Skytrofa Lonapegsomatropin-tcgd 4.3 mg Injection, Powder, Lyophilized, For Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Recombinant Human Growth Hormone class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Great question. Skytrofa is specially designed with a technology called pegylation — basically, the growth hormone is attached to a carrier that releases it slowly over the week. T...
- Why does my child only need this shot once a week instead of every day?
- Most kids have mild side effects like a cold, fever, cough, or stomach upset. Joint pain and mild bruising or nosebleeds have also been reported. In adults, the most common issue i...
- What side effects should I actually watch out for?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Lonapegsomatropin-Tcgd — tap one for details:
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $1,077.84 | — |
| Medicare drug plans payPart D · Q2 2026 | $1,136.44 | — |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Skytrofa 4.3 mgthis 73362-0005-01 | Ascendis | 1 cartridge | — | — | FDA listed | — |
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⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Aug 25, 2033 |
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 73362-0005-01 You're viewing this | 4 BLISTER PACK in 1 CARTON (73362-005-01) / 1 CARTRIDGE in 1 BLISTER PACK (73362-005-02) / 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 CARTRIDGE | 2021-08-25 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE SKYTROFA (lonapegsomatropin-tcgd) is a human growth hormone indicated for the: Treatment of pediatric patients 1 year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone (GH). Replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD). SKYTROFA is a human growth hormone indicated for: Pediatric Patients: Treatment of pediatric patients 1 year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone (GH) ( 1 ).
Adults: Replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD) ( 1 ).
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION SKYTROFA should be administered subcutaneously once weekly into the abdomen, buttock, or thigh with regular rotation of the injection sites ( 2.7 ). Pediatric Patients: Recommended dose is 0.24 mg/kg body weight once weekly ( 2.2 ). Adults: Recommended starting dose is based on age and concomitant use of oral estrogen.
Titrate monthly until the desired clinical response and/or weekly average IGF-1 concentration are achieved ( 2.3 ). See Full Prescribing Information for instructions on preparation and administration of drug ( 2.5 , 2.6 , 2.7 ).
2.1General Dosing Information For subcutaneous injection, once weekly. Therapy with SKYTROFA should be supervised by a healthcare provider who is experienced in the diagnosis and management of patients with growth hormone deficiency (GHD). Perform fundoscopic examination before initiating treatment with SKYTROFA to exclude preexisting papilledema.
If papilledema is identified, evaluate the etiology and treat the underlying cause before initiating treatment with SKYTROFA [see Warnings and Precautions (5.5) ] .
2.2Recommended Dosage for Pediatric Patients The recommended dose of SKYTROFA for treatment-naïve patients and patients switching from another growth hormone product is 0.24 mg/kg body weight, given once weekly. Individualize and titrate the dosage of SKYTROFA based on response. When changing from daily somatropin therapy to once-weekly SKYTROFA, wait at least 8 hours between the final dose of daily somatropin and the first dose of SKYTROFA.
When changing from another once-weekly growth hormone therapy to once-weekly SKYTROFA, wait at least 7 days between the final dose of the previous growth hormone therapy and the first dose of SKYTROFA. Assess compliance and evaluate other causes of poor growth, such as hypothyroidism, under-nutrition, advanced bone age and antibodies to recombinant human growth hormone if patients experience failure to increase height velocity, particularly during the first year of treatment. Patients who were treated with SKYTROFA for GH deficiency in childhood and whose epiphyses are closed should be reevaluated before continuing SKYTROFA.
2.3Recommended Dosage for Adults The recommended starting dose of SKYTROFA in adults with GHD is based on age and concomitant use of oral estrogen [see Dosage Forms and Strengths (3) ] . For treatment-naïve patients or for patients switching from another growth hormone product, start SKYTROFA as described below: 1.4 mg once weekly for adults 30 to 60 years old, with no oral estrogen intake 2.1 mg once weekly for adults under 30 years old, or adults of any age intaking oral estrogen 0.7 mg once weekly for adults over 60 years old, with no oral estrogen intake When changing from daily somatropin therapy to once-weekly SKYTROFA, wait at least 8 hours between the final dose of daily somatropin and the first dose of SKYTROFA.
When changing from another once-weekly growth hormone therapy to once-weekly SKYTROFA, wait at least 7 days between the final dose of the previous growth hormone therapy and the first dose of SKYTROFA. Increase the dose monthly to a higher strength cartridge based on the clinical response and/or IGF-1 concentration. Draw IGF-1 serum sample 4 to 5 days after the prior dose.
Decrease the dose to a lower strength cartridge as needed based on adverse reactions or a weekly average IGF-1 concentration above the age- and sex-specific normal range. The maximum recommended dose is 6.3 mg once weekly.
