SOMATROGON Drug Interactions: What You Need to Know

INTERACTIONS Table 2 includes a list of drugs with clinically significant drug interactions when administered concomitantly with NGENLA and instructions for preventing or managing them.

Table

2 Clinically Significant Drug Interactions with NGENLA Replacement Glucocorticoid Treatment Clinical Impact: Microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) is required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. Growth hormone inhibits 11βHSD-1. Consequently, individuals with untreated GH deficiency have relative increases in 11βHSD-1 and serum cortisol. Initiation of NGENLA may result in inhibition of 11βHSD-1 and reduced serum cortisol concentrations. Intervention: Patients treated with glucocorticoid replacement for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of NGENLA [see Warnings and Precautions (5.7) ] . Examples: Cortisone acetate and prednisone may be affected more than others because conversion of these drugs to their biologically active metabolites is dependent on the activity of 11βHSD-1.

Supraphysiologic Glucocorticoid Treatment Clinical

Impact: Supraphysiologic glucocorticoid treatment may attenuate the growth-promoting effects of NGENLA in pediatric patients. Intervention: Carefully adjust glucocorticoid replacement dosing in pediatric patients receiving glucocorticoid treatments to avoid hypoadrenalism and an inhibitory effect on growth. Cytochrome P450-Metabolized Drugs Clinical Impact: Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. NGENLA may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes. Intervention: Careful monitoring is advisable when NGENLA is administered in combination with drugs metabolized by CYP450 liver enzymes.

Oral Estrogen Clinical

Impact: Oral estrogens may reduce the serum IGF-1 response to NGENLA. Intervention: Patients receiving oral estrogen replacement may require higher NGENLA dosages. Insulin and/or Other Antihyperglycemic Agents Clinical Impact: Treatment with NGENLA may decrease insulin sensitivity, particularly at higher doses. Intervention: Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents [see Warnings and Precautions (5.4) ] .

• Replacement Glucocorticoid Treatment: Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress dose following initiation of NGENLA ( 7 ).
• Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment: Adjust glucocorticoid dosing in pediatric patients to avoid both hypoadrenalism and an inhibitory effect on growth ( 7 ).
• Cytochrome P450-Metabolized Drugs: NGENLA may alter the clearance. Monitor carefully if used with NGENLA ( 7 ).
• Oral Estrogen: Larger doses of NGENLA may be required ( 7 ).
• Insulin and/or Other Antihyperglycemic Agents: Dose adjustment of insulin or antihyperglycemic agent may be required ( 5.4 , 7 ).

4 CONTRAINDICATIONS

• 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) ] .
• Hypersensitivity to somatrogon-ghla or any of the excipients in NGENLA [see Warnings and Precautions (5.2) ] .
• Closed epiphyses.
• Active malignancy due to the risk of malignancy progression [see Warnings and Precautions (5.3) ] .
• Active proliferative or severe non-proliferative diabetic retinopathy [see Warnings and Precautions (5.4) ] .
• 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) ] .
• Acute critical illness ( 4 ).
• Hypersensitivity to somatrogon-ghla or excipients ( 4 ).
• Closed epiphyses ( 4 ).
• Active malignancy ( 4 ).
• Active proliferative or severe non-proliferative diabetic retinopathy ( 4 ).
• Prader-Willi syndrome who are severely obese or have severe respiratory impairment ( 4 ).

AND PRECAUTIONS

• Severe Hypersensitivity : Severe hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention ( 5.2 ).
• Increased Risk of Neoplasms : Monitor patients with preexisting tumors for progression or recurrence. Increased risk of a second neoplasm in childhood cancer survivors treated with somatropin – in particular meningiomas in patients treated with radiation to the head for their first neoplasm ( 5.3 ).
• Glucose Intolerance and Diabetes Mellitus : NGENLA may decrease insulin sensitivity, particularly at higher doses. Monitor glucose levels periodically in all patients receiving NGENLA, especially in patients with existing diabetes mellitus or at risk for its development ( 5.4 ).
• Intracranial Hypertension : Perform fundoscopic examinations prior to initiation of treatment with NGENLA and periodically thereafter. If preexisting papilledema is identified, evaluate the etiology and treat the underlying cause before initiating. If papilledema occurs with NGENLA, stop treatment ( 5.5 ).
• Fluid Retention: May occur and may be dose dependent. Reduce dose as necessary ( 5.6 ).
• Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism ( 5.7 ).
• Hypothyroidism : Monitor thyroid function periodically as hypothyroidism may become evident or worsen after initiation with NGENLA ( 5.8 ).
• Slipped Capital Femoral Epiphysis : May develop. Evaluate patients with the onset of a limp or persistent hip or knee pain ( 5.9 ).
• Progression of Preexisting Scoliosis : Monitor for development or progression of scoliosis ( 5.10 ).
• Pancreatitis : Consider pancreatitis in patients with persistent severe abdominal pain ( 5.11 ).
• Lipoatrophy: May occur if NGENLA is administered in the same location over a long period of time. Rotate injection sites ( 5.12 ).

5.1 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 <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . The safety of continuing NGENLA treatment for the approved indication in patients who concurrently develop these illnesses has not been established.

5.2 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 <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .

5.3 Increased Risk of Neoplasms Active Malignancy There is an increased risk of malignancy progression with somatropin treatment in patients with active malignancy <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . 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.

5.4 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.

5.5 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.

5.6 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.

5.7 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 <span class="opacity-50 text-xs">[see Drug Interactions (7) ]</span> .

5.8 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.

5.9 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.

5.10 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.

5.11 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.

5.12 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 <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) ]</span> .

5.13 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.

5.14 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.