Skytrofa: Uses, Dosage & Side Effects

What Is Skytrofa and What Is It Used For?

Skytrofa contains the active substance lonapegsomatropin, a modified form of recombinant human growth hormone designed for sustained release over one week. Growth hormone (GH), also known as somatropin, is a peptide hormone normally produced by the anterior pituitary gland in short pulses, predominantly during sleep. It acts on virtually every tissue in the body, but its most visible effect in children and adolescents is to stimulate linear growth of long bones at the epiphyseal growth plates. GH also regulates protein synthesis, fat metabolism, glucose homeostasis, and the production of insulin-like growth factor 1 (IGF-1) by the liver, which mediates many of GH's anabolic effects.

Growth hormone deficiency (GHD) is a clinical syndrome in which the pituitary gland produces insufficient growth hormone to support normal growth and metabolic function. In children, GHD is defined by a combination of auxological criteria (short stature, slow growth velocity, delayed bone age) and biochemical confirmation using dynamic GH stimulation tests. The condition may be congenital (present from birth, sometimes due to genetic mutations or structural pituitary abnormalities), acquired (for example following brain tumors, cranial radiotherapy, trauma, or infection), or idiopathic when no underlying cause is identified. Without treatment, children with GHD typically have markedly reduced adult height, and severe cases may also experience metabolic disturbances, reduced muscle mass, increased adiposity, and delayed puberty.

The standard of care for pediatric GHD has historically been daily subcutaneous injections of recombinant human growth hormone (somatropin), which became widely available in the mid-1980s and replaced older, less reliable pituitary-derived preparations. Daily injections have been highly effective in restoring normal growth velocity and allowing children to reach a near-normal adult height, but the long-term treatment burden is substantial: most children require daily injections for many years, often from early childhood until the completion of linear growth in adolescence. The psychological and practical burden of daily injections can affect adherence, with real-world studies showing that missed doses are common and that suboptimal adherence is associated with poorer growth outcomes.

Skytrofa was developed to address this long-standing clinical challenge by providing a growth hormone formulation that only needs to be injected once a week while delivering the same fully active somatropin molecule as conventional daily products. The lonapegsomatropin molecule consists of unmodified recombinant human growth hormone transiently attached to a large, inert methoxy polyethylene glycol (mPEG) carrier through a proprietary self-cleaving TransCon linker. While bound to the PEG carrier, the growth hormone is shielded from receptor binding and metabolic clearance, which allows the drug to persist in the circulation for much longer than free somatropin. Under physiological pH and temperature, the TransCon linker undergoes predictable auto-cleavage at a controlled rate, continuously releasing unmodified somatropin over approximately seven days.

Because the somatropin released from Skytrofa is chemically and structurally identical to the natural hormone, it interacts with the growth hormone receptor in exactly the same way as endogenous GH or conventional somatropin products. This means that the growth-promoting, metabolic, and anabolic effects of Skytrofa should mirror those of daily somatropin, provided that equivalent cumulative weekly exposure is achieved. Regulatory approval of Skytrofa was based on the pivotal phase 3 heiGHt trial, a multicenter randomized controlled study that compared once-weekly lonapegsomatropin (0.24 mg/kg/week) with daily somatropin (0.034 mg/kg/day, equivalent to 0.238 mg/kg/week) in treatment-naïve children with GHD. At 52 weeks, lonapegsomatropin met the pre-specified non-inferiority endpoint for annualized height velocity and numerically exceeded the daily comparator, with a similar overall safety profile.

Skytrofa is approved in the European Union for the replacement of endogenous growth hormone in children and adolescents aged 3 years and above with growth disturbance due to insufficient secretion of growth hormone. In the United States, it is approved for pediatric patients aged 1 year and older who weigh at least 11.5 kg. The drug is not currently approved for the treatment of adult GHD in most markets, though development programs in adult GHD and other indications are ongoing.

What Should You Know Before Taking Skytrofa?

Contraindications

There are specific situations in which Skytrofa must not be used. Understanding these absolute contraindications is essential before starting treatment.

