Growth hormone deficiency, treatment: Children and Adolescents weighing ≥11.5 kg: SUBQ: Initial dose: 0.24 mg/kg/dose once weekly; round dose to the nearest prefilled cartridge(s) as per table. Individualize and titrate dose based on patient response.
|
Weight |
Dose (SUBQ)a |
|---|---|
|
a Individualize and titrate dose based on patient response | |
|
11.5 to <14 kg |
3 mg once weekly |
|
14 to <16.5 kg |
3.6 mg once weekly |
|
16.5 to <20 kg |
4.3 mg once weekly |
|
20 to <24 kg |
5.2 mg once weekly |
|
24 to <29 kg |
6.3 mg once weekly |
|
29 to <35 kg |
7.6 mg once weekly |
|
35 to <42 kg |
9.1 mg once weekly |
|
42 to <51 kg |
11 mg once weekly |
|
51 to <60.5 kg |
13.3 mg once weekly |
|
60.5 to <70 kg |
15.2 mg once weekly (using 2 cartridges of 7.6 mg each) |
|
70 to <85 kg |
18.2 mg once weekly (using 2 cartridges of 9.1 mg each) |
|
85 to 100 kg |
22 mg once weekly (using 2 cartridges of 11 mg each) |
Conversion from daily somatropin therapy: Allow 8 hours between final somatropin dose and first dose of lonapegsomatropin.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cartridge, Subcutaneous [preservative free]:
Skytrofa: Lonapegsomatropin-tcgd 3 mg (1 ea); Lonapegsomatropin-tcgd 11 mg (1 ea); Lonapegsomatropin-tcgd 3.6 mg (1 ea); Lonapegsomatropin-tcgd 4.3 mg (1 ea); Lonapegsomatropin-tcgd 5.2 mg (1 ea); Lonapegsomatropin-tcgd 6.3 mg (1 ea); Lonapegsomatropin-tcgd 7.6 mg (1 ea); Lonapegsomatropin-tcgd 9.1 mg (1 ea); Lonapegsomatropin-tcgd 13.3 mg (1 ea)
No
SUBQ: Cartridges should be used with manufacturer-supplied autoinjector which is designed for automatic reconstitution of cartridge. Autoinjector must be fully charged (requires 2 hours and 30 minutes) prior to first use; ensure sufficient battery life for necessary administration (a full charge should allow ≥4 injections). Device cannot be used when autoinjector is charging. See manufacturer's Instruction for Use for detailed charging instructions. Autoinjector should be used away (>12 inches [30 cm]) from microwave ovens or electronic equipment with antennas such as mobile phones and WiFi transceivers.
If refrigerated, allow cartridge to sit at room temperature for 15 minutes prior to administration. Connect needle (with needle cover on) to dose cartridge. Turn autoinjector on; when autoinjector indicates ready for use, insert cartridge until it clicks into device. Ensure cartridge is standing upright on a flat surface and wait for 4 to 8 minutes for automatic mixing of medication to occur. Once automated mixing is complete, hand mix by turning the autoinjector straight up and straight down 5 to 10 times (an audible click should be heard with each turn); 2 loud beeps will be heard when mixing is complete; if hand mixing is not performed within 2 hours of automatic mixing, the autoinjector will cancel the procedure and that cartridge will be unusable. After hand mixing is complete, keep autoinjector upright for automatic air removal; once complete autoinjector is ready for administration; administer within 2 hours of final mixing. Entire process (from automatic mixing to administration) must occur within 4 hours; if not, cartridge will release from the device and will be unusable. See manufacturer's Instruction for Use for detailed mixing instructions and description of icons.
Immediately prior to administration, pull needle cover off (do not twist) and save for later. View inspection window to ensure medication is mixed; solution should be clear and colorless; some air bubbles may be visible; do not use if particles are visible or solution is discolored. Administer subcutaneously into the abdomen (excluding area around navel), thighs or buttocks; rotate injection site with each dose. Press and hold green top of autoinjector against skin for 10 to 15 seconds; do not remove from skin until autoinjector indicates injection is complete. Following injection, a buzzing sound will occur while autoinjector unlocks cartridge; once unlocked, the needle cover may be replaced; press down on needle cover to release cartridge. Remove cartridge by pulling straight up (do NOT twist) and dispose in appropriate container. If 2 injections are needed to complete dose, repeat entire process with new cartridge. See manufacturer's Instruction for Use for detailed administration instructions and description of icons.
