anyone ever use Geref here

FROM THEIR FILES _ LOOKS INTERESTING BUT I AM WONDERING ABOUT RESULTS COMPARED TO GROWTH.

For subcutaneous injection only
DESCRIPTION
Sermorelin acetate is the acetate salt of an amidated synthetic 29-amino acid peptide (GRF 1-29 NH2 ) that corresponds to the amino-ter-minal
segment of the naturally occurring human growth hormone-releasing hormone (GHRH or GRF) consisting of 44 amino acid residues.
The structural formula for sermorelin acetate is:
Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-
Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-
Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2 • (C2 H4 O2 ) 3-6
The free base of sermorelin has the empirical formula C149 H246 N44 O42 S and a molecular weight of 3,358 daltons.
Geref® is a sterile, non-pyrogenic, lyophilized powder intended for subcutaneous injection after reconstitution with Sodium Chloride
Injection, USP. The reconstituted solution has a pH of 5.0 to 5.5.
Geref® is available in vials. The quantitative composition per vial is:
0.5 mg vial: Each vial contains 0.5 mg sermorelin (as the acetate) and 5 mg mannitol. The pH is adjusted with dibasic sodium phosphate
and monobasic sodium phosphate buffer.
1.0 mg vial: Each vial contains 1.0 mg sermorelin (as the acetate) and 5 mg mannitol. The pH is adjusted with dibasic sodium phosphate
and monobasic sodium phosphate buffer.
CLINICAL PHARMACOLOGY
Geref® (sermorelin acetate for injection) increases plasma growth hormone (GH) concentration by stimulating the pituitary gland to
release GH. Geref® is similar to the native hormone (GRF [1-44]-NH2 ) in its ability to stimulate GH secretion in humans.
Pharmacokinetics
Absorption
In subcutaneous administration of 2 mg sermorelin to 12 normal volunteers, peak concentrations of sermorelin were reached in 5-20
minutes. The mean absolute bioavailability after SC administration is about 6%.
Distribution
After intravenous administration of 0.25-1.0 mg Geref® to 12 normal volunteers, the mean volume of distribution ranged between 23.7-
25.8 liters.
Metabolism
No metabolism studies have been performed in humans.
Elimination
Sermorelin is rapidly cleared from the circulation, with clearance values in adults ranging between 2.4-2.8 L/min. The half life of Geref®
is short, 11-12 minutes after either intravenous or subcutaneous administration.
Special Populations
Gender/Age: No gender data are available in pediatric patients. In normal adults, the clearance of sermorelin in men and women is similar.
No age data are available.
Renal/Hepatic Insufficiency: No data are available.
CLINICAL STUDIES
In one multicenter, open-label clinical study in prepubertal children with idiopathic growth hormone deficiency, 110 children were adminis-tered
Geref® 0.03 mg (30 mcg) per kg per day by subcutaneous injection. Fifty-six patients were evaluable for efficacy at 12 months. Fifty-four
patients were considered unevaluable: 24 for eligibility criteria violations; 10 for protocol discontinuation criteria
1
and 20 for failing to satis-fy
the efficacy criteria at 6 months for continuing in the study. Fifty-six of all 110 patients and 47 of 56 patients in the evaluable patient subset
who initiated and continued with Geref® therapy up to 12 months demonstrated an increase of 2 cm/year or more over the baseline height
velocity (HV). For the 56 patients in the evaluable patient subset, mean height velocity ( + S.D.) increased from 4.1 + 1.0 cm/year at baseline to
8.0 + 1.5 cm/year at 6 months and 7.2 + 1.3 cm/year at 12 months, an increase of 3.1 + 1.4 cm/year (p = 0.0001). Mean height standard deviation
score ( + S.D.) increased from -3.71 + 0.92 at baseline to -3.21 + 0.91 at 12 months, an increase of 0.50 + 0.23 over the 12 month period (p =
0.0001). Mean changes in bone age at 12 months were proportional to gains in height (1.04 + 0.58, ÆBA/ÆHA, n=42).
