mipomersen

Action and Spectrum

Actions and Spectrum: 

mipomersen is a medication used to lower LDL cholesterol levels in certain patients with homozygous familial hypercholesterolemia, a rare genetic disorder that causes extremely high LDL cholesterol levels. 

The mechanism of action of mipomersen involves inhibiting the production of apolipoprotein B (apoB), a protein necessary for the formation of LDL cholesterol. By reducing apoB production, mipomersen lowers LDL cholesterol levels in the blood. 

mipomersen is administered weekly and works by binding to messenger RNA (mRNA) molecules in the liver, which are responsible for producing apoB. By binding to these mRNA molecules, mipomersen prevents the formation of apoB, ultimately leading to a decrease in LDL cholesterol levels. 

mipomersen has a narrow spectrum of activity, as it is only effective in patients with homozygous familial hypercholesterolemia (HoFH) who have extremely high LDL cholesterol levels. It is not used to treat other high cholesterol types or prevent heart disease. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Influenza-like illness (13%) 

Headache (12%) 

Increased hepatic fat >5% (62%) 

Nausea (14%) 

Fatigue (15%) 

Injection site reactions (84%) 

1-10% 

Pyrexia (8%) 

Insomnia (3%) 

Edema (5%) 

Abnormal LFTs (5%) 

Hypertension (7%) 

Abdominal pain (3%) 

AST increased (6%) 

Angina (4%) 

Chills (6%) 

Musculoskeletal pain (4%) 

Hepatic steatosis (7%) 

ALT increased (10%) 

Palpitations (3%) 

Hepatic enzyme increased (3%) 

Vomiting (4%) 

Extremity pain (7%) 

Black Box Warning

Black Box Warning: 

mipomersen carries a black box warning for the risk of liver toxicity. Liver function tests(LFT) should be performed before starting mipomersen and regularly monitored during treatment. If liver function tests show evidence of liver injury, treatment with mipomersen should be discontinued. 

mipomersen may also increase the risk of liver steatosis (fatty liver) and liver enzyme elevations. Patients with a prior history of liver disease or abnormal liver function tests before starting mipomersen should be carefully monitored for worsening liver function during treatment. 

mipomersen may also cause flu-like symptoms such as fever, fatigue, and muscle pain, which may be severe in some patients. If these symptoms occur, patients should contact their healthcare provider. 

Because of the risk of liver toxicity, mipomersen is available through a restricted program known as the mipomersen Risk Evaluation and Mitigation Strategy (REMS) Program. This program requires prescribers to be certified and patients to be enrolled before receiving mipomersen. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

mipomersen is contraindicated in patients with a history of a severe hypersensitivity reaction to mipomersen or any of its components. Hypersensitivity reactions may include anaphylaxis, angioedema, and severe skin reactions. 

mipomersen is also contraindicated in patients with moderate to severe hepatic impairment, including those with active liver diseases like hepatitis or cirrhosis. 

Because mipomersen can cause fetal harm, it is contraindicated in pregnant women. Women of childbearing should use effective method of contraception while taking mipomersen and for at least 12 weeks after the last dose. 

mipomersen is also contraindicated in breastfeeding women, as it is unknown whether mipomersen is excreted in human milk and may harm a nursing infant. 

Finally, mipomersen is not recommended for use in children below the age 18 years, as its safety, efficacy in this age group have yet to be established. 

Caution 

mipomersen should be used with caution in patients with a history of pancreatitis, as it may increase the risk of this condition. 

mipomersen may also increase the risk of bleeding, especially in patients taking anticoagulant medications or having a history of bleeding disorders. 

Because mipomersen can cause flu-like symptoms, patients should be monitored for signs of infection. Treatment should be temporarily discontinued in patients with severe infections until the infection is controlled. 

mipomersen may also interact with other medications, so it is key to tell your healthcare provider about all the medications, supplements, and also herbal products you are taking before starting treatment with mipomersen. 

Finally, mipomersen may cause injection site reactions, including pain, swelling, and also redness at the injection site. Patients should be instructed on proper injection techniques and how to manage any injection site reactions that may occur. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: B 

Lactation:   

Excreted into human milk is Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

mipomersen is an antisense oligonucleotide that works by binding to and inhibiting the production of apolipoprotein B-100 (apoB-100), a protein required for the synthesis and transport of LDL cholesterol. By reducing the production of apoB-100, mipomersen diminishes the production of LDL cholesterol levels in the liver, resulting in lower levels of LDL cholesterol in the blood. 

Pharmacodynamics: 

Mechanism of action: The action involves using an antisense oligonucleotide inhibitor that explicitly targets messenger RNA responsible for encoding apolipoprotein B-100. This apolipoprotein is the primary component of low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), metabolic precursors of LDL. 

Pharmacokinetics: 

Absorption 

mipomersen is administered as a subcutaneous injection and rapidly absorbed into the bloodstream. Maximum plasma concentrations are typically reached within 3-4 hours after injection. 

Distribution 

mipomersen is extensively distributed throughout the body, with a volume of distribution of approximately 0.08 L/kg. 

Metabolism 

mipomersen is metabolized in the liver by nucleases and exonucleases into smaller oligonucleotides and nucleotides, excreted in the urine. The half-life of mipomersen is approximately one month, which allows for once-weekly dosing. 

The cytochrome P450 system does not metabolize mipomersen and does not inhibit/induce cytochrome P450 enzymes. It also does not bind to plasma proteins, which reduces the risk of drug interactions with other medications. 

Elimination and Excretion 

mipomersen is excreted primarily in the urine, with approximately 78% of the administered dose excreted within two weeks after injection. Only a tiny amount of mipomersen is excreted in the feces. 

Adminstartion

Administration: 

Subcutaneous administration 

mipomersen is administered as a subcutaneous injection once a week. The injection is given into the abdomen, thigh, or upper arm. 

mipomersen comes as a prefilled syringe and should be refrigerated until use. Before injecting mipomersen, it should be allowed to come to room temperature for 30 minutes. 

Patients should be instructed on proper injection technique, and the injection site should be rotated each week to reduce the risk of injection site reactions. 

If a dose is missed, taking it as soon as possible is generally recommended. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is important to avoid taking a double dose of the medication to compensate for the missed dose.

It is essential to follow the dosing schedule prescribed by your healthcare provider and consult your physician before stopping or changing the dose of mipomersen. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: mipomersen 

Pronounced: [ MYE-poe-mer-sen ] 

Why do we use mipomersen? 

mipomersen is used to treat homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder that causes extremely high levels of low-density lipoprotein (LDL) cholesterol. 

HoFH is a severe condition that can lead to premature cardiovascular disease, including heart attack and stroke, if left untreated. mipomersen is used to lower LDL cholesterol levels in patients with HoFH who have not responded to other treatments, such as statins and other lipid-lowering medications. 

mipomersen is not used to treat other high cholesterol types or prevent heart disease in patients without HoFH. It is used only in patients with HoFH who have extremely high LDL cholesterol levels and require additional treatment to control their cholesterol levels. 

mipomersen is usually used with other lipid-lowering medications and lifestyle modifications, like a healthy diet and exercise.