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]. 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.
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.
Male patients with one or more of these factors may be at greater risk than females.
Patients with Prader-Willi 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 Prader-Willi syndrome
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].
Neoplasms
Patients with preexisting tumors or growth hormone deficiency secondary to an intracranial lesion
should be examined routinely for progression or recurrence of the underlying disease process.
In pediatric patients, clinical literature has revealed no relationship between somatropin
replacement therapy and central nervous system (CNS) tumor recurrence or new extracranial tumors.
However, in childhood cancer survivors, an increased risk of a second neoplasm has been reported
in patients treated with somatropin 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 adults, it is unknown whether there is any relationship between
somatropin replacement therapy and CNS tumor recurrence.
Patients should be monitored carefully for any malignant transformation of skin lesions.
Glucose Intolerance
Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses in
susceptible patients. As a result, previously undiagnosed impaired glucose tolerance and overt
diabetes mellitus may be unmasked during somatropin treatment. 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. The doses of antihyperglycemic
drugs (i.e., insulin or oral agents) may require adjustment when somatropin therapy is instituted
in these patients.
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 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.
Clinical manifestations of fluid retention are usually transient and dose dependent.
Hypopituitarism
Patients with hypopituitarism (multiple pituitary hormone deficiencies) should have their other hormonal
replacement treatments closely monitored during somatropin treatment.
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, patients treated with somatropin should
have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated
or appropriately adjusted when indicated.
Slipped Capital Femoral Epiphyses in Pediatric Patients
Slipped capital femoral epiphyses may occur more frequently in patients with endocrine disorders
(including GHD and Turner syndrome) 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.
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 Turner syndrome patients. Scoliosis is also commonly seen in untreated patients
with Prader-Willi syndrome. Physicians should be alert to these abnormalities, which may manifest
during somatropin therapy.
Otitis Media and Cardiovascular Disorders in Turner Syndrome
Patients with Turner syndrome should be evaluated carefully for otitis media and other ear
disorders since these patients have an increased risk of ear and hearing disorders.
Somatropin treatment may increase the occurrence of otitis media in patients with Turner syndrome.
In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders
(e.g., stroke, aortic aneurysm/dissection, hypertension) as these patients are also at risk for these conditions.
Local and Systemic Reactions
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].
As with any protein, local or systemic allergic reactions may occur. Parents/Patients should be
informed that such reactions are possible and 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-I may increase during somatropin therapy.
DRUG INTERACTIONS
11 β-Hydroxysteroid Dehydrogenase Type 1
The 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. GH and somatropin inhibit
11βHSD-1. Consequently, individuals with untreated GH deficiency have relative increases in 11βHSD-1 and
serum cortisol. Introduction of somatropin treatment may result in inhibition of 11βHSD-1 and reduced serum
cortisol concentrations. As a consequence, previously undiagnosed central (secondary) hypoadrenalism may be
unmasked and glucocorticoid replacement may be required in patients treated with somatropin. 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; this may be
especially true for patients treated with cortisone acetate and prednisone since conversion of these drugs
to their biologically active metabolites is dependent on the activity of 11βHSD-1.
Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocortioid Treatment
Pharmacologic glucocorticoid therapy and supraphysiologic glucocorticoid treatment may attenuate the growth
promoting effects of somatropin in children. Therefore, glucocorticoid replacement dosing should be carefully
adjusted in children receiving concomitant somatropin and glucocorticoid treatments to avoid both hypoadrenalism
and an inhibitory effect on growth.
Cytochrome P450-Metabolized Drugs
Limited published data indicate that somatropin treatment increases cytochrome P450 (CYP450)-mediated
antipyrine clearance in man. These data suggest that somatropin administration may alter the clearance
of compounds known to be metabolized by CYP450 liver enzymes (e.g., corticosteroids, sex steroids,
anticonvulsants, cyclosporine). Careful monitoring is advisable when somatropin is administered in
combination with other drugs known to be metabolized by CYP450 liver enzymes.