2.4Missed Doses Administer a missed dose as soon as possible and not more than 2 days after the missed dose. To avoid missed doses, SKYTROFA can be taken 2 days before or 2 days after the scheduled dosing day. Resume once-weekly dosing for the next dose at the previously scheduled dosing day.
If more than 2 days have passed from the scheduled day, skip the dose and administer the next dose on the regularly scheduled day. At least 5 days should elapse between doses.
2.5 Administration Instr…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS SKYTROFA is a white to off-white lyophilized powder available in a single-dose, dual-chamber, prefilled cartridge containing lonapegsomatropin-tcgd in one chamber and diluent, Water for Injection, in the other chamber and is available in the following strengths: For injection: 0.7 mg, 1.4 mg, 1.8 mg, 2.1 mg, 2.5 mg, 3 mg, 3.6 mg, 4.3 mg, 5.2 mg, 6.3 mg, 7.6 mg, 9.1 mg, 11 mg, and 13.3 mg. SKYTROFA is a lyophilized powder available in single-dose, dual-chamber, prefilled cartridges containing lonapegsomatropin-tcgd and diluent, Water for Injection, as follows: For injection: 0.7 mg, 1.4 mg, 1.8 mg, 2.1 mg, 2.5 mg, 3 mg, 3.6 mg, 4.3 mg, 5.2 mg, 6.3 mg, 7.6 mg, 9.1 mg, 11 mg, and 13.3 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS SKYTROFA is contraindicated in patients with: Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin [see Warnings and Precautions (5.1) ] . Hypersensitivity to somatropin or any of the excipients in SKYTROFA. Severe systemic hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported [see Warnings and Precautions (5.2) ].
Pediatric patients with closed epiphyses. Active malignancy due to the risk of malignancy progression [see Warnings and Precautions (5.3) ]. Active proliferative or severe non-proliferative diabetic retinopathy because treatment with somatropin may worsen this condition.
Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea or have severe respiratory impairment due to the risk of sudden death [see Warnings and Precautions (5.13) ]. Acute critical illness ( 4 ) Hypersensitivity to somatropin or any of the excipients in SKYTROFA ( 4 ) Children with closed epiphyses ( 4 ) Active malignancy ( 4 ) Active proliferative or severe non-proliferative diabetic retinopathy ( 4 ) Children with Prader-Willi syndrome who are severely obese or have severe respiratory impairment due to risk of sudden death ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Severe Hypersensitivity: Hypersensitivity reactions, including anaphylaxis and angioedema have occurred. In the event of an allergic reaction, seek prompt medical attention ( 5.2 ). Increased Risk of Neoplasms: Monitor patients with preexisting tumors for progressions or recurrence.
Increased risk of a second neoplasm in childhood cancer survivors treated with somatropin – in particular meningiomas in patients treated with radiation to the head for their first neoplasm ( 5.3 ). Glucose Intolerance and Diabetes Mellitus: May be unmasked. Periodically monitor glucose levels in all patients.
Doses of concurrent antihyperglycemic drugs in diabetics may require adjustment ( 5.4 ). Intracranial Hypertension: Exclude preexisting papilledema. May develop and is usually reversible after discontinuation or dose reduction ( 5.5 ).
Fluid Retention (i.e., edema, arthralgia, carpal tunnel syndrome): May occur. Reduce dose as necessary ( 5.6 ). Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism ( 5.7 ).
Hypothyroidism: May first become evident or worsen ( 5.8 ). Slipped Capital Femoral Epiphysis in Pediatric Patients: May develop. Evaluate children with the onset of a limp or persistent hip/knee pain ( 5.9 ).
Progression of Preexisting Scoliosis: May develop ( 5.10 ). Pancreatitis: Consider pancreatitis in patients with persistent severe abdominal pain ( 5.11 ).
5.1Increased Mortality in Patients With Acute Critical Illness Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic doses of somatropin [see Contraindications (4) ]. The safety of continuing SKYTROFA treatment in patients receiving replacement doses for the approved indication who concurrently develop these illnesses has not been established.
5.2Severe Hypersensitivity Severe systemic hypersensitivity reactions, including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropin products, including SKYTROFA. Inform patients and/or caregivers that such reactions are possible, and that prompt medical attention should be sought if an allergic reaction occurs. SKYTROFA is contraindicated in patients with known hypersensitivity to somatropin or any of the excipients in SKYTROFA.
5.3Increased Risk of Neoplasms Active Malignancy There is an increased risk of malignancy progression with somatropin treatment in patients with active malignancy [see Contraindications (4) ]. Any preexisting malignancy should be inactive, and its treatment should be completed prior to instituting therapy with SKYTROFA. Discontinue SKYTROFA if there is evidence of recurrent malignancy.