• Hypersensitivity: Do not use Skytrofa if the patient is allergic to lonapegsomatropin, somatropin, polyethylene glycol (PEG), or any other ingredient of the product.
• Closed epiphyses: Skytrofa must not be used in patients with closed epiphyses for growth promotion, because linear growth can no longer occur once the growth plates have fused. Bone age and epiphyseal status should be assessed before and during treatment.
• Active malignancy: Growth hormone therapy, including Skytrofa, is contraindicated in patients with evidence of active tumor activity. Any pre-existing malignancy must be fully treated and inactive before GH therapy can be considered, and therapy must be discontinued if malignancy develops.
• Acute critical illness: Skytrofa must not be used in patients with acute critical illness due to complications of open-heart or abdominal surgery, multiple accidental trauma, acute respiratory failure, or similar conditions. High-dose somatropin in critically ill adults has been associated with increased mortality in randomized trials.
• Prader-Willi syndrome with severe obesity or respiratory impairment: Skytrofa must not be used in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment, because of the risk of sudden death reported with somatropin in this population.
• Active proliferative or severe non-proliferative diabetic retinopathy: Growth hormone therapy may worsen diabetic eye disease and is not recommended in patients with active sight-threatening retinopathy.

Warnings and Precautions

Before and during treatment with Skytrofa, talk to your doctor about the following:

• Hypothyroidism: Growth hormone therapy can unmask or worsen central hypothyroidism. Thyroid function should be evaluated before starting Skytrofa and monitored periodically during treatment. Adequate thyroid hormone replacement is essential for optimal response to growth hormone therapy.
• Adrenal insufficiency: Patients with known or suspected hypopituitarism may require evaluation of adrenal function. Initiation of growth hormone therapy can reduce serum cortisol levels, potentially unmasking latent central adrenal insufficiency. Patients on glucocorticoid replacement should be monitored and dose adjustments may be needed.
• Glucose intolerance and diabetes: Somatropin increases insulin resistance and can cause hyperglycemia. Blood glucose should be monitored periodically. Children with risk factors for type 2 diabetes (obesity, family history, Turner syndrome) require particular vigilance. Doses of insulin or oral antidiabetic medicines may need to be adjusted.
• Scoliosis progression: Rapid growth during GH therapy may worsen pre-existing scoliosis. Children should be clinically examined for scoliosis before and during treatment, and any progression evaluated and managed appropriately.
• Slipped capital femoral epiphysis (SCFE): Hip or knee pain, or a limp, during GH therapy may indicate SCFE and should be investigated promptly, particularly in patients with endocrinopathies or during rapid growth phases.
• Pancreatitis: Rare cases of pancreatitis have been reported in children treated with somatropin. Persistent severe abdominal pain with nausea or vomiting should prompt evaluation for pancreatitis.
• Neoplasms: In cancer survivors, the risk of second neoplasms should be carefully considered. Skytrofa should not be used when any evidence of recurrent or active malignancy is present. Cranially irradiated patients have a higher baseline risk of secondary intracranial tumors, and surveillance should continue.
• Injection site reactions: Local reactions such as pain, erythema, bruising, or swelling are common with Skytrofa. Rotating injection sites helps minimize these reactions.
• Fluid retention: GH can cause fluid retention, particularly early in treatment or with higher doses, leading to edema, arthralgia, or myalgia. Symptoms are usually mild and transient.
• Anti-drug antibodies: A small proportion of patients develop antibodies against somatropin or the PEG carrier during treatment. In clinical trials, these antibodies were not associated with loss of growth response or hypersensitivity, but clinicians should consider anti-drug antibodies in patients with a suboptimal response.

Monitoring During Treatment

Routine follow-up of children on Skytrofa should include measurement of height, weight, and pubertal stage at least every 3–6 months, with assessment of growth velocity over at least 6-month intervals. Laboratory monitoring typically includes IGF-1 (titrated to keep values within the age- and sex-adjusted normal range), fasting glucose or HbA1c, thyroid function tests, and, where clinically appropriate, lipid profile. Bone age radiography is usually performed annually to assess skeletal maturation. Any signs suggestive of adverse effects (scoliosis, hip pain, persistent headache, visual symptoms) should prompt immediate evaluation.

