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Description:
Saizen is a Human Growth Hormone
somatropin injection derived from recombinant DNA technology.
Saizen is comprised of 191 residue amino acids and has a molecular
weight 22,125 daltons. The sequence of Saizen's amino acids is
completely identical to the sequence of Human Growth Hormone
derived naturally from the pituitary. Saizen is created from a
specific lab strain of the E. coli bacteria as a precursor chemical
that consists of the recombinant Human Growth Hormone molecule that
is preceded by a signal for secretion that originates with a
protein from the E. coli bacteria. This precursor chemical is then
directed to the plasma membranes of the cells. After the E. coli
secretion signal is eliminated, the native protein is deposited
into the periplasm and the protein begins to be folded correctly as
it is synthesized.
Saizen is a pristinely purified
preparation. The biological potency of Saizen is configured through
a cell proliferation bioassay. Upon expiration, Saizen will not
contain more than 15% deamidated GH upon its expiration. Deamidated
Growth Hormone has been studied extensively, and it has been proven
to be safe and completely active.
Saizen is a sterilized liquid that
is intended to be administered with a subcutaneous injection.
Saizen is almost isotonic at a 5mg GH per mL concentration. It has
a pH value of around 6.0.
Every 2 mL container of Saizen holds
10mg (about 30 IU) of somatropin formulated in 17.4 mg NaCl, 4 mg
polysorbate 20, 5 mg phenol, and 10mM sodium citrate.
Clinical
Pharmacology
General
Information
In vivo and in vitro clinical and
preclinical testing have provided ample evidence that Saizen is
equivalent therapeutically to Human Growth Hormone naturally
derived from the pituitary. Children who do not secrete adequate
Growth Hormone levels endogenously, patients who suffer from renal
insufficiency that is chronic in nature, and patients who are
maligned with Turner syndrome all report benefits when taking
Nutropin or Saizen [injectable somatropin derived from recombinant
DNA]. Patients who took Nutropin or Saizen were found to experience
an increase in their rate of growth and also an increase in their
IGF-1 (insulin-like growth factor-I) levels in a manner than is
also seen when normal Human Growth Hormone levels are naturally
produced by the pituitary gland.
Benefits that have been shown
through studies regarding Saizen, somatrem, somatropin, and/or
Human Growth Hormone derived naturally from the pituitary
include:
A. Tissue Growth --
1) Skeletal Growth: Growth Hormone
stimulates skeletal growth in
young patients that experience
growth failure as a result of inadequate secretion of natural
Growth Hormone, or as a secondary effect of chronic kidney
insufficiency or also with patients that suffer from Turner
syndrome. Growth of the long bones of the skeleton is a result of
the expansion of the epiphyseal plates that are located on the ends
of the growing bone. The metabolism and growth of the cells of the
epiphyseal plates are stimulated directly by Growth Hormone and
Insulin-Like Growth Factor-1, an important stimulator of Growth
Hormone. Levels of IGF-1 in the blood serum are low in adolescents
and children who are deficient in GH, but their levels increase
when treated with Growth Hormone. In these young patients, new bone
begins to develop through the epiphyses after Growth Hormone and
IGF-1 have been introduced to the body. As one reaches the end of
puberty, the growth plates fuse and adult height is locked
in.
2) Cell Growth: Human Growth Hormone
leads to an increase in both the size and number of skeletal muscle
cells.
3) Organ Growth: Growth Hormone has
a direct effect on the size of the internal organs, including the
kidneys. It also increases the mass of red cells. Growth Hormone
Treatment of genetic dwarf or hypophysectomized rats leads to organ
development that is in proportion to the growth of the rest of the
body. In healthy rats that were induced with uremia through
nephrectomy, Growth Hormone promoted body and skeletal
growth.
B. Protein
MetabolismProper growth is stimulated in part
by protein synthesis which is encouraged by Growth Hormone. This is
shown through retention of nitrogen that is demonstrated by a lower
level of nitrogen excreted through the urine, as well as clinical
testing for nitrogen in the blood urea which occurs during Growth
Hormone Therapy.
C. Carbohydrate
MetabolismGrowth Hormone is a significant
controlling mechanism in charge of carbohydrate. In patients that
do not adequately secrete Growth Hormone, hypoglycemia is often
experienced during periods of fast. This issue is largely resolved
with Human Growth Hormone Therapy. It is a possibility that Growth
Hormone therapy can lead to a decrease in the body's sensitivity to
insulin. Patients who are not treated for chronic kidney
insufficiency and/or Turner syndrome have a higher risk to develop
intolerance to glucose. Human Growth Hormone treatment provided to
children or adults has resulted in an increase in postprandial
insulin levels and serum fasting. These two results happen most
commonly with those that are overweight or obese. Also,
postprandial glucose, mean fasting, and hemoglobin A 1c levels stay
within a normal range.
D. Lipid
MetabolismIn patients who are Growth Hormone
Deficient, Growth Hormone Therapy led to the mobilization of
lipids, a reduction in stores of body fat, increased fatty acids
entering the plasma, and lower levels of cholesterol in the
plasma.
