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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).

ADVERSE REACTIONS

As with all protein pharmaceuticals, a small percentage of patients may develop antibodies to the protein. GH antibody binding capacities below 2 mg/L have not been associated with growth attenuation. In some cases when binding capacity exceeds 2 mg/L, growth attenuation has been observed. In clinical studies of pediatric patients that were treated with Nutropin® [somatropin (rDNA origin) for injection] for the first time, 0/107 growth hormone-deficient (GHD) patients, 0/125 CRI patients, and 0/112 syndrome patients screened for antibody production developed antibodies with binding capacities >/=2 mg/L at six months. In a clinical study of patients that were treated with Saizen® [somatropin (rDNA origin) injection] for the first time, 0/38 GHD patients screened for antibody production, for up to 15 months, developed antibodies with binding capacities >/=2 mg/L.

Additional short-term immunologic and renal function studies were carried out in a group of patients with chronic renal insufficiency after approximately one year of treatment to detect other potential adverse effects of antibodies to GH. Testing included measurements of C1q, C3, C4, rheumatoid factor, creatinine, creatinine clearance, and BUN. No adverse effects of GH antibodies were noted.

In addition to an evaluation of compliance with the prescribed treatment program and thyroid status, testing for antibodies to GH should be carried out in any patient who fails to respond to therapy.

Injection site discomfort has been reported. This is more commonly observed in children switched from another GH product to Saizen. Experience with Saizen in adults is limited.

Leukemia has been reported in a small number of GHD patients treated with GH. It is uncertain whether this increased risk is related to the pathology of GH deficiency itself, GH therapy, or other associated treatments such as radiation therapy for intracranial tumors. On the basis of current evidence, experts cannot conclude that GH therapy is responsible for these occurrences. The risk to GHD, CRI, or syndrome patients, if any, remains to be established.

Other adverse drug reactions that have been reported in GH-treated patients include the following: 1) Metabolic: Mild, transient peripheral edema. In GHD adults, edema or peripheral edema was reported in 41% of GH-treated patients and 25% of placebo-treated patients. 2) Musculoskeletal: Arthralgias; carpal tunnel syndrome. In GHD adults, arthralgias and other joint disorders were reported in 27% of GH-treated patients and 15% of placebo-treated patients. 3) Skin: Rare increased growth of pre-existing nevi; patients should be monitored for malignant transformation. 4) Endocrine: Gynecomastia. Rare pancreatitis.

OVERDOSAGE

Acute overdosage could lead to hyperglycemia. Long-term overdosage could result in signs and symptoms of gigantism and/or acromegaly consistent with the known effects of excess GH. (See recommended and maximal dosage instructions given below.)

DOSAGE AND ADMINISTRATION

The Saizen dosage and administration schedule should be individualized for each patient. Response to GH therapy in pediatric patients tends to decrease with time. However, in pediatric patients failure to increase growth rate, particularly during the first year of therapy, suggests the need for close assessment of compliance and evaluation of other causes of growth failure, such as hypothyroidism, under-nutrition, and advanced bone age.

Dosage

Pediatric Growth Hormone Deficiency (GHD)

A weekly dosage of up to 0.30 mg/kg of body weight divided into daily subcutaneous injection is recommended.

Adult Growth Hormone Deficiency (GHD)

The recommended dosage at the start of therapy is not more than 0.006 mg/kg given as a daily subcutaneous injection. The dose may be increased according to individual patient requirements to a maximum of 0.025 mg/kg daily in patients under 35 years and to a maximum of 0.0125 mg/kg daily in patients over 35 years.

To minimize the occurrence of adverse events in older or overweight patients, lower doses may be necessary. During therapy, dosage should be decreased if required by the occurrence of side effects or excessive IGF-I levels.

Chronic Renal Insufficiency (CRI)

A weekly dosage of up to 0.35 mg/kg of body weight divided into daily subcutaneous injection is recommended.

Saizen therapy may be continued up to the time of renal transplantation.

In order to optimize therapy for patients who require dialysis, the following guidelines for injection schedule are recommended:

Hemodialysis patients should receive their injection at night just prior to going to sleep or at least 3-4 hours after their hemodialysis to prevent hematoma formation due to the heparin.

Chronic Cycling Peritoneal Dialysis (CCPD) patients should receive their injection in the morning after they have completed dialysis.

Chronic Ambulatory Peritoneal Dialysis (CAPD) patients should receive their injection in the evening at the time of the overnight exchange.

Syndrome

A weekly dosage of up to 0.375 mg/kg of body weight divided into equal doses 3 to 7 times per week by subcutaneous injection is recommended.

Administration

The solution should be clear immediately after removal from the refrigerator. Occasionally, after refrigeration, you may notice that small colorless particles of protein are present in the solution. This is not unusual for solutions containing proteins. Allow the vial to come to room temperature and gently swirl. If the solution is cloudy, the contents MUST NOT be injected.

Before needle insertion, wipe the septum of the Saizen vial with rubbing alcohol or an antiseptic solution to prevent contamination of the contents by microorganisms that may be introduced by repeated needle insertions. It is recommended that Saizen be administered using sterile, disposable syringes and needles. The syringes should be of small enough volume that the prescribed dose can be drawn from the vial with reasonable accuracy.

STABILITY AND STORAGE

Vial contents are stable for 28 days after initial use when stored at 2-8°C/36-46°F (under refrigeration). Avoid freezing the vial of Saizen.

HOW SUPPLIED

Saizen is supplied as 10 mg (approximately 30 IU) of sterile liquid somatropin per vial.

Each carton contains six single vial cartons containing one 2 mL vial of Saizen® [somatropin (rDNA origin) injection] (5 mg/mL). NDC 50242-114-11.

Saizen® [somatropin (rDNA origin) injection]

manufactured by:

Genentech, Inc.

1 DNA Way

South San Francisco, CA 94080-4990

4810903

© 1999 Genentech, Inc. Revised January 1999