warnings and cautions
5 WARNINGS AND PRECAUTIONS Neoplasms: Monitor patients for potential malignant changes of pre-existing nevi; discontinue if there is evidence of recurrent activity. ( 4 , 5.1 ) Acute Critical Illness: Increased mortality due to complication following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure. ( 4 , 5.2 ) Impaired Glucose Tolerance/Diabetes Mellitus (new onset or exacerbation): Monitor blood glucose and adjust concurrent antidiabetic treatment, as needed. ( 5.3 ) Hypersensitivity Reactions: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention. ( 4 , 5.4 ) Lipoatrophy: Rotate injection sites. ( 2.3 , 5.5 ) Fluid Retention: Tissue turgor and musculoskeletal discomfort may resolve spontaneously or require analgesic treatment or a reduction in Zorbtive ® dose. ( 2.1 , 5.6 ) Carpal Tunnel Syndrome: Decrease the dosage of Zorbtive ® , discontinue treatment if symptoms do not resolve. ( 2.1 , 5.7 ) Pancreatitis: Consider pancreatitis in any patient who develops abdominal pain. ( 5.8 ) Hypoadrenalism : Monitor patients for reduced serum cortisol levels and/or need for glucocorticoid dose increases in those with known hypoadrenalism. ( 5.9 , 7.1 ) Hypothyroidism: Evaluate thyroid function in patients with suspected and/or diagnosed hypopituitarism before starting Zorbtive ® and again following 4 weeks of treatment; correct thyroid function, if needed. ( 5.10 ) Intracranial Hypertension: Exclude preexisting papilledema. ( 5.11 ) Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative: Zorbtive ® is not approved for use in pediatric patients ( 5.12 , 8.4 ) 5.1 Neoplasms Zorbtive ® is contraindicated in patients with active malignancy. Any preexisting malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Discontinue somatropin if there is evidence of recurrent activity [see Contraindications (4) ] . In childhood cancer survivors, an increased risk of a second neoplasm has been reported in patients treated with somatropins after their first neoplasm. Intracranial tumors, in particular meningiomas, in patients treated with radiation to the head for their first neoplasm, were the most common of these second neoplasms. In adult cancer survivors, the risk of occurrence is unknown. Given the limited data available, patients under growth hormone therapy should be carefully monitored for progression or recurrence of the tumor. The safety and effectiveness of Zorbtive ® in the treatment for short bowel syndrome in pediatric patients have not been established and Zorbtive ® is not approved for use in pediatric patients. Monitor patients on somatropin therapy carefully for potential malignant changes of preexisting nevi. 5.2 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 after treatment with pharmacologic amounts of somatropin [see Contraindications (4) ]. Two placebo-controlled clinical trials in non-growth hormone deficient 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 to 8 mg per day) compared to those receiving placebo. Discontinue Zorbtive ® if the patient has acute critical illness. 5.3 Impaired Glucose Tolerance/Diabetes Mellitus The use of somatropins have been associated with cases of new onset impaired glucose intolerance, new onset type 2 diabetes mellitus and exacerbation of preexisting diabetes mellitus. Some patients developed diabetic ketoacidosis and diabetic coma. In some patients, these conditions improved when the drug was discontinued, while in others the glucose intolerance persisted. Some patients necessitated initiation or adjustment of antidiabetic treatment (e.g., insulin and/or other oral/injectable hypoglycemic agents) while on somatropin. Monitor blood glucose in patients with other risk factors for glucose intolerance during Zorbtive ® therapy and adjust antidiabetic treatment, as needed . 5.4 Hypersensitivity Reactions Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropin products. Inform patients and caregivers that such reactions are possible and to seek prompt medical attention if a hypersensitivity reaction occurs. [see Contraindications (4) ] . 5.5 Lipoatrophy When somatropins are administered subcutaneously at the same site over a long period of time, tissue atrophy may result. Avoid tissue atrophy by rotating the injection site [see Dosage and Administration (2.3) ] . 5.6 Fluid Retention and Arthralgia Increased fluid retention resulting in tissue turgor (swelling, particularly in the hands and feet) and arthralgia resulting in musculoskeletal discomfort (pain, swelling and/or stiffness) may occur during treatment with Zorbtive ® , but may resolve spontaneously or with analgesic therapy or after reducing the dosage [see Dosage and Administration (2.1) ]. 5.7 Carpal Tunnel Syndrome Carpal tunnel syndrome may occur during treatment with somatropin. If the symptoms of carpal tunnel syndrome do not resolve by decreasing the dosage of Zorbtive ® , discontinue treatment [see Dosage and Administration (2.1) ] . 5.8 Pancreatitis Cases of pancreatitis have been reported in pediatric patients and adults receiving somatropin treatment, with some evidence supporting a greater risk in pediatric patients compared with adults. Published literature indicates that females who have Turner syndrome may be at greater risk than other somatropin-treated pediatric patients. Pancreatitis should be considered in any somatropin-treated patient, especially a pediatric patient who develops abdominal pain. The safety and effectiveness of Zorbtive ® in the treatment for short bowel syndrome in pediatric patients have not been established and Zorbtive ® is not approved for use in pediatric patients. 5.9 Hypoadrenalism Patients receiving somatropin therapy who have or are at risk for pituitary homone 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 Zorbtive ® therapy [see Drug Interactions (7.1) ]. 5.10 Hypothyroidism Growth hormone can affect the metabolism of thyroid hormones by increasing the extrathyroidal conversion of T4 to T3 and this lowering effect on T4 may unmask incipient central hypothyroidism in hypopituitary patients. Evaluate thyroid function in patients with suspected and/or diagnosed hypopituitarism before starting Zorbtive ® therapy and again following 4 weeks of treatment. If hypothyroidism is diagnosed following a course of Zorbtive ® therapy, it should be corrected. 5.11 Intracranial Hypertension No cases of intracranial hypertension (IH) have been observed among patients with short bowel syndrome treated with Zorbtive ® . The syndrome of intracranial hypertension (IH), with papilledema, visual changes, headache, and nausea and/or vomiting has been reported in a small number of pediatric patients with growth failure treated with somatropins. Symptoms usually occurred within the first 8 weeks after the initiation of somatropin therapy. IH-associated signs and symptoms usually resolved after cessation of therapy or a reduction of the somatropin dosage. The safety and effectiveness of Zorbtive ® in the treatment for short bowel syndrome in pediatric patients have not been established and Zorbtive ® is not approved for use in pediatric patients. Funduscopic evaluation of patients is recommended at the initiation of Zorbtive ® therapy and if patients present with symptoms of IH. If papilledema is observed by funduscopy during Zorbtive ® treatment, discontinue treatment. 5.12 Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preservative Zorbtive ® is not approved for use in neonates or infants. Serious and fatal adverse reactions including "gasping syndrome" can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved drugs, including Zorbtive ® when reconstituted with Bacteriostatic Water for Injection, USP. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known (when reconstituted with Bacteriostatic Water for Injection, USP, Zorbtive ® contains 9 mg of benzyl alcohol per mL) [see Use in Specific Populations (8.4) ].