E. Mineral
MetabolismUse of Growth Hormone leads to the
retention of potassium in the body. This retention apparently is
due to the enhanced cell growth that begins to occur. Inorganic
phosphorus levels in the blood serum can sometimes increase
modestly among patients who undergo Growth Hormone Therapy because
they do not produce enough Growth Hormone on their own, have a
chronic kidney deficiency, or suffer from Turner syndrome, because
Growth Hormone enhances the metabolic processes associated the
growth of bone in addition to improving tubular reuptake of
phosphate by the kidneys. Serum calcium levels do not change
significantly among these patients. Retention of sodium also
occurs. Adults that developed a Growth Hormone Deficiency as
children display low levels of bone mineral density (Acronym: BMD).
(See also Precautions:
Laboratory Tests.)
F. Connective Tissue
MetabolismGrowth Hormone chondroitin sulfate
synthesis and collagen synthesis in addition to encouraging the
urinary expulsion of hydroxyproline.
Pharmacokinetics
Absorption after Subcutaneous
InjectionThe total bioavailability of
recombinant Human Growth Hormone after being injected
subcutaneously into a healthy adult male is determined to be 81
plus or minus 20%. The terminal mean t after
subcutaneous injection is much longer than the terminal mean after
intravenous injection (2.1 plus or minus 0.43 hr vs. 19.5 plus or
minus 3.1 min). This indicates that subcutaneous injection of
Growth Hormone causes the compound to be released slowly and at a
more modest rate.
DistributionRecombinant
Human Growth Hormone Animal Research has shown that Growth Hormone
is attracted to organs that are highly perfused, in particular the
kidneys and the liver. The distribution volume at steady state for
Recombinant Human Growth Hormone in a healthy adult male is around
50 mL/kg of body weight, essentially the serum volume.
MetabolismBoth
the kidney and liver have been proven to be essential organs for
the proper metabolism of Growth Hormone. Animal research provides
evidence that the kidneys are the primary organs of clearance.
Growth Hormone filtration occurs at the glomerulus and Growth
Hormone is reabsorbed by the proximal tubules. After that it is
split inside the renal cells into its component amino acids, after
which the acids return to normal circulation.
Elimination--The terminal mean t
after intravenous injection of recombinant Human
Growth Hormone adult males in good health is approximated to be
19.5 plus or minus 3.1 minutes. Elimination of recombinant Human
Growth Hormone after intravenous injection among healthy children
and adults is shown to range from 116-174 mL/hr/kg.
Formulation
bioequivalenceSaizen [somatropin injection
derived from recombinant DNA] has been shown to be the
bioequivalent of Nutropin [somatropininjection derived from
recombinant DNA]. This is based upon statistical evaluation of Area
Under the Curve (AUC) and man C.
Special
Populations
PediatricCurrent
research data suggests that there is no difference in bio identical
Human Growth Hormone clearance between children and
adults.
GenderThere is
no data available for exogenously injected recombinant Human Growth
Hormone. The data that has been collected regarding methionyl rhGH,
naturally produced and extracted pituitary Growth Hormone, and
endogenous Growth Hormone produce no evidence that suggests that
men and women eliminate Growth Hormone at different
rates.
GeriatricsThe
limited amount of published research shows that Growth Hormone
plasma clearance and normal steady-state Growth Hormone plasma
concentration do not appear to be different among young and elderly
populations.
RaceThe
half-life values for endogenous Growth Hormone in healthy black
males is not shown to be any different than the half-life values of
Growth Hormone for healthy white males. There is no available data
regarding other races.
Growth Hormone Deficiency
(GHD)The reported values regarding the
clearance of recombinant Human Growth Hormone in children and
adults suffering from GHD range from 138-245 mL/hr/kg. These values
are similar to those that occur in healthy children and adults. The
terminal mean t values following subcutaneous and
intravenous administration in pediatric and adult Growth Hormone
Deficiency patients have also proven to be similar to the values
observed in the population of healthy adult males.
Kidney
InsufficiencyAdults and children who suffer
from end-stage renal disease (ESRD) and chronic renal failure (CRF)
to clear rhGH at a lower rate than healthy individuals. Endogenous
Growth Hormone production can sometimes increase in particular
individuals suffering from ESRD. Even so, no accumulation of
recombinant Human Growth Hormone has been shown in children with
ESRD of CRF that are given normal Growth Hormone Replacement
Therapy.
Turner
SyndromeNo pharmacokinetic data is currently
available regarding Turner syndrome and Growth Hormone Therapy. It
has been reported, however, that absorption, half life, and
clearance rates for internally produced Growth Hormone for this
population show little difference when compared to the rates of
healthy patients and patients only suffering from Growth Hormone
Deficiency.
Hepatic
InsufficiencyA reduction in recombinant Growth
Hormone clearance has been reported in patients that are suffering
from extreme liver dysfunction. The clinical significance of this
data is still unknown.
