mipomersen

mipomersen

(mi-poe-mer-sen) ,

Kynamro

(trade name)

Classification

Therapeutic: orphan drugs
Pharmacologic: temporary class
Pregnancy Category: B

Indications

Adjunct treatment (with lipid-lowering agents and diet) in the management of homozygous familial hypercholesterolemia (HoFH).

Action

Inhibits lipoprotein synthesis.

Therapeutic effects

Lowering of low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apo B), total cholesterol (TC), and non-high density lipoprotein-cholesterol (non HDL-C).

Pharmacokinetics

Absorption: Well absorbed following subcutaneous administration (54–78%).
Distribution: Unknown.
Protein Binding: ≥90%.
Metabolism and Excretion: Metabolized in tissues by enzymes, excreted in urine.
Half-life: 1–2 mo.

Time/action profile (lowering of lipids)

ROUTEONSETPEAKDURATION
Subcutunknown6 mounknown

Contraindications/Precautions

Contraindicated in: Known hypersensitivity; Moderate to severe hepatic impairment/active liver disease (Child-Pugh B or C).
Use Cautiously in: Females with reproductive potential (effective contraception should be used); Geriatric: ↑ risk of adverse reactions ; Lactation: Breastfeeding should be undertaken with caution; Obstetric: Use in pregnancy only if clearly needed; Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

  • headache (most frequent)

Cardiovascular

  • hypertension

Gastrointestinal

  • hepatotoxicity (life-threatening)
  • nausea (most frequent)
  • ↑ liver enzymes (most frequent)

Local

  • injection site reactions (most frequent)

Metabolic

  • flu-like symptoms (most frequent)

Musculoskeletal

  • extremity pain

Interactions

Drug-Drug interaction

Alcohol consumption >1 drink/day may ↑ risk of serious hepatic reactions.

Route/Dosage

Subcutaneous (Adults) 200 mg once weekly.

Availability

Solution for subcutaneous injection: 200 mg/mL

Nursing implications

Nursing assessment

  • Obtain a dietary history, especially with regard to fat consumption.
  • Assess for injection site reactions (erythema, pain, tenderness, pruritus, local swelling). Occurs intermittently; may result in discontinuation.
  • Monitor for flu-like symptoms (influenza-like illness, pyrexia, chills, myalgia, arthralgia, malaise, fatigue). Usually occurs within 2 days after injection. Occurs intermittently; may result in discontinuation.
  • Monitor for symptoms of liver injury (nausea, vomiting, abdominal pain, fever, anorexia, dark urine, jaundice, lethargy, flu-like symptoms) during therapy. If symptoms of liver injury increases in bilirubin ≥2 x the upper limit of normal, or active liver disease occur, discontinue therapy and investigate cause.
  • Lab Test Considerations: Evaluate serum cholesterol and triglyceride levels before initiating, at least every 3 mo during first year of therapy, and periodically thereafter. Assess LDL-C level after 6 mo to determine if results warrant potential risk of liver toxicity.
    • Monitor AST, ALT, alkaline phosphatase, and total bilirubin before initiating therapy. If AST or ALT ≥3 × and <5 × the upper limit of normal —confirm elevation with repeat measure in 1 wk. If confirmed, withhold dosing, obtain additional liver tests (bilirubin, alkaline phosphatase, and INR) and investigate cause. If resuming mipomersen after AST and ALT resolve to <3 × the upper limit of normal, consider monitoring liver tests more frequently. If AST or ALT ≥5 × the upper limit of normal —withhold dosing, obtain additional liver tests (bilirubin, alkaline phosphatase, and INR) and investigate cause. If resuming mipomersen after AST and ALT resolve to <3 × the upper limit of normal, consider monitoring liver tests more frequently.