Risk of Second Neoplasm in Pediatric Patients In childhood cancer survivors who were treated with radiation to the brain/head for their first neoplasm and who developed subsequent growth hormone deficiency (GHD) and were treated with somatropin, an increased risk of a second neoplasm has been reported. Intracranial tumors, in particular meningiomas, were the most common of these second neoplasms. Monitor all patients with a history of GHD secondary to an intracranial neoplasm while on somatropin therapy for progression or recurrence of the tumor.
New Malignancy During Treatment Because children with certain rare genetic causes of short stature have an increased risk of developing malignancies, thoroughly consider the risks and benefits of starting somatropin in these patients. If treatment with somatropin is initiated, carefully monitor these patients for development of neoplasms. Monitor patients on SKYTROFA therapy carefully for increased growth or potential malignant changes of preexisting nevi.
Advise patients/caregivers to report marked changes in behavior, onset of heada…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following important adverse reactions are described elsewhere in the labeling: Increased mortality in patients with acute critical illness [see Warnings and Precautions (5.1) ] Severe hypersensitivity [see Warnings and Precautions (5.2) ] Increased risk of neoplasms [see Warnings and Precautions (5.3) ] Glucose intolerance and diabetes mellitus [see Warnings and Precautions (5.4) ] Intracranial hypertension [see Warnings and Precautions (5.5) ] Fluid retention [see Warnings and Precautions (5.6) ] Hypoadrenalism [see Warnings and Precautions (5.7) ] Hypothyroidism [see Warnings and Precautions (5.8) ] Slipped capital femoral epiphysis in pediatric patients [see Warnings and Precautions (5.9) ] Progression of preexisting scoliosis in pediatric patients [see Warnings and Precautions (5.10) ] Pancreatitis [see Warnings and Precautions (5.11) ] Lipoatrophy [see Warnings and Precautions (5.12) ] Sudden death in pediatric patients with Prader-Willi syndrome [see Warnings and Precautions (5.13) ] Pediatric Patients: Most common adverse reactions (≥ 5%): viral infection, pyrexia, cough, nausea and vomiting, hemorrhage, diarrhea, abdominal pain, and arthralgia and arthritis ( 6.1 ).
Adults: Most common adverse reaction (≥ 5%): edema peripheral ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Ascendis Pharma Endocrinology, Inc., at 1-844-442-7236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. Pediatric Patients with Growth Hormone Deficiency SKYTROFA was studied in a 52-week, open-label, active-controlled trial in 161 treatment-naïve, prepubertal pediatric patients with growth hormone deficiency (GHD) [see Clinical Studies (14.1) ] .
The subjects ranged in age from 3.2 to 13.1 years with a mean of 8.5 years. One hundred thirty-two (82%) of the subjects were male and 29 (18%) were female. One subject was Asian, 3 were Black or African American, 152 were Caucasian, and 5 were categorized as "other." Table 2 shows common adverse reactions that occurred in ≥ 5% of patients treated with SKYTROFA in this trial.
Table 2: Adverse Reactions Occurring in ≥ 5% SKYTROFA-Treated Pediatric Patients and More Frequently Than in Daily Somatropin-Treated Pediatric Patients (52 Weeks of Treatment) Adverse reactions Daily Somatropin (N = 56) n (%) SKYTROFA (N = 105) n (%) Adverse reactions that are medically related were grouped to a single preferred term. Infection, viral 6 (11%) 16 (15%) Pyrexia 5 (9%) 16 (15%) Cough 4 (7%) 11 (11%) Nausea and vomiting 4 (7%) 11 (11%) Hemorrhage Hemorrhage in the SKYTROFA treatment group included epistaxis (3), contusion (2), petechiae (1) and eye hemorrhage (1).
1 (2%) 7 (7%) Diarrhea 3 (5%) 6 (6%) Abdominal pain 2 (4%) 6 (6%) Arthralgia and arthritis Arthralgia and arthritis in the SKYTROFA treatment group included arthralgia (5) and reactive arthritis (1). 1 (2%) 6 (6%) Laboratory Tests More SKYTROFA-treated patients shifted from normal baseline levels to elevated phosphate and alkaline phosphatase levels at the end of the trial compared to the daily somatropin group (44.2% vs. 30.2% and 19.2% vs.