Research on the effectiveness of
Saizen
Effect of the Bio-synthetic
hormone Nutropin [recombinant DNA derived somatropin for injection]
upon Growth Failure as a result of CRI
Two randomized, controlled,
multi-center clinical trials were conducted in an effort to
determine whether Nutropin treatment before renal transplantation
in patients suffering from chronic renal insufficiency could
possibly lead to an improvement in growth rate and a decrease in
height deficit. One of the studies was a placebo-controlled,
double-blind trial and the other trial was randomized and
open-label. In both of these controlled studies, participants took
a Nutropin dose of 0.05 mg/kg/day (0.35 mg/kg/wk). These doses were
given daily by means of subcutaneous injection. Taking data from
both studies of patients who underwent treatment for two full years
resulted in 62 participants who received Nutropin treatment and 28
participants who were either untreated or treated by placebo. The
year one mean growth rate was 10.8 cm/yr for patients treated with
Nutropin, as compared with a mean growth rate of 6.5 cm/yr for the
untreated/placebo controls (P<0.00004) The year two mean
growth rate was 7.8 cm/yr for the group treated with Nutropin, as
compared with 5.5 cm/yr for the control group (p<0.00005). A
significant increase was revealed in the mean standard deviation
(SD) of height score with the group that was administered Nutropin
(baseline=-2.9, Month 24=-1.5, n=62), but there was no change
worthy of significance in the control group (baseline=-2.8, Month
24=-2.9, n=28). The year three mean growth rate of 7.6 cm/year in
those treated with Nutropin (n=27) provides evidence that Nutropin
can stimulate growth for longer than two years, but there is no
year three control data because after two years patients who were
previously on control began taking Nutropin treatment, themselves.
The height gains were also accompanied by proper advancement of
skeletal age. The data demonstrates that Nutromin hormone therapy
enhances the growth rate and alleviates that acquired height
deficiency that is associated with CRI. At this time there is not
enough data to scientifically show the benefits of continuing
treatment longer than three years. It is hypothesized that final
height is improved through the use of Nutropin therapy, but the
exact effect that the drug has on final adult height has yet to be
studied appropriately.
Growth after
Transplantation
There is a famous study by NAPRTCS
that has produced data regarding growth after transplant in
pediatric patients who didn't receive Growth Hormone. The average
SD score for change in height during the first two years after the
transplant was received was 0.18 (300 total patients, Journal of
Pediatrics 1993;122:397-402).
Controlled studies of Growth Hormone
treatment administered to combat short stature that accompanies CRI
were not underwent to compare the growth rates of untreated and
treated patients after they underwent renal transplant. Even so,
the growth data is available from a small subset of the patients
that were followed for a minimum of 11 months. Among the 7 control
patients, 4 had a higher SD height score and three showed either no
change of significance or a decrease in their SD height score.
Among the 13 patients that received Nutropin [somatropin for
injection derived from recombinant DNA] before their transplant
displayed either no change of significance or an increased SD
height score post transplantation. This indicates that the gains
that were achieved with Growth Hormone Therapy before th renal
transplant were maintained post-transplantation. The deficit
between the heights of the treated and untreated group narrowed as
time passed after renal transplant.
Turner Syndrome
One multi-center, concurrently
controlled, open-label, long-term randomized study, two
multi-center, historically controlled, open-label, long-term
studies, and one randomized, dose-response, long-term study were
conducted to test the efficacy of Growth Hormone in treating girls
who have short stature as a result of Turner syndrome.
In the randomized GDCT study which
compared patients treated with Growth Hormone to a concurrent
control group that did not receive Growth Hormone, the Growth
Hormone-treated patients received a dosage of 0.3 mg/kg/wk 6 times
each week. The mean age of the participants was 11.7 years and the
duration of treatment was a mean of 4.7 years. The group that
received therapy reached a mean height of 146.0 (n=27) as they
reached near final height. The control group reached a near final
height of only 142.1 cm (n=19). Through covariant analysis, the
total effect of Growth Hormone therapy was an increase on mean
height of 5.4 cm (p value=0.001).
In two of these studies, (85-044 and
85-023), the result of long-term Growth Hormone treatment (0.375
mg/kg/wk either daily or three times weekly) on final height upon
adulthood was figured through a comparison of the final adult
height of patients treated with Growth Hormone matched by age with
historical controls of Turner syndrome patients who received no
therapy to promote growth. In Study 85-023, oestrogen replacement
therapy was not given until the patients reached the age of 14.
Growth Hormone therapy led to an adult mean height gain of 7.4 cm
(duration mean of Growth Hormone therapy=7.6 years) when compared
to matched historical controls through covariant
analysis.
