Somatrogon-ghla

Somatrogon-ghla
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kosar Doraghi, M.D.[2]

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Black Box Warning

Severe Hypersensitivity See full prescribing information for complete Boxed Warning. *Severe Hypersensitivity Increased Risk of Neoplasms: Monitor patients with preexisting tumors for progression. Childhood cancer survivors treated with somatropin are at higher risk of second neoplasms. Glucose Intolerance and Diabetes Mellitus Intracranial Hypertension: Conduct fundoscopic examinations before and during treatment. Discontinue NGENLA if papilledema occurs. Fluid Retention: Dosage adjustment may be necessary to manage fluid retention. Hypoadrenalism: Monitor cortisol levels and adjust glucocorticoid doses accordingly. Hypothyroidism: Periodically monitor thyroid function. Slipped Capital Femoral Epiphysis: Assess patients with persistent hip or knee pain. Progression of Preexisting Scoliosis: Monitor for development or worsening of scoliosis. Pancreatitis: Consider pancreatitis in patients with severe abdominal pain. Lipoatrophy: Rotate injection sites to prevent lipoatrophy.

Overview

Somatrogon-ghla is a human growth hormone analog that is FDA approved for the treatment of pediatric patients aged 3 years and older who have growth failure due to inadequate secretion of endogenous growth hormone. There is a Black Box Warning for this drug as shown here. Common adverse reactions include injection site reactions, nasopharyngitis, headache, pyrexia, anemia, cough, vomiting, hypothyroidism, abdominal pain, rash, and oropharyngeal pain.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

There is limited information regarding Somatrogon-ghla FDA-Labeled Indications and Dosage (Adult) in the drug label.

Off-Label Use and Dosage (Adult)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Treatment with NGENLA should be overseen by a healthcare provider experienced in pediatric growth hormone deficiency management.

• Administer NGENLA via subcutaneous injection once weekly, consistently on the same day, in the abdomen, thighs, buttocks, or upper arms, rotating injection sites weekly
• The recommended dosage is 0.66 mg/kg based on actual body weight, given once weekly. Dosage adjustments should be tailored to each patient’s growth response.
• Switching from Daily Growth Hormone: Patients transitioning from daily growth hormone therapy can start NGENLA the day after their last daily injection.
• Multiple Injections: If multiple injections are needed to deliver a complete dose, each injection should be at a different site.
• 24 mg/1.2 mL (20 mg/mL) single-patient-use prefilled pen that delivers a dose in 0.2 mg increments.
• 60 mg/1.2 mL (50 mg/mL) single-patient-use prefilled pen that delivers a dose in 0.5 mg increments.

Off-Label Use and Dosage (Pediatric)

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 who are severely obese or have severe respiratory impairment

Warnings

Severe Hypersensitivity See full prescribing information for complete Boxed Warning. *Severe Hypersensitivity Increased Risk of Neoplasms: Monitor patients with preexisting tumors for progression. Childhood cancer survivors treated with somatropin are at higher risk of second neoplasms. Glucose Intolerance and Diabetes Mellitus Intracranial Hypertension: Conduct fundoscopic examinations before and during treatment. Discontinue NGENLA if papilledema occurs. Fluid Retention: Dosage adjustment may be necessary to manage fluid retention. Hypoadrenalism: Monitor cortisol levels and adjust glucocorticoid doses accordingly. Hypothyroidism: Periodically monitor thyroid function. Slipped Capital Femoral Epiphysis: Assess patients with persistent hip or knee pain. Progression of Preexisting Scoliosis: Monitor for development or worsening of scoliosis. Pancreatitis: Consider pancreatitis in patients with severe abdominal pain. Lipoatrophy: Rotate injection sites to prevent lipoatrophy.

Severe Hypersensitivity: Seek immediate medical attention in case of allergic reactions.

• Increased Risk of Neoplasms: Monitor patients with preexisting tumors for progression. Childhood cancer survivors treated with somatropin are at higher risk of second neoplasms.
• Glucose Intolerance and Diabetes Mellitus: Monitor glucose levels regularly, especially in patients with existing diabetes or at risk.
• Intracranial Hypertension: Conduct fundoscopic examinations before and during treatment. Discontinue NGENLA if papilledema occurs.
• Fluid Retention: Dosage adjustment may be necessary to manage fluid retention.
• Hypoadrenalism: Monitor cortisol levels and adjust glucocorticoid doses accordingly.
• Hypothyroidism: Periodically monitor thyroid function.
• Slipped Capital Femoral Epiphysis: Assess patients with persistent hip or knee pain.
• Progression of Preexisting Scoliosis: Monitor for development or worsening of scoliosis.
• Pancreatitis: Consider pancreatitis in patients with severe abdominal pain.
• Lipoatrophy: Rotate injection sites to prevent lipoatrophy.