Missed dose: Note: To avoid missed doses, doses may be administered 2 days before or 2 days after scheduled dose; resume weekly dosing on the previously scheduled day. Doses should be given at least 5 days apart.
If ≤2 days since scheduled day: Administer dose as soon as possible.
If >2 days since scheduled day: Skip dose and resume at next scheduled dose.
Prior to reconstitution, store cartridges at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light. Do not freeze. Alternatively, outer carton containing blistered cartridges may be stored at room temperature (up to 30°C [86°F]) for up to 6 months and can be returned to refrigeration within the 6 months. Write the date first removed from the refrigerator in the space provided on the outer carton. Do not use beyond the expiration date or 6 months after the date it was first removed from refrigeration (whichever is earlier).
Following reconstitution (using the autoinjector device) use within 4 hours.
Autoinjector device: Store away (>12 inches [30 cm]) from microwave ovens or electronic equipment with antennas such as mobile phones and Wi-Fi transceivers.
Treatment of growth failure due to inadequate endogenous growth hormone secretion (FDA approved in pediatric patients ≥1 year of age who weigh at least 11.5 kg).
Skytrofa may be confused with Skyrizi.
Beers Criteria: Growth hormone is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients ≥65 years of age, except as hormone replacement in patients with growth hormone deficiency due to an established etiology that is based on a rigorous diagnosis by evidence-based criteria due to its minimal impact on body composition and its association with causing edema, arthralgia, carpal tunnel syndrome, gynecomastia, and impaired fasting glucose (Beers Criteria [AGS 2019]).
Fluid retention may occur with growth hormone (GH) therapy; effects are generally transient and dose dependent. Manifestations of fluid retention may include peripheral edema, arthralgia, myalgia, and nerve compression syndromes (including carpal tunnel syndrome or paresthesias).
Mechanism: Dose-dependent. Exact mechanism is unknown (Ref).
Onset: Varied; onset of symptoms consistent with fluid retention generally occur within 1 to 3 months of initiation or dose increase of GH therapy (Ref).
Risk factors:
• Patients being treated for adult-onset GH deficiency, especially those with an increased body mass index (Ref)
Treatment with growth hormone (GH) products, including lonapegsomatropin, may decrease insulin sensitivity. Previously undiagnosed impaired glucose tolerance or diabetes mellitus may be detected; new-onset type 2 diabetes mellitus and exacerbation of preexisting diabetes mellitus may occur (Ref).
Mechanism: Dose-dependent; related to the pharmacologic action. Lonapegsomatropin is a human growth hormone (GH) analog which may antagonize the hepatic and peripheral effects of insulin on glucose metabolism (Ref).
Onset: Delayed; in one long-term observational trial of adults with GH deficiency receiving GH therapy, new diagnosis of type 2 diabetes occurred between 9 and 29 months of GH therapy (Ref) .
Risk factors:
• Preexisting type 1 or 2 diabetes mellitus, pre-diabetes, or risk factors for developing diabetes mellitus (eg, obesity, family history)
Intracranial hypertension (IH) with headache, nausea, papilledema, visual changes, and/or vomiting has been reported in patients treated with growth hormone (GH) products (Ref); signs and symptoms of IH may rapidly resolve after discontinuation or reduction of dose.
Mechanism: Exact mechanism is unknown; may be dose related (Ref).
Onset: Delayed; symptoms usually occur within the first 8 weeks of therapy. IH has also appeared after several years of treatment with GH therapy (Ref).
Risk factors:
• Preexisting IH (eg, preexisting papilledema)
• In general, idiopathic intracranial hypertension is most commonly reported in females of childbearing age and with a high body mass index (Ref)
• Chronic kidney insufficiency (Ref)
Growth hormone (GH) therapy may increase the risk of malignancy progression in patients with active malignancy. Malignant transformation or growth of preexisting nevi may also occur. The use of GH therapy in GH-deficient patients without other risk factors for malignancy does not appear to increase the risk of developing malignancy (Ref).
