INDICATIONS AND USAGE:
Serostim � [somatropin (rDNA origin) for injection] is indicated for the treatment of AIDS wasting or cachexia. This indication is based on analyses of surrogate endpoints in studies of up to 12 weeks in duration. Concomitant anti-viral therapy is necessary (see PRECAUTIONS: General). The continued use of Serostim treatment should be reevaluated in patients who continue to lose weight in the first two weeks of treatment.

CONTRAINDICATIONS:
Growth hormone should not be initiated to treat patients with acute critical illness due to com-plications following open heart or abdominal surgery, multiple accidental trauma or to patients having acute respiratory fail-ure. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions revealed a significant increase in mortality (41.9% vs 19.3%) among somatropin treated patients (doses 5.3-8 mg/day) compared to those receiving placebo (see WARNINGS). Serostim � [somatropin (rDNA origin) for injection] is contraindicated in patients with a known hypersensitivity to growth hormone.

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 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.

PRECAUTIONS:
General: Serostim therapy should be carried out under the regular guidance of a physician who is expe-rienced in the diagnosis and management of AIDS. Inadequate nutritional intake, malabsorption and hypogonadism, which are common in individuals with AIDS and which may contribute to catabolism and weight loss, should also be monitored and treated.

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 sig-nificant growth hormone-associated increase in viral burden was observed. However, the protocol required all participants to be on concomitant nucleoside analogue 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 nucleoside analogue 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 reduc-ing 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 188 study participants with AIDS wasting who were evaluable for antibody assessments and who were treated with Serostim for the first time developed detectable antibodies to growth hormone (> 4 pg binding).

Patients were not rechallenged.

Recombinant Human Growth Hormone (r-hGH) has been associated with acute pancreatitis.

Hyperglycemia may occur in HIV-infected individuals due to a variety of reasons. Serostim use was associated with a min-imal increase of mean blood glucose concentration. Patients with other risk factors for glucose intolerance should be mon-itored closely during Serostim therapy.

No cases of intracranial hypertension (IH) have been observed among patients with AIDS wasting 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.

Information For Patients:
Patients being treated with Serostim should be informed of the potential benefits and risks asso-ciated with treatment. Patients should be instructed to contact their physician should they experience any side effects or discomfort during treatment with Serostim. It is recommended that Serostim be administered using sterile, disposable syringes and needles. Patients should be thoroughly instructed in the importance of proper disposal and cautioned against any reuse of needles and syringes. An appropriate container for the disposal of used syringes and needles should be employed.

Patients should be instructed to rotate injection sites to avoid lipodystrophy.

Drug Interactions:
Formal in vitro drug interaction studies have not been conducted. No data are available on drug inter-actions between Serostim and HIV protease inhibitors or the non-nucleoside reverse transcriptase inhibitors.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term animal studies for carcinogenicity have not been per-formed 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. These preliminary data collected in a limited number of patients with HIV associated fail-ure to thrive appear to be consistent with safety observations in growth hormone treated adults with AIDS wasting.

ADVERSE REACTIONS:
In two placebo-controlled clinical trials in which 205 patients were treated with Serostim the most common adverse reactions judged to be associated with Serostim were musculoskeletal discomfort and increased tissue turgor (swelling, particularly of the hands or feet) (see PRECAUTIONS: General). These symptoms were generally rated by investigators as mild to moderate in severity and usually subsided with continued treatment. Discontinuations as a result of these events were rare.

Because of the diverse clinical manifestations of AIDS, and the frequent occurrence of adverse events associated with underlying disease process, it was often difficult to distinguish adverse events possibly associated with the administration of Serostim from underlying signs or symptoms of AIDS or associated intercurrent illnesses.

Clinical adverse events which occurred during the first 12 weeks of study in at least 10% of those who received Serostim during the two placebo-controlled trials are listed below by treatment group, without regard to causality assessment.

For Table see PDF

Adverse events that occurred in 1% to less than 10% of study participants receiving Serostim in the two placebo-controlled clinical efficacy studies are listed below by body system. The list of adverse events has been compiled regardless of causal relationship to Serostim.