Adverse Reactions

Clinical Trials Experience

severe hypersensitivity, increased risk of neoplasm, glucose intolerance, intracranial hypertension, fluid retention, hypoadrenalism, hypothyroidism, slipped capital femoral epiphysis, progression of preexisting scoliosis, pancreatitis, lipoatrophy, and sudden death in pediatric patients with Prader-Willi syndrome. These adverse reactions are detailed in the warnings and precautions section of the labeling.

• The safety data is from a study involving pediatric patients with GHD, comparing NGENLA administered once weekly (0.66 mg/kg) to somatropin administered once daily (0.034 mg/kg). The study included 109 patients on NGENLA and 115 on somatropin, with a mean age of 7.7 years. Most patients were male (71.9%) and White (74.6%). Adverse reactions occurring in ≥5% of patients are summarized in Table 1. Injection site reactions were monitored through patient diaries.

Postmarketing Experience

More NGENLA-treated patients shifted from normal eosinophil levels at baseline to elevated eosinophil levels at the end of the 12-month study compared to the daily somatropin group (29% vs 12%).

Drug Interactions

• Replacement Glucocorticoid Treatment: Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress dose following initiation of NGENLA
• Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Adjust glucocorticoid dosing in pediatric patients to avoid both hypoadrenalism and an inhibitory effect on growth 
• Cytochrome P450-Metabolized Drugs: NGENLA may alter the clearance. Monitor carefully if used with NGENLA
• Oral Estrogen: Larger doses of NGENLA may be required
• Insulin and/or Other Antihyperglycemic Agents: Dose adjustment of insulin or antihyperglycemic agent may be required

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Somatrogon-ghla in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Somatrogon-ghla in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Somatrogon-ghla during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Somatrogon-ghla in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Somatrogon-ghla in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Somatrogon-ghla in geriatric settings.

Gender

There is no FDA guidance on the use of Somatrogon-ghla with respect to specific gender populations.

Race

There is no FDA guidance on the use of Somatrogon-ghla with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Somatrogon-ghla in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Somatrogon-ghla in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Somatrogon-ghla in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Somatrogon-ghla in patients who are immunocompromised.

Administration and Monitoring

Administration

NGENLA treatment should be overseen by a healthcare provider experienced in managing pediatric patients aged 3 years and older with growth hormone deficiency (GHD).

• Administration: Administer NGENLA via subcutaneous injection once weekly, consistently on the same day, rotating injection sites weekly.
• Inspection: Inspect prefilled pens for particulate matter or discoloration before use. Do not shake the pen.
• Fundoscopic Examination: Perform before starting NGENLA to rule out preexisting papilledema.
• Recommended Dosage: Administer 0.66 mg/kg once weekly based on actual body weight, adjusting dosage according to growth response.
• Dosing Flexibility: Change the dosing day if needed, ensuring at least 3 days between doses.
• Switching from Daily Growth Hormone: Start NGENLA the day after the last daily injection.
• Missed Dose: Administer missed dose within 3 days. If more than 3 days have passed, skip the missed dose and continue with the regular schedule.

Monitoring

There is limited information regarding Somatrogon-ghla Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Somatrogon-ghla and IV administrations.

Overdosage

Acute overdosage may lead initially to hypoglycemia and subsequently to hyperglycemia. Overdose with growth hormone may cause fluid retention. Long-term overdosage could result in signs and symptoms of gigantism consistent with the effects of excess growth hormone.

Pharmacology

There is limited information regarding Somatrogon-ghla Pharmacology in the drug label.

Mechanism of Action

Action Somatrogon-ghla binds to the GH receptor and initiates a signal transduction cascade culminating in changes in growth and metabolism. Somatrogon-ghla binding leads to activation of the STAT5b signaling pathway and increases the serum concentration of Insulin-like Growth Factor (IGF-1). GH and IGF-1 stimulate metabolic changes, linear growth, and enhance growth velocity in pediatric patients with GHD.

Structure

Somatrogon-ghla, a human growth hormone analog, is a fusion protein produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology. It is comprised of the amino acid sequence of human growth hormone (hGH) with one copy of the C-terminal peptide (CTP) from the beta chain of human chorionic gonadotropin (hCG) at the N-terminus and 2 copies of CTP (in tandem) at the C-terminus. Somatrogon-ghla has an approximate molecular weight of 40 KDa.

• NGENLA (somatrogon-ghla) injection is a sterile, clear and colorless to slightly light yellow solution for subcutaneous use supplied in a 24 mg/1.2 mL (20 mg/mL) or 60 mg/1.2 mL (50 mg/mL) single-patient-use prefilled pen.