Pregnancy and Breastfeeding

Skytrofa is primarily used in the pediatric population, but the following information is relevant for adolescent or adult patients of reproductive potential. There are no adequate data on the use of lonapegsomatropin during pregnancy. Skytrofa is not recommended during pregnancy unless considered essential by the treating physician. Female patients of childbearing potential should use effective contraception during treatment. It is not known whether lonapegsomatropin is excreted in human breast milk; a decision should be made whether to discontinue breastfeeding or to discontinue therapy, taking into account the benefit of breastfeeding for the child and the benefit of Skytrofa for the mother.

Special Populations

No dose adjustment is required based on sex. Limited data are available in children with severe renal or hepatic impairment, and these patients should be managed cautiously with close monitoring of growth response, IGF-1, and safety parameters. The safety and efficacy of Skytrofa in children younger than 3 years (EU) or younger than 1 year (US) have not been established in controlled trials.

How Does Skytrofa Interact with Other Drugs?

Drug interactions with Skytrofa reflect the pharmacological effects of somatropin on metabolism, endocrine axes, and hepatic enzyme systems. Always tell your doctor about all medications, dietary supplements, and herbal products being taken so that potential interactions can be identified and managed. Dose adjustments of concomitant medicines may be needed when Skytrofa is started, when the dose is changed, and when Skytrofa is stopped.

Major Interactions

Minor Interactions

The interaction between Skytrofa and glucocorticoid replacement therapy is particularly relevant in children with multiple pituitary hormone deficiencies (hypopituitarism). Initiation of growth hormone therapy can reduce available cortisol, potentially unmasking latent adrenal insufficiency. Pediatric endocrinologists commonly reassess adrenal function prior to starting Skytrofa and may increase hydrocortisone replacement doses to prevent adrenal crisis, especially during intercurrent illness or stress. Similarly, levothyroxine requirements frequently increase after starting growth hormone, and thyroid function should be checked within the first 3 months of therapy and adjusted as needed.

What Is the Correct Dosage of Skytrofa?

Skytrofa should always be used exactly as prescribed by a physician with experience in the diagnosis and management of patients with growth hormone deficiency. The dose must be individualized for each patient based on body weight, clinical response, and biochemical monitoring, and should not be changed without medical supervision. Abrupt changes in treatment schedule should be avoided.

Standard Dosing

How to Administer Skytrofa

Skytrofa is designed for self-administration (by the caregiver or adolescent patient) after appropriate training by a healthcare professional. The Skytrofa system consists of a dual-chamber cartridge containing the lonapegsomatropin powder and sterile water solvent, combined with the Skytrofa auto-injector pen that automatically reconstitutes and delivers the dose. Follow these steps for each injection:

1. Prepare the pen and cartridge: Remove a new cartridge from the refrigerator and allow it to warm to room temperature (approximately 15 minutes) before use. Insert the cartridge into the auto-injector pen according to the manufacturer's instructions. The pen will automatically mix the powder and solvent.
2. Check the solution: After reconstitution, the solution should appear clear and colorless. Do not use the product if it is cloudy, discolored, or contains visible particles.
3. Select the injection site: Suitable sites include the front of the thighs, the abdomen (at least 5 cm from the navel), the upper outer arms, or the buttocks. Rotate the injection site with each dose to minimize local reactions.
4. Clean the skin: Wipe the injection site with an alcohol swab and allow it to dry.
5. Administer the injection: Attach a new pen needle, prime the pen according to instructions, and set the prescribed dose. Press the pen firmly against the skin and depress the injection button until the dose counter returns to zero. Hold the pen in place for the time specified in the pen manual to ensure the full dose is delivered.
6. Dispose of the needle: Remove and discard the used needle in a sharps container.
7. Record the dose: Note the date, time, and injection site in your treatment diary.

Caregivers should be thoroughly trained by a nurse or pharmacist in the safe use of the auto-injector pen before the first at-home dose. Video tutorials, printed instructions, and patient support programs provided by the manufacturer can reinforce correct technique. If you are unsure about any step of the administration procedure, contact your healthcare provider before giving the injection.