In Study 85-044, patients that
received Growth Hormone therapy early were randomly assigned to
receive therapy to replace estrogen (through the use of conjugated
estrogen, initial dose 0.3 mg, escalated over time to 0.625 daily)
at either age twelve or fifteen. When compared to matched,
historical controls, early Growth Hormone therapy (mean duration of
Growth Hormone therapy=5.6 years) in combination with ERT and age
twelve had a total adult height gain ot 5.9 cm (n=26). Those girls
who initiated ERT at age fifteen (mean duration of Growth Hormone
therapy=6.1 years) had a mean total adult height gain of 8.3 cm
(n=29). Patients that began Growth Hormone therapy after age 11
(mean age 12.7 years, mean duration of Growth Hormone therapy=3.8
years) produced a mean total height gain of 5.0 cm
(n=51).
So, in both study 85-023 and study
85-044, the most significant increase in adult height was shown in
patients that received Growth Hormone treatment early along with
ERT after age fourteen.
In a dose-response, blinded,
randomized study, GDCI patients were treated from an average age of
11.1 for an average duration of 5.3 years with a dose of either
0.27 mg/kg/wk or 0.36 mg/kg/wk injected either three or six times
per week. The average near final height of the patients that
received growth hormone was 148.7 cm (n=31). This number represents
a mean increase in adult height of around 5 cm in comparison to the
observation of those girls historically that had untreated Turner
syndrome.
In these research studies, patients
with Turner syndrome (n=181) that were treated until they reached
fully grown height gained a statistically marked average height
gain with a range from 5.0-8.3 cm.
Adult Growth Hormone Deficiency
(GHD)
Two placebo-controlled,
double-blind, multi-center clinical trials were conducted with
Nutropin [somatropin injection derived from recombinant DNA] in
adults who have Growth Hormone Deficiency. One of the studies was
conducted regarding adult-onset Growth Hormone Deficiency, with a
mean age of 48.3 years and 166 participants. The dosage was 0.0125
or 0.00625 mg/kg/day at doses of 0.00625 mg/kg/day. Dose levels of
0.025 mg/kg/day were not tolerated by these participants. A second
research study was conducted with regard to subjects with
childhood-onset Growth Hormone Disorder who had previously been
treated with Human Growth Hormone. The mean age was 23.8 years old
and there were 64 total participants. They were randomly given
assigned to take doses of 0.025 or 0.0125 mg/kg/day. These studies
were designed to learn more about the effects of Growth Hormone
Replacement therapy and its effect on body composition.
Hormone replacement therapy and weight
loss
Marked changed in body composition
(i.e., trunk percentage fat mass, total body percentage lean mass
by DEXA scan, and total body percentage fat mass) from baseline to
one year of treatment were shown in all Nutropin groups in both
studies (p<0.0001 for the change from the baseline and in
relationship to the placebo). There was no statistically marked
change that was seen in either group that was given placebo. In the
study that dealt with adult-onset GHD, the Nutropin group decreased
in total mean body fat from 35.0% to 31.5%, and the mean of trunk
fat decreased from 33.9% to 29.5%, and the mean total lean body
mass increased from 62.2% to 65.7%. The placebo group experienced
mean changes less than or equal to 0.2% (p=insignificant). Because
of the possibility that Growth Hormone-induced retention of fluids
can possibly have an effect on DEXA lean mass measurements, DEXA
scans were given again around three weeks after therapy was
completed; the mean percentage lean body mass in the Nutropin
participants averaged 65%, which was a change of 2.8% in regard to
baseline, as compared to a 0.4% chance in the group that received
placebo (p<0.0001 between the two groups).
In the childhood-onset GHD study,
the group that took a higher dose of Nutropin decreased their total
mean body fat from 38.4% to 32.1%, average trunk fat from 36.7% to
29.0%, and average lean body mass from 59.1% to 65.5%; the group
that took a low dose of Nutropin decreased total mean body fat from
37.1% to 31.3%, decreased mean trunk fat from 37.9% to 30.6%, and
average lean body mass increased from 60.0% to 60.0%. The group
that received placebo experienced mean changes of less than or
equal to 0.6% (insignificant p).
In the study of adult-onset GHD,
significant decreases in levels of LDL (bad) cholesterol and the
ratio of LDL:HDL over the course of the initial year of treatment
were found in the Nutropin patients in comparison with the placebo
patients (p<0.02). No statistically marked difference was
discovered between the control group and the experimental group in
regard to changes in triglycerides or HDL cholesterol in the first
year of treatment. In the childhood-onset GHD study, significant
drops in year one of LDL cholesterol, total cholesterol, and the
ration of LDL to HDL cholesterol in comparison to the placebo group
were only seen in the group that took a high dose of Nutropin
(p< 0.05). There was no statistically significant difference
between groups in regard to triglycerides or HDL cholesterol in the
first year of treatment.
Quality of life, physical endurance,
and muscle strength measurements were not abnormal in a significant
manner at baseline, and Nutropin had no no statistically
significant effect on these three factors in these three
studies.
Indications and
Usage
Among Pediatric Patients
Saizen [somatropin injection derived
from recombinant DNA] is meant for the long-term therapy of
inadequate growth due to an inefficient level of endogenous Human
Growth Hormone secretion.