Each 1.2 mL of solution contains either 24 mg or 60 mg of somatrogon-ghla, and the inactive ingredients citric acid monohydrate (0.3 mg), histidine (1.9 mg), metacresol (4 mg, as a preservative), poloxamer 188 (2 mg), sodium chloride (10 mg) and sodium citrate (2.8 mg) in water for injection. NGENLA has a pH of approximately 6.6.

Pharmacodynamics

Following single dose administration of somatrogon, dose-dependent increases in IGF-1 response were observed. Following multiple dosing, IGF-1 SDS levels were in the normal range for pediatric patients with GHD, similar to daily somatropin. IGF-1 levels peak approximately 2 days (48 hours) post-dose, with the average weekly IGF-1 occurring approximately 4 days post-dose.

Pharmacokinetics

Somatrogon-ghla pharmacokinetics (PK) was assessed using a population PK approach for NGENLA in 151 pediatric patients (aged 3 to 15.5 years) with GHD.

• Following subcutaneous injection, serum concentrations increased slowly, peaking 6 to 25 hours with a median of 11 hours after dosing.

In pediatric patients with GHD, somatrogon-ghla exposure increases in a dose-proportional manner for doses of 0.25 mg/kg/wk, 0.48 mg/kg/wk, and 0.66 mg/kg/wk. There is no accumulation of somatrogon-ghla after once weekly administration. In pediatric patients with GHD, the mean population PK estimated steady-state peak concentrations (mean ± SD) following 0.66 mg/kg/wk was 495 ± 90 ng/mL.

• In pediatric patients with GHD, the mean population PK estimated apparent central volume of distribution was 0.342 L/kg and apparent peripheral volume of distribution was 0.671 L/kg.
• In pediatric patients with GHD, the mean population PK estimated apparent clearance was 0.0398 L/h/kg. The mean population PK estimated effective half-life was 37.7 hours, which allows for weekly dosing. Somatrogon-ghla will be present in the circulation for about 8 days after the last dose.
• The metabolism of somatrogon-ghla is believed to be classical protein catabolism, with subsequent recovery of the amino acids and return to the systemic circulation.
• Excretion

Excretion was not evaluated in clinical studies.

Nonclinical Toxicology

There is limited information regarding Somatrogon-ghla Nonclinical Toxicology in the drug label.

Clinical Studies

A multi-center, randomized, open-label, active-controlled, parallel-group phase 3 study (NCT 02968004) was conducted in 224 treatment-naïve, prepubertal pediatric subjects with growth hormone deficiency (GHD). The primary efficacy endpoint was annualized height velocity at Week 52. One hundred nine (109) subjects received 0.66 mg/kg/week NGENLA, and 115 subjects received 0.034 mg/kg/day daily somatropin. The subjects age ranged from 3 to 12 years, with a mean of 7.7 years. One hundred sixty-one (71.9%) subjects were male and 63 (28.1%) were female. One hundred sixty-seven (74.6%) subjects were White, 45 (20.1%) subjects were Asian, 2 (0.9%) subjects were Black or African-American, 1 (0.5%) subject was American Indian or Alaska Native, 1 (0.5%) subject was Native Hawaiian or Other Pacific Islander, and for 8 (3.6%) subjects race information was missing; 24 (10.7%) subjects identified as Hispanic or Latino. The subjects had a mean baseline height standard deviation score (SDS) of -2.9. Treatment with once-weekly NGENLA for 52 weeks resulted in an annualized height velocity of 10.1 cm/year. Patients treated with daily somatropin achieved an annualized height velocity of 9.8 cm/year after 52 weeks of treatment Annualized Height Velocity at Week 52 in Pediatric Patients with GHD

How Supplied

Storage

Before first use: Store refrigerated at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light.

After first use: Store the pen refrigerated at 36°F to 46°F (2°C to 8°C) between each use, for up to 28 days.

Do not freeze or shake. Do not expose to heat. Do not use if it has been frozen. Store away from direct sunlight.

Always remove and safely discard the needle after each injection and store the NGENLA prefilled pen without an injection needle attached. Always use a new needle for each injection. Replace the cap on your prefilled pen when it is not in use. Write the date of first use in the space provided on the pen label. The prefilled pen should not be used more than 28 days after first use.

Images

Drug Images

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Package and Label Display Panel

One single-patient-use disposable prefilled pen Rx only NDC 0069-0505-02

24mg

Ngenla® (somatrogon-ghla) Injection 24 mg/1.2 mL (20 mg/mL) For Subcutaneous Injection Only {{#ask: Label Page::Somatrogon-ghla |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Somatrogon-ghla Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Somatrogon-ghla interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Somatrogon-ghla Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Somatrogon-ghla Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.