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
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.