Saizen [somatropin injection derived
from recombinant DNA] is also meant for the therapy of inadequate
growth as a result of CRI until renal transplantation occurs.
Saizen treatment can and should be used in tandem with medical
management of CRI
Saizen [somatropin injection derived
from recombinant DNA] is also intended for as a long-term therapy
to combat short stature that is a symptom of Turner
syndrome.
Among Adult Patients
Saizen [somatropin injection derived
from recombinant DNA] is intended to be a replacement for
endogenous Growth Hormone in patients that have adult GHD and who
meet the following criteria concurrently:
Diagnosis of adult Growth Hormone
Deficiency displayed through a less than optimal response to a
biochemical test of standard GH stimulation (peak Growth
Hormone</=5 g/L)
and
In those with adult-onset: Patients
that have either adult Growth Hormone Deficiency only, or have
hypopituitarism because of trauma, radiation therapy, surgery,
hypothalamic disease, or pituitary disease.
or
In those with childhood-onset:
Patients that had a Growth Hormone deficiency during childhood that
was confirmed in adulthood before undergoing Saizen HRT.
Hormone Replacement Therapy
Contraindications
Saizen should not be prescribed as
therapy for patients that have a critical acute illness that is due
to complications after abdominal or open heart surgery, multiple
trauma due to an accident, or acute respiratory failure. Two
clinical trials controlled by placebo among non-GHD adult patients
(n-522) that had these conditions showed a significant increase in
rate of mortality (41.9% vs. 19.3%) among those patients that were
treated with somatropin doses of 5.3-8 mg/day in comparison to
those who were treated with placebo (for more information,
see Warnings).
Saizen also should not be
administered to promote growth in pediatric patients that have
closed epiphyses.
Saizen should be avoided by patients
that have active neoplasia. If neoplasia develops during treatment,
Growth Hormone Therapy should be discontinued.
Warnings
View Contraindicationsto see more information regarding higher rates
of mortality in patients who take Growth Hormone in addition to
being treated for acute critical illness in ICU as a result of
complications after abdominal or open-heart surgery, multiple
trauma as a result of an accident, or acute respiratory failure. It
has not been established if it is safe to receive replacement doses
of Growth Hormone treatment for approved indications after
concurrently developing the above afflictions. For this reason, the
possible benefits of continuing Saizen treatment while also dealing
with an acute critical illness should be discussed in terms of
potential risk. Make sure you discuss your desires to undergo such
a treatment with one of our many highly qualified
bioequivolent
hormone replacement therapy doctors here at Bio-Identical Hormone Replacement Therapy MD. We
are always here and happy to answer any questions you may have.
Call us, email us, or drop by!
Precautions
General: Saizen must be prescribed
by a bioidentical hormones doctor
who is experienced in the management
and diagnosis of patients with Growth Hormone deficiency, CRI, or
turner syndrome. There have been no completed studies regarding
Saizen treatment and those that have undergone renal transplants.
Also, at this time there is no research regarding the treatment of
patients that have functioning renal allographs.
There is limited research regarding
prolonged recombinant Human Growth Hormone treatment in
adults.
Elderly Use: Clinical research
studies of Saizen have yet to include sufficient numbers of
participants age 65 or older to test as to whether they respond
differently than younger patients. Clinical practitioners have not
reported any difference between the responses of younger patients
and the elderly, however. As a point of caution, dosage selection
for elderly patients should be modest, generally beginning at the
low level of the range of dosage, especially since the elderly have
a higher frequency of decreased cardiac, renal, and hepatic
function, along with other concomitant diseases and other drug
therapies.
Those patients with closed
epiphyseal plates who start Growth Bio Identical Hormones Therapy
when in childhood need to be re-evaluated in accordance with the
criteria listed in the Indications and Usage section before they continue to undergo Growth
Hormone Therapy at a lower dosage level that is required to
maintain proper hormone levels in Growth Hormone Deficient
adults.
Saizen can reduce sensitivity to
insulin, therefore patients need to be properly monitored for
glucose intolerance.
In patients that suffer from
diabetes mellitus, the insulin dosage may need to be adjusted as
Growth Bio Hormone Replacement begins and continues. Since Growth
Hormone can lead to a reduced sensitivity to insulin, especially in
individuals that are obese, patients ideally need to be observed to
monitor levels of glucose tolerance. Patients that have a glucose
intolerance or diabetes need to be closely monitored as Growth
Hormone Therapy progresses.
Nutropin treatment for adults with
adult-onset Growth Hormone Deficiency has been associated with an
increased level of median fasting insulin among those that receive
Nutropin 0.0125mg/kg/day from a level of 9.0 'U/mL initially to a
level of 13.0 'U/mL after one year. One returns to baseline median
after a three week period post-washout after Growth Hormone
Therapy. Among placebo participants, no change was noted from the
8.0 'U/mL between the initial baseline and one year. The median
after the post-washout period was 9.0 'U/mL. The difference between
the treatment groups in the change from baseline to one year was
significant (p<0.0001). In the group of adults that suffered
from childhood onset GHD, there was a change in the median fasting
level of insulin in the 0.025 mg/kg/day Nutropin group from an
initial level of 11.0 'U/mL at the initial baseline to a level of
20.0 'U/mL after one year. With the 0.0125 mg/kg/day Nutropin group
the level increased from 8.5 'U/mL to a level of 11.0 'U/mL. The
difference between these treatment groups was significant
(p=0.0007).