9.4%, respectively); these laboratory changes occurred intermittently [see Warnings and Precautions (5.14) ] . Adults with Growth Hormone Deficiency SKYTROFA was studied in a 38-week parallel-arm, placebo-controlled (double-blind) and active-controlled (open label) trial in 259 adults with growth hormone deficiency (GHD) [see Clinical Studies (14.2) ] . The mean (range) age at enrollment was 43 (23 to 81) years old, with 119 (46%) females (55 on oral estrogen) and 140 (54%) males.
One subject was American Indian or Alaska Native, one was Black or African American, 28 were Asian, and 218 were…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Table 4 includes a list of drugs with clinically important drug interactions when administered concomitantly with SKYTROFA and instructions for preventing or managing them. Table 4: Clinically Important Drug Interactions with SKYTROFA Replacement Glucocorticoid Treatment Clinical Impact: Microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) is required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. Somatropin inhibits 11βHSD-1.
Consequently, individuals with untreated growth hormone deficiency (GHD) have relative increases in 11βHSD-1 and serum cortisol. Initiation of SKYTROFA may result in inhibition of 11βHSD-1 and reduced serum cortisol concentrations. Intervention: Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of SKYTROFA [see Warnings and Precautions (5.7) ] Examples Cortisone acetate and prednisone may be affected more than others because conversion of these drugs to their biologically active metabolites is dependent on the activity of 11βHSD-1.
Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment Clinical Impact: Pharmacologic glucocorticoid therapy and supraphysiologic glucocorticoid treatment may attenuate the growth-promoting effects of SKYTROFA in pediatric patients. Intervention: Carefully adjust glucocorticoid replacement dosing in pediatric patients receiving glucocorticoid treatments to avoid both hypoadrenalism and an inhibitory effect on growth. Cytochrome P450-Metabolized Drugs Clinical Impact: Limited published data indicate that somatropin treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance.
SKYTROFA may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes. Intervention: Careful monitoring is advisable when SKYTROFA is administered in combination with drugs metabolized by CYP450 liver enzymes. Oral Estrogen Clinical Impact: Oral estrogens may reduce the serum insulin-like growth factor-1 (IGF-1) response to SKYTROFA.
Intervention: Patients receiving oral estrogen replacement may require higher SKYTROFA dosages. Insulin and/or Other Antihyperglycemic Agents Clinical Impact: Treatment with SKYTROFA may decrease insulin sensitivity, particularly at higher doses. Intervention: Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents [see Warnings and Precautions (5.4) ] .
Replacement Glucocorticoid Treatment: Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of SKYTROFA ( 7 ). Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment: Adjust glucocorticoid dosing in pediatric patients to avoid both hypoadrenalism and an inhibitory effect on growth ( 7 ). Cytochrome P450-Metabolized Drugs: SKYTROFA may alter the clearance.
Monitor carefully if used with SKYTROFA ( 7 ). Oral Estrogen: Larger doses of SKYTROFA may be required ( 7 ). Insulin and/or Other Antihyperglycemic Agents: Dose adjustment of insulin or antihyperglycemic agent may be required ( 7 ).
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary There are no available data on lonapegsomatropin-tcgd use in pregnant patients to evaluate a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Available published data over several decades for somatropin, the active component of lonapegsomatropin-tcgd, have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, there was no evidence of embryo-fetal or neonatal harm when pregnant rats were administered subcutaneous lonapegsomatropin-tcgd at doses up to 13-fold the clinical pediatric dose of 0.24 mg/kg/week and approximately 30-fold the maximum clinical therapeutic dose for adult GHD of 6.3 mg hGH/week (see Data ) .
The estimated background risk of birth defects and miscarriages for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data No embryonic or fetal development toxicities occurred in rats administered subcutaneous lonapegsomatropin-tcgd at doses up to 13-fold the clinical pediatric dose of 0.24 mg/kg/week and approximately 30-fold the maximum clinical therapeutic dose for adult GHD of 6.3 mg hGH/week. In a peri- and post-natal developmental study in rats, there were no adverse effects on the pregnant/lactating female or on development of the conceptus and the offspring following exposure of the female from implantation through weaning to doses of a structurally related pegylated somatropin prodrug up to 13-fold the clinical pediatric dose of 0.24 mg/kg/week and approximately 30-fold the maximum clinical therapeutic dose for adult GHD of 6.3 mg hGH/week.
8.2Lactation Risk Summary There are no data on the presence of lonapegsomatropin-tcgd in human milk, effects on the breastfed infant, or effects on milk production. High molecular weight therapeutic proteins, including lonapegsomatropin-tcgd, are expected to have low passage into human milk and limited systemic exposure in the breastfed infant. Additionally, published data indicate that exogenous somatropin does not increase normal human milk concentrations of growth hormone.
