Ngenla
(somatrogon-ghla)Dosage & Administration
Ngenla Prescribing Information
NGENLA is indicated for the treatment of pediatric patients aged 3 years and older who have growth failure due to an inadequate secretion of endogenous growth hormone.
Important Dosing and Administration Information
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- NGENLA treatment should be supervised by a healthcare provider who is experienced in the diagnosis and management of pediatric patients aged 3 years and older with growth failure due to growth hormone deficiency (GHD) [see Indications and Usage (1)].
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- Refer patient to the Instructions for Use for complete administration instructions.
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- Administer NGENLA 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. Rotate the injection site weekly.
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- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If flakes, particles or discoloration are observed, do not use the pen. Do not shake; shaking can damage the product.
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- Prefilled pens deliver somatrogon-ghla in 0.2 mg or 0.5 mg increments.
Perform Fundoscopic Examination Prior to Initiation of NGENLA
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- Perform fundoscopic examination before initiating treatment with NGENLA to exclude preexisting papilledema. If papilledema is identified, evaluate the etiology and treat the underlying cause before initiating treatment with NGENLA [see Warnings and Precautions (5.4)].
Recommended Dosage and Monitoring for Pediatric Patients with GHD
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- Recommended dosage of NGENLA is 0.66 mg/kg based on actual body weight administered once weekly by subcutaneous (SC) injection.
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- Individualize dosage for each patient based on the growth response.
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- The day of weekly administration can be changed if necessary as long as the time between 2 doses is at least 3 days. After selecting a new dosing day, the once weekly dosing should be continued.
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- When switching from daily growth hormone, the once-weekly NGENLA may be initiated on the day following their last daily injection.
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- If more than one injection is required to deliver a complete dose, each injection should be administered at a different injection site.
Missed Dose
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- If a dose is missed, administer NGENLA as soon as possible within 3 days after the missed dose.
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- If more than 3 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day.
NGENLA (somatrogon-ghla) is a clear and colorless to slightly light yellow solution available as:
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- Injection: 24 mg/1.2 mL (20 mg/mL) in a single-patient-use, disposable prefilled pen that delivers a dose in 0.2 mg increments.
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- Injection: 60 mg/1.2 mL (50 mg/mL) in a single-patient-use, disposable prefilled pen that delivers a dose in 0.5 mg increments.
Pregnancy
Risk Summary
There are no available data on NGENLA 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 (see Data).
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.
Data
Animal Data
In an embryo-fetal development toxicity study in rats, no adverse maternal or embryo-fetal effects were observed when somatrogon-ghla was administered via subcutaneous injection every 2 days from gestation day (GD) 6 to 18 at doses up to 30 mg/kg (45 times the maximum recommended human dose based on Cav exposure).
In a pre- and postnatal development study in rats, somatrogon-ghla was administered via subcutaneous injection to pregnant rats every 2 days from GD 6 to lactation day 20 at doses up to 30 mg/kg. There was no evidence of maternal toxicity and no adverse effects on the first generation (F1) offspring. Somatrogon-ghla elicited an increase in F1 mean body weights in both sexes and increased the mean copulatory interval in F1 females at the highest dose (30 mg/kg), consistent with a longer estrous cycle length. However, there were no effects on mating indices in F1 females.
Lactation
Risk Summary
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 NGENLA and any potential adverse effects on the breastfed infant from NGENLA or from the underlying maternal condition.
Females and Males of Reproductive Potential
Pregnancy Testing
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 NGENLA 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 [see Clinical Studies (14.1)]. The use of NGENLA 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:
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- Increased risk of second neoplasm in pediatric cancer survivors treated with radiation to the brain and/or head [see Warnings and Precautions (5.3)]
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- Slipped capital femoral epiphysis [see Warnings and Precautions (5.9)]
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- Progression of preexisting scoliosis [see Warnings and Precautions (5.10)]
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- Pancreatitis [see Warnings and Precautions (5.11)]
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- Sudden death in pediatric patients with Prader-Willi Syndrome. NGENLA is not indicated for the treatment of pediatric patients with growth failure secondary to genetically confirmed Prader‑Willi syndrome. [see Warnings and Precautions (5.13)]
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- Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with somatropin [see Warnings and Precautions (5.1)].
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- Hypersensitivity to somatrogon-ghla or any of the excipients in NGENLA [see Warnings and Precautions (5.2)].
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- Closed epiphyses.
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- Active malignancy due to the risk of malignancy progression [see Warnings and Precautions (5.3)].
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- Active proliferative or severe non-proliferative diabetic retinopathy [see Warnings and Precautions (5.4)].
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- 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 [see Warnings and Precautions (5.13)].
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 [see Contraindications (4)]. The safety of continuing NGENLA 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. NGENLA is contraindicated in patients with known hypersensitivity to somatrogon-ghla or any excipients in NGENLA [see Contraindications (4)].
Increased Risk of Neoplasms
Active Malignancy
There is an increased risk of malignancy progression with somatropin treatment in patients with active malignancy [see Contraindications (4)]. Any preexisting malignancy should be inactive, and its treatment should be completed prior to instituting therapy with NGENLA. Discontinue NGENLA if there is evidence of recurrent malignancy.
Risk of Second Neoplasm in Pediatric Patients
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, 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 NGENLA therapy for progression or recurrence of the tumor.
New Malignancy During Treatment
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 NGENLA in these patients. If treatment with NGENLA is initiated, carefully monitor these patients for development of neoplasms.
Monitor patients on NGENLA 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 NGENLA, 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 NGENLA 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 NGENLA to exclude preexisting papilledema and periodically thereafter. If papilledema is identified prior to initiation, evaluate the etiology and treat the underlying cause before initiating NGENLA. NGENLA should be temporarily discontinued in patients with clinical or fundoscopic evidence of IH. If IH is confirmed, restart treatment with NGENLA at a lower dose after IH-associated signs and symptoms have resolved.
Fluid Retention
Fluid retention during NGENLA 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 NGENLA treatment. Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism [see Drug Interactions (7)].
Hypothyroidism
Undiagnosed/untreated hypothyroidism may prevent an optimal response to NGENLA 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. Slipped capital femoral epiphysis may lead to osteonecrosis. Cases of slipped capital femoral epiphysis with or without osteonecrosis have been reported in pediatric patients with short stature receiving somatropin. Evaluate pediatric patients receiving NGENLA 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
NGENLA 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 NGENLA is administered subcutaneously at the same site over a long period of time, lipoatrophy may result. Rotate injection sites when administering NGENLA to reduce this risk [see Dosage and Administration (2.1)].
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. NGENLA 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 NGENLA therapy. If a patient is found to have abnormal laboratory tests, monitor as appropriate.