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]
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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 pediatric patients ≥2 years of age 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; malignant neoplasia; history of malignancy.
Dosage and Administration
Dosing: Pediatric
Primary insulin-like growth factor 1 deficiency (IGFD) growth failure: Children ≥2 years and Adolescents: SubQ: Initial: 0.04 to 0.08 mg/kg/dose twice daily; if tolerated for 7 days, may increase by 0.04 mg/kg/dose; maximum dose: 0.12 mg/kg/dose twice daily; higher doses have not been studied and due to hypoglycemic risks should not be used. Note: 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.
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
Macimorelin: Growth Hormone Products may diminish the diagnostic effect of Macimorelin. Avoid combination
Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Monoamine Oxidase 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
Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones 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
>10%:
Endocrine & metabolic: Hypoglycemia (42%)
Immunologic: Antibody development
Respiratory: Tonsillar hypertrophy (15%)
1% to 10%:
Cardiovascular: Heart murmur (≥5%)
Endocrine & metabolic: Severe hypoglycemia (7%), thymus hypertrophy (≥5%)
Gastrointestinal: Vomiting (≥5%)
Local: Bruising at injection site (≥5%), lipotrophy at injection site (≥5%)
Nervous system: Hypoglycemic seizure (≤6%), loss of consciousness (≤6%), dizziness (≥5%), headache (≥5%), seizure (≥5%), intracranial hypertension (4%)
Neuromuscular & skeletal: Arthralgia (≥5%), limb pain (≥5%)
Otic: Abnormal tympanometry (≥5%), fluid in ear (≥5%; middle ear), hypoacusis (≥5%), otalgia (≥5%), otitis media (≥5%), serous otitis media (≥5%)
Respiratory: Snoring (≥5%)
Frequency not defined:
Cardiovascular: Cardiomegaly, heart valve disease
Dermatologic: Thickening of the soft tissues of the face
Endocrine & metabolic: Hypercholesterolemia, hypertriglyceridemia, increased lactate dehydrogenase
Hepatic: Increased serum alanine aminotransferase, increased serum aspartate transaminase
Neuromuscular & skeletal: Scoliosis progression
<1%, postmarketing, and/or case reports: Abnormal hair texture, alopecia, anaphylaxis, angioedema, avascular necrosis of bones, benign neoplasm, dyspnea, hypersensitivity reaction, injection site pruritus, injection site reaction, malignant neoplasm, osteonecrosis, slipped capital femoral epiphysis, urticaria, urticaria at injection site
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.
- Malignancy: Malignant neoplasms have been reported; generally observed in patients with rare genetic conditions of short stature associated with cancer risk, other cancer predisposing conditions, and use of higher-than-recommended doses and doses that produced elevated age- and sex-matched insulin-like growth factor-1 (IGF-1) levels. Use is contraindicated in patients with malignant neoplasia or history of malignancy. Discontinue use if neoplasia develops.
- 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 suggest 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: 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
Pregnancy Considerations
Treatment is not recommended in for growth promotion in patients with closed epiphyses; use during pregnancy would not be expected.
Patient Education
What is this drug used for?
- It is used to help children grow.
Frequently reported side effects of this drug
- Injection site irritation
- Painful extremities
- Bruising
- Joint pain
Other side effects of this drug: Talk with your doctor right away if your child has any of these signs of:
- Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating
- Dizziness
- Passing out
- Pale skin
- Clammy skin
- Headache
- Vision changes
- Snoring
- Sleep apnea
- Enlarged tonsils
- Ear pain
- Trouble hearing
- Nausea
- Vomiting
- Hip or knee pain
- Injection site skin changes like thick or thin
- Abnormal heartbeat
- Limp
- Seizures
- Signs of a significant reaction like 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. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