No adverse effects on the breastfed infant have been reported with somatropin. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for SKYTROFA and any potential adverse effects on the breastfed infant from SKYTROFA or from the underlying maternal condition.
8.4Pediatric Use Safety and effectiveness of SKYTROFA have been established in pediatric patients 1 year and older and who weigh at least 11.5 kg. Pediatric use was established in a controlled study of 161 treatment-naïve pediatric patients ages 3 to 13 years and by supportive data in pediatric patients 1 year and older [see Adverse Reactions (6) and Clinical Studies (14) ] . The safety and effectiveness of SKYTROFA in children less than 1 year of age have not been established.
Use of somatropin in pediatric patients with Prader-Willi syndrome has been associated with reports of sudden death. SKYTROFA is not indicated for the treatment of pediatric patients with growth failure due to genetically confirmed Prader-Willi syndrome [see Warnings and Precautions (5.13) ] .
8.5Geriatric Use Of the 249 patients who received SKYTROFA in clinical studies, 24 (10%) patients were 65 years of age and older, and 4 (2%) patients were 75 years of age and older. Geriatric patients may be at an increased risk for adverse reactions. Initiate SKYTROFA at 0.7 mg once weekly in patients 60 years of age and older, not on estrogen therapy [see Dosage and Administration (2.3) ] .
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no available data on lonapegsomatropin-tcgd use in pregnant patients to evaluate a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Available published data over several decades for somatropin, the active component of lonapegsomatropin-tcgd, have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, there was no evidence of embryo-fetal or neonatal harm when pregnant rats were administered subcutaneous lonapegsomatropin-tcgd at doses up to 13-fold the clinical pediatric dose of 0.24 mg/kg/week and approximately 30-fold the maximum clinical therapeutic dose for adult GHD of 6.3 mg hGH/week (see Data ) .
The estimated background risk of birth defects and miscarriages for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data Animal Data No embryonic or fetal development toxicities occurred in rats administered subcutaneous lonapegsomatropin-tcgd at doses up to 13-fold the clinical pediatric dose of 0.24 mg/kg/week and approximately 30-fold the maximum clinical therapeutic dose for adult GHD of 6.3 mg hGH/week. In a peri- and post-natal developmental study in rats, there were no adverse effects on the pregnant/lactating female or on development of the conceptus and the offspring following exposure of the female from implantation through weaning to doses of a structurally related pegylated somatropin prodrug up to 13-fold the clinical pediatric dose of 0.24 mg/kg/week and approximately 30-fold the maximum clinical therapeutic dose for adult GHD of 6.3 mg hGH/week.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of SKYTROFA have been established in pediatric patients 1 year and older and who weigh at least 11.5 kg. Pediatric use was established in a controlled study of 161 treatment-naïve pediatric patients ages 3 to 13 years and by supportive data in pediatric patients 1 year and older [see Adverse Reactions (6) and Clinical Studies (14) ] . The safety and effectiveness of SKYTROFA in children less than 1 year of age have not been established.
Use of somatropin in pediatric patients with Prader-Willi syndrome has been associated with reports of sudden death. SKYTROFA is not indicated for the treatment of pediatric patients with growth failure due to genetically confirmed Prader-Willi syndrome [see Warnings and Precautions (5.13) ] .
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 249 patients who received SKYTROFA in clinical studies, 24 (10%) patients were 65 years of age and older, and 4 (2%) patients were 75 years of age and older. Geriatric patients may be at an increased risk for adverse reactions. Initiate SKYTROFA at 0.7 mg once weekly in patients 60 years of age and older, not on estrogen therapy [see Dosage and Administration (2.3) ] .
🆘 Overdosage ▾
10 OVERDOSAGE Acute overdosage may lead initially to hypoglycemia and subsequently to hyperglycemia. Overdose with somatropin may cause fluid retention. Long-term overdosage may result in signs and symptoms of gigantism consistent with the known effects of excess growth hormone.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action SKYTROFA is a pegylated human growth hormone (somatropin) for once-weekly subcutaneous injection [see Clinical Pharmacology (12.3) ] . Somatropin binds to the growth hormone (GH) receptor in the cell membrane of target cells resulting in intracellular signal transduction and a host of pharmacodynamic effects. Somatropin has direct tissue and metabolic effects, and indirect effects mediated by insulin-like growth factor-1 (IGF-1), including stimulation of chondrocyte differentiation and proliferation, stimulation of hepatic glucose output, protein synthesis and lipolysis.
Somatropin stimulates skeletal growth in pediatric patients with growth hormone deficiency (GHD) as a result of effects on the growth plates (epiphyses) of long bones.
