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
Camptosar Indications, Dosage, Storage, Stability - Irinotecan Hcl
Camptosar Indications, Dosage, Storage, Stability - Irinotecan Hcl
INDICATIONS AND USAGE
CAMPTOSAR Injection is indicated as a component of first-line
therapy in combination with 5-fluorouracil and leucovorin for patients with
metastatic carcinoma of the colon or rectum. CAMPTOSAR is also indicated for
patients with metastatic carcinoma of the colon or rectum whose disease has
recurred or progressed following initial fluorouracil-based therapy.
DOSAGE AND ADMINISTRATION
Combination-Agent Dosage
Dosage Regimens
CAMPTOSAR Injection in Combination with 5-Fluorouracil (5-FU)
and Leucovorin (LV)
CAMPTOSAR should be administered as an intravenous infusion
over 90 minutes (see Preparation of Infusion Solution). For all regimens, the
dose of LV should be administered immediately after CAMPTOSAR, with the administration
of 5-FU to occur immediately after receipt of LV. CAMPTOSAR should be used as
recommended; the currently recommended regimens are shown in Table 12.
|
Table 12. Combination-Agent Dosage Regimens & Dose
Modificationsa
|
|
Regimen 1 6-wk cycle with bolus 5-FU/LV (next cycle begins on
day 43)
|
CAMPTOSAR
|
125 mg/m2 IV over 90 min, d 1,8,15,22
|
|
LV
|
20 mg/m2 IV bolus, d 1,8,15,22
|
|
5-FU
|
500 mg/m2 IV bolus, d 1,8,15,22
|
| |
Starting Dose & Modified Dose Levels (mg/m2)
|
|
Starting Dose
|
Dose Level -1
|
Dose Level -2
|
|
CAMPTOSAR
|
125
|
100
|
75
|
|
LV
|
20
|
20
|
20
|
|
5-FU
|
500
|
400
|
300
|
|
Regimen 2 6-wk cycle with infusional 5- U/LV(next cycle begins on day
43)
|
CAMPTOSAR
|
180 mg/m2 IV over 90 min, d 1,15,29
|
|
LV
|
200 mg/m2 IV over 2 h, d 1,2,15,16,29,30
|
|
5-FU Bolus
|
400 mg/m2 IV bolus, d 1,2,15,16,29,30
|
|
5-FU Infusionb
|
600 mg/m2 IV over 22 h, d 1,2,15,16,29,30
|
| |
|
Starting Dose & Modified Dose Levels (mg/m2)
|
| |
|
Starting Dose
|
Dose Level -1
|
Dose Level -2
|
| |
CAMPTOSAR |
180 |
150
|
120
|
| |
LV
|
200
|
200
|
200
|
| |
5-FU Bolus
|
400
|
320
|
240
|
| |
5-FU Infusionb
|
600
|
480
|
360
|
|
aDose reductions beyond dose level –2 by decrements
of »20% may be warranted for patients
continuing to experience toxicity. Provided intolerable toxicity does
not develop, treatment with additional cycles may be continued indefinitely
as long as patients continue to experience clinical benefit.
|
|
bInfusion follows bolus administration.
|
Dosing for patients with bilirubin >2 mg/dL cannot be recommended
since such patients were not included in clinical studies. It is recommended
that patients receive premedication with antiemetic agents. Prophylactic or
therapeutic administration of atropine should be considered in patients experiencing
cholinergic symptoms. See PRECAUTIONS, General.
Dose Modifications
Patients should be carefully monitored for toxicity and assessed
prior to each treatment. Doses of CAMPTOSAR and 5-FU should be modified as necessary
to accommodate individual patient tolerance to treatment. Based on the recommended
dose-levels described in Table 12, Combination-Agent Dosage Regimens & Dose
Modifications, subsequent doses should be adjusted as suggested in Table 13,
Recommended Dose Modifications for Combination Schedules. All dose modifications
should be based on the worst preceding toxicity. After the first treatment,
patients with active diarrhea should return to pre-treatment bowel function
without requiring antidiarrhea medications for at least 24 hours before the
next chemotherapy administration.
A new cycle of therapy should not begin until the toxicity
has recovered to NCI grade 1 or less. Treatment may be delayed 1 to 2 weeks
to allow for recovery from treatment-related toxicity. If the patient has not
recovered, consideration should be given to discontinuing therapy. Provided
intolerable toxicity does not develop, treatment with additional cycles of CAMPTOSAR/5-FU/LV
may be continued indefinitely as long as patients continue to experience clinical
benefit.
|
Table 13. Recommended Dose Modifications for CAMPTOSAR/5-Fluorouracil
(5-FU)/Leucovorin (LV) Combination Schedules
|
|
Patients should return to pre -treatment bowel function
without requiring antidiarrhea medications for at least 24 hours before
the next chemotherapy administration. A new cycle of therapy should not
begin until the granulocyte count has recovered to ³1500/mm3,
and the platelet count has recovered to ³100,000/mm3,
and treatment-related diarrhea is fully resolved. Treatment should be
delayed 1 to 2 weeks to allow for recovery from treatment-related toxicities.
