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Acute Critical Illness: Treatment with somatropin is contraindicated 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.
Prader-Willi Syndrome in Children: Somatropin is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment. There have been reports of sudden death when somatropin was used in such patients. Saizen® is not indicated for the long term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.
Active Malignancy: Somatropin is contraindicated in the presence of active malignancy. Any pre-existing malignancy should be inactive and its treatment complete prior to instituting therapy with somatropin. Somatropin should be discontinued if there is evidence of recurrent activity. Since growth hormone deficiency may be an early sign of the presence of a pituitary tumor (or rarely, other brain tumors), the presence of such tumors should be ruled out prior to initiation of treatment. Somatropin should not be used in patients with any evidence of progression or recurrence of an underlying intracranial tumor.
Diabetic Retinopathy: Somatropin is contraindicated in patients with active proliferative or severe non-proliferative diabetic retinopathy.
Closed Epiphyses: Somatropin should not be used for growth promotion in pediatric patients with closed epiphyses.
Hypersensitivity: Saizen® is contraindicated in patients with a known hypersensitivity to somatropin or any of its excipients. Localized reactions are the most common hypersensitivity reactions. Saizen® reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol.
WARNINGS AND PRECAUTIONS:
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.
Prader-Willi Syndrome in Children: There have been reports of fatalities 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. Patients with Prader-Willi syndrome should be evaluated for signs of upper airway obstruction and sleep apnea before initiation of treatment with somatropin.
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. 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 monitored carefully for development of neoplasms.
Monitor patients on somatropin therapy carefully for increased growth, or potential malignant changes of preexisting nevi.
Glucose Intolerance/Diabetes Mellitus: Previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during somatropin treatment and new onset type 2 diabetes mellitus has been reported in patients. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, 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 impaired glucose tolerance should be monitored closely during somatropin therapy and the dose of antihyperglycemic drug may require adjustment.
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 Turner syndrome, chronic renal insufficiency, and Prader-Willi syndrome may be at increased risk for the development of IH.
Fluid Retention: Fluid retention during somatropin replacement therapy in adults may occur and are usually transient and dose dependent.
Hypothyroidism: Undiagnosed/untreated hypothyroidism may prevent an optimal response to somatropin, in particular, the growth response in children. Patients with Turner syndrome have an inherently increased risk of developing autoimmune thyroid disease and primary hypothyroidism. In patients with growth hormone deficiency, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Therefore, thyroid function should be periodically monitored in patients treated with somatropin.
Slipped Capital Femoral Epiphysis in Pediatric Patients: Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders or in patients undergoing rapid growth. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during somatropin therapy should be carefully evaluated.
Progression of Preexisting Scoliosis in Pediatric Patients: Progression of scoliosis can occur in patients who experience rapid growth. Somatropin has not been shown to increase the occurrence of scoliosis.
Reevaluation of Childhood Onset Adult GHD: Patients with epiphyseal closure who were treated with somatropin replacement therapy in childhood should be reevaluated before continuation of somatropin.
Local and Systemic Reaction: Injection site should be rotated to avoid tissue atrophy. Local or systemic allergic reactions may occur. Parents/Patient should be informed that such reactions are possible and that prompt medical attention should be sought if allergic reactions occur.
Hypopituitarism: Patients with hypopituitarism should have their other hormonal replacement therapy closely monitored during somatropin treatment.
Laboratory Tests: Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone (PTH), and IGF-1 may increase with somatropin therapy.
Pancreatitis: Cases of pancreatitis have been reported rarely in children and adults. Girls who have Turner syndrome 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.
Benzyl Alcohol: Benzyl alcohol, a component of this product, has been associated with serious adverse events and death, particularly in pediatric patients. The “gasping syndrome,” has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.
Growth Hormone Deficient Pediatric Patients: In clinical studies in which Saizen® was administered to growth hormone deficient children, the following events were infrequently seen: local reactions at the injection site (such as pain, numbness, redness and swelling), hypothyroidism, hypoglycemia, seizures, exacerbation of preexisting psoriasis and disturbances in fluid balance.
Growth Hormone Deficient Adult Patients: Arthralgia, myalgia, headache, peripheral edema, other types of edema, carpal tunnel syndrome, paraesthesia and hypoaesthesia were common (>5%) in the somatropin-treated patients and reported more frequently than in the placebo group. These types of adverse events are thought to be related to the fluid accumulating effects of somatropin. Hypothyroidism, chest pain, depression and insomnia were also reported in 5% of the treated patients. Abnormalities of glucose tolerance may occur.
Saizen® is a registered trademark of Merck KGaA, Darmstadt, Germany or its affiliates.