Skytrofa (lonapegsomatropin-tcgd)

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

No formal studies evaluating the potential for drug-drug interactions with lonapegsomatropin-tcgd have been conducted.

There is no significant mechanistic potential for drug-drug interactions from lonapegsomatropin-tcgd or mPEG; however, GH can induce changes in cytochrome P-450 (CYP) isoenzyme activity.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Agents Affecting Growth Hormone/Macimorelin

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Agents affecting growth hormone may impact the accuracy of the macimorelin diagnostic test.(1)

CLINICAL EFFECTS: Concurrent use of agents affecting growth hormone may impact the accuracy of the macimorelin diagnostic test.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of macimorelin states concurrent use with agents affecting growth hormone may impact the accuracy of the macimorelin diagnostic test. Discontinue growth hormone products at least 1 week before administering the macimorelin diagnostic test. Sufficient washout time of drugs affecting growth hormone release prior to administration of macimorelin is recommended.(1) Agents affecting growth hormone include: - Drugs that directly affect the pituitary secretion of growth hormone (e.g. somatostatin, insulin, glucocorticoids, cyclooxygenase inhibitors) - Drugs that may transiently elevate growth hormone concentrations (e.g. clonidine, levodopa, insulin) - Drugs that may blunt the growth hormone response (e.g. muscarinic antagonists, anti-thyroid medications, growth hormone products)

DISCUSSION: Concurrent use of agents affecting growth hormone may impact the accuracy of the macimorelin diagnostic test.(1)

Growth Hormone/Selected Retinoids (Systemic)

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Both systemic retinoids(1-8,11) and growth hormones(9-11) have been independently associated with medication-induced intracranial hypertension.

CLINICAL EFFECTS: The concurrent use of oral retinoids(1-8) with growth hormones(9-10) may increase the risk of intracranial hypertension (pseudotumor cerebri). Early signs of intracranial hypertension include papilledema (inflammation of the optic nerve), headache, nausea, vomiting, and visual disturbances such as blurred vision, double vision, and loss of vision.(12)

PREDISPOSING FACTORS: Women of childbearing age with high body mass may have a higher risk of developing intracranial hypertension.(8)

PATIENT MANAGEMENT: The US manufacturer of tretinoin advises avoiding concomitant use of other products that can cause intracranial hypertension.(1) Patients who present with symptoms of intracranial hypertension should be screened for papilledema. If papilledema is present, they should discontinue the drug and be referred to a neurologist for further treatment.(1-8)

DISCUSSION: Vitamin A derivatives and growth hormone have both been strongly associated with intracranial hypertension. A review of ocular side effects from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization, the Food and Drug Administration, and medical journals from 1979 to 2003 found 21 patients who developed intracranial hypertension while taking tretinoin, acitretin, or etretinate at prescribed doses. Symptom onset occurred at an average of 2-3 months after starting retinoid therapy and all except 3 cases resolved within a few months after discontinuing therapy.(8) In a systematic review of 580 reported cases of medication-induced intracranial hypertension between January 1900 and June 2019 found in MEDLINE, EMBASE, and Cochrane Review Databases, there were 259 verifiable cases of intracranial hypertension. Vitamin A derivatives were implicated in 84 cases, though 25 cases occurred with excessive vitamin A supplementation. Growth hormone was implicated in 24 cases, all of which occurred in pediatric patients and involved frequent or higher doses of growth hormone.(12)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Growth Hormone/Oral Estrogens

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Growth hormone (somatropin or lonapegsomatropin-tcgd) binds to growth hormone receptors and stimulates Janus activating tyrosine kinases (JAK 1 and 2) and signal transducer activators of transcription (STAT1, STAT3, STAT5) to increase gene transcription and metabolism to produce and secrete insulin like growth factor-1 (IGF-1). IGF-1 promotes cell growth, proliferation, and survival. Estrogens block STAT phosphorylation and inhibit IGF-1 secretion and production.(1,2) Higher quantities of growth hormone are required to raise serum IGF-1 concentrations to the normal range.

CLINICAL EFFECTS: Oral estrogens may reduce the IGF-1 response to growth hormone (somatropin and lonapegsomatropin-tcgd).(1-9)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of somatropin states a larger dose of somatropin may be required to achieve the treatment goal.(3-9) The manufacturer of lonapegsomatropin-tcgd states adults of any age concurrently taking oral estrogen should increase the dose of lonapegsomatropin-tcgd to 2.1 mg once weekly.(3) The American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for growth hormone deficiency states that higher recombinant human growth hormone (rhGH) doses are advised in women on oral estrogen therapy and that switching women to transdermal estrogen patches may allow lower rhGH doses to be used for equivalent IGF-1 responses.(10)

