Mipomersen (Injection)

Overview

Mipomersen is a subcutaneous injection; it is administered through the skin on arms, thighs or stomach. It is used together with other medications to treat high cholesterol levels in patients with homozygous familial hypercholesterolemia (HoFH), a rare inherited condition which causes high levels of cholesterol and increases the risk of serious heart disease. Although it is not known if the medicine will lower the risk of heart disease, it does prevent fatty substances from forming to help control the cholesterol levels and is paired with a proper diet low in cholesterol and an exercise routine. This medicine should be taken even when the person feels healthy because it is used to lower and maintain healthy cholesterol levels.

Mipomersen is available only when prescribed by a doctor certified through a restricted program, and filled at a pharmacy which is also certified through the program. The FDA requires doctors, pharmacies and even the patient to be enrolled in Risk Evaluation and Mitigation Strategy (REMS), a program developed just for educating patients, doctor and pharmacists about the dangers of liver damage and strategies to monitor by regularly testing for signs of damage to the liver. It offers a medication guide, implementation system and safety information. Only those doctors certified through the restricted program can prescribe mipomersen.

Do not take mipomersen if an active liver disease or abnormal liver function is a problem. Because it causes liver enzymes to be too high, the doctor will run tests to determine if the patient has any medical conditions which make using this medicine unsafe. The doctor then performs regular blood tests to monitor for any liver damage symptoms. Do not take if pregnant, planning to become pregnant or breastfeeding because it can harm a baby. The doctor will recommend female patients take an effective birth control while taking this medicine.

Conditions Treated

  • Homozygous familial hypercholesterolemia (HoHF)

Type Of Medicine

  • Antisense oligonucleotide (ASO) inhibitors

Side Effects

The doctor must check the patient's progress because of the dangers of liver damage. Tell the doctor immediately if any symptoms of liver damage occur. Also, report any flu-like symptoms that occur especially with a couple of days of taking the injection. Within two days after an injection, 30% of patients reported flu-like symptoms. The most common side effects, 84%, occur around the injection site and should be reported to the doctor along with other common side effects especially if they worsen or become bothersome. Not all side effects are reported and it is important to tell the doctor about any symptoms occurring after starting injections.

Signs of liver damage

  • Dark urine
  • Pale stools
  • Upper stomach pain
  • Loss of appetite
  • Nausea or vomiting
  • Yellow eyes or skin

Flu-like symptoms

  • Fever or chills
  • Fatigue
  • Muscle or joint pain
  • General discomfort or ill feeling

Injection site reactions

  • Itchiness or rash
  • Pain or tenderness
  • Hematoma, swelling, or redness
  • Discoloration or redness

Common side effects

  • Cough
  • Diarrhea
  • Headache
  • Runny nose
  • Shivering
  • Sore throat
  • Sweating
  • Trouble sleeping
  • Pain in arms or legs
  • Skin reactions at injection site

Dosage

The injection is given under the skin in the abdomen, thighs, or upper arms; except the naval area and two inches around it. To decrease the skin reaction side effects, it is recommended to rotate the spots on the body where the injection is given. Avoid areas of skin with cuts, infections, scars, tattoos, sunburn, or any skin condition. The average adult dosages of mipomersen are 200mg injected once a week on the same day, and if a dose is missed, skip it if the day for the next injection is three or fewer days away. Consult a doctor for children's dosing schedule and follow it exactly to reduce the risk of liver damage. In addition to prescribing medicine, the doctor may change a patient's diet or exercise routine. The dose is different for each person, and it is important to follow the exact dosing schedule the doctor prescribes.

The injection comes in pre-filled single doses and vials in which the doctor will explain how to use whichever they prescribe. The syringe must be removed from the refrigerator 30 minutes before injection to allow it to get to room temperature. Do not try to heat the solution in any way and do not mix with any other injectable medicine. Before injection, check the solution to ensure it is either colorless or slightly yellow and clear of particles. Do not use if coloring is off or any particles are observed. Each pre-filled syringe is a single dose, do not reuse the syringe instead properly dispose of it in a container which will not puncture easily.

The doctor may adjust the dose if tests show elevated transaminases, various enzymes produced by the liver because it is a sign of liver damage. When these elevations are accompanied by liver damage, the doctor may discontinue the treatment with mipomersen. Always follow any dose adjustments the doctor makes or stop using if the doctor wants to try a different treatment option. The risk of liver damage is high enough that the doctor may stop the medicine or lower the amount and it is important for the patient to keep all appointments with the doctor, lab, or another testing to monitor cholesterol levels and check for signs of liver damage.

Interactions

Combining any of these with mipomersen increases the risk of liver damage and should be avoided. This includes common over-the-counter cold medicines, Tylenol, and prescriptions for certain diseases or disorders. It is recommended to drink only one alcoholic beverage a day while taking injections to avoid liver damage. This is not a complete list; there it is important to talk to the doctor before starting any new medications including over-the-counter, vitamins, and herbal supplements. The doctor may change dose or treatment options depending on how medicines for other problems interact with mipomersen. Taking it with any of these mean some should be avoided while others need closer monitoring.

