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
Sandimmune Indications, Dosage, Storage, Stability - Cyclosporine
Sandimmune Indications, Dosage, Storage, Stability - Cyclosporine
INDICATIONS
Sandimmune® (cyclosporine) is indicated for the prophylaxis of organ
rejection in kidney, liver, and heart allogeneic transplants. It is always
to be used with adrenal corticosteroids. The drug may also be used in
the treatment of chronic rejection in patients previously treated with
other immunosuppressive agents.
Because of the risk of anaphylaxis, Sandimmune® injection (cyclosporine
concentrate for injection, USP) should be reserved for patients who are
unable to take the soft gelatin capsules or oral solution.
DOSAGE AND ADMINISTRATION
Sandimmune® Soft Gelatin Capsules (cyclosporine capsules, USP) and
Sandimmune® Oral Solution (cyclosporine oral solution, USP)
Sandimmune® soft gelatin capsules (cyclosporine capsules, USP) and Sandimmune®
oral solution (cyclosporine oral solution, USP) have decreased bioavailability
in comparison to Neoral® soft gelatin capsules (cyclosporine capsules
for microemulsion) and Neoral® oral solution (cyclosporine oral solution
for microemulsion). Sandimmune® and Neoral® are not bioequivalent and
cannot be used interchangeably without physician supervision.
The initial oral dose of Sandimmune® (cyclosporine) should be given 4-12
hours prior to transplantation as a single dose of 15 mg/kg. Although
a daily single dose of 14-18 mg/kg was used in most clinical trials, few
centers continue to use the highest dose, most favoring the lower end
of the scale. There is a trend towards use of even lower initial doses
for renal transplantation in the ranges of 10-14 mg/kg/day. The initial
single daily dose is continued postoperatively for 1-2 weeks and then
tapered by 5% per week to a maintenance dose of 5-10 mg/kg/day. Some centers
have successfully tapered the maintenance dose to as low as 3 mg/kg/day
in selected renal transplant patients without an apparent rise in rejection
rate.
(See Blood Level Monitoring below)
In pediatric usage, the same dose and dosing regimen may be used as in
adults although in several studies children have required and tolerated
higher doses than those used in adults.
Adjunct therapy with adrenal corticosteroids is recommended. Different
tapering dosage schedules of prednisone appear to achieve similar results.
A dosage schedule based on the patient’s weight started with 2.0 mg/kg/day
for the first 4 days tapered to 1.0 mg/kg/day by 1 week, 0.6 mg/kg/day
by 2 weeks, 0.3 mg/kg/day by 1 month, and 0.15 mg/kg/day by 2 months and
thereafter as a maintenance dose. Another center started with an initial
dose of 200 mg tapered by 40 mg/day until reaching 20 mg/day. After 2
months at this dose, a further reduction to 10 mg/day was made. Adjustments
in dosage of prednisone must be made according to the clinical situation.
To make Sandimmune® oral solution (cyclosporine oral solution, USP) more
palatable, the oral solution may be diluted with milk, chocolate milk,
or orange juice preferably at room temperature. Patients should avoid
switching diluents frequently. Sandimmune® soft gelatin capsules and oral
solution should be administered on a consistent schedule with regard to
time of day and relation to meals.
Take the prescribed amount of Sandimmune® (cyclosporine) from the container
using the dosage syringe supplied after removal of the protective cover,
and transfer the solution to a glass of milk, chocolate milk, or orange
juice. Stir well and drink at once. Do not allow to stand before drinking.
It is best to use a glass container and rinse it with more diluent to
ensure that the total dose is taken. After use, replace the dosage syringe
in the protective cover. Do not rinse the dosage syringe with water or
other cleaning agents either before or after use. If the dosage syringe
requires cleaning, it must be completely dry before resuming use. Introduction
of water into the product by any means will cause variation in dose.
