Introduction

Somatrogon-ghla is a human growth hormone analog.

Uses for Somatrogon (Systemic)

Somatrogon-ghla has the following uses:

Somatrogon-ghla is indicated for treatment of pediatric patients 3 years of age and older who have growth failure due to inadequate secretion of endogenous growth hormone.

Somatrogon (Systemic) Dosage and Administration

General

Somatrogon-ghla is available in the following dosage form(s) and strength(s):

Injection:

• 24 mg/1.2 mL (20 mg/mL) in a single-patient-use prefilled pen that delivers a dose in 0.2 mg increments

• 60 mg/1.2 mL (50 mg/mL) in a single-patient-use prefilled pen that delivers a dose in 0.5 mg increments

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Pediatric Patients

Dosage and Administration

• Somatrogon-ghla treatment should be supervised by a healthcare provider who is experienced in the diagnosis and management of pediatric patients with growth hormone deficiency.

• Administer somatrogon-ghla by subcutaneous injection once weekly, on the same day each week, at any time of the day in the abdomen, thighs, buttocks, or upper arms with weekly rotation of injection site.

• The recommended dosage in pediatric patients ≥3 years of age is 0.66 mg/kg based on actual body weight administered once weekly.

• Individualize dosage for each patient based on the growth response.

• Patients switching from daily growth hormone may initiate treatment with once-weekly somatrogon-ghla on the day following their last daily injection.

• If more than one injection is required to deliver a complete dose, each injection should be administered at a different injection site.

Contraindications

• Acute critical illness.

• Hypersensitivity to somatrogon-ghla or excipients.

• Closed epiphyses.

• Active malignancy.

• Active proliferative or severe non-proliferative diabetic retinopathy.

• Prader-Willi syndrome in patients who are severely obese or have severe respiratory impairment.

Warnings/Precautions

Increased 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 with somatropin. The safety of continuing somatrogon-ghla treatment for the approved indication in patients who concurrently develop these illnesses has not been established.

Severe Hypersensitivity

Severe systemic hypersensitivity reactions including anaphylaxis and angioedema have been reported with somatropin. Inform patients and/or caregivers that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs. Somatrogon-ghla is contraindicated in patients with known hypersensitivity to somatrogon-ghla or any excipients in the product.

Increased Risk of Neoplasms

There is an increased risk of malignancy progression with somatropin treatment in patients with active malignancy. Any preexisting malignancy should be inactive, and its treatment should be completed prior to instituting therapy with somatrogon-ghla. Discontinue somatrogon-ghla if there is evidence of recurrent malignancy.

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 somatrogon-ghla therapy for progression or recurrence of the tumor.

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 somatrogon-ghla in these patients. If treatment with somatrogon-ghla is initiated, carefully monitor these patients for development of neoplasms.

Monitor patients on somatrogon-ghla therapy carefully for increased growth or potential malignant changes of preexisting nevi. 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 and Diabetes Mellitus

Treatment with growth hormone may decrease insulin sensitivity, particularly at higher doses. New onset type 2 diabetes mellitus has been reported in patients receiving growth hormone. Patients with undiagnosed pre-diabetes and diabetes mellitus may experience worsened glycemic control and become symptomatic. Monitor glucose levels periodically in all patients receiving somatrogon-ghla, especially in those with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. Patients with preexisting type 1 or type 2 diabetes mellitus or pre-diabetes should be monitored closely. The doses of antidiabetic agents may require adjustment when somatrogon-ghla is initiated.

Intracranial Hypertension

Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in patients treated with somatropin. Symptoms usually occurred within the first eight (8) weeks after the initiation of somatropin therapy. In all reported cases, IH-associated signs and symptoms rapidly resolved after cessation of therapy or a reduction of somatropin dose.

Perform fundoscopic examination before initiating treatment with somatrogon-ghla to exclude preexisting papilledema and periodically thereafter. If papilledema is identified prior to initiation, evaluate the etiology and treat the underlying cause before initiating somatrogon-ghla. Somatrogon-ghla should be temporarily discontinued in patients with clinical or fundoscopic evidence of IH. If IH is confirmed, restart treatment with somatrogon-ghla at a lower dose after IH-associated signs and symptoms have resolved.

Fluid Retention

Fluid retention during somatrogon-ghla therapy may occur. Clinical manifestations of fluid retention (e.g. edema and nerve compression syndromes including carpal tunnel syndrome/paresthesia) are usually transient and dose dependent.