Body as a Whole: rigors, flu-like symptoms, back pain, malaise, asthenia, carpal tunnel syndrome (see PRECAUTIONS: General), chest pain, hot flashes, allergic reaction. Gastrointestinal System: oral leukoplakia, flatulence, dyspepsia, dry mouth, constipation, ulcerative stomatitis, increased amylase, dysphagia, esophagitis, colitis, pancreatitis, rectal disorder, gastritis, tongue ulceration, gingivitis. Musculoskeletal System: muscle weakness. Central and Peripheral Nervous System: dizziness, convulsions, hypertonia, neuralgia, tremor, encephalopathy, nystagmus, meningism. Respiratory System: dyspnea, coughing, sinusitis, upper respiratory tract infection, pharyngitis, rhinitis, pneumonia, bronchitis, increased sputum, respiratory disorder, bronchospasm, pneumonitis, pleurisy. White Blood Cell and Reticuloendothelial System Disorders: cervical lym-phadenopathy, eosinophilia. Skin and Appendages: skin disorder, folliculitis, rash, alopecia, photosensitivity reaction, erythematous rash, pruritus, abnormal pigmentation, seborrhea, dermatitis, skin ulceration, acne, skin discoloration, verruca.

Psychiatric: depression, anxiety, somnolence, nervousness, appetite increased, amnesia, abnormal thinking. Metabolic and

Nutritional: hypertriglyceridemia, increased alkaline phosphatase, dehydration, increased creatinine phosphokinase, increased LDH, glycosuria, hypokalemia, cachexia, thirst, acidosis. Immune System Dysfunction: moniliasis, bacterial infection, Pneumocystis carinii infection, viral infection, infection, Herpes simplex, sepsis, abscess, fungal infection, Herpes zoster.

Urinary System: hematuria, urinary tract infection, nocturia. Liver and Biliary System: abnormal hepatic function,
hepatomegaly, hepatitis. Vision: retinitis, abnormal vision, photophobia. Platelet, Bleeding and Clotting: thrombocytopenia, purpura. Cardiovascular, General: abnormal ECG, heart murmur, hypertension, hypotension. Application Site: injection site pain, injection site reaction. Neoplasms: Kaposi�s sarcoma. Male Reproductive: epididymitis, penis disorder, inguinal hernia.

Hearing and Vestibular: earache, ear disorder, decreasing hearing. Endocrine:gynecomastia, male breast pain. The types and incidences of adverse events reported in an open-label, extension trial and in a single, foreign trial, for up to one year, were not different from, or greater in frequency, than those observed in the primary, placebo-controlled, clinical trials.

OVERDOSAGE
Glucose intolerance can occur with overdosage. Long-term overdosage with growth hormone could result in signs and symptoms of acromegaly.

DOSAGE AND ADMINISTRATION
Serostim� [somatropin (rDNA origin) for injection] should be administered subcutaneously daily at bedtime according to the following dosage recommendations:

For Table see PDF

In patients who weigh less than 35 kg, Serostim should be administered at a dose of 0.1 mg/kg subcutaneously daily at bedtime.

Dose reductions for side effects felt to be related to treatment with Serostim, which are unresponsive to symptomatic treat-ment, may be effected by reducing the total daily dose or the number of doses given per week.

In patients who continue to lose weight at week 2, reevaluate for concurrent opportunistic infections or other clinical events.

\Injection sites should be rotated.

Safety and effectiveness in pediatric patients with AIDS have not been established.

Each vial of Serostim 4 mg, 5 mg or 6 mg is reconstituted with 1 mL sterile water for injection. To reconstitute Serostim, inject the diluent into the vial of Serostim aiming the liquid against the glass vial wall. Swirl the vial with a gentle rotary motion until contents are dissolved completely. The Serostim solution should be clear immediately after reconstitution. DO NOT INJECT Serostim if the reconstituted product is cloudy immediately after reconstitution or refrigeration. Occasionally, after refrigeration, small colorless particles may be present in the Serostim solution. This is not unusual for proteins like Serostim.

STABILITY AND STORAGE
Before reconstitution: Serostim should be stored at room temperature, 59� - 86�F (15� - 30�C). Expiration dates are stated on product labels.

After reconstitution: Use within 24 hours after reconstitution with diluent. The reconstituted solution should be stored under refrigerated conditions (36� - 46�F/2� - 8�C).

Sterile Diluent, 1 mL (Sterile Water for Injection, USP) should be stored at room temperature, 59� - 86�F (15� - 30�C). Avoid freezing vials of Serostim and Sterile Diluent.

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" That which does not kill me, will make me stronger"