If the patient has not recovered after a 2-week delay, consideration should
be given to discontinuing therapy
|
|
Toxicity NCI CTC Grade a (Value)
|
During a Cycle of Therapy
|
At the Start of Subsequent
Cycles of Therapy b
|
|
No toxicity
|
Maintain dose level
|
Maintain dose level
|
|
Neutropenia
|
|
1 (1500 to 1999/mm3)
|
Maintain dose level
|
Maintain dose level
|
|
2 (1000 to 1499/mm3)
|
¯ 1 dose level
|
Maintain dose level
|
|
3 (500 to 999/mm3)
|
Omit dose until resolved to £
grade 2, then ¯ 1 dose level
|
¯ 1 dose level
|
|
4 (<500/mm3)
|
Omit dose until resolved to £
grade 2, then ¯ 2 dose Levels
|
¯ 2 dose levels
|
|
Neutropenic fever
|
Omit dose until resolved, then
|
¯ 2 dose levels
|
|
Other hematologic toxicities
|
Dose modifications for leukopenia or thrombocytopenia
during a cycle of therapy and at the start of subsequent cycles of therapy
are also based on NCI toxicity criteria and are the same as recommended
for neutropenia above.
|
|
Diarrhea
|
|
1 (2-3 stools/day > pretxc)
|
Delay dose until resolved to baseline, then give same
dose
|
Maintain dose level
|
|
2 (4-6 stools/day > pretx)
|
Omit dose until resolved to baseline, then ¯
1 dose level
|
Maintain dose level
|
|
3 (7-9 stools/day > pretx)
|
Omit dose until resolved to baseline, then ¯
1 dose level
|
¯ 1 dose level
|
|
4 (³10 stools/day >
pretx)
|
Omit dose until resolved to baseline, then ¯
2 dose levels
|
¯ 2 dose levels
|
|
Other nonhematologic toxicitiesd
|
Maintain dose level
|
Maintain dose level
|
|
1
|
Omit dose until resolved to £
grade 1, then ¯ 1 dose level
|
Maintain dose level
|
|
2
|
Omit dose until resolved to £
grade 2, then ¯ 1 dose level
|
¯ 1 dose level
|
|
3
|
Omit dose until resolved to £
grade 2, then ¯ 2 dose
|
¯ 2 dose levels
|
|
4
|
levels
|
|
|
|
For mucositis/stomatitis decrease only 5-FU, not CAMPTOSAR
|
For mucositis/stomatitis decrease only 5-FU, not CAMPTOSAR.
|
|
a National Cancer Institute Common Toxicity Criteria
(version 1.0)
|
|
b Relative to the starting dose used in the previous
cycle
|
|
c Pretreatment
|
|
d Excludes alopecia, anorexia, asthenia
|
Single-Agent Dosage Schedules
Dosage Regimens
CAMPTOSAR should be administered as an intravenous infusion
over 90 minutes for both the weekly and once-every-3-week dosage schedules (see
Preparation of Infusion Solution). Single-agent dosage regimens are shown in
Table 14.
|
Table 14. Single-Agent Regimens of CAMPTOSAR and Dose
Modifications
|
|
Weekly Regimena
|
125 mg/m2 IV over 90 min, d 1,8,15,22 then
2-wk rest
|
|
Starting Dose & Modified Dose Levelsc (mg/m2)
|
|
Starting Dose
|
Dose Level -1
|
Dose Level –2
|
|
125
|
100
|
75
|
|
Once-Every-3-Week Regimenb
|
350 mg/m2 IV over 90 min, once every 3 wksc
|
|
Starting Dose & Modified Dose Levels (mg/m2)
|
|
Starting Dose
|
Dose Level -1
|
Dose Level -2
|
|
350
|
300
|
250
|
|
aSubsequent doses may be adjusted as high
as 150 mg/m2 or to as low as 50 mg/m2 in 25 to 50
mg/m2 decrements depending upon individual patient tolerance.
|
|
bSubsequent doses may be adjusted as low as
200 mg/m2 in 50 mg/m2 decrements depending upon
individual patient tolerance.
|
|
cProvided intolerable toxicity does not develop,
treatment with additional cycles may be continued indefinitely as long
as patients continue to experience clinical benefit.
|
A reduction in the starting dose by one dose level of CAMPTOSAR
may be considered for patients with any of the following conditions: age ³
65 years, prior pelvic/abdominal radiotherapy, performance status of 2, or increased
bilirubin levels. Dosing for patients with bilirubin >2 mg/dL cannot be recommended
since such patients were not included in clinical studies.
