Nutropin AQ NuSpin 10

5 WARNINGS AND PRECAUTIONS Acute critical illness: Evaluate potential benefit of treatment continuation against potential risk ( 5.1 ). PWS: Evaluate for signs of upper airway obstruction and sleep apnea before initiating therapy. Discontinue treatment if these signs occur. ( 5.2 ). Neoplasm: Monitor patients with preexisting tumors for progression or reoccurrence. 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 ). Impaired glucose tolerance (IGT) and Diabetes Mellitus (DM): Periodically monitor glucose levels in all patients, as IGT and DM may be unmasked during somatropin therapy. Doses of concurrent antihyperglycemic drugs in patients with DM may require adjustment. ( 5.4 ). Intracranial hypertension (IH): Exclude preexisting papilledema. IH may develop, but is usually reversible after discontinuation or dose reduction ( 5.5 ). Hypersensitivity: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention ( 5.6 ). Fluid retention (e.g., edema, arthralgia, carpal tunnel syndrome- especially in adults): Reduce dose as necessary if such signs develop ( 5.7 ). Hypoadrenalism: Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increase in those with known hypoadrenalism ( 5.8 ). Hypothyroidism: Monitor thyroid function periodically as it may first become evident or worsen after initiation of somatropin ( 5.9 ). Slipped capital femoral epiphysis (SCFE): Evaluate any child with onset of a limp or hip/knee pain for possible SCFE and osteonecrosis ( 5.10 ). Progression of preexisting scoliosis: Monitor any child with scoliosis for progression of the curve ( 5.11 ). Pancreatitis: Consider pancreatitis in patients with persistent severe abdominal pain ( 5.16 ). 5.1 Acute Critical Illness Increased mortality in patients with acute critical illnesses due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic amounts of somatropin [see Contraindications (4) ] . Two placebo-controlled clinical trials in non-GHD adult patients (n = 522) with these conditions in intensive care units revealed a significant increase in mortality (42% vs. 19%) among somatropin-treated patients (doses 5.3–8 mg/day) compared to those receiving placebo. The safety of continuing somatropin treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. Therefore, the potential benefit of treatment continuation with somatropin in patients having acute critical illnesses should be weighed against the potential risk. 5.2 Prader-Willi Syndrome (PWS) in Children There have been reports of fatalities after initiating therapy with somatropin in pediatric patients with PWS 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. Patients with PWS syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin. If during treatment with somatropin, patients show signs of upper airway obstruction (including onset of or increased snoring) and/or new onset sleep apnea, treatment should be interrupted. All patients with PWS treated with somatropin should also have effective weight control and be monitored for signs of respiratory infection, which should be diagnosed as early as possible and treated aggressively [see Contraindications (4) ] . Nutropin AQ is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed PWS. 5.3 Neoplasms 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. In adults, it is unknown whether there is any relationship between somatropin replacement therapy and CNS tumor recurrence [see Contraindications (4) ] . Monitor all patients with a history of GHD secondary to an intracranial neoplasm routinely while on somatropin 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, practitioners should thoroughly consider the risks and benefits of starting somatropin in these patients. If treatment with somatropin is initiated, these patients should be carefully monitored for development of neoplasms. Monitor patients on somatropin therapy carefully for increased growth, or potential malignant changes, of preexisting nevi. 5.4 Glucose Intolerance and Diabetes Mellitus Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses in susceptible patients. As a result, previously undiagnosed impaired glucose tolerance (IGT) and overt diabetes mellitus may be unmasked during somatropin treatment, and new onset type 2 diabetes mellitus has been reported in patients taking somatropin. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes, such as obesity, Turner syndrome (TS), or a family history of diabetes mellitus. Patients with preexisting type 1 or type 2 diabetes mellitus or IGT should be monitored closely during somatropin therapy. The doses of antihyperglycemic drugs (i.e. insulin or oral/injectable agents) may require adjustment when somatropin therapy is instituted in these patients. 5.5 Intracranial Hypertension Intracranial Hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in a small number of patients treated with somatropin products. 