KYNAMRO
Clinical safety rating
cautionComprehensive clinical and safety monograph for KYNAMRO (KYNAMRO).
Comprehensive clinical and safety monograph for KYNAMRO (KYNAMRO).
Adjunct to lipid-lowering medications and diet to reduce LDL-C, apoB, total cholesterol, and non-HDL-C in patients with homozygous familial hypercholesterolemia (HoFH)
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).
| 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. |
| Molecular Weight | 359.4 |
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. |
| 1st trimester | No adequate human studies; animal studies show fetal harm. Use only if benefit outweighs risk. |
| 2nd trimester | No adequate human studies; animal studies show fetal harm. Avoid use unless clearly needed. |
| 3rd trimester | No adequate human studies; animal studies show fetal harm. Avoid use in third trimester due to potential neonatal effects. |
Clinical note
Comprehensive clinical and safety monograph for KYNAMRO (KYNAMRO).
| Placental transfer | Likely crosses placenta due to molecular weight <500 Da; no human data. |
| Breastfeeding | Not known if excreted in human milk. Due to molecular weight and high protein binding, likely low levels but unknown effects. Use caution. |
| Lactation Rating | L3 |
| 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 | Monitor liver function tests (ALT, AST, bilirubin) before and during therapy. Monitor for injection site reactions and hypersensitivity. No specific fetal monitoring required outside routine prenatal care. |
| Fertility Effects | No human data on fertility effects. Animal studies showed no impairment of fertility at clinically relevant doses. |
■ 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.
| Serious Effects |
Hypersensitivity to mipomersen or any componentSevere hepatic impairment (Child-Pugh class B or C)
| 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. |
| Food/Dietary | Avoid high-fat meals before and after injection. Take KYNAMRO at least 2 hours after any food and at least 1 hour before the next meal to minimize gastrointestinal side effects. No specific food-drug interactions known; however, the drug can increase hepatic fat, so a low-fat diet is generally recommended. |
| Clinical Pearls | KYNAMRO (mipomersen) is an antisense oligonucleotide for homozygous familial hypercholesterolemia (HoFH). It reduces LDL-C by inhibiting apo B-100 synthesis. Monitor for hepatotoxicity; require ALT, AST, alkaline phosphatase, and bilirubin before each dose. Injection site reactions are common; rotate sites. Consider a statin first-line in HoFH if tolerated; mipomersen is adjunctive. Avoid in patients with significant liver disease or unexplained persistent transaminase elevations. Do not use in pregnancy due to risk of embryofetal toxicity. |
| Patient Advice | KYNAMRO is a weekly injection under the skin for homozygous familial hypercholesterolemia. · You must have blood tests to check your liver before each dose. · Common side effects include injection site redness, swelling, pain, or itching; flu-like symptoms; and nausea. · Do not take KYNAMRO if you are pregnant or planning to become pregnant; use effective contraception. · Take KYNAMRO on the same day each week, at least 2 hours after a meal and at least 1 hour before any food or other oral medications. · Store KYNAMRO in the refrigerator; do not freeze. Allow to warm to room temperature for 30 minutes before injecting. · Contact your doctor immediately if you experience yellowing of skin or eyes, dark urine, or severe abdominal pain. |
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