INDICATIONS AND USAGE
Geref® (sermorelin acetate for injection) is indicated for the treatment of idiopathic growth hormone deficiency in children with growth
failure. Most of these short, slowly growing children retain pituitary responsiveness to growth hormone releasing hormone.
Selection of Patients and Evaluation of Growth
All children should be pre-pubescent and treatment should be initiated at a bone age of < 7.5 years for females, and < 8 years for males.
Prior to initiation of treatment, a growth hormone (GH) stimulation test with Geref® should be performed in all children. Children who do
not adequately respond (i.e., peak GH level < 2 ng/mL) should be excluded from Geref® therapy. The relative growth hormone response to
the stimulation test with Geref® is not predictive of the growth response to Geref® therapy. Clinical results are better in children with
delayed bone age and in whom treatment is initiated as early as possible in the prepubertal period. Height should be assessed at least every six
months during treatment. During Geref® therapy, failure to maintain a pattern of growth consistent with a child’s age and stage of development
requires investigation. Children should be treated with Geref® for an initial period of 6 months and treatment with growth hormone should
be initiated for those children with a poor or waning response to Geref®.
CONTRAINDICATIONS
Geref® (sermorelin acetate for injection) should not be used by patients with a known sensitivity to sermorelin or any of the excipients.
WARNINGS
Following reconstitution of Geref® (sermorelin acetate for injection) with the diluent provided, the solution should be administered imme-diately.
Any unused solution should be discarded.
PRECAUTIONS
General: Geref® (sermorelin acetate for injection) therapy should be carried out under the regular guidance of a physician who is experi-enced
in the diagnosis and management of growth disorders.
The growth response of children treated with Geref® should be evaluated on a periodic basis and children with a poor or waning
response should be considered for treatment with growth hormone. The effect of Geref® therapy beyond one year and on final adult height
remains to be determined.
In clinical studies, the incidence of hypothyroidism during Geref® therapy was 6.5%. In the largest clinical study, 8 of 110 enrolled
patients were on thyroid replacement therapy prior to Geref® therapy and an additional 5 after initiating therapy. Untreated hypothyroidism
can jeopardize the response to Geref®. Therefore, thyroid hormone determinations should be performed before the initiation and through-out
the duration of Geref® therapy. Thyroid hormone replacement therapy should be initiated when indicated.
Bone age should be monitored periodically during Geref® administration, especially in patients who are pubertal and/or receiving con-comitant
thyroid replacement therapy. Under these circumstances, epiphyseal maturation may progress rapidly.
Patients with growth hormone deficiency secondary to an intracranial lesion were not studied in clinical trials. It is not recommended that
such patients be treated with Geref®.
As with the administration of any peptide, local or systemic allergic reactions may occur. Parents/Patients 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, GH and IGF-I may increase with
Geref® therapy.
Drug Interaction: Concomitant glucocorticoid therapy may inhibit the response to Geref®. There was no evidence in the
controlled studies of Geref®’s interaction with drugs commonly used in the treatment of routine pediatric problems/illnesses.
However, formal drug interaction studies have not been conducted.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term animal studies for carcinogenicity and impair-ment
of fertility have not been performed with Geref®. There has been no evidence from studies to date of Geref®-induced
genetic toxicity. Geref® was not mutagenic in a battery of In vivoand In vitro genetic toxicity assays either in the presence
or absence of metabolic activator (bacterial mutation tests, gene conversion-DNA repair test, forward mutation test,
micronucleus test, chromosome aberration in Chinese hamster bone marrow).
Pregnancy: Pregnancy Category C. During teratology studies Geref® produced minor variations in fetuses of rats and
rabbits when given at a subcutaneous dose of 0.5 mg/kg/day. This dose is approximately 3 and 6 times the daily human sub-cutaneous
dose calculated on a body surface area (mg/m
2
) basis, for rats and rabbits, respectively. There are no adequate and
well controlled studies in pregnant women. Geref® should be used during pregnancy only if the potential benefit justifies the
potential risk to the fetus.