Dose Adjustments

The dose of Skytrofa may be adjusted in the following circumstances:

• Suboptimal growth response: If growth velocity remains below expectations despite confirmed adherence, the dose may be increased under specialist supervision.
• Elevated IGF-1 levels: If IGF-1 values are persistently above the upper limit of the normal range, the dose should be reduced to minimize the theoretical risk of long-term adverse effects.
• Adverse effects: Dose reduction or temporary interruption may be required if clinically significant side effects develop (e.g., intracranial hypertension symptoms, severe fluid retention, hyperglycemia).
• Puberty: Some clinicians increase the dose during puberty to mirror the physiological rise in GH secretion; others maintain a constant weight-based dose. This decision is individualized by the pediatric endocrinologist.
• Switching from daily somatropin: Patients currently on daily somatropin therapy can typically transition to a total equivalent weekly dose of Skytrofa (approximately 7 times the daily dose), with subsequent titration based on response and IGF-1 monitoring.

Missed Dose

If a weekly dose is missed, administer it as soon as possible, provided fewer than 2 days have passed since the scheduled dose. Then resume the regular weekly dosing schedule. If more than 2 days have passed, skip the missed dose and inject the next dose on the originally scheduled day. Do not inject a double dose to compensate for a missed injection. Consistent weekly timing is important for maintaining stable somatropin exposure and optimal growth response.

Overdose

Accidental administration of a higher-than-prescribed dose of Skytrofa can cause acute symptoms such as hypoglycemia shortly after injection (due to increased insulin sensitivity) followed by hyperglycemia. Chronic overdose may lead to fluid retention, acromegalic-like features, and signs of excess IGF-1 activity. If an overdose is suspected, contact a poison control center, emergency services, or your physician immediately and bring the Skytrofa packaging and patient leaflet with you. Treatment is supportive; there is no specific antidote for somatropin overdose.

What Are the Side Effects of Skytrofa?

Like all medicines, Skytrofa can cause side effects, although not everyone gets them. The adverse event profile of lonapegsomatropin is generally similar to that of conventional daily somatropin, because the active moiety released from the prodrug is the same growth hormone molecule. In the phase 3 heiGHt and fliGHt trials and subsequent open-label extensions (enliGHten), the overall frequency and type of treatment-related adverse events were comparable between lonapegsomatropin and daily somatropin, although injection site reactions related to the weekly formulation were somewhat more prominent.

Frequency of Side Effects

Injection Site Reactions

Because Skytrofa is a large prodrug molecule administered subcutaneously once per week, local reactions at the injection site are among the most commonly reported adverse events. Typical reactions include transient pain, redness, mild swelling, itching, and occasional bruising, usually lasting a few hours to one or two days. Severe or persistent reactions are uncommon. Strategies to reduce injection site reactions include rotating injection sites with each dose, allowing the cartridge to reach room temperature before injection, applying gentle pressure after the injection, and using a short needle as recommended in the pen instructions. If local reactions persist, intensify, or are accompanied by systemic symptoms such as fever or rash, medical review is warranted to exclude hypersensitivity.

Metabolic and Endocrine Effects

Growth hormone reduces insulin sensitivity and can cause mild, usually clinically insignificant, increases in fasting glucose and insulin. In children without underlying risk factors, these changes rarely progress to diabetes, but regular monitoring of fasting glucose and, where indicated, HbA1c is recommended. Weight gain, body composition changes, and improvements in bone mineral density are typically beneficial. However, Skytrofa can unmask or exacerbate central hypothyroidism or adrenal insufficiency in children with multiple pituitary hormone deficiencies, necessitating dose adjustments of levothyroxine and hydrocortisone replacement therapy.

Comparison with Daily Somatropin

In head-to-head comparisons, the overall safety profile of lonapegsomatropin closely resembles that of daily somatropin. Annualized height velocity, IGF-1 standard deviation scores, and rates of serious adverse events have been similar between weekly and daily regimens. Some differences have been observed: injection site reactions may be slightly more frequent with weekly formulations because of the larger single injection volume, while patient-reported outcomes and caregiver-reported convenience favor once-weekly dosing in most studies. Long-term post-marketing surveillance continues to refine our understanding of rare and late-emerging adverse events with long-acting GH products.

