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Mecasermin

Pronunciation

(mek a SER min)

Index Terms

  • Mecasermin (rDNA Origin)
  • Recombinant Human Insulin-Like Growth Factor-1
  • rhIGF-1 (Mecasermin [Increlex®])

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous:

Increlex: 40 mg/4 mL (4 mL) [contains benzyl alcohol]

Brand Names: U.S.

  • Increlex

Pharmacologic Category

  • Growth Hormone

Pharmacology

Mecasermin is an insulin-like growth factor (IGF-1) produced using recombinant DNA technology to replace endogenous IGF-1. Endogenous IGF-1 circulates predominately bound to insulin-like growth factor-binding protein-3 (IGFBP-3) and a growth hormone-dependent acid-labile subunit (ALS). Acting at receptors in the liver and other tissues, endogenous growth hormone (GH) stimulates the synthesis and secretion of IGF-1. In patients with primary severe IGF-1 deficiency, growth hormone receptors in the liver are unresponsive to GH, leading to reduced endogenous IGF-I concentrations and decreased growth (skeletal, cell, and organ). Endogenous IGF-1 also suppresses liver glucose production, stimulates peripheral glucose utilization, and has an inhibitory effect on insulin secretion.

Distribution

Vd: Severe primary IGFD: 0.257 (± 0.073) L/kg

Metabolism

Hepatic and renal

Time to Peak

Serum: 2 hours

Half-Life Elimination

Severe primary IGFD: ~5.8 hours

Protein Binding

>80% bound to IGFBP-3 and an acid-labile subunit (IGFBP-3 reduced with severe primary IGFD)

Use: Labeled Indications

Primary insulin-like growth factor-1 deficiency: Treatment of growth failure in children with severe primary insulin-like growth factor 1 (IGF-1) deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.

Contraindications

Hypersensitivity to mecasermin or any component of the formulation; patients with closed epiphyses; active or suspected neoplasia; intravenous administration

Dosing: Pediatric

Primary insulin-like growth factor-1 deficiency (IGFD): SubQ: Children ≥2 years and Adolescents: Initial: 0.04-0.08 mg/kg twice daily; if tolerated for 7 days, may increase by 0.04 mg/kg/dose (maximum dose: 0.12 mg/kg twice daily). Must be administered within 20 minutes of a meal or snack; omit dose if patient is unable to eat. Reduce dose if hypoglycemia occurs despite adequate food intake; dose should not be increased to make up for ≥1 omitted dose.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Administration

For SubQ injection only; do not administer IV Omit dose and do not make up for omitted dose if patient is unable to eat. To help prevent lipohypertrophy, rotate injection site(upper arm, thigh, buttock, abdomen). Must be administered within 20 minutes of a meal or snack. May cause hypoglycemic effects; patients should avoid high-risk activities within 2-3 hours of dosing until a tolerated dose is established.

Dietary Considerations

Must be administered within 20 minutes of a meal or snack.

Storage

Store vials under refrigeration at 2°C to 8°C (35°F to 46°F); keep refrigerated and use within 30 days of initial vial entry. Do not freeze. Protect from direct light.

Drug Interactions

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Adverse Reactions

≥5%:

Cardiovascular: Heart murmur

Central nervous system: Dizziness, headache, seizure

Endocrine & metabolic: Hypoglycemia (42%), lipohypertrophy (injection site), thymus hypertrophy

Gastrointestinal: Vomiting

Local: Bruising at injection site

Neuromuscular & skeletal: Arthralgia, limb pain

Otic: Abnormal tympanometry, fluid in ear (middle ear), hypoacusis, otalgia, otitis media, serous otitis media

Respiratory: Tonsillar hypertrophy (15%), snoring

<5% (Limited to important or life-threatening): Anaphylaxis, cardiomegaly, heart valve disease, hypercholesterolemia, hypersensitivity, hypertriglyceridemia, hypoglycemic seizure, increased lactate dehydrogenase, increased serum ALT, increased serum AST, intracranial hypertension, obstructive sleep apnea syndrome, osteonecrosis (occasionally associated with slipped capital femoral epiphysis)

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Hypersensitivity reactions (localized skin reactions to anaphylaxis) have been reported. If hypersensitivity is suspected; discontinue and instruct patient to seek immediate medical attention.

• Hypoglycemia: May cause hypoglycemic effects, especially in small children (due to inconsistent oral intake); patients should avoid high-risk activities (eg, driving) within 2 to 3 hours after dosing, particularly at initiation of treatment, until a tolerated dose is established. Do not administer on days a patient cannot or will not eat. Should be administered with a meal or a snack.

• Intracranial hypertension: Intracranial hypertension with headache, nausea, papilledema, visual changes, and/or vomiting has been reported with growth hormone product; funduscopic examinations are recommended at initiation of therapy and periodically thereafter.

• Lymphoid hypertrophy: Has been reported and may lead to complications such as snoring, sleep apnea, and chronic middle-ear effusions.

• Slipped capital femoral epiphyses: Patients with growth hormone deficiency can develop slipped capital femoral epiphyses more frequently; evaluate any child with new onset of a limp or with complaints of hip or knee pain.

Disease-related concerns:

• Diabetes: Use with caution in patients with diabetes or with risk factors for glucose intolerance; may decrease insulin sensitivity.

• Scoliosis: Progression of scoliosis may occur in children experiencing rapid growth.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate use: Correct thyroid or nutritional deficiencies prior to therapy. Not intended for use in patients with secondary forms of IGF-1 deficiency (GH deficiency, malnutrition, hypothyroidism, chronic anti-inflammatory steroid therapy).

Monitoring Parameters

Preprandial glucose during treatment initiation and dose adjustment; hypersensitivity reactions; facial features; lymphoid tissue; funduscopic examination (at initiation and periodically thereafter); growth; new onset of a limp or complaints of hip or knee pain; progression of scoliosis. Monitor small children closely due to potentially erratic food intake.

Target treatment IGF-1 level: 0 to +2 SD score for age

Decrease dose for adverse events and/or IGF-1 levels ≥3 SD above normal

Pregnancy Risk Factor

C

Pregnancy Considerations

Teratogenic effects were not observed in animal studies

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, vomiting, or joint pain. Have caregiver report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), severe headache, vision changes, eye pain, severe eye irritation, snoring, sleep apnea, enlarged tonsils, ear pain, severe nausea, severe vomiting, hip or knee pain, limp, or seizures (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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