The 5.8-mg and 13.8-mg presentations of GENOTROPIN Lyophilized Powder contain m-Cresol as a preservative. These products should not be used by patients with a known sensitivity to this preservative. The GENOTROPIN 1.5-mg and GENOTROPIN MINIQUICK presentations are preservative-free (see HOW SUPPLIED).
See CONTRAINDICATIONS for information on increased mortality in patients with acute critical illnesses in intensive care units due to complications following open heart or abdominal surgery, multiple accidental trauma, or with acute respiratory failure. The safety of continuing growth hormone 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 growth hormone in patients having acute critical illnesses should be weighed against the potential risk.
There have been reports of fatalities after initiating therapy with growth hormone 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 growth hormone. If during treatment with growth hormone 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 growth hormone should also have effective weight control and be monitored for signs of respiratory infections, which should be diagnosed as early as possible and treated aggressively (see CONTRAINDICATIONS).
Treatment with GENOTROPIN Lyophilized Powder, as with other growth hormone preparations, should be directed by physicians who are experienced in the diagnosis and management of patients with GHD or Prader-Willi syndrome (PWS), or those who were born small for gestational age (SGA).
Patients and caregivers who will administer GENOTROPIN in medically unsupervised situations should receive appropriate training and instruction on the proper use of GENOTROPIN from the physician or other suitably qualified health professional.
Patients with GHD secondary to an intracranial lesion should be examined frequently for progression or recurrence of the underlying disease process. Review of literature reports of pediatric use of somatropin replacement therapy reveals no relationship between this therapy and recurrence of central nervous system (CNS) tumors. In adults, it is unknown whether there is any relationship between somatropin treatment and CNS tumor recurrence.
Patients should be monitored carefully for any malignant transformation of skin lesions.
Caution should be used if growth hormone is administered to patients with diabetes mellitus, and insulin dosage may need to be adjusted. Patients with diabetes or glucose intolerance should be monitored closely during treatment with GENOTROPIN. Patients with risk factors for glucose intolerance, such as obesity (including obese patients with PWS) or a family history of Type II diabetes, should be monitored closely as well. Because growth hormone may induce a state of insulin resistance, patients should be observed for evidence of glucose intolerance.
In patients with hypopituitarism (multiple hormonal deficiencies) standard hormonal replacement therapy should be monitored closely when treatment with GENOTROPIN is instituted. Hypothyroidism may develop during treatment with GENOTROPIN, and inadequate treatment of hypothyroidism may prevent optimal response to GENOTROPIN. Therefore, patients should have periodic thyroid function tests and be treated with thyroid hormone when indicated.
Pediatric patients with endocrine disorders, including GHD, have a higher incidence of slipped capital femoral epiphyses. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during growth hormone therapy should be evaluated.
Progression of scoliosis can occur in patients who experience rapid growth. Because growth hormone increases growth rate, patients with a history of scoliosis who are treated with growth hormone should be monitored for progression of scoliosis. However, growth hormone has not been shown to increase the incidence of scoliosis. Scoliosis is commonly seen in untreated patients with PWS. Physicians should be alert to this abnormality, which may manifest during growth hormone therapy.
Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting has been reported in a small number of patients treated with growth hormone products. Symptoms usually occurred within the first 8 weeks of the initiation of growth hormone therapy. In all reported cases, IH-associated signs and symptoms resolved after termination of therapy or a reduction of the growth hormone dose. Funduscopic examination of patients is recommended at the initiation, and periodically during the course of, growth hormone therapy. Patients with PWS may be at increased risk for development of IH.
Before continuing treatment as an adult, a post-pubertal GHD patient who received growth hormone replacement therapy in childhood should be reevaluated with proper testing as described in INDICATIONS AND USAGE. If continued treatment is appropriate, GENOTROPIN should be administered at the reduced dose level recommended for adult GHD patients.
Concomitant glucocorticoid treatment may inhibit the growth-promoting effect of growth hormone. Pediatric GHD patients with coexisting ACTH deficiency should have their glucocorticoid replacement dose carefully adjusted to avoid an inhibitory effect on growth (see also PRECAUTIONS - General). Limited published data indicate that growth hormone treatment increases cytochrome P450 (CP450) mediated antipyrine clearance in man. These data suggest that growth hormone administration may alter the clearance of compounds known to be metabolized by CP450 liver enzymes (e.g. corticosteroids, sex steroids, anticonvulsants, cyclosporine). Careful monitoring is advisable when growth hormone is administered in combination with other drugs known to be metabolized by CP450 liver enzymes.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
Carcinogenicity studies have not been conducted with rhGH. No potential mutagenicity of rhGH was revealed in a battery of tests including induction of gene mutations in bacteria (the Ames test), gene mutations in mammalian cells grown in vitro (mouse L5178Y cells), and chromosomal damage in intact animals (bone marrow cells in rats). See PREGNANCY section for effect on fertility.
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.
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.
The safety and effectiveness of GENOTROPIN in patients aged 65 and over has not been evaluated in clinical studies. Elderly patients may be more sensitive to the action of GENOTROPIN and may be more prone to develop adverse reactions.