Hypoadrenalism

Patients receiving growth hormone 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. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatrogon-ghla treatment. Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism.

Hypothyroidism

Undiagnosed/untreated hypothyroidism may prevent an optimal response to somatrogon-ghla therapy. In patients with GH deficiency, central (secondary) hypothyroidism may first become evident or worsen during treatment with growth hormone therapy. Therefore, patients should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated.

Slipped Capital Femoral Epiphysis

Slipped capital femoral epiphysis may occur more frequently in patients undergoing rapid growth. Evaluate pediatric patients with the onset of a limp or complaints of persistent hip or knee pain.

Progression of Preexisting Scoliosis

Somatrogon-ghla increases growth rate, and progression of preexisting scoliosis can occur in patients who experience rapid growth. Growth hormone treatment has not been shown to increase the occurrence of scoliosis. Monitor patients with a history of scoliosis for disease progression.

Pancreatitis

Cases of pancreatitis have been reported in patients receiving somatropin. The risk may be greater in pediatric patients compared with adults. Consider pancreatitis in patients who develop persistent severe abdominal pain.

Lipoatrophy

When somatrogon-ghla is administered subcutaneously at the same site over a long period of time, lipoatrophy may result. Rotate injection sites when administering somatrogon-ghla to reduce this risk.

Sudden Death in Pediatric Patients With Prader-willi Syndrome

There have been reports of sudden death after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Somatrogon-ghla 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 phosphorus, alkaline phosphatase, and parathyroid hormone may increase with somatrogon-ghla therapy. If a patient is found to have abnormal laboratory tests, monitor as appropriate.

Specific Populations

Pregnancy

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

The background risk of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

There are no data on the presence of somatrogon-ghla in human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for somatrogon-ghla and any potential adverse effects on the breastfed infant from somatrogon-ghla or from the underlying maternal condition.

Females and Males of Reproductive Potential

Although somatrogon-ghla did not interfere with hCG pregnancy testing in a limited number of commercial tests, interference with hCG blood and urine pregnancy testing in patients receiving somatrogon-ghla may be possible, leading to either false positive or false negative results. Alternative methods (i.e., not reliant on hCG) are recommended to determine pregnancy.

Pediatric Use

The safety and effectiveness of somatrogon-ghla have been established for the treatment of growth failure due to inadequate secretion of endogenous growth hormone (GH) in pediatric patients aged 3 years and older. The use of somatrogon-ghla for this indication is supported by evidence from a 52-week, multi-center, randomized, open-label, active-controlled, parallel-group phase 3 study in 224 treatment-naïve, prepubertal pediatric subjects with growth hormone deficiency.

Risks in pediatric patients associated with growth hormone use include:

• Increased risk of second neoplasm in pediatric cancer survivors treated with radiation to the brain and/or head.

• Slipped capital femoral epiphysis.

• Progression of preexisting scoliosis.

• Pancreatitis.

• Sudden death in pediatric patients with Prader-Willi Syndrome. Somatrogon-ghla is not indicated for the treatment of pediatric patients with growth failure secondary to genetically confirmed Prader-Willi syndrome.

Common Adverse Effects

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

General

Somatrogon-ghla is available in the following dosage form(s) and strength(s):

Injection:

• 24 mg/1.2 mL (20 mg/mL) in a single-patient-use prefilled pen that delivers a dose in 0.2 mg increments

• 60 mg/1.2 mL (50 mg/mL) in a single-patient-use prefilled pen that delivers a dose in 0.5 mg increments

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Pediatric Patients

Dosage and Administration

• Somatrogon-ghla treatment should be supervised by a healthcare provider who is experienced in the diagnosis and management of pediatric patients with growth hormone deficiency.

• Administer somatrogon-ghla by subcutaneous injection once weekly, on the same day each week, at any time of the day in the abdomen, thighs, buttocks, or upper arms with weekly rotation of injection site.

• The recommended dosage in pediatric patients ≥3 years of age is 0.66 mg/kg based on actual body weight administered once weekly.

• Individualize dosage for each patient based on the growth response.

• Patients switching from daily growth hormone may initiate treatment with once-weekly somatrogon-ghla on the day following their last daily injection.

• If more than one injection is required to deliver a complete dose, each injection should be administered at a different injection site.