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.

Mipomersen
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

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

Major: hepatic impairmentModerate: renal dysfunction

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%.