Risk factors:
• Presence of preexisting malignancy, especially active malignancies or patients with malignancies who have not yet completed treatment
Note: The American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) guidelines for the management of GH deficiency in adults suggest waiting ≥5 years after cancer remission before initiating low dose recombinant human GH therapy due to the increased risk of secondary neoplasm (particularly adult survivors of childhood cancers); specific data on the effects of recombinant GH replacement and cancer risk are lacking (Ref).
• Presence of preexisting nevi
• Pediatric patients with short stature (genetic cause) have increased baseline risk of developing malignancies
Pediatric patients receiving growth hormone (GH) therapy can develop slipped capital femoral epiphyses (SCFE) at an incidence rate higher than the general population (Ref).
Mechanism: Exact mechanism is unknown; recombinant GH may reduce resistance to shear stresses and contributes to the widening of the weakest zone of the epiphyseal plate enhancing weakness of the growth plate (Ref).
Onset: Varied; the median onset from the start of GH therapy ranges from 0.4 to 2.5 years (Ref) though there seems to be no correlation between the occurrence of SCFE and duration of GH therapy (Ref).
Risk factors:
• Rapid growth (Ref)
• Prior cancer diagnosis (Ref), including craniopharyngioma and cranial tumor (Ref)
• Total body irradiation (Ref) or radiation exposure to the spinal area (Ref)
• Trauma (Ref)
• Obesity (Ref)
• Turner syndrome (Ref)
• Panhypopituitarism (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Increased serum phosphate (44%)
Gastrointestinal: Nausea and vomiting (11%)
|
Drug (Lonapegsomatropin) |
Comparator (Somatropin) |
Population |
Indication |
Number of Patients (Lonapegsomatropin) |
Number of Patients (Somatropin) |
|---|---|---|---|---|---|
|
11% |
7% |
Children and adolescents |
Growth hormone deficiency |
105 |
56 |
Hepatic: Increased serum alkaline phosphatase (19%)
Infection: Viral infection (15%)
Respiratory: Cough (11%)
Miscellaneous: Fever (15%)
1% to 10%:
Gastrointestinal: Abdominal pain (6%), diarrhea (6%)
Hematologic & oncologic: Hemorrhage (7%; including bruise, epistaxis, eye hemorrhage, petechia)
Immunologic: Antibody development (6%)
Neuromuscular & skeletal: Arthralgia (≤6%), arthritis (≤6%)
|
Drug (Lonapegsomatropin) |
Comparator (Somatropin) |
Population |
Indication |
Number of Patients (Lonapegsomatropin) |
Number of Patients (Somatropin) |
Comments |
|---|---|---|---|---|---|---|
|
6% |
2% |
Children and adolescents |
Growth hormone deficiency |
105 |
56 |
Described as "arthralgia and arthritis" |
Postmarketing: Hypersensitivity: Severe hypersensitivity reaction (including anaphylaxis and angioedema)
Hypersensitivity to lonapegsomatropin, somatropin, or any component of the formulation; acute critical illness after open heart surgery, abdominal surgery, or multiple accidental trauma; acute respiratory failure; closed epiphyses; active malignancy; active proliferative or severe nonproliferative diabetic retinopathy; Prader-Willi syndrome in patients who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment.
Concerns related to adverse effects:
• Pancreatitis: Has been rarely reported in pediatric patients receiving somatropin; incidence in children may be greater than adults. Consider pancreatitis diagnosis if abdominal pain occurs.
Disease-related concerns:
• Acute critical illness: Initiation of lonapegsomatropin is contraindicated with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma, or acute respiratory failure; mortality may be increased. Discontinuation of therapy may be necessary in patients with an acute critical illness.
• Hypoadrenalism: Patients who have or are at risk for pituitary hormone deficiency(ies) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism with somatropin therapy; patients with previously diagnosed hypoadrenalism may require increased dosages of glucocorticoids due to the effects of somatropin. Excessive glucocorticoid therapy may inhibit the growth-promoting effects of somatropin in children.