If any side effects occur, including those not listed here, talk to the treating doctor, pharmacist, or nurse. Suspected adverse reactions can also be reported directly to national pharmacovigilance authorities (such as the EMA in Europe, the FDA MedWatch program in the United States, or the MHRA Yellow Card scheme in the United Kingdom) to support continued monitoring of the benefit-risk balance of Skytrofa.

How Should You Store Skytrofa?

Proper storage is essential to maintain the stability and potency of Skytrofa. Follow these storage recommendations carefully:

• Refrigerated storage: Store Skytrofa cartridges in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. This is the preferred long-term storage condition.
• Do not freeze: Skytrofa must not be frozen. If a cartridge has been frozen, it should be discarded and not used.
• Temporary room-temperature storage: As described in the current product labeling, unopened cartridges may be stored at room temperature (below 30°C / 86°F) for a limited period, after which they must be used or discarded. Refer to the patient information leaflet for the specific time limit that applies to your product presentation.
• Protect from light: Always keep the cartridge in the original carton until just before use.
• Auto-injector pen: The Skytrofa pen can be kept at room temperature between injections. Do not expose the pen to extreme heat, direct sunlight, or moisture.
• After reconstitution: Once the cartridge has been inserted into the pen and the powder has been reconstituted with the solvent, the solution should be used promptly. Any unused medication remaining in a partially used cartridge should be disposed of according to local regulations once the cartridge is removed from the pen.
• Expiry date: Do not use Skytrofa after the expiry date printed on the cartridge label and carton. The expiry date refers to the last day of the stated month.

Keep Skytrofa, needles, and the auto-injector pen out of the sight and reach of children when not in use. Dispose of used needles and cartridges in an approved sharps container. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines no longer required. These measures help protect the environment and prevent accidental needlestick injuries.

What Does Skytrofa Contain?

Active Substance

The active substance is lonapegsomatropin, a long-acting prodrug of recombinant human growth hormone (somatropin). Each cartridge contains one of the following amounts of lonapegsomatropin in 0.6 mL after reconstitution: 3 mg, 3.6 mg, 4.3 mg, 5.2 mg, 6.3 mg, 7.6 mg, 9.1 mg, 11 mg, or 13.3 mg. The lonapegsomatropin molecule consists of unmodified somatropin attached via a cleavable TransCon linker to an inert methoxy polyethylene glycol (mPEG) carrier with a nominal molecular weight of approximately 40 kDa. Under physiological conditions, the linker auto-hydrolyzes at a predictable rate, continuously releasing fully active somatropin over approximately seven days.

Inactive Ingredients (Excipients)

The Skytrofa cartridge contains the following excipients in the powder and solvent chambers:

• Succinic acid (buffering agent)
• Disodium succinate hexahydrate (buffering agent)
• L-histidine (pH modifier)
• Sodium chloride (isotonicity agent)
• Mannitol (stabilizer/tonicity modifier)
• Trehalose dihydrate (stabilizer)
• Polysorbate 80 (surfactant)
• Sodium hydroxide (pH adjustment)
• Hydrochloric acid (pH adjustment)
• Water for injections (solvent)

The exact quantitative composition of excipients varies slightly between cartridge strengths; refer to the approved Summary of Product Characteristics or patient information leaflet for complete details. Patients with known hypersensitivity to any of these ingredients, to polyethylene glycol, or to somatropin should not use Skytrofa.

Appearance and Packaging

Skytrofa is supplied as a dual-chamber cartridge, with the lonapegsomatropin as a white to off-white lyophilized powder in one chamber and clear, colorless sterile solvent in the other. After automatic reconstitution in the Skytrofa auto-injector pen, the resulting solution is clear and colorless to slightly yellow. Each package contains a specified number of cartridges, a patient information leaflet, and appropriate pen needles. The Skytrofa auto-injector pen is supplied separately and is a reusable device intended for use with Skytrofa cartridges only.

Marketing Authorization Holder

Ascendis Pharma Endocrinology Division A/S, Tuborg Boulevard 12, 2900 Hellerup, Denmark. For further information about Skytrofa, consult the European Medicines Agency (EMA) website, the U.S. Food and Drug Administration prescribing information, or other applicable regulatory authority resources in the country of use.