It is recommended that patients receive premedication with
antiemetic agents. Prophylactic or therapeutic administration of atropine should
be considered in patients experiencing cholinergic symptoms. See PRECAUTIONS,
General.
Dose Modifications
Patients should be carefully monitored for toxicity and doses
of CAMPTOSAR should be modified as necessary to accommodate individual patient
tolerance to treatment. Based on recommended dose-levels described in Table
14, Single-Agent Regimens of CAMPTOSAR and Dose Modifications,
subsequent doses should be adjusted as suggested in Table 15, Recommended Dose
Modifications for Single-Agent Schedules. All dose modifications should be based
on the worst preceding toxicity.
A new cycle of therapy should not begin until the toxicity
has recovered to NCI grade 1 or less. Treatment may be delayed 1 to 2 weeks
to allow for recovery from treatment-related toxicity. If the patient has not
recovered, consideration should be given to discontinuing this combination therapy.
Provided intolerable toxicity does not develop, treatment with additional cycles
of CAMPTOSAR may be continued indefinitely as long as patients continue to experience
clinical benefit.
|
Table 15. Recommended Dose Modifications For Single-Agent
Schedulesa
|
|
A new cycle of therapy should not begin until the granulocyte
count has recovered to ³1500/mm3,
and the platelet count has recovered to ³100,000/mm3,
and treatment-related diarrhea is fully resolved. Treatment should be
delayed 1 to 2 weeks to allow for recovery from treatment-related toxicities.
If the patient has not recovered after a 2-week delay, consideration should
be given to discontinuing CAMPTOSAR.
|
|
Worst Toxicity
NCI Grade b (Value)
|
During a Cycle of Therapy
|
At the Start of the Next Cycles of Therapy (After Adequate
Recovery), Compared with the Starting Dose in the Previous Cyclea
|
| |
Weekly
|
Weekly
|
Once Every 3 Weeks
|
|
No toxicity
|
Maintain dose level
|
25 mg/m2
up to a maximum dose of 150 mg/m2
|
Maintain dose level
|
|
Neutropenia
|
|
1 (1500 to 1999/mm3)
|
Maintain dose level
|
Maintain dose level
|
Maintain dose level
|
|
2 (1000 to 1499/mm3)
|
¯ 25 mg/m2
|
Maintain dose level
|
Maintain dose level
|
|
3 (500 to 999/mm3)
|
Omit dose until resolved to £
grade 2, then ¯ 25 mg/m2
|
¯ 25 mg/m2
|
¯ 50 mg/m2
|
|
4 (<500/mm3)
|
Omit dose until resolved to £
grade 2, then ¯ 50 mg/m2
|
¯ 50 mg/m2
|
¯ 50 mg/m2
|
|
Neutropenic fever
|
Omit dose until resolved, then ¯
50 mg/m2 when resolved
|
¯ 50 mg/m2
|
¯ 50 mg/m2
|
|
Other hematologic toxicities
|
Dose modifications for leukopenia, thrombocytopenia,
and anemia during a cycle of therapy and at the start of subsequent cycles
of therapy are also based on NCI toxicity criteria and are the same as
recommended for neutropenia above.
|
|
Diarrhea
|
|
1 (2-3 stools/day > pretxc)
|
Maintain dose level
|
Maintain dose level
|
Maintain dose level
|
|
2 (4-6 stools/day > pretx)
|
¯ 25 mg/m2
|
Maintain dose level
|
Maintain dose level
|
|
3 (7-9 stools/day > pretx)
|
Omit dose until resolved to £
grade 2, then ¯ 25 mg/m2
|
¯ 25 mg/m2
|
¯ 50 mg/m2
|
|
4 (³10 stools/day >
pretx)
|
Omit dose until resolved to £
grade 2 then ¯ 50 mg/m2
|
¯ 50 mg/m2
|
¯ 50 mg/m2
|
|
Other nonhematologicd toxicitie
|
|
1
|
Maintain dose level
|
Maintain dose level
|
Maintain dose level
|
|
2
|
¯ 25 mg/m2
|
¯ 25 mg/m2
|
¯ 50 mg/m2
|
|
3
|
Omit dose until resolved to £
grade 2, then ¯ 25 mg/m2
|
¯ 25 mg/m2
|
¯ 50 mg/m2
|
|
4
|
Omit dose until resolved to £
grade 2, then ¯ 50 mg/m2
|
¯ 50 mg/m2
|
¯ 50 mg/m2
|
|
a All dose modifications should be based on
the worst preceding toxicity
|
|
b National Cancer Institute Common Toxicity
Criteria (version 1.0)
|
|
c Pretreatment
|
|
d Excludes alopecia, anorexia, asthenia
|
Preparation & Administration Precautions
As with other potentially toxic anticancer agents, care should
be exercised in the handling and preparation of infusion solutions prepared
from CAMPTOSAR Injection. The use of gloves is recommended. If a solution of
CAMPTOSAR contacts the skin, wash the skin immediately and thoroughly with soap
and water. If CAMPTOSAR contacts the mucous membranes, flush thoroughly with
water. Several published guidelines for handling and disposal of anticancer
agents are available.1-7
Preparation of Infusion Solution
Inspect vial contents for particulate matter and repeat inspection
when drug product is withdrawn from vial into syringe.