• Hypothyroidism: Patients who have or are at risk for pituitary hormone deficiency(ies) may be at risk for unmasking of central hypothyroidism with somatropin therapy. Untreated/undiagnosed hypothyroidism may decrease response to therapy, particularly the growth response in children.
• Prader-Willi syndrome: Sudden death has been reported in pediatric patients with Prader-Willi syndrome following the use of somatropin. The reported fatalities occurred in patients with ≥1 risk factor, including severe obesity, history of upper airway obstruction or sleep apnea, respiratory impairment, or unidentified respiratory infection; male patients may be at greater risk. Use of lonapegsomatropin is not indicated for the treatment of pediatric patients who have growth failure due to Prader-Willi syndrome.
• Scoliosis: Progression of scoliosis may occur in children experiencing rapid growth.
Special populations:
• Pediatric: Failure to increase growth rate, particularly during the first year of therapy, indicates need for close assessment of compliance and evaluation for other causes of growth failure, such as hypothyroidism, undernutrition, advanced bone age, and antibodies to recombinant human growth hormone.
Other warnings/precautions:
• Autoinjector: The autoinjector device should never be used for more than one person (even if the needle is changed) because of the risk of infection.
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.
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
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of Corticosteroids (Systemic). Risk C: Monitor therapy
Cortisone: May diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of Cortisone. Risk C: Monitor therapy
Estrogen Derivatives: May diminish the therapeutic effect of Growth Hormone Analogs. Management: Initiate somapacitan at 2 mg once weekly in patients receiving oral estrogens. Monitor for reduced efficacy of growth hormone analogs; increased doses may be required. Risk D: Consider therapy modification
Macimorelin: Products that Affect Growth Hormone may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Pegloticase: May diminish the therapeutic effect of PEGylated Drug Products. Risk C: Monitor therapy
Pegvaliase: PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor therapy
PredniSONE: May diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of PredniSONE. Risk C: Monitor therapy
Embryonic or fetal developmental toxicities were not observed in animal studies.
Somatropin is released following administration of lonapegsomatropin; also refer to the somatropin monograph for information.
Fundoscopic exam to evaluate for papilledema (at baseline and periodically during therapy); blood glucose, serum cortisol, thyroid function tests, phosphate, alkaline phosphatase, and parathyroid hormones (periodically as clinically appropriate). Monitor for fluid retention, limp, hip or knee pain, lipoatrophy at injection sites, and changes in moles or skin pigmentation. Monitor scoliosis progression (in patients with history of scoliosis).
Lonapegsomatropin is a long-acting, pegylated prodrug of a human growth hormone (somatropin). Somatropin is a purified polypeptide hormone of recombinant DNA origin; it contains the identical sequence of amino acids found in human growth hormone. Human growth hormone assists growth of linear bone, skeletal muscle, and organs by stimulating chondrocyte proliferation and differentiation, lipolysis, protein synthesis, and hepatic glucose output; stimulates erythropoietin, which increases red blood cell mass; exerts both insulin-like and diabetogenic effects; enhances the transmucosal transport of water, electrolytes, and nutrients across the gut.
Note: Following subcutaneous administration, lonapegsomatropin releases fully active somatropin via autocleavage of the link to the methoxypolyethylene glycol carrier; cleavage follows first-order kinetics.
Distribution: Vd: Lonapegsomatropin: Pediatric patients: 0.13 L/kg; Somatropin is expected to be similar.
Metabolism: Somatropin: Occurs in liver and kidneys via protein catabolism; methoxypolyethylene glycol carrier: Cleared by kidneys.
Half-life elimination: Pediatric patients: Lonapegsomatropin: 30.7 ± 12.7 hours; Somatropin: ~25 hours.
Time to peak: SUBQ: Pediatric patients: Lonapegsomatropin: 25 hours; Somatropin: 12 hours.
Cartridge (Skytrofa Subcutaneous)
3 mg (per each): $786.60
3.6 mg (per each): $943.92
4.3 mg (per each): $1,127.46
5.2 mg (per each): $1,363.44
6.3 mg (per each): $1,651.86
7.6 mg (per each): $1,992.72
9.1 mg (per each): $2,386.02
11 mg (per each): $2,884.20
13.3 mg (per each): $3,487.26
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