Benzyl Alcohol as a preservative in Bacteriostatic Water for Injection, USP has been associated with toxicity in newborns. If sensitivity to the diluent occurs, Serostim® [somatropin (rDNA origin) for injection] may be reconstituted with Sterile Water for Injection, USP. When Serostim® is reconstituted in this manner, the reconstituted solution should be used immediately and any unused portion should be discarded.

See CONTRAINDICATIONS for information regarding increased mortality in growth hormone-treated patients with acute critical illnesses in intensive care units due to complications following open heart or abdominal surgery, multiple accidental trauma or 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 developing acute critical illnesses should be weighed against the potential risk.

General: Serostim® [somatropin (rDNA origin) for injection] therapy should be carried out under the regular guidance of a physician who is experienced in the diagnosis and management of HIV infection. Inadequate nutritional intake, malabsorption and hypogonadism, which are common in individuals with HIV infection and which may contribute to catabolism and weight loss, should be diagnosed and treated.

There are limited data in women with HARS, especially those taking estrogen. The 47 women treated with Serostim®, 6 of whom were taking estrogen, showed no difference from placebo with respect to reduction in VAT after 12 weeks of induction treatment. It is well established that GH deficient women concomitantly treated with oral estrogen replacement therapy require substantially more rhGH to obtain comparable rhGH-related treatment effects. In addition, women with HARS have lower baseline VAT levels; lower baseline VAT levels have been demonstrated by several authors to predict a lesser reduction in VAT in response to treatment with rhGH.

HIV and Growth Hormone Considerations: In some experimental systems, recombinant human growth hormone (r-hGH) has been shown to potentiate HIV replication in vitro at concentrations ranging from 50-250 ng/ml. There was no increase in virus production when the antiretroviral agents, zidovudine, didanosine or lamivudine were added to the culture medium. Additional in vitro studies have shown that r-hGH does not interfere with the antiviral activity of zalcitabine or stavudine. In the controlled clinical trials, no significant growth hormone-associated increase in viral burden was observed. However, the protocol required all participants to be on concomitant antiretroviral therapy for the duration of the study. In view of the potential for acceleration of virus replication, it is recommended that HIV patients be maintained on antiretroviral therapy for the duration of Serostim® treatment.

Increased tissue turgor (swelling, particularly in the hands and feet) and musculoskeletal discomfort (pain, swelling and/or stiffness) may occur during treatment with Serostim®, but may resolve spontaneously, with analgesic therapy, or after reducing the frequency of dosing (see DOSAGE AND ADMINISTRATION).

Carpal tunnel syndrome may occur during treatment with Serostim®. If the symptoms of carpal tunnel syndrome do not resolve by decreasing the weekly number of doses of Serostim®, it is recommended that treatment be discontinued.

Patients should be informed that allergic reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs. None of the 651 study participants with HIV-associated wasting treated with Serostim® for the first time developed detectable antibodies to growth hormone ( > 4 pg binding). Patients were not rechallenged. None of the Serostim®-treated HARS study participants with available test results developed detectable antibodies to rhGH during the induction or maintenance phases of treatment.

Recombinant human growth hormone (rhGH) has been associated with acute pancreatitis.

Hyperglycemia may occur in HIV infected individuals due to a variety of reasons. In wasting patients, treatment with Serostim® 0.1 mg/kg daily and 0.1 mg/kg every other day for 12 weeks was associated with approximately 10 mg/dL and 6 mg/dL increases in mean fasting blood glucose concentrations, respectively. The increases occurred early in treatment. Patients with other risk factors for glucose intolerance should be monitored closely during Serostim® therapy.

In HARS patients who had normal fasting glucose levels at screening, treatment with Serostim® 4 mg daily and 4 mg qod for 12 weeks (vs. placebo) was associated with approximately 7 and 6 mg/dL increases in mean fasting blood glucose concentrations, respectively. With respect to the induction phase, peak sugars on-study usually occurred early after initiation of Serostim® treatment, and, most often decreased spontaneously with continued Serostim® therapy or responded to dose reduction. Transient and occasionally sustained peak sugars between 100 and 126 mg/dL (and transient sugars in excess of 126 mg/dL) occurred in a substantial minority of patients (including patients with normal fasting blood glucose levels at baseline). Treatment with Serostim® 4 mg daily resulted in a greater number of glucose intolerance-related adverse reactions than treatment with Serostim® 4 mg qod (see ADVERSE REACTIONS). In HARS Study 2, hemoglobin A1c increased from a mean of 5.0% at baseline to 5.3% at Week 12 after treatment with Serostim® 4 mg daily, but it remained in the desirable range (less than 7.0%) in all patients. HARS patients are often insulin resistant and even glucose intolerant to some degree at baseline, and therefore are very susceptible to more overt glucose intolerance after treatment with large pharmacologic amounts of rhGH. Therefore, if HARS patients are treated with Serostim®, they should be very closely monitored for glucose intolerance.

During safety surveillance of patients with HIV-associated wasting and HARS, cases of new onset impaired glucose intolerance, new onset type 2 diabetes mellitus and exacerbation of preexisting diabetes mellitus have been reported in patients receiving Serostim®. Some patients developed diabetic ketoacidosis and diabetic coma. In some patients, these conditions improved when Serostim® was discontinued, while in others, the glucose intolerance persisted. Some of these patients required initiation or adjustment of antidiabetic treatment while on Serostim®.

No cases of intracranial hypertension (IH) have been observed among patients treated with Serostim®. The syndrome of IH, with papilledema, visual changes, headache, and nausea and/or vomiting has been reported in a small number of children with growth failure treated with growth hormone products. Nevertheless, funduscopic evaluation of patients is recommended at the initiation and periodically during the course of Serostim® therapy.

Kaposi's sarcoma, lymphoma, and other malignancies are common in HIV+ individuals. There was no increase in the incidence of Kaposi's sarcoma, lymphoma, or in the progression of cutaneous Kaposi's sarcoma in clinical studies of Serostim®. Patients with internal KS lesions were excluded from the studies. Potential effects on other malignancies are unknown.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term animal studies for carcinogenicity have not been performed with Serostim®. There is no evidence from animal studies to date of Serostim®-induced mutagenicity or impairment of fertility.

Pregnancy: Pregnancy Category B. Reproduction studies have been performed in rats and rabbits. Doses up to 5 to 10 times the human dose, based on body surface area, have revealed no evidence of impaired fertility or harm to the fetus due to Serostim®. 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 Women: It is not known whether Serostim® is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Serostim® is administered to a nursing woman.

Pediatric Use: In two small studies, 11 children with HIV-associated failure to thrive were treated subcutaneously with human growth hormone. In one study, five children (age range, 6 to 17 years) were treated with 0.04 mg/kg/day for 26 weeks. In a second study, six children (age range, 8 to 14 years) were treated with 0.07 mg/kg/day for 4 weeks. Treatment appeared to be well tolerated in both studies. The preliminary data collected on a limited number of patients with HIV-associated failure to thrive appear to be consistent with safety observations in growth hormone-treated adults with AIDS wasting.

Geriatric Use: Clinical studies with Serostim® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients may be more sensitive to growth hormone action, and may be more prone to develop adverse reactions. Thus, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range.

Bookmark this page: