Somatropin

HUMATROPE is a recombinant human growth hormone indicated for: Pediatric Patients: growth failure due to inadequate secretion of endogenous growth hormone (GH), short stature associated with Turner syndrome, Idiopathic Short Stature (ISS), height standard deviation score (SDS) <-2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range, short stature or growth failure in short stature homeobox-containing gene (SHOX) deficiency, short stature born small for gestational age (SGA) with no catch-up growth by 2 years to 4 years of age. Adult Patients: replacement of endogenous GH in adults with GH deficiency.

Somatropin binds to dimeric GH receptors located within the cell membranes of target tissue cells. This interaction results in intracellular signal transduction and subsequent induction of transcription and translation of GH-dependent proteins including IGF-1, IGF BP-3 and acid-labile subunit. Somatropin has direct tissue and metabolic effects or mediated indirectly by IGF-1, including stimulation of chondrocyte differentiation, and proliferation, stimulation of hepatic glucose output, protein synthesis and lipolysis. Somatropin stimulates skeletal growth in pediatric patients with GHD as a result of effects on the growth plates (epiphyses) of long bones. The stimulation of skeletal growth increases linear growth rate (height velocity) in most somatropin-treated pediatric patients. Linear growth is facilitated in part by increased cellular protein synthesis.

Administer by subcutaneous injection to the back of upper arm, abdomen, buttock, or thigh with regular rotation of injection sites. Pediatric Dosage - divide the calculated weekly dosage into equal doses given either 6, or 7 days per week. GHD: 0.18 mg/kg/week to 0.3 mg/kg/week. Turner Syndrome: Up to 0.375 mg/kg/week. ISS: Up to 0.37 mg/kg/week. SHOX Deficiency: 0.35 mg/kg/week. SGA: Up to 0.47 mg/kg/week. Adult Dosage - Either of the following two dosing regimens may be used: Non-weight based dosing: Initiate with a dose of approximately 0.2 mg/day (range: 0.15 mg/day-0.3 mg/day) and increase the dose every 1-2 months by increments of approximately 0.1 mg/day-0.2 mg/day, according to individual patient requirements.

HUMATROPE is contraindicated in patients with: 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 use of pharmacologic doses of somatropin. Pediatric patients with 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. Active malignancy. Known hypersensitivity to somatropin or any of the excipients in HUMATROPE. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropins.

Increased Risk of Neoplasm: Second neoplasms have occurred in childhood cancer survivors. Monitor patients with preexisting tumors for progression or recurrence. Glucose Intolerance and Diabetes Mellitus: HUMATROPE may decrease insulin sensitivity, particularly at higher doses. Monitor glucose levels periodically in all patients receiving HUMATROPE, especially in patients with existing diabetes mellitus or at risk for development. Intracranial Hypertension (IH): Has been reported usually within 8 weeks of initiation. Perform fundoscopic examinations prior to initiation and periodically thereafter. If papilledema occurs, stop treatment. Hypersensitivity: Serious hypersensitivity reactions may occur. In the event of an allergic reaction, seek prompt medical attention. Fluid Retention: May occur in adults and may be dose dependent.

The following important adverse reactions are also described elsewhere in the labeling: Increased mortality in patients with acute critical illness Fatalities in children with Prader-Willi syndrome Neoplasms Glucose intolerance and diabetes mellitus Intracranial hypertension Severe hypersensitivity Fluid retention Hypoadrenalism Hypothyroidism Slipped capital femoral epiphysis in pediatric patients Progression of preexisting scoliosis in pediatric patients Pancreatitis Lipoatrophy Common adverse reactions reported in adult and pediatric patients include: upper respiratory infection, fever, pharyngitis, headache, otitis media, edema, arthralgia, paresthesia, myalgia, carpal tunnel syndrome, peripheral edema, flu syndrome, hypothyroidism, hyperglycemia, and impaired glucose tolerance.

Table 8 includes a list of drugs with clinically important drug interactions when administered concomitantly with HUMATROPE and instructions for preventing or managing them. Table 8: Clinically Important Drug Interactions with HUMATROPE 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. HUMATROPE inhibits 11βHSD-1. Consequently, individuals with untreated GH deficiency have relative increases in 11βHSD-1 and serum cortisol. Initiation of HUMATROPE 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 HUMATROPE.

Store in the original carton to protect HUMATROPE from light.