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.
References in periodicals archive ?
Mipomersen sodium (Kynamro) is given subcutaneously once a week as an adjunct to lipid-lowering medications.
NEW ORLEANS -- in patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study presented at the meeting.
In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins," said Dr.
regulatory clearance of mipomersen to treat high cholesterol and the pill eliglustat for Gaucher disease.
Carlsbad, CA) have begun a phase 3 study of mipomersen in patients with heterozygous familial hypercholesterolemia (heFH), a genetic disorder that causes exceptionally high levels of LDL cholesterol.
The FDA has indicated that reduction of LDL-cholesterol is an acceptable surrogate endpoint for accelerated approval of mipomersen for use in patients with homozygous familial hypercholesterolemia (hoFH).
The company said its cholesterol-lowering drug mipomersen was effective in a late-stage clinical trial, but safety concerns pushed the company's shares lower.
Carlsbad, CA) have entered a major strategic alliance in which Genzyme will develop and commercialize mipomersen, Isis' lipid-lowering treatment for high risk cardiovascular patients that utilizes novel antisense technology.
The FDA report concluded that this "imbalance in neoplasms will need to be assessed further in on-going and future studies and post-marketing (if approved)," and that "the potential for a contributing effect of mipomersen cannot be ruled out" in the patient deaths.
The drug, mipomersen, cut levels of "bad" LDL cholesterol by 25% after 26 weeks of treatment compared to 3% for those on placebo.
Genzyme said it agreed to develop and market Isis's mipomersen and will make an initial payment of $325 million to Isis.