Adult Dosing

Homozygous familial hypercholesterolemia

• 200 mg SC q wk

• Before initiating therapy, measure ALT, AST, alkaline phosphatase, and total bilirubin

Pediatric Dosing

• Safety and effectiveness in the pediatric population have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Homozygous familial hypercholesterolemia (HoFH)
• 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)

• Safety and effectiveness in patients with hypercholesterolemia who do not have HoFH have not been established
• Effect on cardiovascular morbidity and mortality has not been determined
• Use as an adjunct to LDL apheresis is not recommended

• Hypersensitivity to any of the ingredients of the product
• Moderate-to-severe hepatic impairment (Child-Pugh B or C)
• Active liver disease
• Unexplained persistent increased serum transaminases

• Therapy may lead to elevations in transaminases
• Measurement of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin before initiating treatment, and then ALT and AST regularly, is recommended
• If the ALT or AST is = >3 times the upper limit of normal (ULN), withhold the dose
• Discontinue therapy in clinically significant liver toxicity
• Therapy may increase hepatic fat (hepatic steatosis) with or without concomitant increases in transaminases which may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis
• Available only through a restricted access program due risk of hepatotoxicity

Renal Dose Adjustment

• Renal impairment: Dose adjustments not defined
• Safety and efficacy in patients with known renal impairment or in patients undergoing renal dialysis, have not been established
• Not recommended in patients with severe renal impairment or clinically significant proteinuria, or in those on renal dialysis

Hepatic Dose Adjustment

• Mild impairment: Dose adjustments not defined
• Moderate-severe impairment: Contraindicated
• Contraindicated in active liver disease and unexplained persistent increase in serum transaminases

• Therapy may lead to elevations in transaminases [US black box warning]
• Measurement of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin before initiating treatment, and then ALT and AST regularly, is recommended [US black box warning]
• If the ALT or AST is = >3 times the upper limit of normal (ULN) withhold the dose [US black box warning]
• Discontinue therapy in clinically significant liver toxicity [US black box warning]
• Therapy may increase hepatic fat (hepatic steatosis) with or without concomitant increases in transaminases which may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis [US black box warning]
• Available only through a restricted access program because of the risk of hepatotoxicity [US black box warning]
• Injection site reactions such aserythema, pain, tenderness, pruritus and local swelling have been reported
• Flu-like symptoms such as influenza-like illness, pyrexia, chills, myalgia, arthralgia, malaise or fatigue have been reported in patients receiving therapy

Pregnancy Category:B

Breastfeeding: It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

• CV: Angina pectoris, hypertension, palpitations
• GI: Nausea vomiting, abdominal pain
• HEPA: Hepatic steatosis, hepatic enzyme increased, alanine aminotransferase increased, aspartate aminotransferase increased, liver function test abnormal
• CNS: Fatigue, pyrexia chills, headache, insomnia
• MUSC: Pain in extremity, musculoskeletal pain
• MISC: Influenza like illness, injection site reactions, edema peripheral

• Antisense oligonucleotide inhibitor; targets messenger RNA for apolipoprotein B-100, the principal apolipoprotein of LDL and its metabolic precursor, VLDL
• Bioavailability: 54-78%
• Metabolized in tissues by endonucleases to form shorter oligonucleotides
• Excretion: <4% urine over 24 hours
• Half-life: 1-2 months

US Trade Name(s)

• Kynamro

US Availability

Kynamro

• INJ (prefilled syringe): 200 mg/mL (1 mL prefilled syringe)

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Cardiovascular

Lipid Lowering Agent

lipoprotein Synthesis Inhibitors