KYNAMRO (Mipomersen) Lipid lowering drug in patients with Homozygous Familial Hypercholesterolemia

KYNAMRO (mipomersen sodium) Injection Solution

Mipomersen is an antisense oligonucleotide targeted to human messenger ribonucleic 399 acid (mRNA) for apo B-100, the principal apolipoprotein of LDL and its metabolic 400 precursor, VLDL. Mipomersen is complementary to the coding region of the mRNA for 401 apo B-100, and binds by Watson and Crick base pairing. The hybridization of 402 mipomersen to the cognate mRNA results in RNase H-mediated degradation of the 403 cognate mRNA thus inhibiting translation of the apo B-100 protein.

KYNAMRO (mipomersen sodium) Injection Solution for Subcutaneous Injection

Initial U.S. Approval: 2013

WARNING: RISK OF HEPATOTOXICITY

• KYNAMRO can cause elevations in transaminases
• Measure alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin before initiating treatment and then ALT and AST regularly as recommended.
• During treatment, withhold the dose of KYNAMRO if the ALT or AST is ≥3 times the upper limit of normal (ULN)
• Discontinue KYNAMRO for clinically significant liver toxicity. KYNAMRO increases hepatic fat (hepatic steatosis) with or without concomitant increases in transaminases. 
• Hepatic steatosis associated with KYNAMRO may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis. Because of the risk of hepatotoxicity, KYNAMRO is available only through a restricted program called the KYNAMRO REMS

INDICATIONS AND USAGE

• KYNAMRO™ is an oligonucleotide inhibitor of apolipoprotein B-100 synthesis indicated as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apo B), total cholesterol (TC), and non-high density lipoprotein-cholesterol (non HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). 
• Limitations of Use:
• The safety and effectiveness of KYNAMRO have not been established in patients with hypercholesterolemia who do not have HoFH. 
• The effect of KYNAMRO on cardiovascular morbidity and mortality has not been determined. 

DOSAGE AND ADMINISTRATION

• 200 mg once weekly as a subcutaneous injection.
• Before treatment, measure ALT, AST, alkaline phosphatase, and total bilirubin.
• DOSAGE FORMS AND STRENGTHS
• Single-use vial containing 1 mL of a 200 mg/mL solution. 
• Single-use pre-filled syringe containing 1 mL of a 200 mg/mL solution

CONTRAINDICATIONS

• Moderate or severe hepatic impairment, or active liver disease, including unexplained persistent elevations of serum transaminases 
• Known sensitivity to product components 

WARNINGS AND PRECAUTIONS

• Injection site reactions occur in 84% of patients and typically consist of one or more of the following: erythema, pain, tenderness, pruritus and local swelling.
• Flu-like symptoms, which typically occur within 2 days after injection, occur in 30% of patients and include one or more of the following: influenza-like illness, pyrexia, chills, myalgia, arthralgia, malaise or fatigue.

ADVERSE REACTIONS

The most commonly reported adverse reactions (incidence ≥ 10% and greater than placebo) are injection site reactions, flu-like symptoms, nausea, headache, and elevations in serum transaminases, specifically ALT.

 

USE IN SPECIFIC POPULATIONS\

• Nursing mothers: Discontinue drug or nursing. 
• Pediatric Patients: Safety and effectiveness not established.