  • Acetaminophen
  • Alcohol
  • Amiodarone
  • Doxycycline
  • ISO tretinoin
  • Lomitapide
  • Methotrexate
  • Minocycline
  • Propacetamol
  • Tamoxifen
  • Tetracycline

Warnings

Tell the doctor about any allergies including food, animals, preservatives, and medication. Discuss all medication or supplements taken before starting injections, including vitamins, herbal, and over-the-counter medicines. Also, tell the doctor about any medical conditions especially the following since it is not recommended to use with mipomersen. It is helpful to make a list to give to the doctor if the person takes multiple medications for disorders or diseases. Discuss any pregnancy or nursing because this medicine is dangerous for babies and the doctor will recommend female patients to use birth control to avoid getting pregnant. Tell the doctor right away if pregnancy does occur while taking mipomersen.

Medical conditions not recommended for use with

  • Kidney disease
  • Dialysis treatment
  • Proteinuria
  • Liver disease, damage, or enzymes

The doctor will run tests before starting the injections to check for any liver damage or other medical conditions that may cause adverse reactions with mipomersen. They measure ALT, AST, total bilirubin and alkaline before treatment and then regularly test for them monthly for the first year of treatment. The doctor then monitors the patient's condition every three months. If tests show any signs or the patient experiences any side effects of liver damage, the doctor may adjust the dosage, monitor more often, or select a different treatment option.

The doctor prescribing the medicine must be certified by REMS after reviewing prescribing information and program introduction then completing a knowledge assessment before they can prescribe it. The patient and any others handling mipomersen are required to enrol in the program as well. Patients and the doctor are required to complete an acknowledgement form together and the doctor then consul the patient on the risk of liver damage, liver functioning monitoring, and appropriate patient selection. This program was set especially for mipomersen because of the high risk of liver damage and the need to carefully monitor patients. It is extremely important to keep all appointments with the doctor, labs or for testing to monitor cholesterol levels and check for liver damage.

Storage

The pre-filled syringes and vials should be kept in the refrigerator; however, do let medicine freeze. It can also be stored at 86 degrees Fahrenheit for up to 14 days if no refrigeration is available. Keep away from heat and light in the original package until time for the injection. This is a dangerous medicine which can hurt children and pets, find a place in the refrigerator where they cannot reach it but do not store in the freezer.

Unused or out of date medicine should be properly disposed of; however, do not flush down the toilet. Talk with the doctor, pharmacist or local recycling department to find out about local medicine take-back programs. These programs are the best way to dispose of unused or outdated medicine. Also, used syringes should be disposed of in a closed container which is hard enough that they will not puncture it, and keep it out of children and pets reaches.

Once used, syringes should immediately be disposed in a puncture-resistant container, and FDA approved containers are available through pharmacies, healthcare providers, medical supply companies or online. These containers are durable, leak-proof, and closed tightly; however, if an FDA approved container is not accessible then a hard container such as one for laundry detergent can be used. Talk to the doctor or pharmacist about proper disposal when the container is full of used syringes.

Syringes which are not properly disposed of are a risk to children, other people and animals as they can transmit certain diseases. To avoid an accidental stick, do not dispose of syringes in a household or public trash cans. Never flush syringes or medicine down the toilet because it poses a risk to others and animals. If there is an accidental needle stick, immediately wash the exposed area with soap and water or sterilize with skin disinfectant such as hand sanitizer and contact the doctor.

Summary

Mipomersen was approved by the FDA in 2013 and is used in combination with lipid-lowering medications, diet and exercise to lower cholesterol in patients with homozygous familial hypercholesterolemia (HoFH). One out of one million people inherit this condition and they experience high cholesterol symptoms at a young age. If left untreated, people with HoFH die in their 20's or 30's usually from heart disease as they have a higher risk for it.

Clinical trials involving 51 people with HoFH showed a reduction of 24.7% in low-density lipoprotein cholesterol. Side effects reported were a slight increase in liver fat content by 62% of patients, 16% of the patients reported alanine amniotransase one value above the normal limit, and flu-like symptoms occurring two days after injection were reported by 30% of the patients. The approved dosage was 200mg per 1mL of saline solution injected under the skin once weekly.

While mipomersen has significantly reduced cholesterol levels, concerns about its effect on the liver have led to careful monitoring and development of a restricted program to teach patients and doctors about mipomersen. It is not recommended for anyone with liver disease or damage as well as anyone who is pregnant or nursing. It is advised to drink no more than one alcoholic beverage a day while taking mipomersen.

Mipomersen is administered to reduce plasma lipids in patients and anyone involved in handling the medicine, including the patient, must be approved by the restricted program REMS. Taking it with other medications with a risk of liver damage will increase that risk, so do not start any new medicines or supplements without first talking to the doctor to avoid dangerous interactions. Keep this medicine out of children and pets reach and properly dispose of unused medicine and syringes.