Ngenla (somatrogon-ghla)

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Administer somatrogon-ghla by subcutaneous injection once weekly, on the same day each week, at any time of day. Administer the dose in the abdomen, thighs, buttocks, or upper arms. Rotate the injection site each week, and use a new needle with each injection. If more than 1 injection is required to administer a complete dose, administer each injection at a different injection site.

Somatrogon-ghla treatment should be supervised by a healthcare provider who is experienced in the diagnosis and management of pediatric patients >=3 years of age with growth failure due to growth hormone deficiency (GHD).

The day that somatrogon-ghla is administered each week can be changed as long as there are >=3 days between 2 doses. Once a new day is chosen, continue the once weekly dosing.

In patients being switched from daily growth hormone, once-weekly somatrogon-ghla may be initiated on the day after their last daily injection.

If a dose is missed, administer somatrogon-ghla as soon as possible within 3 days after the missed dose. If >3 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day.

Somatrogon-ghla injection is a clear and colorless to slightly light yellow solution containing a preservative and supplied as a single-patient-use disposable prefilled pen containing 24 mg/1.2 mL (20 mg/mL) or 60 mg/1.2 mL (50 mg/mL). The 24 mg/1.2 mL prefilled pen delivers a dose in 0.2 mg increments, and the 60 mg/1.2 mL prefilled pen delivers a dose in 0.5 mg increments.

Inspect the solution visually for particulate matter and discoloration prior to administration. If flakes, particles, or discoloration are observed, do not use the pen.

Before first use, store somatrogon-ghla at 2-8oC in the original carton to protect from light. Once opened (after first use), store at 2-8oC between each use, for up to 28 days. Do not freeze or shake; do not use if somatrogon-ghla has been frozen. Do not expose to heat; store away from direct sunlight.

Always remove and safely discard the needle after each injection, and store the prefilled pen without an injection needle attached. Replace the cap on the prefilled pen when it is not in use. Do not use the prefilled pen more than 28 days after first use.

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No dosing information is available for this tab.

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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 due to risk of increased mortality with somatropin.

*Hypersensitivity to somatrogon-ghla or any excipient in the product.

*Closed epiphyses.

*Active malignancy.

*Active proliferative or severe non-proliferative diabetic retinopathy.

*Prader-Willi syndrome in patients who are severely obese or have a history of upper airway obstruction or sleep apnea or have severe respiratory impairment due to risk of sudden death.

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

• Intracranial hypertension
• Malignancy

• Adrenocortical insufficiency
• Diabetes mellitus
• Edema
• Hypothyroidism
• Scoliosis
• Slipped capital epiphyses

Adverse effects reported in >=5% of patients receiving somatrogon-ghla include injection site reactions, nasopharyngitis, headache, pyrexia, anemia, cough, vomiting, hypothyroidism, abdominal pain, rash, and oropharyngeal pain.

Less Frequent

• Anaphylaxis
• Angioedema
• Intracranial hypertension
• Lipodystrophy
• Malignancy
• Pancreatitis

Rare or Very Rare

• Aseptic necrosis of head of femur

More Frequent

• Acute abdominal pain
• Anemia
• Cough
• Fever
• Headache disorder
• Hypothyroidism
• Injection site sequelae
• Pain in oropharynx
• Pharyngitis
• Skin rash
• Vomiting

Less Frequent

• Adrenocortical insufficiency
• Body fluid retention
• Bronchitis
• Eosinophilia
• Slipped capital epiphyses
• Tonsillitis

No enhanced messaging available.

The safety and efficacy of somatrogon-ghla are established for the treatment of growth failure due to inadequate endogenous growth hormone secretion in pediatric patients >=3 years of age. The use of somatrogon-ghla for this indication is supported by evidence from a randomized, open-label, 52-week study involving 224 prepubertal pediatric patients with GHD who had not received prior treatment.

The risks of growth hormone use in pediatric patients include an increased risk of second neoplasm in cancer survivors with previous radiation treatment to the brain and/or head, slipped capital femoral epiphysis, progression of preexisting scoliosis, pancreatitis, and sudden death in patients with Prader-Willi Syndrome. Somatrogon-ghla is not indicated for use in pediatric patients with growth failure secondary to Prader-Willi syndrome.

No data are available on the use of somatrogon-ghla in pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In reproduction studies with pregnant rats, there was no evidence of embryo-fetal toxicity with subcutaneous administration of somatrogon-ghla during the period of organogenesis at doses up to 45 times the maximum recommended human dose based on exposure.

No data are available on the presence of somatrogon-ghla in human or animal milk. The effects of somatrogon-ghla on the breast-fed infant or on milk production are also unknown.

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

The manufacturer makes no specific dosage recommendations for geriatric patients.

Somatrogon-ghla has not been studied in geriatric patients.