KYNAMRO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KYNAMRO (KYNAMRO).

How it works

Kynamro (mipomersen) is an antisense oligonucleotide that specifically binds to the mRNA of apolipoprotein B-100 (apoB-100), inhibiting its translation and reducing the production of apoB-100-containing lipoproteins, including LDL, VLDL, and Lp(a).

What the body does with it

Metabolism	Primarily metabolized by endonucleases and exonucleases. Not a substrate for CYP450 enzymes.
Excretion	Primarily hepatobiliary elimination; less than 1% excreted unchanged in urine. Mipomersen is metabolized by endonucleases and exonucleases to shorter oligonucleotides, which are excreted in bile and feces.
Half-life	Terminal elimination half-life is approximately 28-31 days (range 21-40 days) in patients with homozygous familial hypercholesterolemia, supporting weekly subcutaneous dosing.
Protein binding	Greater than 90% bound to plasma proteins, predominantly albumin.
Volume of Distribution	Approximately 9.6 L/kg, indicating extensive tissue distribution (e.g., liver, kidney).
Bioavailability	Subcutaneous administration: approximately 90% bioavailability; not administered intravenously clinically.
Onset of Action	Reductions in LDL-C are observed within 4-8 weeks after initiation of 200 mg subcutaneous weekly dosing; maximal effect typically achieved by 6 months.
Duration of Action	LDL-C reductions persist for weeks after discontinuation; gradual return to baseline over several months due to long half-life and accumulation in tissues.

Classification & Brands

Dosing & administration

Kynamro (mipomersen) is administered subcutaneously at a dose of 200 mg once weekly.

Dosage form	SOLUTION
Renal impairment	No dose adjustment is required for mild to moderate renal impairment (CrCl >30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or dialysis; use with caution.
Liver impairment	Contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh class B or C). No dose adjustment recommended for mild hepatic impairment (Child-Pugh class A).
Pediatric use	Safety and efficacy in pediatric patients have not been established; not recommended for use in patients under 18 years of age.
Geriatric use	No specific dose adjustments for elderly patients; clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for KYNAMRO (KYNAMRO).

Breastfeeding	It is unknown if KYNAMRO is excreted in human milk. No M/P ratio available. A risk to the breastfed infant cannot be excluded; decision to discontinue breastfeeding or drug should consider importance of drug to mother.
Teratogenic Risk	No adequate and well-controlled studies in pregnant women. In animal reproduction studies, no fetal harm was observed; however, caution is advised. KYNAMRO is not recommended during pregnancy unless clearly necessary.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Risk of hepatotoxicity: Kynamro can cause elevations in serum transaminases and hepatic steatosis. Monitor liver function before and during treatment. Do not use in patients with moderate or severe hepatic impairment.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Moderate or severe hepatic impairment (Child-Pugh class B or C)","Hypersensitivity to mipomersen or any component of the formulation","Active liver disease or unexplained persistent elevations of serum transaminases"]

Clinical Precautions

Precautions

["Hepatotoxicity: monitor ALT, AST, alkaline phosphatase, and total bilirubin before each dose; discontinue if clinically significant toxicity occurs.","Hepatic steatosis: may cause fatty liver; advise patients to report symptoms of liver injury.","Injection site reactions: common and may be severe.","Flu-like symptoms: common; may require symptomatic treatment.","Allergic reactions: including angioedema and urticaria.","Immune system effects: possible development of anti-drug antibodies and platelet count reductions."]

Clinical Tips & Counseling

Drug interactions

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KYNAMRO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for KYNAMRO (KYNAMRO).

How it works

What the body does with it

Metabolism	Primarily metabolized by endonucleases and exonucleases. Not a substrate for CYP450 enzymes.
Excretion	Primarily hepatobiliary elimination; less than 1% excreted unchanged in urine. Mipomersen is metabolized by endonucleases and exonucleases to shorter oligonucleotides, which are excreted in bile and feces.
Half-life	Terminal elimination half-life is approximately 28-31 days (range 21-40 days) in patients with homozygous familial hypercholesterolemia, supporting weekly subcutaneous dosing.
Protein binding	Greater than 90% bound to plasma proteins, predominantly albumin.
Volume of Distribution	Approximately 9.6 L/kg, indicating extensive tissue distribution (e.g., liver, kidney).
Bioavailability	Subcutaneous administration: approximately 90% bioavailability; not administered intravenously clinically.
Onset of Action	Reductions in LDL-C are observed within 4-8 weeks after initiation of 200 mg subcutaneous weekly dosing; maximal effect typically achieved by 6 months.
Duration of Action	LDL-C reductions persist for weeks after discontinuation; gradual return to baseline over several months due to long half-life and accumulation in tissues.

Classification & Brands

Dosing & administration

Kynamro (mipomersen) is administered subcutaneously at a dose of 200 mg once weekly.

Dosage form	SOLUTION
Renal impairment	No dose adjustment is required for mild to moderate renal impairment (CrCl >30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or dialysis; use with caution.
Liver impairment	Contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh class B or C). No dose adjustment recommended for mild hepatic impairment (Child-Pugh class A).
Pediatric use	Safety and efficacy in pediatric patients have not been established; not recommended for use in patients under 18 years of age.
Geriatric use	No specific dose adjustments for elderly patients; clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for KYNAMRO (KYNAMRO).

Breastfeeding	It is unknown if KYNAMRO is excreted in human milk. No M/P ratio available. A risk to the breastfed infant cannot be excluded; decision to discontinue breastfeeding or drug should consider importance of drug to mother.
Teratogenic Risk	No adequate and well-controlled studies in pregnant women. In animal reproduction studies, no fetal harm was observed; however, caution is advised. KYNAMRO is not recommended during pregnancy unless clearly necessary.
Fetal Monitoring