Mipomersen

Mipomersen is a prescription medication used to lower cholesterol in people with homozygous familial hypercholesterolemia (HoFH, a hereditary disorder that causes high cholesterol levels). Mipomersen belongs to a group of drugs called antisense oligonucleotides. This drug lowers cholesterol levels by removing a main part of "bad" cholesterol.

This medication comes in an injectable form to be given just under the skin, once a week. Mipomersen comes in single-use (1 time) vials, or as single-use pre-filled syringes.

Common side effects include skin reactions at the injection site, fever, chills, and headache.

Mipomersen is a prescription medicine used along with diet and other lipid-lowering treatments in people with homozygous familial hypercholesterolemia (HoFH) to reduce:

• LDL (“bad”) cholesterol
• total cholesterol
• a protein that carries “bad” cholesterol in the blood (apolipoprotein B)
• non-high-density lipoprotein cholesterol (non-HDL-C)

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Mipomersen may be found in some form under the following brand names:

• Kynamro

Mipomersen can cause serious side effects, including:  

• See “Drug Precautions” section
• injection site problems
• flu-like symptoms

Call your doctor right away if you have any of the serious side effects of mipomersen.

The most common side effects of mipomersen include:

• injection site problems.  Skin reactions can happen in some people including redness or discoloration of the skin, pain, tenderness, itching, and swelling around the injection site. You may also get a reaction at a former site of injection, when injecting at a different site, or after an injury to an injection site.
• flu-like symptoms, including fever, chills, aches, and tiredness. These symptoms usually happen within 2 days of an injection.
• nausea
• headache

Tell your doctor about any side effect that bothers you or that does not go away.

These are not all the possible side effects of mipomersen. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

No significant drug interactions have been identified, however, you should tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Not all drug interactions are known or reported and new drug interactions are continually being reported.

Because mipomersen has the potential to cause liver damage, caution should be exercised when mipomersen is used with other medications known to potentially cause liver damage.

Know the medicines you take.  Keep a list of them to show your doctor and pharmacist when you get a new medicine. 

• Mipomersen is available only through certified pharmacies that are enrolled in the Mipomersen REMS Program.  Your doctor must be enrolled in the program in order for you to be prescribed mipomersen.

Mipomersen may cause serious side effects, including liver problems such as increased liver enzymes or increased fat in the liver.

• Your doctor should do blood tests to check your liver before you start mipomersen.
• Tell your doctor if you have had liver problems, including liver problems while taking other medicines.
• Tell your doctor right away if you have any of these symptoms of liver problems while taking mipomersen:
  • nausea
  • vomiting
  • fever
  • loss of appetite
  • you are more tired than usual
  • yellowing of your eyes or skin
  • dark urine
  • itching
  • stomach pain
• Drinking alcohol may increase your chance of having liver problems or make your liver problems worse. You should not have more than 1 alcoholic drink each day while using mipomersen.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of mipomersen there are no specific foods that you must exclude from your diet when receiving this medication.

Before you take mipomersen, tell your doctor if you:

• have liver problems
• have kidney problems
• drink alcohol
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.  

Tell your doctor if you are pregnant or plan to become pregnant. If you are a female who can get pregnant, you should use effective birth control while using mipomersen.  Talk with your doctor to find the best method of birth control for you.  If you become pregnant while taking mipomersen, stop taking mipomersen and call your doctor right away.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Mipomersen falls into category B. There are no well-done studies that have been done in humans with mipomersen. But in animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

It is not known if mipomersen crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using mipomersen.

• Mipomersen is given by injection under your skin (subcutaneous) 1 time each week. Mipomersen is available in single-use (1 time) vials, or as a single-use pre-filled syringe.
• Take mipomersen exactly as your doctor tells you to take it.
• Make sure that you or your caregiver are trained by your doctor or other healthcare professional on how to inject mipomersen the right way.
• Do not try to give yourself or have another person give you injections at home until you or both of you understand and are comfortable with how to prepare for your dose and give the injection.
• Take mipomersen on the same day of the week at the same time of day.
• If you miss a dose or forget to take your dose of mipomersen at your usual weekly time, you can take it when you remember, unless it is less than 3 days until your next weekly dose. If it is less than 3 days until your next weekly dose, wait and take your next weekly dose at your regularly scheduled time. Do not take a double dose at the same time to make up for a forgotten or missed dose.
• It is important that mipomersen is at room temperature when it is injected.
• Do not mix mipomersen with other injectable medicines.
• Do not use mipomersen at the same time as other injectable medicines.
• If you use too much mipomersen, call your doctor right away.
• Do not stop taking mipomersen without talking to your doctor.

Take this medication exactly as prescribed. Follow the directions on your prescription label carefully.

The recommended dose of mipomersen is 200 mg given subcutaneously (just under the skin) once a week. The injection should be given on the same day every week. If a dose is missed, the injection should be given at least 3 days from the next weekly dose.

If you inject too much mipomersen, call your doctor right away. There have been no reports of overdose with mipomersen treatment. 

In clinical trials, patients receiving higher doses of mipomersen (300 mg and 400 mg once weekly for 13 weeks) experienced adverse reactions similar to the adverse reactions experienced by patients receiving treatment with 200 mg once weekly but at slightly higher rates and greater severity.

• Store mipomersen in a refrigerator between 36°F to 46°F (2°C to 8°C). If a refrigerator is not available, mipomersen can be stored at or below 86°F (30°C) for up to 14 days if it is kept away from heat.  
• Protect mipomersen from light and store in the original carton.
• Safely throw away medicine that is out of date or no longer needed.

Keep mipomersen and all medicines out of the reach of children.

WARNING: RISK OF HEPATOTOXICITY

Mipomersen can cause elevations in transaminases. In the mipomersen clinical trial in patients with HoFH, 4 (12%) of the 34 patients treated with mipomersen compared with 0% of the 17 patients treated with placebo had at least one elevation in alanine aminotransferase (ALT) ≥ 3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR) or partial thromboplastin time (PTT).

Mipomersen also increases hepatic fat, with or without concomitant increases in transaminases. In the trials in patients with heterozygous familial hypercholesterolemia (HeFH) and hyperlipidemia, the median absolute increase in hepatic fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging (MRI).  Hepatic steatosis is a risk factor for advanced liver disease; including steatohepatitis and cirrhosis. 

Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT, AST regularly as recommended. During treatment, withhold the dose of mipomersen if the ALT or AST are ≥ 3x ULN. Discontinue mipomersen for clinically significant liver toxicity.

Because of the risk of hepatotoxicity, mipomersen is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Mipomersen REMS.