Sandimmune® Injection (cyclosporine concentrate for injection, USP)
FOR INFUSION ONLY
Note: Anaphylactic reactions have occurred with Sandimmune® injection
(cyclosporine concentrate for injection, USP). (See WARNINGS)
Patients unable to take Sandimmune® soft gelatin capsules or oral solution
pre- or postoperatively may be treated with the I.V. concentrate. Sandimmune®
injection (cyclosporine concentrate for injection, USP) is administered
at 1/3 the oral dose. The initial dose of Sandimmune® injection (cyclosporine
concentrate for injection, USP) should be given 4-12 hours prior to transplantation
as a single I.V. dose of 5-6 mg/kg/day. This daily single dose is continued
postoperatively until the patient can tolerate the soft gelatin capsules
or oral solution. Patients should be switched to Sandimmune® soft gelatin
capsules or oral solution as soon as possible after surgery. In pediatric
usage, the same dose and dosing regimen may be used, although higher doses
may be required.
Adjunct steroid therapy is to be used.
Immediately before use, the I.V. concentrate should be diluted 1 mL Sandimmune®
injection (cyclosporine concentrate for injection, USP) in 20 mL-100 mL
0.9% Sodium Chloride Injection or 5% Dextrose Injection and given in a
intravenous infusion over approximately 2-6 hours.
Diluted infusion solutions should be discarded after 24 hours.
The Cremophor® EL (polyoxyethylated castor oil) contained in the concentrate
for intravenous infusion can cause phthalate stripping from PVC.
Parenteral drug products should be inspected visually for particulate
matter and discoloration prior to administration, whenever solution and
container permit.
Blood Level Monitoring
Several study centers have found blood level monitoring of cyclosporine
useful in patient management. While no fixed relationships have yet been
established, in one series of 375 consecutive cadaveric renal transplant
recipients, dosage was adjusted to achieve specific whole blood 24-hour
trough levels of 100-200 ng/mL as determined by high-pressure liquid chromatography
(HPLC).
Of major importance to blood level analysis is the type of assay used.
The above levels are specific to the parent cyclosporine molecule and
correlate directly to the new monoclonal specific radioimmunoassays (mRIA-sp).
Nonspecific assays are also available which detect the parent compound
molecule and various of its metabolites. Older studies often cited levels
using a nonspecific assay which were roughly twice those of specific assays.
Assay results are not interchangeable and their use should be guided by
their approved labeling. If plasma specimens are employed, levels will
vary with the temperature at the time of separation from whole blood.
Plasma levels may range from 1/2-1/5 of whole blood levels. Refer to individual
assay labeling for complete instructions. In addition, Transplantation
Proceedings (June 1990) contains position papers and a broad consensus
generated at the Cyclosporine-Therapeutic Drug Monitoring conference that
year. Blood level monitoring is not a replacement for renal function monitoring
or tissue biopsies.
HOW SUPPLIED
Sandimmune® Soft Gelatin Capsules (cyclosporine capsules, USP)
25mg
Oblong, pink, branded " 78/240". SandoPak® unit-dose packages of 30 capsules,
3 blister cards of 10 capsules (NDC 0078-0240-15).
50mg
Oblong, corn-yellow, branded " 78/242". SandoPak® unit-dose packages
of 30 capsules, 3 blister cards of 10 capsules (NDC 0078-0242-15).
100mg
Oblong, dusty rose, branded " 78/241". SandoPak® unit-dose packages of
30 capsules, 3 blister cards of 10 capsules (NDC 0078-0241-15).
Store and Dispense
In the original unit-dose container at temperatures below 86°F (30°C).
An odor may be detected upon opening the unitdose container, which will
dissipate shortly thereafter. This odor does not affect the quality of
the product.
Sandimmune® Oral Solution (cyclosporine oral solution, USP)
Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL (NDC
0078-0110-22). A dosage syringe is provided for dispensing.
Store and Dispense
In the original container at temperatures below 86°F (30°C). Do not store
in the refrigerator. Protect from freezing. Once opened, the contents
must be used within 2 months.
Sandimmune® Injection (cyclosporine concentrate for injection, USP)
FOR INTRAVENOUS INFUSION
Supplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per
mL, in boxes of 10 ampuls (NDC 0078-0109-01).
Store and Dispense
At temperatures below 86°F (30°C) and protected from light.
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