12.2Pharmacodynamics Somatropin released from SKYTROFA produces a linear IGF-1 dose response. In pediatric patients with GHD, with a dose change of 0.02 mg/kg/week on average resulting in a mean change in weekly average IGF-1 standard deviation score (SDS) of 0.17. In adults with GHD, a dose change of 1 mg/week results in a mean change in weekly average IGF-1 SDS of 0.7 (range, 0.3 to 1.2).
At steady state, IGF-1 levels peak approximately 2 days post-dose, with the weekly average IGF-1 occurring approximately 4.5 days post-dose. IGF-1 levels are in the normal range for GHD patients for the majority of the week, similar to daily somatropin.
12.3Pharmacokinetics Absorption Following subcutaneous dose administration, SKYTROFA releases fully active somatropin via autocleavage of the TransCon linker that follows first-order kinetics. In pediatric patients with GHD, following subcutaneous dose administration of 0.24 mg/kg/week SKYTROFA, the observed mean (CV%) steady-state peak serum concentration (C max ) of lonapegsomatropin-tcgd was 1230 (86.3) ng hGH/mL, and the median time to reach maximum concentrations (T max ) was 25 hours. For released somatropin, C max was 15.2 (83.4) ng/mL with a median T max of 12 hours.
The mean (CV%) somatropin exposure over the one-week dose interval (area under the curve) was 500 (83.8) h*ng/mL. Following subcutaneous dose administration of 0.24 mg/kg/week SKYTROFA, mean C max (CV%) of the methoxypolyethylene glycol carrier was 13.1 (28.1) mcg/mL with a median T max of 36 hours. In adult patients with GHD, following subcutaneous administration of 6.3 mg/week SKYTROFA, the estimated median steady-state C max of lonapegsomatropin-tcgd was 69.3 ng hGH/mL, and the T max was 31 hours.
For released somatropin, the estimated median C max was 2.47 ng/mL with a median T max of 13 hours. The median somatropin exposure over the one-week dose interval (area under the curve) was 75.4 h*ng/mL. Following subcutaneous dose administration of 6.3 mg/week SKYTROFA, the estimated median C max of the methoxypolyethylene glycol carrier was 4.60 mcg/mL with a median T max of 34 hours.
No significant accumulation of lonapegsomatropin-tcgd and somatropin following repeat dose administration was observed. Distribution In pediatric patients with GHD, the mean (CV%) steady-state apparent volume of distribution of lonapegsomatropin-tcgd after subcutaneous administration of 0.24 mg/kg/week SKYTROFA was 0.13 (109) L/kg. In adult patients with GHD, the median steady-state apparent volume of distribution of lonapegsomatropin-tcgd after subcutaneous administration of 6.3 mg/week SKYTROFA was
0.13L/kg. A similar distribution pattern as observed for daily somatropin is expected once somatropin is released from lonapegsomatropin-tcgd. Elimination Metabolism The metabolism of somatropin involves protein catabolism in both the liver and kidneys.
The methoxypolyethylene glycol carrier is cleared by the kidneys. Excretion In pediatric patients with GHD, the mean (CV%) lonapegsomatropin-tcgd apparent clearance at steady state was 3.2 (67) mL/h/kg following subcutaneous administration of 0.24 mg/kg/week SKYTROFA with a mean (±SD) observed half-life of 30.7 (±…
🧬 Mechanism of Action ▾
12.1Mechanism of Action SKYTROFA is a pegylated human growth hormone (somatropin) for once-weekly subcutaneous injection [see Clinical Pharmacology (12.3) ] . Somatropin binds to the growth hormone (GH) receptor in the cell membrane of target cells resulting in intracellular signal transduction and a host of pharmacodynamic effects. Somatropin has direct tissue and metabolic effects, and indirect effects mediated by insulin-like growth factor-1 (IGF-1), including stimulation of chondrocyte differentiation and proliferation, stimulation of hepatic glucose output, protein synthesis and lipolysis.
Somatropin stimulates skeletal growth in pediatric patients with growth hormone deficiency (GHD) as a result of effects on the growth plates (epiphyses) of long bones.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied SKYTROFA (lonapegsomatropin-tcgd) for injection is a sterile, preservative-free, white to off-white lyophilized powder available in a single-dose, dual-chamber, prefilled cartridge containing lonapegsomatropin-tcgd in one chamber and the diluent, Water for Injection, in the second chamber. The dual-chamber glass cartridge is available in 14 strengths (in somatropin equivalents) as described in Table 9. Table 9: SKYTROFA Presentations SKYTROFA NDC 0.7 mg 73362-012-01 1.4 mg 73362-013-01 1.8 mg 73362-014-01 2.1 mg 73362-015-01 2.5 mg 73362-016-01 3 mg 73362-003-01 3.6 mg 73362-004-01 4.3 mg 73362-005-01 5.2 mg 73362-006-01 6.3 mg 73362-007-01 7.6 mg 73362-008-01 9.1 mg 73362-009-01 11 mg 73362-010-01 13.3 mg 73362-011-01 Each carton contains 4 single-dose prefilled cartridges and 6 sterile, single-use, disposable 0.25 mm × 4 mm (31-gauge × 5/32 inch) needles.
