Lonapegsomatropin

Lonapegsomatropin is a human growth hormone indicated for:

• treatment of pediatric patients aged 1 year and older who weigh 11.5 kg or more 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)

Lonapegsomatropin is available under the following different brand names: Skytrofa, lonapegsomatropin-tcgd

Common side effects of lonapegsomatropin include:

• viral infection
• fever
• cough
• nausea and vomiting
• hemorrhage
• diarrhea
• abdominal pain
• arthralgia and arthritis
• edema
• secondary hypothyroidism

Serious side effects of lonapegsomatropin include:

• increased mortality in patients with acute critical illness
• severe hypersensitivity
• increased risk of neoplasms
• glucose intolerance and diabetes mellitus
• intracranial hypertension
• fluid retention
• hypoadrenalism
• hypothyroidism
• slipped capital femoral epiphysis in pediatric patients
• progression of preexisting scoliosis in pediatric patient
• pancreatitis
• lipoatrophy
• sudden death in pediatric patients with Prader-Willi syndrome

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and Pediatric dosage

Injection, lyophilized powder for reconstitution

• 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
• 13.3 mg
• Available in a single-dose, dual-chamber, prefilled cartridge containing lonapegsomatropin in one chamber and water for injection (diluent) in second chamber

Growth Hormone Deficiency

Adult dosage

• Initial dose for treatment-naïve patients or those switching from other GH
• Adults aged less than 30 years taking estrogen: 2.1 mg SC once weekly
• No estrogen intake
  • 30-60 years: 1.4 mg SC once weekly
  • Older than 60 years: 0.7 mg SC once weekly
• Initiating dose
  • Changing from daily somatropin: Wait at least 8 hr between the final dose of daily somatropin and the first lonapegsomatropin dose
  • Changing from another once-weekly GH: Wait at least 7 days between the final dose of previous weekly GH and the first lonapegsomatropin dose
• Titrating dose
  • Draw IGF-1 serum sample 4-5 days after the previous dose
  • Increase dose monthly to higher strength based on clinical response and/or IGF-1 concentration
  • Decrease dose to lower strength as needed based on adverse reactions or weekly average IGF-1 concentration above age- and sex-specific normal range
  • Maximum recommended dose: 6.3 mg SC once weekly
• Pediatric dosage
  • Children younger than a year: Safety and efficacy not established
  • Children aged 1 year and above and weighing 11.5 kg and more
    • Treatment-naïve patients or those switching from other GH: 0.24 mg/kg SC once weekly
    • Individualize and titrate dosage based on response
    • Changing from daily somatropin: Wait at least 8 hr between the final dose of daily somatropin and first lonapegsomatropin dose
    • Changing from another once-weekly GH: Wait at least 7 days between the final dose of previous weekly GH and the first lonapegsomatropin dose
    • Weight based dosing
      • 11.5-13.9 kg: 3 mg/week
      • 14-16.4 kg: 3.6 mg/week
      • 16.5-19.9 kg: 4.3 mg/week
      • 20-23.9 kg: 5.2 mg/week
      • 24-28.9 kg: 6.3 mg/week
      • 29-34.9 kg: 7.6 mg/week
      • 35- 41.9 kg: 9.1 mg/week
      • 42-50.9 kg: 11 mg/week
      • 51-60.4 kg: 13.3 mg/week
      • 60.5-69.9 kg: 15.2 mg/week (use 2 cartridges of 7.6 mg each)
      • 70-84.9 kg: 18.2 mg/week (use 2 cartridges of 9.1 mg each)
      • 85-100 kg: 22 mg/week (use 2 cartridges of 11 mg each)

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

Drug interaction overview

• Replacement glucocorticoid treatment
  • Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress dose following initiation
  • Microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) is required for the conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue
  • Initiating lonapegsomatropin may result in the inhibition of 11βHSD-1 and reduced serum cortisol concentrations
• Pharmacologic glucocorticoid therapy and supraphysiologic glucocorticoid treatment
  • Carefully adjust glucocorticoid replacement dosing in pediatric patients receiving glucocorticoid treatments to avoid both hypoadrenalism and an inhibitory effect on growth
  • Pharmacologic glucocorticoid therapy and supraphysiologic glucocorticoid treatment may potentiate the growth-promoting effects of lonapegsomatropin in pediatric patients
• Cytochrome P450-metabolizing drugs
  • Carefully monitor when used in combination with drugs metabolized by cytochrome P450 (CYP450) liver enzymes
  • Limited published data indicate that somatropin treatment increases CYP450-mediated antipyrine clearance
  • Lonapegsomatropin may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes
• Oral estrogen
  • Patients receiving oral estrogen replacement may require higher lonapegsomatropin dosages
  • Oral estrogens may reduce the serum insulinlike growth factor-1 response to lonapegsomatropin
• Insulin and/or other antihyperglycemic agents
  • Patients with diabetes mellitus may require dosage adjustments of their insulin and/or other antihyperglycemic agents
  • Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses

Contraindications

• Acute critical illness after open heart surgery, abdominal surgery, multiple accidental traumas, or those with acute respiratory failure
• Hypersensitivity to somatropin or any of the excipients
• Pediatric patients with closed epiphyses
• Active malignancy, owing to risk of malignancy progression
• Active proliferative or severe nonproliferative diabetic retinopathy
• 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

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Lonapegsomatropin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Lonapegsomatropin?”