Nursing Women: It is not known whether Geref® is excreted in human milk. Because many drugs are excreted in human
milk, caution should be exercised when Geref® is administered to a nursing woman.
Information For Patients: Patients being treated with Geref® and/or their parents should be informed of the potential bene-fits
and risks associated with treatment. If home use is determined to be desirable by the physician, instructions on appropri-ate
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).
ADVERSE REACTIONS
A large proportion of patients develop anti-GRF antibodies at least once during treatment with Geref® (sermorelin acetate
for injection). The significance of these antibodies is not clear and often a positive test at one growth assessment will
become negative by the next assessment. The presence of antibodies does not appear to affect growth or appear to be relat-ed
to a specific adverse reaction profile. No generalized allergic reactions to Geref® have been reported.
The most common treatment-related adverse event (occurring in about 1 patient in 6) is local injection reaction character-ized
by pain, swelling or redness. Of 350 patients exposed to Geref® in clinical trials, three discontinued therapy due to
injection reactions. Other treatment-related adverse events had individual occurrence rates of less than 1% and include:
headache, flushing, dysphagia, dizziness, hyperactivity, somnolence and urticaria.
When administered intravenously for diagnostic use, the following adverse reactions have been noted: flushing of the face,
injection site pain, redness and/or swelling, nausea, headache, vomiting, dysgeusia, pallor and tightness in the chest.
DRUG ABUSE AND DEPENDENCE
The clinical pharmacology suggests that Geref® is very unlikely to be associated with drug abuse or dependence and
there have been no reports of this from clinical trials.
OVERDOSAGE
The recommended dosage of Geref® (sermorelin acetate for injection) should not be exceeded.
DOSAGE AND ADMINISTRATION
A dosage of 0.03 mg (30 mcg) per kg of body weight once daily at bedtime by subcutaneous injection is recommended. It
is also recommended that subcutaneous injection sites be periodically rotated.
Treatment with Geref® should be discontinued when the epiphyses are fused. Patients who fail to respond adequately while
on Geref® therapy should be evaluated to determine the cause of unresponsiveness.
Height should be assessed at least every six months during treatment. During Geref® therapy, care should be taken to
ensure that the child continues to grow at a rate consistent with the child’s age and stage of development, and treatment with
Geref® should be reevaluated if the response is inadequate. Treatment with growth hormone should be considered for chil-dren
with a poor or waning response to Geref®.
To prevent possible contamination, wipe the rubber vial stopper with an antiseptic solution before puncturing it with the
needle. It is recommended that Geref® 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.
After determining the appropriate patient dose, reconstitute each vial of Geref® with 0.5-1.0 mL of Sodium Chloride
Injection, USP.
To reconstitute Geref®, inject the diluent into the vial of Geref® aiming the liquid against the glass vial wall. Swirl the vial
with a GENTLE rotary motion until contents are dissolved completely. Do not administer Geref® if particles are visible in the
reconstituted solution or if the reconstituted solution is cloudy.
HOW SUPPLIED
Before Reconstitution - Vials of Geref® (sermorelin acetate for injection) should be stored refrigerated (2°-8°C/36°-46°
F). Expiration dates are stated on the labels.
After Reconstitution - When reconstituted with Sodium Chloride Injection, USP, the reconstituted solution should be
administered immediately. Any unused solution should be discarded.
Geref® (sermorelin acetate for injection) is a sterile, nonpyrogenic, lyophilized powder supplied in packages containing:
1 vial 0.5 mg Geref® and 1 vial 2 mL Sodium Chloride Injection, USP NDC 44087-4005-1
1 vial 1.0 mg Geref® and 1 vial 2 mL Sodium Chloride Injection, USP NDC 44087-4010-1
Rx only
Product information as of April 1999
Manufactured for:
Serono Laboratories, Inc.
Randolph, MA 02368
® Registered trademark of Serono Laboratories, Inc.
Serono, Inc.
100 Longwater Circle
Norwell, MA 02061
www.howkidsgrow.com