The cartridges are for use only with the SKYTROFA Auto-Injector, packaged in a separate carton. The SKYTROFA Auto-Injector is not supplied with SKYTROFA cartridges but is available for patients with a prescription for SKYTROFA through the Ascendis Pharma Customer Support by calling the toll-free number at 1-844-442-7236 (1-844-44ASCENDIS). Storage and Handling For patients : Refrigerate SKYTROFA cartridges at 36°F to 46°F (2°C to 8°C) in the outer carton to protect from light until the expiration date.
Do not freeze. Alternatively, SKYTROFA outer carton containing blistered cartridges may be stored at room temperature [up to 86°F (30°C)] 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 SKYTROFA beyond the expiration date or 6 months after the date it was first removed from refrigeration (whichever is earlier). For pharmacy long-term storage : Store SKYTROFA cartridges refrigerated at 36°F to 46°F (2°C to 8°C) in the outer carton to protect from light until the expiration date. Do not freeze.
📦 Storage and Handling ▾
Storage and Handling For patients : Refrigerate SKYTROFA cartridges at 36°F to 46°F (2°C to 8°C) in the outer carton to protect from light until the expiration date. Do not freeze. Alternatively, SKYTROFA outer carton containing blistered cartridges may be stored at room temperature [up to 86°F (30°C)] 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 SKYTROFA beyond the expiration date or 6 months after the date it was first removed from refrigeration (whichever is earlier). For pharmacy long-term storage : Store SKYTROFA cartridges refrigerated at 36°F to 46°F (2°C to 8°C) in the outer carton to protect from light until the expiration date.
Do not freeze.
📋 Description ▾
11 DESCRIPTION Lonapegsomatropin-tcgd is a long-acting prodrug of a human growth hormone (somatropin) produced by recombinant DNA technology using E. coli . Lonapegsomatropin-tcgd consists of a parent drug, somatropin, that is conjugated to a methoxypolyethylene glycol carrier (4 × 10 kDa mPEG) via a proprietary TransCon Linker and has a molecular weight of 63 kDa (released somatropin is 22 kDa). In vitro assay confirms the minimum potency of released somatropin is NLT
2.5IU/mg. SKYTROFA (lonapegsomatropin-tcgd) for injection is a sterile, preservative-free, white to off-white lyophilized powder available in a single-dose, dual-chamber, prefilled cartridge containing lonapegsomatropin-tcgd in one chamber and the diluent, Water for Injection, in the other chamber. SKYTROFA prefilled cartridge must be used with SKYTROFA Auto-Injector to provide an automatic mixing step for reconstitution prior to subcutaneous use.
After reconstitution, each prefilled cartridge delivers: 0.327 mL containing 0.7 mg lonapegsomatropin-tcgd, succinic acid (0.39 mg), trehalose dihydrate (29.8 mg) and tromethamine for pH adjustment to 5.0. 0.327 mL containing 1.4 mg lonapegsomatropin-tcgd, succinic acid (0.39 mg) trehalose dihydrate (29.1 mg) and tromethamine for pH adjustment to 5.0. 0.327 mL containing 1.8 mg lonapegsomatropin-tcgd, succinic acid (0.39 mg) trehalose dihydrate (28.8 mg) and tromethamine for pH adjustment to 5.0.
0.327 mL containing 2.1 mg lonapegsomatropin-tcgd, succinic acid (0.39 mg) trehalose dihydrate (28.4 mg) and tromethamine for pH adjustment to 5.0. 0.327 mL containing 2.5 mg lonapegsomatropin-tcgd, succinic acid (0.39 mg) trehalose dihydrate (28.1 mg) and tromethamine for pH adjustment to 5.0. 0.273 mL containing 3 mg lonapegsomatropin-tcgd, succinic acid (0.32 mg), trehalose dihydrate (22.7 mg) and tromethamine for pH adjustment to 5.0.
