mecasermin (Rx)

>10%

Hypoglycemia (42%)

Tonsillar hypertrophy (15%)

1-10%

Cardiac murmur (>5%)

Dizziness (>5%)

Convulsion (>5%)

Headache (>5%)

Lipohypertrophy (>5%)

Thymus hypertrophy (>5%)

Arthralgia (>5%)

Ear problems (>5%)

Otitis media (>5%)

<1%

Anaphylaxis

Generalized urticaria

Angioedema

Dyspnea

Local allergic reactions at the injection site (eg, pruritus, urticaria)

Alopecia, hair texture abnormal

Postmarketing Reports

Systemic hypersensitivity: anaphylaxis, generalized urticaria, angioedema, dyspnea

Local allergic reactions at the injection site: pruritus, urticaria

Skin and Subcutaneous Tissue Disorders: alopecia, hair texture abnormal

General disorders and administrative site conditions: Injection site reactions (eg, erythema, pain, hematoma, hemorrhage, induration, rash, swelling)

Musculoskeletal and connective tissue disorders: Osteonecrosis/avascular necrosis (occasionally associated with slipped capital femoral epiphysis)

Neoplasms Benign, Malignant and Unspecified (including cysts and polyps)

Contraindications

Hypersensitivity to product or components

Closed epiphyses

Active or suspected neoplasia; discontinue if neoplasia develops

IV administration

Pediatric patients with malignant neoplasia or a history of malignancy

Cautions

Do not give without meal/snack 20 min before/after (risk of hypoglycemia)

Not a substitute for GH treatment

Contains benzyl alcohol as preservative (associated with fatal "Gasping Syndrome" in preemies)

Possibility of thickening of facial soft tissues

Allergic reactions reported include localized (injection site) reactions to severe systemic reactions, including anaphylaxis requiring hospitalization

Symptoms associated with intracranial hypertension including nausea, headache, papilledema, vomiting, visual changes reported; funduscopic examinations are recommended

Lymphoid hypertrophy that may lead to complications such as chronic middle ear effusions, snoring, and sleep apnea reported

Children experiencing rapid growth may have progression of scoliosis

Caution in patients at risk for diabetes or patients being treated for diabetes

Treat thyroid deficiency prior to therapy

Evaluate any child with onset of a limp or hip/knee pain for possible slipped capital femoral epiphysis

Patients should avoid engaging in high-risk activities (eg, driving, exercise, etc.) within 2 to 3 hours after dosing, particularly during initiation of treatment until tolerability and stable dose established

There have been postmarketing reports of malignant neoplasms in pediatric patients who have received treatment; unknown whether there is relationship between therapy and new occurrence of neoplasia; monitor all patients receiving therapy carefully for development of neoplasms; advise patients/caregivers to report development of new neoplasms; if malignant neoplasia develops, discontinue treatment

Pregnancy

There are no available data on use in pregnant women; exposure during pregnancy is unlikely because the drug is not indicated for use after epiphyseal closure

Animal data

• In animal reproduction studies, there were no observed embryo-fetal development abnormalities with intravenous administration to pregnant rats and rabbits during fetal organogenesis given at exposures up to 11 and 3 times maximum recommended human dose (MRHD) of 0.24 mg/kg/day based on body surface area (BSA), respectively

Lactation

There is no information available on presence of mecasermin in human or animal milk, effects on breastfed infant, or on milk production; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breast-fed child from treatment or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant human IGF-1 used as replacement therapy in patients primary severe IGF-I deficiency, growth hormone receptors in the liver that are unresponsive to GH

Pharmacokinetics

Metabolism: Liver, kidney

Half-Life: 5.8 hr (mecasermin); >12 hr (mecasermin rinfabate)

Excretion: Likely as native proteins

Vd: 0.184-0.33 L/kg

Protein binding: 80% bound to IFGBP-3 and an acid-labile subunit

SC Injection

Give shortly before/after meal or snack (~20 minutes) to avoid hypoglycemia

If hypoglycemia occurs with recommended doses despite adequate food intake, the dose should be reduced

Rotate injection site to avoid lipodystrophy

Storage

Refrigerate unopened vials; after opening, vial contents are stable for 30 days when refrigerated