In participants with adult-onset
Growth Hormone deficiency, there was not a difference between
treatment groups regarding change from baseline to year one in
average HbA1c (p=0.08). Among participants with childhood-onset
GHD, average HbA1c levels were increased in the 0.025 mg/kg/day
Nutropin group from a level of 5.2% at the initial baseline to 5.5%
after one year. In the 0.0125 mg/kg/day Nutropin group, levels of
HbA1c did not change from 5.1% at baseline, nor did they change
from 5.3% from the baseline of the placebo group. The difference
between treatment groups was significant (p=0.009).
Patients that have a history of
intracranial lesion need to be examined with frequency to monitor
for the recurrence of progression of the lesion. In child patients,
the clinical research literature has shown no relationship between
recurrence of central nervous system tumors, development of
extracranial tumors, and Growth Hormone Replacement Therapy.
However, in adults it is not known if there is any relationship
between the recurrence of CNS tumors and Growth Hormone Replacement
Therapy.
Patients that experience failure of
growth concurrent with CRI need to be tested periodically for
evidence as to whether renal osteopystrophy is progressing. In
children that are in an advanced stage of renal osteodystrophy,
avascular necrosis or epiphysis of the head of the femoral bone may
occur, and it is unclear whether these problems are affected in any
way by Growth Hormone Therapy. Patients should undergo hip x-rays
before starting Growth Hormone Therapy if they suffer from CRI.
Parents and bioidentical hormone therapy
doctorsneed to make
sure the child does not develop a limp, and they need to ask the
child if he or she is experiencing hip or knee pain as they undergo
Saizen treatment.
Patients that suffer from endocrine
disorders and those who are growing rapidly may experience slipped
capital femoral epiphysis more often than the general
population.
Scoliosis progression may also occur
in those patients who are experiencing rapid growth. Since Growth
Hormone boost the growth rate, those patients that have a history
of scoliosis and are treated with Growth Hormone need to be
monitored to check for further scoliosis progression. There is no
evidence that Growth Hormone leads to an increased incidence of
scoliosis. Those that have Turner syndrome and leave it untreated
often develop abnormalities of the skeletal system such as
scoliosis. Bioidentical hormones doctors must be very alert to the
potential for these abnormalities because they may appear as the
patient undergoes Saizen treatment.
Those patients that have Turner
Syndrome need to be monitored carefully for otitis media and other
disorders of the ear because this subset of patients has a greater
risk of developing hearing or other ear disorders.
In a controlled, randomized trial,
there was found to be a statistically significant increase in ear
disorders (18% vs. 5%) and otitis media (43% vs. 26%) in patients
receiving GHT when compared to those that were untreated controls.
In addition to this, patients that are maligned with Turner
syndrome need to be monitored very closely for disorders of the
cardiovascular system such as hypertension, aortic aneurism, and
stroke because there are higher incidences for these conditions as
compared to the general population.
Intracranial hypertension (IH) with
vomiting, nausea, visual changes, and/or papilledema occurs in a
small minority of patients that are treated with Growth Hormone
products. These symptoms usually appeared within the first two
months of Growth Hormone therapy. In all of these cases that were
reported, symptoms and signs of intracranial hypertension were
resolved after Growth Hormone treatment was terminated or the
Growth Hormone dosage was modified. It is recommended that patients
undergo funduscopic examination at the beginning of treatment and
then periodically throughout the regimen of Growth Hormone Therapy.
Patients that suffer from Turner syndrome and CRI could possibly be
at an elevated risk for IH.
As is true with any protein,
systemic or local allergic reactions may occur. The patient and/or
the parents of the patient need to be informed about how these
reactions are a possibility and that immediate medical attention
should be sought in the case of an adverse allergic
reaction.
Lab Tests: Serum levels of
parathyroid hormone (PTH), alkaline phosphotase, and inorganic
phosphorus may elevate due to Saizen therapy.
Hypothyroidism, when left untreated,
can hinder the medicinal ability of Saizen. Those patients that
have Turner syndrome have a significantly increased chance of
developing autoimmune thyroid disease. Levels of thyroid hormone in
serum may drop during the course of Saizen treatment. For this
reason, patients need to undergo tests of thyroid function
periodically, and when it is indicated that levels are lower than
normal, they should have thyroid hormone replacement therapy
administered as well as Saizen.
Drug Interaction: Intensive
glucocorticoid therapy will undermine the growth promotional effect
of Saizen. Patients that have an ACTH deficiency should make sure
that their dosage of glucocorticoid-replacement is adjusted to take
into account this inhibitive effect on Human Growth
Hormone.