DISCUSSION: A prospective study compared growth hormone replacement requirements in women with elevated estrogen (on oral estrogen), women without elevated estrogen (no estrogen therapy or on transdermal estrogen), and growth hormone treated adult hypopituitary males. Women on oral estrogen required 10.6 +/-0.7 mcg/kg/day or 867 +/- 45 mcg/day growth hormone, women not taking oral estrogen required 5.0 +/- 0.7 mcg/kg/day or 424 +/-57 mcg/day, and men required 4.1 +/- 0.6 mcg/kg/day or 376 +/-49 mcg/day.(1) A randomized cross-over study compared one month of treatment with ethinyl estradiol (20 mcg), conjugated equine estrogen (1.25 mg Premarin), and estradiol valerate (2 mg). All three formulations resulted in a significant reduction in IGF-1 levels compared to baseline.(11) A study compared IGF-1 concentrations in premenopausal women and postmenopausal women before and after 2 months of cyclical replacement therapy with either oral ethinyl estradiol (20 mcg daily) or transdermal 17 beta-estradiol (100 mcg patch applied twice weekly). Oral ethinyl estradiol significantly reduced circulating IGF-1 (0.70 +/- 0.09 to 0.47 +/- 0.04 units/mL, P < 0.02) levels. Transdermal 17-beta estradiol increased IGF-1 levels (0.86 +/- 0.15 to 1.10 +/- 0.14 units/mL, P < 0.005).(12) In a clinical trial, somapacitan administered once weekly was compared to somatropin once daily injections in patients with and without oral estrogen replacement therapy. Patients with oral estrogen therapy were administered 2 mg/wk compared to 1 mg/wk for patients without estrogen replacement therapy. Observed doses after titration for somapacitan and somatropin were highest for females on oral estrogen.(13) An open-label, randomized crossover study in growth hormone deficient women compared oral estrogen with transdermal estrogen treatment while on growth hormone. Women received incremental doses of growth hormone (0.5, 1.0, 2.0 units/day for 1 week; increased to next dose each week) for 8 weeks and estradiol valerate (2 mg/day) or transdermal estrogen patches (Estraderm-TTS 100 mcg). IGF-1 levels were significantly reduced during oral estrogen treatment and rose dose-dependently during growth hormone administration by a lower magnitude compared with transdermal treatment (change in IGF-1: 109 +/-43% vs. 135 +/-41%).(14)

*Acute critical illness after open heart surgery, abdominal surgery, or multiple accidental trauma, or those with acute respiratory failure.

*Hypersensitivity to somatropin or any of the excipients; severe systemic hypersensitivity reactions (e.g., anaphylactic reactions, angioedema) have been reported.

*Pediatric patients with closed epiphyses.

*Active malignancy.

*Active proliferative or severe non-proliferative 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 due to the risk of sudden death.

• Acute respiratory failure
• Diabetic retinopathy
• Major traumatic injury
• Morbid obesity
• Sleep apnea

• Adrenocortical insufficiency
• Idiopathic intracranial hypertension
• Malignancy
• Pancreatitis
• Slipped capital epiphyses
• Untreated hypothyroidism

• Carpal tunnel syndrome
• Diabetes mellitus
• Edema
• Hyperphosphatemia
• Progression of nevus
• Scoliosis

Adverse effects reported in >=5% of pediatric patients include viral infection, pyrexia, cough, nausea and vomiting, hemorrhage, diarrhea, abdominal pain, and arthralgia and arthritis.

The most common adverse effect reported in >=5% of adult patients is peripheral edema.

More Frequent

• Hemorrhage

Rare or Very Rare

• Adrenocortical insufficiency
• Anaphylaxis
• Angioedema
• Hypersensitivity drug reaction
• Hypothyroidism
• Intracranial hypertension
• Malignancy
• Pancreatitis
• Slipped capital epiphyses

More Frequent

• Acute abdominal pain
• Arthralgia
• Arthritis
• Cough
• Diarrhea
• Fever
• Nausea
• Viral infection
• Vomiting

Less Frequent

• Body fluid retention
• Hyperglycemia
• Peripheral edema

Rare or Very Rare

• Avascular necrosis of bone

No enhanced messaging available.

The safety and efficacy of lonapegsomatropin-tcgd have been established in pediatric patients with GHD who are >=1 year of age and who weigh >=11.5 kg.

The safety and efficacy is not established in pediatric patients <1 year of age.

Lonapegsomatropin-tcgd is not indicated in pediatric patients with growth failure due to genetically confirmed Prader-Willi syndrome due to the association between somatropin use and reports of sudden death in those patients.

There are no available data on lonapegsomatropin-tcgd use in pregnant patients; however, available somatropin data have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

The American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) and Endocrine Society (ES) guidelines state that due to insufficient evidence of safety or efficacy, routine use of somatropin for conception or continued use during pregnancy in women with GHD is not recommended.

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 per week and approximately 30-fold the maximum clinical therapeutic dose for adult GHD of 6.3 mg/week.

The manufacturer reports a similar lack of observed adverse effects when a structurally related pegylated somatropin prodrug (up to 13-fold the clinical pediatric dose of 0.24 mg/kg per week and approximately 30-fold the maximum clinical therapeutic dose for adult GHD of 6.3 mg/week) was administered to female rats from implantation through weaning.

There are no data on the presence of lonapegsomatropin-tcgd in human milk, effects on infants fed human milk, or effects on human milk production.

High molecular weight therapeutic proteins, including lonapegsomatropin-tcgd, are expected to have low passage into human milk and limited systemic exposure in infants fed human milk.

Published data indicate that exogenous somatropin does not increase normal human milk GH concentrations.

No adverse effects on infants fed human milk have been reported with somatropin.

Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for lonapegsomatropin-tcgd and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

The manufacturer makes no specific dosage recommendations for geriatric patients.

Of the 249 patients who were administered lonapegsomatropin-tcgd in clinical trials, 24 (10%) patients were >=65 years of age and 4 (2%) patients were >=75 years of age. An increased risk for adverse reactions may be seen in geriatric patients receiving therapy.

In patients >=60 years of age, not on estrogen therapy, lonapegsomatropin-tcgd should be initiated at a dose of 0.7 mg once weekly.