Mipomersen

What is Mipomersen?

• Mipomersen (Kynamro) is an oligonucleotide inhibitor of apolipoprotein B-100 synthesis is a drug used to treat homozygous familial hypercholesterolemia and is administered by subcutaneous injection.

Mipomersen sodium

Mipomersen

Mipomersen sodium colored

What are the uses of this medicine?

• Mipomersen (Kynamro) 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)

Limitations of Use:

• It is not known if Kynamro can decrease problems from high cholesterol, such as heart attack, stroke, death or other health problems.
• It is not known if Kynamro is safe in people with high cholesterol but who do not have HoFH.
• It is not known if Kynamro is safe and effective as an additional treatment to LDL apheresis.
• It is not known if Kynamro is safe and effective in people with kidney and liver problems, including people who are on kidney dialysis.
• It is not known if Kynamro is safe and effective when used in children under the age of 18.
• It cannot be freely prescribed; instead every person put on mipomersen is enrolled in a Risk Evaluation and Mitigation Strategies (REMS) program approved by the FDA.

How does this medicine work?

• Mipomersen (Kynamro) is an antisense oligonucleotide that binds to the mRNA that encodes apolipoprotein B.
• Mipomersen is an antisense oligonucleotide targeted to human messenger ribonucleic acid (mRNA) for apo B-100, the principal apolipoprotein of LDL and its metabolic precursor, VLDL.
• Mipomersen is complementary to the coding region of the mRNA for apo B-100, and binds by Watson and Crick base pairing.
• The hybridization of mipomersen to the cognate mRNA results in RNase H-mediated degradation of the cognate mRNA thus inhibiting translation of the apo B-100 protein.

What drug interactions can this medicine cause?

• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.

Especially tell your doctor if you take:

• acetaminophen (Tylenol, in other medications for pain) and if you are taking amiodarone (Cordarone, Pacerone)
• other medications for high cholesterol
• methotrexate (Rheumatrex, Trexall)
• tamoxifen (Soltamox)
• tetracycline antibiotics such as doxycycline (Doryx, Vibra-Tabs, Vibramycin), minocycline (Dynacin, Minocin), and tetracycline (Sumycin).

Is this medicine FDA approved?

• In January 2013, The United States Food and Drug Administration approved mipomersen for the treatment of homozygous familial hypercholesterolemia.

How should this medicine be used?

• Before beginning treatment with Kynamro, measure transaminases (ALT, AST), alkaline phosphatase, and total bilirubin.

Recommended dosage:

• The recommended dose of Kynamro is 200 milligrams (mg) once weekly as a subcutaneous injection.
• After initiation of Kynamro therapy lipid levels should be monitored at least every 3 months for the first year.
• Maximal reduction of LDL-C may be seen with Kynamro therapy after approximately 6 months.

Administration:

• Mipomersen injection comes as a solution to inject under the skin.
• Kynamro is given by injection under your skin (subcutaneous) 1 time each week. Kynamro is available in single-use (1 time) vials, or as a single-use prefilled syringe.
• Take Kynamro 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 in how to inject Kynamro 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 Kynamro 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 Kynamro 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 Kynamro is at room temperature when it is injected.
• Do not mix Kynamro with other injectable medicines.
• Do not use Kynamro at the same time as other injectable medicines.
• If you use too much Kynamro, call your doctor right away.
• Do not stop taking Kynamro without talking to your doctor.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Single-use vial containing 1 mL of a 200 mg/mL solution
• Single-use pre-filled syringe containing 1 mL of a 200 mg/mL solution

This medicine is available in fallowing brand namesː

• Kynamro

What side effects can this medication cause?

The most common side effects of this medicine 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

Kynamro can cause serious side effects, including:

• liver problems such as increased liver enzymes or increased fat in the liver
• injection site problems
• flu-like symptoms

What special precautions should I follow?

• Kynamro can cause elevations in transaminases. Measure alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin before initiating treatment and then ALT and AST regularly as recommended.
• During treatment, withhold the dose of Kynamro if the ALT or AST is ≥3 times the upper limit of normal (ULN). Discontinue Kynamro for clinically significant liver toxicity.
• Kynamro increases hepatic fat (hepatic steatosis) with or without concomitant increases in transaminases.
• Hepatic steatosis associated with Kynamro may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.
• Because of the risk of hepatotoxicity, Kynamro is available only through a restricted program called the Kynamro REMS.
• Injection site reactions occur in 84% of patients and typically consist of one or more of the following: erythema, pain, tenderness, pruritus and local swelling.
• Flu-like symptoms, which typically occur within 2 days after an injection, occur in 30% of patients and include one or more of the following: influenza-like illness, pyrexia, chills, myalgia, arthralgia, malaise or fatigue.
• Drinking alcohol increases the risk that you will develop liver damage during your treatment with mipomersen injection. Do not drink more than one alcoholic beverage per day while you are using this medication.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• Liver-related tests should be monitored.
• Although there is no information on the effect of hemodialysis in treating an overdose with mipomersen, hemodialysis is unlikely to be useful in overdose management since mipomersen is highly bound to plasma proteins.

Can this medicine be used in pregnancy?

• Kynamro may cause harm to your unborn baby.
• If you are a female who can get pregnant, you should use effective birth control while using Kynamro.Talk with your doctor to find the best method of birth control for you. If you become pregnant while taking Kynamro, stop taking Kynamro and call your doctor right away.

Can this medicine be used in children?

• It is not known if Kynamro is safe and effective when used in children under the age of 18.

What are the active and inactive ingredients in this medicine?

• Active ingredient: mipomersen sodium
• Inactive ingredient: sterile water, hydrochloric acid, and sodium hydroxide

Who manufactures and distributes this medicine?

• Genzyme Corporation
• Kendall Street
• Cambridge, MA

• KYNAMRO is a trademark of Genzyme Corporation.

What should I know about storage and disposal of this medication?

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

Lipid lowering medications

• Bile Acid Resins/Sequestrants

• • Cholestyramine
  • Colesevelam
  • Colestipol

• Fibrates
  • Clofibrate
  • Fenofibrate
  • Gemfibrozil

• Monoclonal Antibodies - Anti-PCSK9
  • Alirocumab
  • Evolocumab

• Niacin (Nicotinic Acid)

• • Omega-3 Fatty Acids,
  • Icosapent Ethyl
  • Omega-3 Acid Ethyl Esters
  • Omega-3 Carboxylic Acids

• Statins
  • Atorvastatin
  • Fluvastatin
  • Lovastatin
  • Pitavastatin
  • Pravastatin
  • Rosuvastatin
  • Simvastatin

• Miscellaneous
  • Ezetimibe
  • Lomitapide
  • Mipomersen

• Dailymed label info on Mipomersen
• FDA Mipomersen

Mipomersen Resources
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