WARNINGS
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.
Benzyl alcohol as a preservative in Bacteriostatic Water for Injection, USP, has been associated with toxicity in newborns. When administering Nutropin to newborns, reconstitute with Sterile Water for Injection, USP. USE ONLY ONE DOSE PER NUTROPIN VIAL AND DISCARD THE UNUSED PORTION.
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 infection, which should be diagnosed as early as possible and treated aggressively (see CONTRAINDICATIONS). Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Nutropin is not indicated for the long-term treatment of pediatric patients who have growth failure due to genetically confirmed Parader-Willi syndrome.
PRECAUTIONS
General: Nutropin should be prescribed by physicians experienced in the diagnosis and management of patients with GH deficiency, Turner syndrome, or chronic renal insufficiency. No studies have been completed of Nutropin therapy in patients who have received renal transplants. Currently, treatment of patients with functioning renal allografts is not indicated.
Experience with prolonged rhGH treatment in adults is limited.
Geriatric Usage: Clinical studies of Nutropin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Patients with epiphyseal closure who were treated with GH-replacement therapy in childhood should be re-evaluated according to the criteria in the INDICATIONS AND USAGE section before continuation of GH therapy at the reduced dose level recommended for GH-deficient adults.
Because Nutropin may reduce insulin sensitivity, patients should be monitored for evidence of glucose intolerance.
For patients with diabetes mellitus, the insulin dose may require adjustment when GH therapy is instituted. Because GH may reduce insulin sensitivity, particularly in obese individuals, patients should be observed for evidence of glucose intolerance. Patients with diabetes or glucose intolerance should be monitored closely during GH therapy.
Nutropin therapy in adults with GHD of adult onset was associated with an increase of median fasting insulin in the Nutropin 0.0125 mg/kg/day group from 9.0 µU/mL at baseline to 13.0 µU/mL at Month 12 with a return to the baseline median after a 3-week post-washout period off GH therapy. In the placebo group there was no change from 8.0 µU/mL at baseline to Month 12, and after the post-washout the median was 9.0 µU/mL. The between-treatment-groups difference in change from baseline to Month 12 was significant, p<0.0001. In childhood-onset subjects, there was a change of median fasting insulin in the Nutropin 0.025 mg/kg/day group from 11.0 µU/mL at baseline to 20.0 µU/mL at Month 12, in the Nutropin 0.0125 mg/kg/day group from 8.5 µU/mL to 11.0 µU/mL, and in the placebo group from 7.0 µU/mL to 8.0 µU/mL. The between-treatment-groups difference for these changes was significant, p=0.0007.
In subjects with adult-onset GHD, there was no between-treatment-group difference in changes from baseline to Month 12 in mean HbAIc, p=0.08. In childhood-onset, mean HbAIc increased in the Nutropin 0.025 mg/kg/day group from 5.2% at baseline to 5.5% at Month 12, and did not change in the Nutropin 0.0125 mg/kg/day group from 5.1% at baseline or in the placebo group from 5.3% at baseline. The between-treatment-groups difference was significant, p=0.009.
Patients with a history of an intracranial lesion should be examined frequently for progression or recurrence of the lesion. In pediatric patients, clinical literature has demonstrated no relationship between GH-replacement therapy and central nervous system (CNS) tumor recurrence or new extracranial tumors. In adults, it is unknown whether there is any relationship between GH-replacement therapy and CNS tumor recurrence.
Patients with growth failure secondary to chronic renal insufficiency should be examined periodically for evidence of progression of renal osteodystrophy. Slipped capital femoral epiphysis or avascular necrosis of the femoral head may be seen in children with advanced renal osteodystrophy, and it is uncertain whether these problems are affected by GH therapy. X-rays of the hip should be obtained prior to initiating GH therapy for CRI patients. Physicians and parents should be alert to the development of a limp or complaints of hip or knee pain in patients treated with Nutropin.
Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders or in patients undergoing rapid growth.
Progression of scoliosis can occur in patients who experience rapid growth. Because GH increases growth rate, patients with a history of scoliosis who are treated with GH should be monitored for progression of scoliosis. GH has not been shown to increase the incidence of scoliosis. Skeletal abnormalities including scoliosis are commonly seen in untreated Turner syndrome patients. Physicians should be alert to these abnormalities, which may manifest during GH therapy.
Patients with Turner syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear or hearing disorders. In a randomized, controlled trial, there was a statistically significant increase, as compared to untreated controls, in otitis media (43% vs. 26%) and ear disorders (18% vs. 5%) in patients receiving GH. In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders (e.g., stroke, aortic aneurysm, hypertension) as these patients are also at risk for these conditions.
Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in a small number of patients treated with GH products. Symptoms usually occurred within the first eight (8) weeks of the initiation of GH therapy. In all reported cases, IH-associated signs and symptoms resolved after termination of therapy or a reduction of the GH dose. Funduscopic examination of patients is recommended at the initiation and periodically during the course of GH therapy. Patients with CRI and Turner syndrome may be at increased risk for development of IH.
See WARNINGS for use of Bacteriostatic Water for Injection, USP, (benzyl alcohol preserved), in newborns.
As with any protein, local or systemic allergic reactions may occur. Parents/Patient 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, and parathyroid hormone (PTH) may increase with Nutropin therapy.
Untreated hypothyroidism prevents optimal response to Nutropin. Patients with Turner syndrome have an inherently increased risk of developing autoimmune thyroid disease. Changes in thyroid hormone laboratory measurements may develop during Nutropin treatment. Therefore, patients should have periodic thyroid function tests and should be treated with thyroid hormone when indicated.
Drug Interactions: Excessive glucocorticoid therapy will inhibit the growth-promoting effect of human GH. Patients with ACTH deficiency should have their glucocorticoid-replacement dose carefully adjusted to avoid an inhibitory effect on growth.
The use of Nutropin in patients with chronic renal insufficiency receiving glucocorticoid therapy has not been evaluated. Concomitant glucocorticoid therapy may inhibit the growth-promoting effect of Nutropin. If glucocorticoid replacement is required, the glucocorticoid dose should be carefully adjusted.
There was no evidence in the controlled studies of Nutropin's interaction with drugs commonly used in chronic renal insufficiency patients. Limited published data indicate that GH treatment increases cytochrome P450 (CP450) mediated antipyrine clearance in man. These data suggest that GH administration may alter the clearance of compounds known to be metabolized by CP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, cyclosporin). Careful monitoring is advisable when GH is administered in combination with other drugs known to be metabolized by CP450 liver enzymes.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenicity, mutagenicity, and reproduction studies have not been conducted with Nutropin.
Pregnancy: Pregnancy (Category C). Animal reproduction studies have not been conducted with Nutropin. It is also not known whether Nutropin can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Nutropin should be given to a pregnant woman only if clearly needed.
Nursing Mothers: It is not known whether Nutropin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Nutropin is administered to a nursing mother.
Information for Patients: Patients being treated with GH and/or their parents should be informed of the potential benefits and risks associated with treatment. If home use is determined to be desirable by the physician, instructions on appropriate use should be given, including a review of the contents of the Patient Information Insert. This information is intended to aid in the safe and effective administration of the medication. It is not a disclosure of all possible adverse or intended effects.
If home use is prescribed, a puncture-resistant container for the disposal of used syringes and needles should be recommended to the patient. Patients and/or parents should be thoroughly instructed in the importance of proper disposal and cautioned against any reuse of needles and syringes (see Patient Information Insert).
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