0.327 mL containing 3.6 mg lonapegsomatropin-tcgd, succinic acid (0.39 mg), trehalose dihydrate (27.1 mg) and tromethamine for pH adjustment to 5.0. 0.391 mL containing 4.3 mg lonapegsomatropin-tcgd, succinic acid (0.46 mg) and trehalose dihydrate (32.5 mg) and tromethamine for pH adjustment to 5.0. 0.473 mL containing 5.2 mg lonapegsomatropin-tcgd, succinic acid (0.56 mg) and trehalose dihydrate (39.3 mg) and tromethamine for pH adjustment to 5.0.
0.286 mL containing 6.3 mg lonapegsomatropin-tcgd, succinic acid (0.34 mg) and trehalose dihydrate (21.2 mg) and tromethamine for pH adjustment to 5.0. 0.345 mL containing 7.6 mg lonapegsomatropin-tcgd, succinic acid (0.41 mg) and trehalose dihydrate (25.5 mg) and tromethamine for pH adjustment to 5.0. 0.414 mL containing 9.1 mg lonapegsomatropin-tcgd, succinic acid (0.49 mg) and trehalose dihydrate (30.6 mg) and tromethamine for pH adjustment to 5.0.
0.5mL containing 11 mg lonapegsomatropin-tcgd, succinic acid (0.59 mg) and trehalose dihydrate (37 mg) and tromethamine for pH adjustment to 5.0. 0.605 mL containing 13.3 mg lonapegsomatropin-tcgd, succinic acid (0.71 mg) and trehalose dihydrate (44.8 mg) and tromethamine for pH adjustment to 5.0.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Administration Instructions Advise patients and/or caregivers to read the accompanying FDA-approved patient labeling SKYTROFA Auto-Injector Instructions for Use (also available at www.Skytrofa.com/IFU) prior to administration. Advise patients and/or caregivers to call the Ascendis Pharma Customer Support toll-free number at 1-844-442-7236 (1-844-44ASCENDIS) for assistance or additional training, if needed. Advise patients and/or caregivers to refer to the Instructions for Use that accompanies the SKYTROFA Auto-Injector for complete mixing and administration instructions with illustrations [see Dosage and Administration (2.7) ].
Instruct patients and/or caregivers of proper needle disposal and caution against any reuse of needles. An appropriate container for the disposal of used cartridge and needle should be used. Advise patients and/or caregivers to administer SKYTROFA once weekly, at any time of day.
Advise patients and/or caregivers that doses can be taken 2 days before or 2 days after the scheduled dosing day. Advise patients and/or caregivers to resume once-weekly dosing for the next dose. If more than 2 days have passed from the schedule dosing day, advise patients and/or caregivers to skip the missed dose and take the next dose on the regularly scheduled day.
If subsequently changing the regular dosing day to a different day of the week, advise patients and/or caregivers to ensure that at least 5 days will elapse between the last dose and the newly established regular dosing day. Hypersensitivity Reactions Advise patients and/or caregivers that severe and/or serious systemic hypersensitivity reactions (anaphylaxis and angioedema) have been reported, and to seek prompt medical attention should an allergic reaction occur [see Warnings and Precautions (5.2) ] . Neoplasms Advise childhood cancer survivors and/or caregivers that individuals treated with brain and/or head radiation are at increased risk of secondary neoplasms and, as a precaution, need to be monitored for recurrence.
Advise patients and/or caregivers to report marked changes in behavior, onset of headaches, vision disturbances and/or changes in skin pigmentation or changes in the appearance of preexisting nevi. Glucose Intolerance/Diabetes Mellitus Advise patients and/or caregivers that new onset impaired glucose intolerance/type 2 diabetes mellitus or exacerbation of preexisting diabetes mellitus can occur and monitoring of blood glucose during treatment with SKYTROFA may be needed. Intracranial Hypertension Advise patients and/or caregivers to report to their healthcare provider any visual changes, headache, and nausea and/or vomiting.
Fluid Retention Advise patients and/or caregivers that fluid retention during SKYTROFA replacement therapy may occur. Inform patients and/or caregivers of the clinical manifestations of fluid retention (e.g., edema, arthralgia, myalgia, nerve compression syndromes, including carpal tunnel syndrome/paresthesia) and to report to their healthcare provider if any of these signs or symptoms occur during treatment with SKYTROFA. Hypoadrenalism Advise patients and/or caregivers that patients who have or who are at risk for pituitary hormone deficiency(s) that hypoadrenalism may develop and to report to their healthcare provider if they experience hyperpigmentation, extreme fatigue, dizziness, weakness, or weight loss.
Hypothyroidism Advise patients and/or caregivers that undiagnosed/untreated hypothyroidism may prevent an optimal response to SKYTROFA. Advise patients/caregivers that patients may require periodic thyroid function tests. Pancreatitis Advise patients and/or caregivers that pancreatitis may develop and to report to their healthcare provider any new onset abdominal pain.