has not been extensively studied in individuals who have kidney disease. If you have severe kidney disease or are on dialysis, Kynamro is not recommended.
  • Individuals who have an allergy to any ingredient in the medication.

There have not been adequate studies performed in women who are pregnant or nursing. Therefore, if you become pregnant while on therapy or wish to become pregnant, you should notify your healthcare provider.

 

Will This Medication Interact with Any Other Drugs That I Am Taking?

At this time, it does not appear that there are a lot of medications that interact with Kynamro. However, drug interactions have not been extensively tested with this medication. In some studies, other medications – such as Coumadin (warfarin), Zocor (simvastatin), and Zetia (ezetimibe) – were taken with Kynamro. No drug interactions were noted in these studies. Due to the effect Kynamro has on the liver, you may want to be cautious about taking any other substances that can elevate your liver enzymes, such as alcohol, acetaminophen, and isotretinoin. Since it is not known if Kynamro interacts with any other medications, you should notify all of your healthcare providers of all medications and natural products that you are taking.

 

Bottom Line

Studies have shown that Kynamro can significantly lower apo B-100 levels, LDL levels, total cholesterol levels, and other non-HDL particles in individuals who have homozygous familial hypercholesterolemia. Although effective, Kynamro is also associated with the risk of hepatotoxicity – resulting in this medication only being prescribed and distributed by individuals knowledgeable of those risks. When deciding on whether or not to prescribe Kynamro for you, your healthcare provider will weigh these risks and benefits of the drug.

 

Sources:

Kynamro ® (mipomersen) Package Insert. Genzyme Corporation. March 2015.

Raal FJ, Santas RD, Blum DJ, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled trial. Lancet 2010;375:998-1006.

Stein EA, Dufour R, Gagne C, et al. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia. Circulation 2012; 126:2283-2292.

Santos RD, Duell PB, East C, et al. Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolemia: 2-year interim results of an open-label extension. Eur Heart J 2015;36:566-575.

Continue Reading