The effect of Saizen upon patients
that also have CRI and are concurrently undergoing glucocorticoid
therapy has not bee clinically evaluated. glucocorticoid therapy
could potentially undermine the growth promotional effect of
Saizen. If a patient must be on both a glucocorticoid replacement
therapy at the same time that they are on Saizen, the dose of the
glucocorticoid should be adjusted carefully.
There has been no sufficient
evidence released that discusses the interaction of Growth Hormone
Replacement Therapies with other drugs that are used to treat CRI
patients. There is a limited amount of released data that indicated
that Growth Hormone Treatment increases the rate at which
antipyrene is evacuated from the human body through the enzymatic
actions of cytochrome P450 (CP450). The collected data suggests
that the administration of Growth Hormone might alter the
evacuation of the various compounds that CP450 liver enzymes are
known to metabolize (including sex steroids, corticosteroids,
cyclosporin, and anticonvulsants). It is recommended that patients
who are undergoing Saizen therapy in combination with other drugs
that are metabolized through the CP450 liver enzyme remain under
careful monitoring.
Mutagenesis, carcinogenesis, and
Fertility Impairment:
There have yet to be proper studies
conducted regarding mutagenicity, carcinogenicity, and fertility in
regard to Saizen therapy.
Pregnancy (Category C): There have
been no released studies regarding Saizen and animal reproduction.
It is unclear whether Saizen therapy can lead to fetal harm when
injected into a pregnant woman, nor have there been studies as to
whether Saizen has any effect upon a woman's reproductive capacity.
It is only advisable to administer Saizen to a pregnant woman if it
is clearly and absolutely needed.
Nursing Mothers: It is not cleat if
Saizen is present in human milk. Since many drugs do pass into the
mother's milk, one should exercise caution in administering Saizen
to a mother who is nursing.
Parental information: Patients that
are undergoing Growth Hormone Treatment and/or the parents of
patients should be properly informed about the potential risks of
HRT and benefits that are associated with Saizen treatment. If the
HRT doctor feels that home therapy is a more desirable course of
action than clinical therapy, the patient and/or caregiver should
be given proper instruction on appropriate use of Saizen. Included
in this information should be a review of the content within the
Patient Information Insert. The information is included to assist
in the effective and safe administration of Saizen. It should not
be considered a full disclosure of all wanted and unwanted effects
associated with Saizen.
If Saizen treatment is prescribed
for home use, it is recommended that the patient acquire a
container which is puncture-resistant in which to dispose of used
needles and syringes. It is essential that patients and/or parents
of patients be properly instructed of the vital importance of
appropriate disposal. It is also important that they are cautioned
upon why it is important that they do not reuse needles and
syringes (for more information see the Patient Information
Insert).
Side-Effects and Reactions...Is
hormone replacement therapy safe?
As is true with all protein
medicines and therapies, a small minority of patients might develop
antibodies to the particular protein. Growth Hormone antibodies
that have binding capacities lower than 2 mg/L have no effect on
the efficacy of Saizen therapy. In the small number of cases where
the binding capacity is greater than 2 mg/L, attenuation of growth
has resulted. In clinical research studies, pediatric patients who
were for the first time treated with Nutropin [somatropin for
injection derived from Recombinant DNA] were screened for antibody
production. In this survey, 0/125 CRI patients, 0/107 GHD patients,
and 0/112 Turner syndrome patients developed antibodies that had
binding capacities great than or equal to 2 mg/L over the course of
6 months. In a separate clinical research study of patients that
were for the first time treated with Saizen [somatropin injection
derived from recombinant DNA], none of the 38 Growth Hormone
Deficient patients that were screened for the production of
antibodies were found to have developed antibodies that had binding
capacities that were greater than or equal to 2 mg/L over the
course of 15 months.
Additionally, short-term renal
function and immunologic studies were conducted with a group of
patients that suffered from CRI. Researchers monitored the year of
treatment for adverse effects that could be attributed to Growth
Hormone antibodies. The scientists tested for BUN, creatinine
evacuation, creatinine, rheumatoid factor, C4, C3, and Clq. There
were no adverse effects found that were attributed to Growth
Hormone antibodies.
In addition to making sure that a
patient is properly following their Growth Hormone Treatment
regimen, any patient who fails to properly respond to Growth
Hormone therapy should be tested for Growth Hormone antibodies as
well as for thyroid status.
There is some report of discomfort
around the injection site with Saizen. This is most commonly
reported in children that have switched to Saizen from a different
Growth Hormone product. Reports of discomfort among adults taking
Saizen are limited.
Growth HRT and
cancer
Leukemia has occurred in a small
minority of Growth Hormone Deficient patients that have been
treated with GH. It is unclear if this higher risk of leukemia is
associated with the pathology ofGrowth Hormone Deficiency, the Growth Hormone
Therapy, or treatments for intracranial tumors such as radiation
therapy. The current field of evidence does not allow experts to
reach a conclusion as to whether leukemia can sometimes manifest
due to Growth Hormone Therapy. The risk of leukemia to Turner
syndrome, CRI, or GHD patients, if any risk exists, has yet to be
established.