However, formal drug interaction studies have not been conducted.
Oral Estrogen
In patients on oral estrogen replacement, a larger dose of somatropin may be required to achieve the
defined treatment goal [see Dosage and Administration].
Insulin and/or Oral Hypoglycemic Agents
In patients with diabetes mellitus requiring drug therapy, the dose of insulin and/or oral agent
may require adjustment when somatropin therapy is initiated [see Warnings and Precautions].
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category B. Reproduction studies carried out with GENOTROPIN at doses of 0.3, 1, and
3.3 mg/kg/day administered SC in the rat and 0.08, 0.3, and 1.3 mg/kg/day administered intramuscularly
in the rabbit (highest doses approximately 24 times and 19 times the recommended human therapeutic
levels, respectively, based on body surface area) resulted in decreased maternal body weight gains but
were not teratogenic. In rats receiving SC doses during gametogenesis and up to 7 days of pregnancy,
3.3 mg/kg/day (approximately 24 times human dose) produced anestrus or extended estrus cycles in
females and fewer and less motile sperm in males. When given to pregnant female rats (days 1 to 7 of
gestation) at 3.3 mg/kg/day a very slight increase in fetal deaths was observed. At 1 mg/kg/day
(approximately seven times human dose) rats showed slightly extended estrus cycles, whereas at
0.3 mg/kg/day no effects were noted.
In perinatal and postnatal studies in rats, GENOTROPIN doses of 0.3, 1, and 3.3 mg/kg/day produced
growth-promoting effects in the dams but not in the fetuses. Young rats at the highest dose showed
increased weight gain during suckling but the effect was not apparent by 10 weeks of age.
No adverse effects were observed on gestation, morphogenesis, parturition, lactation, postnatal
development, or reproductive capacity of the offsprings due to GENOTROPIN.
There are, however, no adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response, this drug should
be used during pregnancy only if clearly needed.
Nursing Mothers
There have been no studies conducted with GENOTROPIN in nursing mothers. It is not known whether this
drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be
exercised when GENOTROPIN is administered to a nursing woman.
Geriatric Use
The safety and effectiveness of GENOTROPIN in patients aged 65 and over have not been evaluated in
clinical studies. Elderly patients may be more sensitive to the action of GENOTROPIN, and therefore
may be more prone to develop adverse reactions. A lower starting dose and smaller dose increments
should be considered for older patients [see Dosage and Administration].
PATIENT COUNSELING INFORMATION
Patients being treated with GENOTROPIN (and/or their parents) should be informed about the potential benefits and
risks associated with GENOTROPIN treatment [in particular, see Adverse Reactions for a listing of the
most serious and/or most frequently observed adverse reactions associated with somatropin treatment in
children and adults]. This information is intended to better educate patients (and caregivers);
it is not a disclosure of all possible adverse or intended effects.
Patients and caregivers who will administer GENOTROPIN should receive appropriate training and
instruction on the proper use of GENOTROPIN from the physician or other suitably qualified health
care professional. A puncture-resistant container for the disposal of used syringes and needles
should be strongly recommended. Patients and/or parents should be thoroughly instructed in the
importance of proper disposal, and cautioned against any reuse of needles and syringes.
This information is intended to aid in the safe and effective administration of the medication.
GENOTROPIN is supplied in a two-chamber cartridge, with the lyophilized powder in the front chamber and
a diluent in the rear chamber. A reconstitution device is used to mix the diluent and powder.
The two-chamber cartridge contains overfill in order to deliver the stated amount of GENOTROPIN
The GENOTROPIN 5 mg and 12 mg cartridges are color-coded to help ensure proper use with the
GENOTROPIN Pen delivery device. The 5 mg cartridge has a green tip to match the green pen window on
the Pen 5, while the 12 mg cartridge has a purple tip to match the purple pen window on the Pen 12.
Follow the directions for reconstitution provided with each device. Do not shake; shaking may
cause denaturation of the active ingredient.
Please see accompanying directions for use of the reconstitution and/or delivery device.