General

**REMS Drug**

**Off Market Drug**
This medication is no longer available in the United States. Information provided here is for reference purposes only.

Pronunciation:
mi-poe-mer-sen

Trade Name(s)

• Kynamro

Ther. Class.

orphan drugs

lipid-lowering agents

Pharm. Class.

lipoprotein synthesis inhibitors

Indications

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

Action

Inhibits lipoprotein synthesis.

Therapeutic Effect(s):

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)

Contraindication/Precautions

Contraindicated in:

• Known hypersensitivity
• Moderate to severe hepatic impairment/active liver disease (Child-Pugh B or C).

Use Cautiously in:

• Geri:  ↑ risk of adverse reactions
• Lactation: Breastfeeding should be undertaken with caution
• OB:  Use in pregnancy only if clearly needed
• Rep:  Women of reproductive potential
• Pedi:  Safety and effectiveness not established.

Adverse Reactions/Side Effects

CV: hypertension

GI: HEPATOTOXICITY, nausea, ↑ liver enzymes

Local: injection site reactions

Metabolic: flu-like symptoms

MS: extremity pain

Neuro: headache

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

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

Route/Dosage

SUBQ (Adults): 200 mg once weekly.

Availability

Solution for subcutaneous injection (prefilled syringes): 200 mg/mL

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 abnormal, conduct work-up to explain baseline abnormalities. Avoid administration to patients with unexplained persistently elevated levels.  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.
• Measure AST and ALT at least monthly during first year of therapy. Measure AST and ALT every 3 mo after first year. If results abnormal at any time, withhold dose and monitor as recommended. Discontinue therapy if elevated levels are persistent or clinically significant.

Potential Diagnoses

• Risk for impaired skin integrity (Adverse Reaction) 

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.
• SUBQ 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.