Mipomersen

Mechanism of Action

Antisense oligonucleotide inhibitor that targets messenger RNA for apolipoprotein B-100, the principal apolipoprotein of LDL and its metabolic precursor, VLDL

Absorption

Bioavailability: 54-78%

Peak plasma time: 3-4 hr

Distribution

Protein bound: ≥90%

Distribution half-life: 2-5 hr

Steady-state typically reached within 6 months

Metabolism

Metabolized in tissues by endonucleases to form shorter oligonucleotides that are then substrates for additional metabolism by exonucleases

Elimination

Half-life: 1-2 months

Excretion: <4% urine over 24 hr

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 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.

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.  

• 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.

• It is used to lower cholesterol.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time mipomersen is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take mipomersen or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to mipomersen. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

• Kynamro

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class B or C), active liver disease, or unexplained persistent elevations of hepatic transaminases.

ALT or AST ≥3 x and <5 x ULN: First, repeat measurement within 1 week to confirm elevation. Once confirmed, withhold mipomersen and obtain additional liver function tests (eg, total bilirubin, alkaline phosphatase, and INR); investigate for probable cause. If resumed when AST or ALT <3 x ULN, monitor liver function tests more frequently.

ALT or AST ≥5 x ULN: Withhold mipomersen and obtain additional liver function tests (eg, total bilirubin, alkaline phosphatase, and INR); investigate for probable cause. If resumed when AST or ALT <3 x ULN, monitor liver function tests more frequently.

Clinical symptoms of liver injury (eg, nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like symptoms), bilirubin increase ≥2 x ULN, or active liver disease: Discontinue mipomersen; investigate for probable cause.

Mipomersen is intended for subcutaneous use only.

Transaminases (ALT, AST), alkaline phosphatase, and total bilirubin should be measured before beginning treatment with mipomersen.

After initiation of therapy lipid levels should be monitored at least every 3 months for the first year. Maximal reduction of LDL-C may be seen after approximately 6 months. The patient's LDL-C level should be assessed after 6 months to determine if the LDL-C reduction achieved is sufficient robust to warrant the potential risk of liver toxicity.

Mipomersen vials or syringes should be stored in the refrigerator and removed at least 30 minutes prior to administration.

The first injection administered by the patient or caregiver should be performed under the supervision of a healthcare provider.

Mipomersen should be injected into the abdomen, thigh region, or outer area of the upper arm. It should not be injected in areas of active skin disease or injury (e.g., sunburns, skin rashes, inflammation, skin infections, active areas of psoriasis). Areas of tattooed skin and scarring should also be avoided.