Potential Nursing Diagnoses

Risk for impaired skin integrity (Adverse Reactions)

Implementation

  • Available only through a limited program, KYNAMRO REMS. Only certified health care professionals and pharmacies may prescribe and distribute mipomersen.
  • Allow solution to reach room temperature for at least 30 min prior to injection. Store in refrigerator; may be stored at room temperature for 14 days. Do not mix with other medications.
  • Subcutaneous: Administer once weekly; rotate sites to prevent irritation. Pinch skin slightly and inject needed at a 90° angle. Inject slowly over 10 seconds into abdomen (2 inches away from navel), thigh, or outer area of upper arm. Avoid areas of sunburn, rash, inflammation, infection, psoriasis, tattoos, and scarring. Do not rub area after injection; may cause redness and pain. Solution should be clear and colorless to slightly yellow; do not administer solution that is discolored or contains particulate matter.

Patient/Family Teaching

  • Instruct patient and caregiver on correct technique for injection and disposal of materials. First injection should be completed under supervision. Injection should be on the same day of the wk and same time of the day. Take missed doses as soon as remembered unless it is less than 3 days until next dose. If less than 3 days until next dose, wait and take weekly dose at regularly scheduled time; do not double doses. Do not stop taking without consulting health care professional.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Caution patient not to drink more than 1 alcoholic drink/day; may increase hepatic fat (steatosis) and liver injury.
  • Advise female patients that mipomersen is teratogenic. Caution patient to use effective contraception during therapy and to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • Reduce LDL-C, total cholesterol, apolipoprotein B, and non-high-density lipoprotein cholesterol levels. Maximal reduction of LDL-C is seen after 6 mo of therapy.
Drug Guide, © 2015 Farlex and Partners
References in periodicals archive ?
(11) Alternative drugs approved for homozygous familial hypercholesterolemia treatment, including a microsomal triglyceride transfer protein inhibitor (lomitapide) and an antisense RNA compound (mipomersen), may be feasible for treating FCS.
Novel agents include the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (that have shown to lead to a reduction in CVD morbidity), mipomersen, cholesterol ester transfer protein (CETP) inhibitors and bempedoic acid.
Although there are no data available for children, oral lomitapide and injectable mipomersen have recently been approved in the United States (US) as adjunct therapies for HoFH in patients aged [greater than or equal to]18 and [greater than or equal to]12 years, respectively (1).
Access to inhibitors of PCSK9 and more costly medications, such as mipomersen or lomitapide, may depend on a diagnosis of FH in some countries (25-28).
Mipomersen (inhibitor of apolipoprotein B-100), an antisense oligonucleotide complementary to the coding region of human apo-B mRNA, was approved by the FDA in January 2013.
(18, 19) In addition, injectable mipomersen, an antisense RNA therapy is approved in the USA from 12 years old and can reduce LDL-C up to 25%.
No reports describing the use of mipomersen (Kynamro), an oligonucleotide inhibitor of apolipoprotein B-100 synthesis, in human pregnancy have been located.
* Kynamro (mipomersen; Sanofi): What factors will determine whether Kynamro reaches the European market?
Kastle Therapeutics, a biopharmaceutical company, has signed a contract to acquire global rights to develop and commercialise Kynamro (mipomersen sodium) injection from Ionis Pharmaceuticals.
US-based drugmaker Kastle Therapeutics, LLC has acquired global rights to develop and commercialize Kynamro (mipomersen sodium) injection from Ionis Pharmaceuticals, Inc.
(22) For patients with HoFH, in whom the condition is more quickly life-threatening, there are additional choices, including LDL apheresis and medications such as mipomersen and lomitapide.
The potential future therapeutic options for targeted Lp(a) control include cholesterol-ester transfer protein inhibitors (CETPI), anti-sense oligonucleopeptides (ASO) and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK-9I) and L-carnitine.22,23 The CETP inhibitor Anacetrapib has been shown to reduce Lp(a) plasma levels by up to 50%.24 The ASO Mipomersen lowers Lp(a) by up to 50% in phase 2 trials with single injections given fortnightly.25 Maximum reductions occur after 3-6 months of continuous therapy, and slowly return to baseline after cessation of therapy.25 The PCSK-9I, AMG-145, has similar effects on Lp(a) levels with once monthly injections.26 Carnitine supplementation therapy in doses of up to 1gm daily leads to 10-15% reduction (Table-2).23,24