Version May 2024
(For additional information see "Mecasermin (recombinant human insulin-like growth factor I): Pediatric drug information")
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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥2 years and Adolescents: There are no dosage adjustments provided in the manufacturer’s labeling; has not been studied.
Children ≥2 years and Adolescents: There are no dosage adjustments provided in the manufacturer’s labeling; has not been studied.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>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
Hypersensitivity to mecasermin or any component of the formulation; patients with closed epiphyses; malignant neoplasia; history of malignancy.
Canadian labeling: Additional contraindications (not in the US labeling): Use in neonates or premature babies (formulation contains benzyl alcohol).
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; may suppress hepatic glucose production and stimulate peripheral glucose utilization, thereby increasing the risk of hypoglycemia.
• 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).
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]
No
Solution (Increlex Subcutaneous)
40 mg/4 mL (per mL): $1,764.60
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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]
SubQ: Must be administered within 20 minutes of a meal or snack; omit dose if patient is unable to eat and do not make up for omitted dose. Rotate injection site (upper arm, thigh, buttock, abdomen) to help prevent lipohypertrophy. May cause hypoglycemic effects; patients should avoid high-risk activities (driving, operating machinery) within 2 to 3 hours of dosing until a tolerated dose is established.
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.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Macimorelin: Products that Affect Growth Hormone may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Evaluate pregnancy status prior to use; contraception is recommended in patients who could become pregnant.
Treatment is not recommended for growth promotion in patients with closed epiphyses; use during pregnancy would not be expected.
It is not known if mecasermin is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother
Must be administered within 20 minutes of a meal or snack.
Preprandial glucose during treatment initiation and dose adjustment and as clinically indicated; 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.
Severe primary IGFD is defined as follows:
Height standard deviation score ≤ -3.0 and
Basal IGF-1 standard deviation score ≤ -3.0 and
Growth hormone: Normal or increased
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 insulin-like growth factor-1 deficiency (IGFD): 0.257 (± 0.073) L/kg
Protein binding: >80% bound to IGFBP-3 and an acid-labile subunit (IGFBP-3 reduced with severe primary IGFD)
Metabolism: Hepatic and renal
Bioavailability: 100% (healthy subjects)
Half-life elimination: Severe primary IGFD: ~5.8 hours
Time to peak serum concentration: 2 hours
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