CAMPTOSAR Injection must be diluted prior to infusion. CAMPTOSAR
should be diluted in 5% Dextrose Injection, USP, (preferred) or 0.9% Sodium
Chloride Injection, USP, to a final concentration range of 0.12 to 2.8 mg/mL.
In most clinical trials, CAMPTOSAR was administered in 250 mL to 500 mL of 5%
Dextrose Injection, USP.
The solution is physically and chemically stable for up to
24 hours at room temperature (approximately 25°C) and in ambient fluorescent
lighting. Solutions diluted in 5% Dextrose Injection, USP, and stored at refrigerated
temperatures (approximately 2° to 8°C), and protected from light are physically
and chemically stable for 48 hours. Refrigeration of admixtures using 0.9% Sodium
Chloride Injection, USP, is not recommended due to a low and sporadic incidence
of visible particulates. Freezing CAMPTOSAR and admixtures of CAMPTOSAR may
result in precipitation of the drug and should be avoided. Because of possible
microbial contamination during dilution, it is advisable to use the admixture
prepared with 5% Dextrose Injection, USP, within 24 hours if refrigerated (2°
to 8°C, 36° to 46°F). In the case of admixtures prepared with 5% Dextrose Injection,
USP, or Sodium Chloride Injection, USP, the solutions should be used within
6 hours if kept at room temperature (15° to 30°C, 59° to 86°F).
Other drugs should not be added to the infusion solution. Parenteral
drug products should be inspected visually for particulate matter and discoloration
prior to administration whenever solution and container permit.
HOW SUPPLIED
Each mL of CAMPTOSAR Injection contains 20 mg irinotecan (on
the basis of the trihydrate salt); 45 mg sorbitol; and 0.9 mg lactic acid. When
necessary, pH has been adjusted to 3.5 (range, 3.0 to 3.8) with sodium hydroxide
or hydrochloric acid.
CAMPTOSAR Injection is available in single-dose amber glass
vials in the following package sizes:
2 mL NDC 0009-7529-02
5 mL NDC 0009-7529-01
This is packaged in a backing/plastic blister to protect against
inadvertent breakage and leakage. The vial should be inspected for damage and
visible signs of leaks before removing the backing/plastic blister. If damaged,
incinerate the unopened package.
Store at controlled room temperature 15° to 30°C (59° to 86°F).
Protect from light. It is recommended that the vial (and backing/plastic blister)
should remain in the carton until the time of use.
REFERENCES
1. ONS Clinical Practice Committee. Cancer Chemotherapy
Guidelines and Recommendations for Practice Pittsburgh, Pa: Oncology Nursing
Society; 1999:32-41.
2. Recommendations for the safe handling of parenteral antineoplastic
drugs. Washington, DC: Division of Safety, National Institutes of Health; 1983.
US Dept of Health and Human Services, Public Health Service publication NIH
83-2621.
3. AMA Council on Scientific Affairs. Guidelines for handling
parenteral antineoplastics. JAMA. 1985;253:1590-1592.
4. National Study Commission on Cytotoxic Exposure. Recommendations
for handling cytotoxic agents. 1987. Available from Louis P. Jeffrey, Chairman,
National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy
and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115.
5. Clinical Oncological Society of Australia. Guidelines
and recommendations for safe handling of antineoplastic agents. Med J Australia.
1983;1:426-428.
6. Jones RB, Frank R, Mass T. Safe handling of chemotherapeutic
agents: a report from the Mount Sinai Medical Center. CA-A Cancer J for Clin.
1983;33:258-263.
7. American Society of Hospital Pharmacists. ASHP technical
assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp
Pharm. 1990;47:1033-1049.
8. Controlling Occupational Exposure to Hazardous Drugs.
(OSHA Work-Practice Guidelines.). Am J Health-SystPharm. 1996;53-1669-1685
Manufactured by Pharmacia & Upjohn Company
A subsidiary of Pharmacia Corporation Kalamazoo, Michigan 49001, USA
Licensed from Yakult Honsha Co., LTD, Japan,
and Daiichi Pharmaceutical Co., LTD, Japan Revised May 2002 816 907 113 Draft
November 2003 June 24, 2004 692839
top