Cautions

• Increased mortality with acute critical illness
  • Contraindicated
    • Increased mortality reported with pharmacologic doses in patients with acute critical illness owing to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory
    • Safety of continuing treatment in patients receiving replacement doses who concurrently develop these illnesses has not been established
• Severe Hypersensitivity
  • Contraindicated with known hypersensitivity
  • Severe systemic hypersensitivity reactions, including anaphylactic reactions and angioedema reported
  • Inform patients and/or caregivers that prompt medical attention should be sought if an allergic reaction occurs
• Increased risk of neoplasms
  • May increase the risk of malignancy progression in patients with active malignancy
  • Any preexisting malignancy should be inactive and its treatment complete before initiating somatotropin; discontinue therapy if there is evidence of recurrent activity
• Risk of second neoplasm in pediatric patients
  • Increased risk of second neoplasm reported in childhood cancer survivors who were treated with radiation to the brain/head for their first neoplasm and who developed subsequent GHD and were treated with somatropin
  • 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 tumor progression or recurrence
• New malignancy during treatment
  • Because pediatric patients with certain rare genetic causes of short stature have an increased risk of developing malignancies, thoroughly consider the risks and benefits of starting treatment in these patients; monitor for the development of neoplasms if initiating treatment
  • Monitor for increased growth, or potential malignant changes of preexisting nevi; advise patients/caregivers to report marked changes in behavior, onset of headaches, vision disturbances, and/or changes in skin pigmentation or changes in appearance of preexisting nevi
• Glucose intolerance and diabetes mellitus
  • Somatropin may decrease insulin sensitivity, particularly at higher doses
  • Previously undiagnosed impaired glucose tolerance and overt type 2 diabetes mellitus may be unmasked
  • Monitor glucose levels in all patients, especially in those with risk factors for type 2 diabetes mellitus (e.g., obesity, family history of type 2 diabetes mellitus)
  • Closely monitoring when initiating in patients with preexisting type 1 or type 2 diabetes mellitus or impaired glucose tolerance and adjust doses of antihyperglycemic drugs as needed
• Intracranial hypertension (IH)
  • IH with papilledema, visual changes, headache, nausea, and/or vomiting reported
  • In reported cases, IH-associated signs and symptoms rapidly resolved after discontinuing therapy or reducing the dose
  • Perform funduscopic examination routinely before initiating treatment to exclude preexisting papilledema, and periodically thereafter
  • If papilledema observed by fundoscopy, stop somatropin treatment
  • If somatropin-induced IH is confirmed, restart treatment at a lower dose once IH-associated signs and symptoms resolve
• Fluid retention
  • Fluid retention may occur
  • Clinical manifestations of fluid retention (eg, edema, arthralgia, myalgia, nerve compression syndromes, including carpal tunnel syndrome/paresthesia) are usually transient and dose dependent
• Hypoadrenalism
  • Patients receiving somatropin therapy who have or are at risk for pituitary hormone deficiency(s) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism
  • Additionally, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require increased maintenance or stress doses after initiating somatropin
  • Monitor for reduced serum cortisol levels and/or need for glucocorticoid dose increases in patients with known hypoadrenalism
• Hypothyroidism
  • Undiagnosed or untreated hypothyroidism may prevent optimal response
  • In patients with GHD, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment
  • Perform periodic thyroid function tests in patients and initiate or appropriately adjust thyroid hormone replacement therapy when indicated
  • Slipped capital femoral epiphysis in pediatric patients
  • Slipped capital femoral epiphysis may occur more frequently in patients undergoing rapid growth and may lead to osteonecrosis
  • Cases with or without osteonecrosis have been reported in pediatric patients with short stature receiving somatropin
  • Evaluate pediatric patients receiving somatropin with the onset of a limp or complaints of persistent hip or knee pain for slipped capital femoral epiphysis and osteonecrosis and manage accordingly
• Progression of preexisting scoliosis in pediatric patients
  • Progression of existing scoliosis can occur in patients who experience rapid growth
  • Somatropin has not been shown to increase the occurrence of scoliosis
  • Monitor patients with a history of scoliosis for disease progression
• Pancreatitis
  • Pancreatitis reported in pediatric patients
  • Risk may be greater in pediatric patients than in adults
  • Consider pancreatitis in patients who develop persistent severe abdominal pain
• Lipoatrophy
  • Lipoatrophy may result with SC administration at same site over a long period of time
  • Rotate injection sites to reduce this risk
  • Sudden death in pediatric patients with Prader-Willi syndrome
  • Reports of fatalities after initiating therapy in pediatric patients with Prader-Willi syndrome who had at least 1 risk factor (e.g., severe obesity, history of upper airway obstruction, sleep apnea, unidentified respiratory infection)
  • Male patients with these factors may be at greater risk than females
  • Lonapegsomatropin is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome
• Laboratory tests
  • Serum levels of alkaline phosphatase, phosphate, and parathyroid hormone may increase
  • If abnormal laboratory tests discovered, monitor as appropriate

Pregnancy and Lactation

• There are no available data on use in pregnant females 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, have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
• Lactation
  • No data are available on the presence of lonapegsomatropin in human milk, its effects on the breastfed infant, or on milk production
  • High-molecular–weight therapeutic proteins, including lonapegsomatropin, are expected to have low passage into human milk and limited systemic exposure in breastfed infants
  • No adverse effects on breastfed infants have been reported with somatropin