A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Sandostatin Warnings, Precautions, Pregnancy, Nursing, Abuse - Octreotide (Injection)
Sandostatin Warnings, Precautions, Pregnancy, Nursing, Abuse - Octreotide (Injection)
WARNINGS
Single doses of Sandostatin® (octreotide acetate) have
been shown to inhibit gallbladder contractility and decrease bile secretion
in normal volunteers. In clinical trials (primarily patients with acromegaly
or psoriasis), the incidence of biliary tract abnormalities was 63% (27%
gallstones, 24% sludge without stones, 12% biliary duct dilatation). The
incidence of stones or sludge in patients who received Sandostatin®
(octreotide acetate) for 12 months or longer was 52%. Less than 2% of
patients treated with Sandostatin® (octreotide acetate)
for 1 month or less developed gallstones. The incidence of gallstones
did not appear related to age, sex or dose. Like patients without gallbladder
abnormalities, the majority of patients developing gallbladder abnormalities
on ultrasound had gastrointestinal symptoms. The symptoms were not specific
for gallbladder disease. A few patients developed acute cholecystitis,
ascending cholangitis, biliary abstraction, cholestatic hepatitis, or
pancreatitis during Sandostatin® (octreotide acetate) therapy
or following its withdrawal. One patient developed ascending cholangitis
during Sandostatin® (octreotide acetate) therapy and died.
PRECAUTIONS
General
Sandostatin® (octreotide acetate) alters the balance between
the counter-regulatory hormones, insulin, glocagon and growth hormone,
which may result in hypoglycemia or hyperglycemia. Sandostatin®
(octreotide acetate) also suppresses secretion of thyroid stimulating
hormone, which may result in hypothyroidism. Cardiac conduction abnormalities
have also occurred during treatment with Sandostatin® (octreotide
acetate). However, the incidence of these adverse events during long-term
therapy was determined vigorously only is acromegaly patients who, due
to their underlying disease and/or the subsequent treatment they receive,
are at an increased risk for the development of diabetes mellitus, hypothyroidism,
and cardiovascular disease. Although the degree to which these abnormalities
are related to Sandostatin® (octreotide acetate) therapy
is not clear, new abnormalities of glycemic control, thyroid function
and ECG developed during Sandostatin® (octreotide acetate)
therapy as described below.
The hypoglycemia or hyperglycemia which occurs during Sandostatin®
(octreotide acetate) therapy is usually mild, but may result in overt
diabetes mellitus or necessitate dose changes in insulin or other hypoglycemic
agents.
Hypoglycemia and hyperglycemia occurred on Sandostatin®
(octreotide acetate) in 3% and 16% of acromegalic patients, respectively.
Severe hyperglycemia, subsequent pneumonia, and death following initiation
of Sandostatin® (octreotide acetate) therapy was reported
in one patient with no history of hyperglycemia.
In acromegalic patients, 12% developed biochemical hypothyroidism only,
8% developed goiter, and 4% required initiation of thyroid replacement
therapy while receiving Sandostatin® (octreotide acetate).
Baseline and periodic assessment of thyroid function (TSH, total and/or
free T4) is recommended during chronic therapy.
In acromegalics, bradycardia (<50 bpm) developed in 25%; conduction
abnormalities occurred in 10% and arrhythmias occurred in 9% of patients
during Sandostatin® (octreotide acetate) therapy. Other
EKG changes observed included QT prolongation, axis shifts, early repolarization,
low voltage, R/S transition, and early R wave progression. These ECG changes
are not uncommon in acromegalic patients. Dose adjustments in drugs such
as beta-blockers that have bradycardia effects may be necessary. In one
acromegalic patient with severe congestive heart failure, initiation of
Sandostatin® (octreotide acetate) therapy resulted is worsening
of CHF with improvement when drug was discontinued. Confirmation of a
drug effect was obtained with a positive rechallenge.
Several cases of pancreatitis have been reported in patients receiving
Sandostatin® (octreotide acetate) therapy.
Sandostatin® (octreotide acetate) may alter absorption
of dietary fats in some patients.
In patients with severe renal failure requiring dialysis, the half-life
of Sandostatin® (octreotide acetate) may be increased,
necessitating adjustment of the maintenance dosage.