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 the somatropin dose. Funduscopic examination should be performed routinely before initiating treatment with somatropin to exclude preexisting papilledema, and periodically during the course of somatropin therapy. If papilledema is observed by funduscopy during somatropin treatment, treatment should be stopped. If somatropin-induced IH is diagnosed, treatment with somatropin can be restarted at a lower dose after IH-associated signs and symptoms have resolved. Patients with TS, chronic kidney disease (CKD), and PWS may be at increased risk for the development of IH. 5.6 Severe Hypersensitivity Serious systemic hypersensitivity reactions including anaphylactic reaction and angioedema have been reported with postmarketing use of somatropin products. Patients and caregivers should be informed that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs. 5.7 Fluid Retention Fluid retention during somatropin replacement therapy in adults may occur. Clinical manifestations of fluid retention (e.g., edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias) are usually transient and dose dependent. 5.8 Hypoadrenalism Patients receiving somatropin 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 somatropin treatment [see Section 7.1, 11-β Hydroxysteroid Dehydrogenase Type 1 ]. 5.9 Hypothyroidism Undiagnosed/untreated hypothyroidism may prevent an optimal response to somatropin, in particular, the growth response in children. Patients with TS have an inherently increased risk of developing autoimmune thyroid disease and primary hypothyroidism. In patients with GHD, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Therefore, patients treated with somatropin should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated. 5.10 Slipped Capital Femoral Epiphysis (SCFE) in Pediatric Patients SCFE may occur more frequently in patients with endocrine disorders (including GHD and TS) or in patients undergoing rapid growth. SCFE may lead to osteonecrosis. Cases of SCFE with or without osteonecrosis have been reported in pediatric patients with short stature receiving somatropin, including NUTROPIN AQ. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during NUTROPIN AQ therapy should be evaluated for SCFE and osteonecrosis and managed accordingly. 5.11 Progression of Preexisting Scoliosis in Pediatric Patients Progression of scoliosis can occur in patients who experience rapid growth. Because somatropin increases growth rate, patients with a history of scoliosis who are treated with somatropin should be monitored for progression of scoliosis. However, somatropin has not been shown to increase the occurrence of scoliosis. Skeletal abnormalities including scoliosis are commonly seen in untreated TS patients. Scoliosis is also commonly seen in untreated patients with PWS. Physicians should be alert to these abnormalities, which may manifest during somatropin therapy. 5.12 Otitis Media and Cardiovascular Disorders in Patients with Turner Syndrome Patients with TS should be evaluated carefully for otitis media and other ear disorders, as these patients have an increased risk of ear and hearing disorders. Somatropin treatment may increase the occurrence of otitis media in patients with TS. In addition, patients with TS should be monitored closely for cardiovascular disorders (e.g., hypertension, aortic aneurysm or dissection, stroke) as these patients are also at increased risk for these conditions. 5.13 Osteodystrophy in Pediatric Patients with Chronic Kidney Disease Children with growth failure secondary to CKD should be examined periodically for evidence of progression of renal osteodystrophy. SCFE or avascular necrosis of the femoral head may be seen in children with advanced renal osteodystrophy, and it is uncertain whether these problems are affected by somatropin therapy. X-rays of the hip should be obtained prior to initiating somatropin therapy in CKD patients and physicians and parents should be alert to the development of a limp or complaints of hip or knee pain in these patients treated with Nutropin AQ. No studies have been completed evaluating Nutropin AQ therapy in patients who have received renal transplants. Currently, treatment of patients with functioning renal allografts is not indicated. 5.14 Lipoatrophy When somatropin is administered subcutaneously at the same site over a long period of time, tissue atrophy may result. This can be avoided by rotating the injection site [see Dosage and Administration (2.3) ] . 5.15 Laboratory Tests Serum levels of inorganic phosphorus, alkaline phosphatase, and parathyroid hormone (PTH), and IGF-1 may increase during somatropin therapy. 5.16 Pancreatitis Cases of pancreatitis have been reported rarely in children and adults receiving somatropin treatment, with some evidence supporting a greater risk in children compared with adults. Published literature indicates that girls who have TS may be at greater risk than other somatropin-treated children. Pancreatitis should be considered in any somatropin–treated patient, especially a child, who develops persistent severe abdominal pain.