Mipomersen is an oligonucleotide drug used for the treatment of homozygous familial hypercholesterolemia.
- Brand Names
- Generic Name
- DrugBank Accession Number
Mipomersen sodium, which was known as the investigational drug, isis-301012, is the salt form of a synthetic phosphorothioate oligonucleotide. Mipomersen sodium prevents the formation of apo B-100, resulting in a decrease in the levels of apolipoprotein B (apo B), low density lipoprotein (LDL), and total cholesterol. Mipomersen is indicated in patients with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering medications. It is marketed under the brand name Kynamro in the United States, and the FDA label includes a black box warning of hepatoxicity. Specifically, elevations in the liver enzymes, i.e. transaminases, and in liver fat (hepatic steatosis) have been reported. Due to this serious risk of liver toxicity, mipomersen sodium is only available to patients under the restricted program called Kynamro Risk Evaluation and Mitigation Strategy program.
- Approved, Investigational
- Biologic Classification
- Gene Therapies
- External IDs
- ISIS 301012
Used in patients with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering medications.Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.
- Associated Conditions
- Contraindications & Blackbox Warnings
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Mipomersen sodium decreases the levels of apolipoprotein B (apo B), low density lipoprotein (LDL) non-high density lipoprotein-cholesterol, and total cholesterol.
- Mechanism of action
Mipomersen binds to the mRNA that codes for apoB-100. This binding leads to double-stranded RNA, which is degraded by RNase H and prevents translation of the mRNA to form the apo B-100 protein.
Target Actions Organism AmRNA of ApoB-100binder Humans
The maximum mipomersen concentration is reached in about 3-4 hours after subcutaneous injection. Additionally the bioavailability of mipomersn is dose-dependant and ranges from 54%-78%.
- Volume of distribution
The volume of distribution for mipomersen was not quantified.
- Protein binding
Plasma protein binding for mipomersen is greater than or equal to 90%.
Mipomersem is metabolized by endonucleases. Once degraded into shorter oligonucleotides, it is metabolized further by exonucleases.
- Route of elimination
24 hours after mipomersem administration, less than 4% of mipomersem and/or it's metabolites were excreted in the urine.
Mipomersem has a very long half life of 1-2 months.
Clearance of mipomersem was not quantified.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.
The FDA label includes a black box warning of mipomersem induced hepatoxicity. Other less serious adverse effects include nausea, headache, fatigue, local injection site reactions, and flu-like symptoms.
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Acetaminophen Acetaminophen may increase the hepatotoxic activities of Mipomersen. Amiodarone Amiodarone may increase the hepatotoxic activities of Mipomersen. Demeclocycline Demeclocycline may increase the hepatotoxic activities of Mipomersen. Doxycycline Doxycycline may increase the hepatotoxic activities of Mipomersen. Eravacycline Eravacycline may increase the hepatotoxic activities of Mipomersen. Ethanol Ethanol may increase the hepatotoxic activities of Mipomersen. Isotretinoin Isotretinoin may increase the hepatotoxic activities of Mipomersen. Lomitapide Lomitapide may increase the hepatotoxic activities of Mipomersen. Lymecycline Lymecycline may increase the hepatotoxic activities of Mipomersen. Metacycline Metacycline may increase the hepatotoxic activities of Mipomersen.Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more
- Food Interactions
- Avoid excessive or chronic alcohol consumption. Alcohol may increase the risk of liver injury.
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Mipomersen sodium 18EAY4870E 629167-92-6 OSGPYAHSKOGBFY-KMHHXCEHSA-A
- International/Other Brands
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Kynamro Injection, solution 200 mg/1mL Subcutaneous Genzyme Corporation 2013-01-29 2013-01-29 Kynamro Injection, solution 200 mg/1mL Subcutaneous Kastle Therapeutics, Llc 2016-05-02 Not applicable Kynamro Injection, solution 200 mg/1mL Subcutaneous Genzyme Corporation 2013-01-29 2017-10-31
- ATC Codes
- C10AX11 — Mipomersen
- Drug Categories
- Anticholesteremic Agents
- Antisense Elements (Genetics)
- Antisense Oligonucleotides
- Apolipoprotein B-100 Synthesis Inhibitor
- Compounds used in a research, industrial, or household setting
- Decreased Protein Synthesis
- DNA, Antisense
- Hepatotoxic Agents
- Hypolipidemic Agents
- Hypolipidemic Agents Indicated for Hyperlipidemia
- Laboratory Chemicals
- Lipid Modifying Agents
- Lipid Modifying Agents, Plain
- Lipid Regulating Agents
- Molecular Probes
- Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia
- Nucleic Acid Probes
- Nucleic Acids
- Nucleic Acids, Nucleotides, and Nucleosides
- Oligodeoxyribonucleotides, Antisense
- Not classified
- Affected organisms
- Humans and other mammals
- CAS number
- General References
- Kastelein JJ, Wedel MK, Baker BF, Su J, Bradley JD, Yu RZ, Chuang E, Graham MJ, Crooke RM: Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation. 2006 Oct 17;114(16):1729-35. Epub 2006 Oct 9. [Article]
- Hair P, Cameron F, McKeage K: Mipomersen sodium: first global approval. Drugs. 2013 Apr;73(5):487-93. doi: 10.1007/s40265-013-0042-2. [Article]
- FDA label
- Download (923 KB)
- Download (567 KB)
- Clinical Trials
- Not Available
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 200 mg/1mL
- Not Available
Patent Number Pediatric Extension Approved Expires (estimated) Region US7407943 No 2008-08-05 2021-08-01 US7015315 No 2006-03-21 2023-03-21 US7511131 No 2009-03-31 2025-12-13 US6451991 No 2002-09-17 2017-02-11 US6166197 No 2000-12-26 2017-12-26 US7101993 No 2006-09-05 2023-09-05
- Experimental Properties
- Not Available
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Drug created at November 18, 2007 18:25 / Updated at September 05, 2022 12:50