Depressed vitamin B12 levels and abnormal Schilling’s tests have been
observed in some patients receiving Sandostatin® (octreotide
acetate) therapy, and monitoring of vitamin B12 levels is recommended
during chronic Sandostatin® (octreotide acetate) therapy.
Information for Patients
Careful instruction is sterile subcutaneous injection technique should
be given to the patients and to other persons who may administer Sandostatin®
(octreotide acetate) Injection.
Laboratory Tests
Laboratory tests that may be helpful as biochemical markers in determining
and following patient response depend on the specific tumor. Based on
diagnosis, measurement of the following substances may be useful in monitoring
the progress of therapy:
| Acromegaly: |
|
Growth Hormone, IGF-I (somatomedin C) |
| |
|
Responsiveness to Sandostatin® (octreotide acetate)
may be evaluated by determining growth hormone levels at 1-4 hour
intervals for 8-12 hours post dose. Alternatively, a single measuremen
to IGF-I (somatomedin C) level may be made two weeks after drug
initiation or dosage change.
|
| Carcinoid: |
|
5- HIAA( urinary 5-hydroxyindole acetic acid), plasma
serotonin, plasma Substance P |
| VIPoma: |
|
VIP( plasma vasoactive intestinal peptide)
|
Baseline and periodic total and/or free T4 measurements should be performed
during chronic therapy (see General).
Drug Interactions
Sandostatin® (octreotide acetate) has been associated
with alterations in nutrient absorption, so it may have an effect on absorption
of orally administered drugs. Concomitant administration of Sandostatin®(octreotide
acetate) with cyclosporine may decrease blood levels of cyclosporine and
result in transplant rejection.
Patients receiving insulin, oral hypoglycemic agents, beta blockers,
calcium channel blockers, or agents to control fluid and electrolyte balance,
may require dose adjustments of these therapeutic agents.
Drug Laboratory Test Interactions
No known interference exists with clinical laboratory tests, including
amine or peptide determinations.
Carcinogenesis/Mutagenesis/Impairment of Fertility
Studies in laboratory animals have demonstrated no mutagenic potential
of Sandostatin® (octreotide acetate).
No carcinogenic potential may demonstrated in mice treated subcutaneously
for 85-99 weeks at doses up to 2000 mcg/kg/day (8x the human exposure
based on body surface area). In a 116-week subcutaneous study in rats,
a 27% and 12% incidence of injection site sarcomas or squamous cell carcinomas
was observed in males and females, respectively, at the highest dose level
of 1250 mcg/kg/ day (10x the human exposure based on body surface area)
compared to an incidence of 8%-10% in the vehicle control groups. The
increased incidence of injection site tumors was most probably caused
by irritation and the high sensitivity of the rat to repeated subcutaneous
injections at the same site. Rotating injection sites would prevent chronic
irritation in humans. There have been no reports of injection site tumors
in patients treated with Sandostatin® (octreotide acetate)
for up to 5 years. There was also a 15% incidence of uterine adenocarcinomas
in the 1250 mcg/kg/day females compared to 7% in the saline control females
and 0% in the vehicle control females. The presence of endometritis coupled
with the absence of corpora lutea, the reduction in mammary fibroadenomas,
and the presence of uterine dilatation suggest that the uterine tumors
were associated with estrogen dominance in the aged female rats which
does not occur in humans.
Sandostatin® (octreotide acetate) did not impair fertility
in rats at doses up to 1000 mcg/kg/day, which represents 7x the human
exposure based on body surface area.
Pregnancy Category B
Reproduction studies have been performed in rats and rabbits at doses
up to 16 times the highest human dose based on body surface area and have
revealed no evidence of impaired fertility or harm to the fetus due to
Sandostatin® (octreotide acetate). 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 Mothers
It is not known whether this drug is excreted in human milk. Because
many drugs are excreted in milk, caution should be exercised when Sandostatin®
(octreotide acetate) is administered to a nursing woman.
Pediatric Use
Experience with Sandostatin® (octreotide acetate) in the
pediatric population is limited. The youngest patient to receive the drug
was 1 month old. Doses of 1-10 mcg/kg body weight were well tolerated
in the young patients. A single case of an infant (nesidioblastosis) was
complicated by a seizure thought to be independent of Sandostatin®
(octreotide acetate) therapy.
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