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
Rapamune Indications, Dosage, Storage, Stability - Sirolimus
Rapamune Indications, Dosage, Storage, Stability - Sirolimus
INDICATIONS
AND USES
Rapamune is indicated for the prophylaxis of organ rejection in patients receiving
renal transplants. It is recommended that Rapamune be used in a regimen with
cyclosporine and corticosteroids.
DOSAGE AND ADMINISTRATION
It is recommended that Rapamune Oral Solution and Tablets be used in a regimen
with cyclosporine and corticosteroids. Two-mg Rapamune oral solution has been
demonstrated to be clinically equivalent to 2-mg Rapamune oral tablets; hence,
are interchangeable on a mg to mg basis. However, it is not known if higher
doses of Rapamune oral solution are clinically equivalent to higher doses of
tablets on a mg to mg basis. (See CLINICAL PHARMACOLOGY: Absorption
). Rapamune is to be administered orally once daily. The initial dose of
Rapamune should be administered as soon as possible after transplantation. For
de novo transplant recipients, a loading dose of Rapamune of 3 times
the maintenance dose should be given. A daily maintenance dose of 2 mg is recommended
for use in renal transplant patients, with a loading dose of 6 mg. Although
a daily maintenance dose of 5 mg, with a loading dose of 15 mg was used in clinical
trials of the oral solution and was shown to be safe and effective, no efficacy
advantage over the 2 mg dose could be established for renal transplant patients.
Patients receiving 2 mg of Rapamune Oral Solution per day demonstrated an overall
better safety profile than did patients receiving 5 mg of Rapamune Oral Solution
per day.
To minimize the variability of exposure to Rapamune, this drug should be taken
consistently with or without food. Grapefruit juice reduces CYP3A4-mediated
metabolism of Rapamune and must not be administered with Rapamune or used for
dilution.
It is recommended that sirolimus be taken 4 hours after administration of
cyclosporine oral solution (MODIFIED) and/or cyclosporine capsules (MODIFIED).
Dosage Adjustments
The initial dosage in patients ≥13 years who weigh less than 40 kg should
be adjusted, based on body surface area, to 1 mg/m 2 /day. The loading
dose should be 3 mg/m 2 .
It is recommended that the maintenance dose of Rapamune be reduced by approximately
one third in patients with hepatic impairment. It is not necessary to modify
the Rapamune loading dose. Dosage need not be adjusted because of impaired renal
function.
Blood Concentration Monitoring
Routine therapeutic drug level monitoring is not required in most patients.
Blood sirolimus levels should be monitored in pediatric patients, in patients
with hepatic impairment, during concurrent administration of strong CYP3A4 inducers
and inhibitors, and/or if cyclosporine dosing is markedly reduced or discontinued.
In controlled clinical trials with concomitant cyclosporine, mean sirolimus
whole blood trough levels, as measured by immunoassay, were 9 ng/mL (range 4.5
- 14 ng/mL [10 th to 90 th percentile]) for the 2 mg/day
treatment group, and 17 ng/mL (range 10 - 28 ng/mL [10 th to 90 th
percentile]) for the 5 mg/day dose.
Results from other assays may differ from those with an immunoassay. On average,
chromatographic methods (HPLC UV or LC/MS/MS) yield results that are approximately
20% lower than the immunoassay for whole blood concentration determinations.
Adjustments to the targeted range should be made according to the assay utilized
to determine sirolimus trough concentrations. Therefore, comparison between
concentrations in the published literature and an individual patient concentration
using current assays must be made with detailed knowledge of the assay methods
employed. A discussion of the different assay methods is contained in Clinical
Therapeutics, Volume 22, Supplement B, April 2000.
Instructions for Dilution and Administration of Rapamune® Oral Solution Bottles
The amber oral dose syringe should be used to withdraw the prescribed amount
of Rapamune® Oral Solution from the bottle. Empty the correct amount of Rapamune
from the syringe into only a glass or plastic container holding at least two
(2) ounces (1/4 cup, 60 mL) of water or orange juice. No other liquids, including
grapefruit juice, should be used for dilution. Stir vigorously and drink at
once. Refill the container with an additional volume (minimum of four [4] ounces
(1/2 cup, 120 mL)) of water or orange juice, stir vigorously, and drink at once.
Pouches
When using the pouch, squeeze the entire contents of the pouch into only a
glass or plastic container holding at least two (2) ounces (1/4 cup, 60 mL)
of water or orange juice. No other liquids, including grapefruit juice, should
be used for dilution. Stir vigorously and drink at once. Refill the container
with an additional volume (minimum of four [4] ounces (1/2 cup, 120 mL)) of
water or orange juice, stir vigorously, and drink at once.
Handling and Disposal
Since Rapamune is not absorbed through the skin, there are no special precautions.
However, if direct contact with the skin or mucous membranes occurs, wash thoroughly
with soap and water; rinse eyes with plain water.
HOW SUPPLIED
Rapamune® Oral Solution is supplied at a concentration of 1 mg/mL in:
1. Cartons:
NDC # 0008-1030-06, containing a 2 o (60 mL fill) amber glass bottle.
NDC # 0008-1030-15, containing a 5 o (150 mL fill) amber glass bottle.
In addition to the bottles, each carton is supplied with an oral syringe adapter
for fitting into the neck of the bottle, sufficient disposable amber oral syringes
and caps for daily dosing, and a carrying case.
2. Cartons:
NDC # 0008-1030-03, containing 30 unit-of-use laminated aluminum pouches
of 1 mL.
NDC # 0008-1030-07, containing 30 unit-of-use laminated aluminum pouches
of 2 mL.
NDC # 0008-1030-08, containing 30 unit-of-use laminated aluminum pouches
of 5 mL.
Rapamune® Tablets are available as follows: 1 mg, white, triangular-shaped
tablets marked "RAPAMUNE 1 mg" on one side.
NDC # 0008-1031-05, bottle of 100 tablets.
NDC # 0008-1031-10, Redipak® cartons of 100 tablets (10 blister cards of
10 tablets each).
Storage
Rapamune® Oral Solution bottles and pouches should be stored protected from
light and refrigerated at 2°C to 8°C (36°F to 46°F). Once the bottle is opened,
the contents should be used within one month. If necessary, the patient may
store both the pouches and the bottles at room temperature up to 25°C (77°F)
for a short period of time (e.g., several days, but not longer than 30 days).
An amber syringe and cap are provided for dosing and the product may be kept
in the syringe for a maximum of 24 hours at room temperatures up to 25°C (77°F)
or refrigerated at 2°C to 8°C (36°F to 46°F). The syringe should be discarded
after one use. After dilution, the preparation should be used immediately.
Rapamune Oral Solution provided in bottles may develop a slight haze when refrigerated.
If such a haze occurs allow the product to stand at room temperature and shake
gently until the haze disappears. The presence of this haze does not affect
the quality of the product.
Rapamune® Tablets should be stored at 20° to 25°C (USP Controlled Room Temperature)
(68°-77°F). Use cartons to protect blister cards and strips from light. Dispense
in a tight, light-resistant container as defined in the USP.
Rx only
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