Saizen® (somatropin) for injection

Important Risk Information

CONTRAINDICATIONS

Saizen should not be used in patients with acute critical illness, Prader-Willi syndrome, active malignancy, hypersensitivity to somatropin or any of its excipients, diabetic retinopathy or papilledema, or with children with closed epiphyses. Saizen is reconstituted with Bacteriostatic Water for Injection and should not be administered to patients with a known sensitivity to benzyl alcohol.

WARNINGS AND PRECAUTIONS

Acute Critical Illness: Increased mortality has been reported in patients with acute critical illness due to complications following surgery, multiple accidental trauma, or acute respiratory failure.

Prader-Willi Syndrome: Fatalities have been reported in patients with Prader-Willi syndrome who were also obese or had history of an upper airway obstruction, sleep apnea, or unidentified respiratory infection.

Neoplasms: Patients with pre-existing tumors should be monitored for progression or reoccurrence, in particular, meningiomas. Monitor patients carefully for preexisting nevi.

Glucose Intolerance/Diabetes Mellitus: Previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked during treatment. Glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus.

Intracranial Hypertension: Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported. Funduscopic examination should be performed prior to initiating treatment with Saizen and periodically during the course of treatment. If papilledema is observed, treatment should be stopped and restarted at a lower dose after IH-associated symptoms have resolved.

Severe Hypersensitivity: Serious systemic hypersensitivity reactions including anaphylactic reactions 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.

Fluid Retention: Fluid retention in adults may occur. Clinical manifestations (e.g. edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias) are usually transient and dose dependent.

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.

Hypothyroidism: Patients should be monitored closely for the onset or worsening of hypothyroidism.

Slipped Capital Femoral Epiphysis and Progress of Preexisting Scoliosis: Slipped capital femoral epiphysis and progression of scoliosis may occur more frequently in patients undergoing rapid growth.

Reevaluation of Childhood Onset Adult GHD: Patients with epiphyseal closure who were treated with somatropin replacement therapy in childhood should be reevaluated.

Lipoatrophy: Rotate the injection site to avoid tissue atrophy. Inform patients that prompt medical attention should be sought if allergic reactions occur.

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. Consider pancreatitis in patients who develop persistent severe abdominal pain.

Benzyl Alcohol: Benzyl alcohol has been associated with serious adverse events including gasping syndrome and death, particularly in pediatric patients and neonates.

ADVERSE REACTIONS

Adverse events reported in pediatric GHD clinical studies included injection site reactions (such as pain, numbness, redness and swelling), hypothyroidism, hypoglycemia, seizures, exacerbation of preexisting psoriasis and fluid retention. Arthralgia, myalgia, headache, peripheral edema, other types of edema, carpal tunnel syndrome, paresthesia, hypoesthesia, and glucose intolerance were reported in >5% of patients of adult patients treated with Saizen.

SPECIAL POPULATIONS

Somatropin should be used during pregnancy only if clearly needed and with caution in nursing mothers because it is not known whether somatropin is excreted in human milk. The safety and effectiveness of somatropin in patients with hepatic or renal

Please see Saizen® Prescribing Information.

Saizen® is a registered trademark of Merck KGaA, Darmstadt, Germany or its affiliates.