Mipomersen
Mipomersen Uses, Dosage, Side Effects, Food Interaction and all others data.
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.
Mipomersen sodium decreases the levels of apolipoprotein B (apo B), low density lipoprotein (LDL) non-high density lipoprotein-cholesterol, and total cholesterol.
| Trade Name | Mipomersen |
| Availability | Discontinued |
| Generic | Mipomersen |
| Mipomersen Other Names | Mipomersen |
| Related Drugs | Zetia, Praluent, Repatha, atorvastatin, simvastatin, rosuvastatin, Lipitor, ezetimibe, Crestor, Zocor |
| Weight | 200mg/ml, |
| Type | Subcutaneous Solution, Subcutaneous |
| Formula | C230H324N67O122P19S19 |
| Weight | Average: 7177.11 Monoisotopic: 7172.091682609 |
| Protein binding | Plasma protein binding for mipomersen is greater than or equal to 90%. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Mipomersen is an oligonucleotide drug used for the treatment of homozygous familial hypercholesterolemia.
Used in patients with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering medications.
Mipomersen is also used to associated treatment for these conditions: Homozygous Familial Hypercholesterolemia
How Mipomersen works
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.
Toxicity
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.
Food Interaction
- Avoid excessive or chronic alcohol consumption. Alcohol may increase the risk of liver injury.
[Major] GENERALLY AVOID: Coadministration with alcohol may increase the risk of hepatotoxicity associated with the use of mipomersen.
Mipomersen can cause elevations in serum transaminases and hepatic steatosis.
In a premarketing clinical trial, 12% (4<34) of patients treated with mipomersen had at least one elevation in alanine aminotransferase (ALT) 3 times the upper limit of normal (ULN) or greater, and 9% (3<34) had at least one elevation in ALT 5 times ULN or greater, compared to 0% of the 17 patients treated with placebo.
There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or partial thromboplastin time (PTT).
Mipomersen also increases hepatic fat, with or without concomitant increases in transaminases.
In clinical trials of patients with heterozygous familial hypercholesterolemia and hyperlipidemia, the median absolute increase in hepatic fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging.
The long-term consequences of hepatic steatosis associated with mipomersen therapy are unknown.
Hepatic steatosis may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.
MANAGEMENT: Since alcohol may increase levels of hepatic fat and induce or exacerbate liver injury, the manufacturer recommends that patients taking mipomersen not consume more than one alcoholic drink per day.
Mipomersen Disease Interaction
Volume of Distribution
The volume of distribution for mipomersen was not quantified.
Elimination Route
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%.
Half Life
Mipomersem has a very long half life of 1-2 months.
Clearance
Clearance of mipomersem was not quantified.
Elimination Route
24 hours after mipomersem administration, less than 4% of mipomersem and/or it's metabolites were excreted in the urine.
Innovators Monograph
You find simplified version here Mipomersen
