Included as part of the PRECAUTIONS section.
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]. 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 5.3-8 mg/day) compared to those receiving
placebo. 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 experiencing 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 (including onset of or increased snoring) 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].
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 [see CONTRAINDICATIONS]. 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 [see CONTRAINDICATIONS].
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 carefully monitored for development of neoplasms.
Monitor patients on somatropin therapy carefully for
increased growth, or potential malignant changes, of preexisting nevi.
Impaired Glucose Tolerance And Diabetes Mellitus
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, and new onset type 2 diabetes mellitus has been reported in
patients taking somatropin. 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. [See DRUG INTERACTIONS]
Intracranial Hypertension (IH)
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.
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 [see CONTRAINDICATIONS].
Fluid retention during somatropin replacement therapy in
adults may frequently occur. Clinical manifestations of fluid retention (e.g.
edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel
syndrome/paraesthesias) are usually transient and dose dependent.
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 treatment [see DRUG INTERACTIONS, 11-β
Hydroxysteroid Dehydrogenase Type 1]
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 and should have their
thyroid function checked prior to initiation of somatropin therapy. In patients
with GHD, 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 Epiphysis In Pediatric Patients
Slipped capital femoral epiphysis 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
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
Confirmation Of Childhood Onset Adult GHD
Patients with epiphyseal closure who were treated with
somatropin replacement therapy in childhood should be reevaluated according to
the criteria in Indications and Usage (1.2) before continuation of somatropin
therapy at the reduced dose level recommended for GH deficient adults.
Otitis Media And Cardiovascular Disorders In Turner
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.
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].
Serum levels of inorganic phosphorus, alkaline
phosphatase, parathyroid hormone (PTH) and IGF-I may increase after somatropin
Cases of pancreatitis have been reported rarely in
children and adults receiving somatropin treatment, with some evidence
supporting a greater risk in children compared with adults. Published
literature indicates that 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, a component of Omnitrope Cartridge 5
mg/1.5 mL and the diluent for Omnitrope for injection 5.8 mg/vial, has been
associated with serious adverse events and death, particularly in pediatric
patients. The “gasping syndrome,” (characterized by central nervous system
depression, metabolic acidosis, gasping respirations, and high levels of benzyl
alcohol and its metabolites found in the blood and urine) 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.
Patient Counseling Information
See FDA-approved patient
labeling (Instructions For Use: Omnitrope Pen 5 Instructions For Use, Omnitrope
Pen 10 Instructions For Use, Instructions For Omnitrope 5.8 mg/Vial).
Patients being treated with
Omnitrope (and/or their parents) should be informed about the potential risks
and benefits associated with somatropin treatment. 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 Omnitrope
should receive appropriate training and instruction on the proper use of
Omnitrope 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. Counsel patients and parents that
they should never share an Omnitrope Pen with another person, even if the
needle is changed. Sharing of the pen between patients may pose a risk of
transmission of infection.
If patients are prescribed Omnitrope Cartridge 5 mg/1.5
mL or 10 mg/1.5 mL (to be inserted into Omnitrope Pen 5 or Pen 10 delivery
systems), physicians should instruct patients to read the corresponding Instructions
For Use provided with the Omnitrope Pens delivery systems and the Omnitrope
If patients are prescribed Omnitrope for injection,
physicians should instruct patients to read the Instructions For Use leaflets
provided with the Omnitrope for injection 5.8 mg/vial.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenicity, mutagenicity, and fertility studies have
not been conducted with Omnitrope See Use in Specific Populations for
effect on fertility.
Use In Specific Populations
Pregnancy Category B
Animal reproduction studies have not been conducted with
Omnitrope. It is not known whether Omnitrope can cause fetal harm when
administered to a pregnant woman or can affect reproductive capacity.
Reproduction studies carried out with another somatropin
product at doses of 0.3, 1, and 3.3 mg/kg/day administered subcutaneously 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 subcutaneous 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, doses of 0.3,
1, and 3.3 mg/kg/day of this other somatropin product 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
offspring due to this other somatropin product. 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.
It is not known whether Omnitrope is excreted in human
milk. Because many drugs are excreted in human milk, caution should be
exercised when Omnitrope is administered to a nursing woman.
The safety and effectiveness of Omnitrope in patients
aged 65 and over have not been evaluated in clinical studies. Elderly patients
may be more sensitive to the action of somatropin, 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