Other bio identical hormone
replacement therapy side effectsthat have been displayed in patients treated
with Growth Hormone Therapy include the following:
Metabolic: Transient, mild
peripheral edema. In Growth Hormone Deficient adults, peripheral
edema or edema was reported in 41% patients treated with Growth
Hormone and 25% of patients treated with placebo.
Musculoskeletal: Carpal tunnel;
arthralgias. In adults with Growth Hormone Deficiency, joint
disorders such as arthralgias were reported in 27% of Growth
Hormone treated patients and 15% of patients treated with
placebo.
Skin: Rarely, increased development
of pre-existing birthmarks and pigmentations occur; patients must
be monitored closely for malignant transformation.
Endocrine: Gynecomastia is sometimes
reported. Pancreatitis is very rarely reported.
Our physicians here at the Conscious Evolution Medical Institute are some of the most qualified in America. You can trust
us to steer you through treatment safely and effectively. However,
if any of these issues seem overly problematic, we also suggest
that you research natural alternatives to HRT.
Overdose
Complications
Acute overdose can cause
hyperglycemia. Overdose over a long period of time can result in
symptoms and signs of acromegaly and gigantism that are consistent
with the known effects of having an excess of Growth Hormone (Read
below for recommended and max dosage instruction).
Administration and
Dosage
Saizen administration and dosage is
dependent upon the needs and restrictions of the individual.
Response to Growth Hormone Therapy among pediatric patients has a
tendency to drop over time. However, among those pediatric patients
who show no enhancement of growth rate, especially in the initial
year of treatment it is often the case that there are compliance
issues. Patients should be assessed intently to ensure that they
are properly undergoing the regimen. Also, other potential causes
of growth failure should be investigated, such as advanced bone
age, undernutrition, and hypothyroidism.
Dosage
For patients with pediatric GHD it
is recommended that a dosage of as much as 0.30 mg/kg/wk should be
administered daily through subcutaneous injection.
For patients with adult GHD it is
recommended that therapy begins at a level no greater than 0.006
milligrams/kilogram daily administered by subcutaneous injection.
This dosage can be increased according to the needs of the patient
upward to a top level of 0.025 milligrams/kilogram/day in patients
that are under 35 years old. In patients that are older then 35,
the maximum dosage should be 0.0125
milligrams/kilogram/day.
In order to minimize occurrence of
side effects among overweight and older patients, it may be
necessary to administer lower doses. Over the course of therapy,
the dosage of Saizen is recommended to be decreased if excessive
Insulin-Like Growth Factor-1 levels occur in the serum or if side
effects begin to occur.
For patients suffering from Chronic
Renal Insufficiency (CRI), a dosage of up to 0.35 mg/kg/wk is
recommended and should be administered in equal portions daily by
means of subcutaneous injection. Saizen therapy can continue up
until the point of renal transplantation.
As a means to optimize therapy in
those patients who require dialysis, the below injection schedule
guidelines are recommended:
Patients undergoing Hemodialysis are
recommended to receive administration nightly just before going to
sleep, or at a minimum three to four hours after undergoing
hemodialysis. This prevents the formation of hematomas from the
heparin.
Patients undergoing CCPD are
recommended to receive injection every morning after dialysis has
been completed.
Patients undergoing CAPD are
recommended to receive injection each night at the time of their
exchange overnight.
Turner Syndrome
It is recommended that patients take
a dose of up to 0.375 mg/kg/wk administered by subcutaneous
injection in equal portions from three to seven times each
week.
Administration
When removed from refrigeration, the
solution of Saizen should be clear. Sometimes after refrigeration,
you might notice that there are small and colorless particles in
the solution. These are merely the proteins, and this is in no way
unusual. Let the vial reach room temperature, then gently
swirl. Do not
shake! If the contents
are cloudy, do not inject
the solution!
Before inserting the needle, clean
the septum of the vial of Saizen with an antiseptic solution or
with rubbing alcohol so that the contents are not contaminated by
microorganisms that could possibly be introduced through repeated
insertions of the needle. It is vitally recommended that you
administer Saizen using disposable, sterilized needles and
syringes. The size of the syringe should be of a small volume so
that the proper dose can be pulled from the vial with significant
accuracy.
Storage and
Stability
Saizen within the vial is stable for
28 days after the first use as long as it is refrigerated at 2-8
degrees Celsius (36-46 degrees Fahrenheit). Do not freeze the
Saizen vial.
How Supplied
Saizen is packaged with 10 mg (about
30 IU) of sterile liquid somatropin in each vial.
Every carton holds 6 single vial containers
holding one 2 mL vial of Saizen [somatropin injection derived from
recombinant DNA] which contains 5 mg of somatropin per mL. NDC
50242-114-11
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