CAMPTOSAR Solution for injection Ref.[49708] Active ingredients: Irinotecan

2.1 Colorectal Cancer Combination Regimens 1 and 2

Administer CAMPTOSAR as a 90-minute intravenous infusion followed by LV and 5-FU. The currently recommended regimens are shown in Table 1.

A reduction in the starting dose by one dose level of CAMPTOSAR may be considered for patients with any of the following conditions: prior pelvic/abdominal radiotherapy, performance status of 2, or increased bilirubin levels. Dosing for patients with bilirubin >2 mg/dL cannot be recommended because there is insufficient information to recommend a dose in these patients.

Table 1. Combination-Agent Dosage Regimens and Dose Modifications*:

^* Dose 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.
^† Infusion follows bolus administration.

Dosing for patients with bilirubin >2 mg/dL cannot be recommended because there is insufficient information to recommend a dose in these patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

Dose Modifications

Based on recommended dose levels described in Table 1, Combination Regimens of CAMPTOSAR and Dose Modifications, subsequent doses should be adjusted as suggested in Table 2, Recommended Dose Modifications for Combination Regimens. All dose modifications should be based on the worst preceding toxicity.

Table 2. Recommended Dose Modifications for CAMPTOSAR/5-Fluorouracil (5-FU)/Leucovorin (LV) Combination Schedules

^* National Cancer Institute Common Toxicity Criteria (version 1.0)
^† Relative to the starting dose used in the previous cycle
^‡ Pretreatment
^§ Excludes alopecia, anorexia, asthenia

2.2 Colorectal Single Agent Regimens 1 and 2

Administer CAMPTOSAR as a 90-minute intravenous infusion. The currently recommended regimens are shown in Table 3.

A reduction in the starting dose by one dose level of CAMPTOSAR may be considered for patients with any of the following conditions: prior pelvic/abdominal radiotherapy, performance status of 2, or increased bilirubin levels. Dosing for patients with bilirubin >2 mg/dL cannot be recommended because there is insufficient information to recommend a dose in these patients.

Table 3. Single-Agent Regimens of CAMPTOSAR and Dose Modifications:

^* Subsequent doses may be adjusted as high as 150 mg/m or to as low as 50 mg/m in 25 to 50 mg/m decrements depending upon individual patient tolerance.
^† Provided intolerable toxicity does not develop, treatment with additional cycles may be continued indefinitely as long as patients continue to experience clinical benefit.
^‡ Subsequent doses may be adjusted as low as 200 mg/m in 50 mg/m decrements depending upon individual patient tolerance.

Dose Modifications

Based on recommended dose-levels described in Table 3, Single-Agent Regimens of CAMPTOSAR and Dose Modifications, subsequent doses should be adjusted as suggested in Table 4, Recommended Dose Modifications for Single-Agent Schedules. All dose modifications should be based on the worst preceding toxicity.

Table 4. Recommended Dose Modifications For Single-Agent Schedules*:

^* All dose modifications should be based on the worst preceding toxicity
^† National Cancer Institute Common Toxicity Criteria (version 1.0)
^‡ Pretreatment
^§ Excludes alopecia, anorexia, asthenia

2.3 Dosage in Patients With Reduced UGT1A1 Activity

When administered in combination with other agents, or as a single-agent, consider a reduction in the starting dose by at least one level of CAMPTOSAR for patients known to be homozygous for the UGT1A1*28 or *6 alleles (*28/*28, *6/*6) or compound heterozygous for the UGT1A1*28 and *6 alleles (*6/*28) [see Dosage and Administration (2.1, 2.2), Warnings and Precautions (5.3), and Clinical Pharmacology (12.3, 12.5)]. Subsequent dosage modifications may be required based on individual patient tolerance to treatment [see Dosage and Administration (2.1, 2.2)].

2.4 Premedication

It is recommended that patients receive premedication with antiemetic agents. In clinical studies of the weekly dosage schedule, the majority of patients received 10 mg of dexamethasone given in conjunction with another type of antiemetic agent, such as a 5-HT³ blocker (e.g., ondansetron or granisetron). Antiemetic agents should be given on the day of treatment, starting at least 30 minutes before administration of CAMPTOSAR. Physicians should also consider providing patients with an antiemetic regimen (e.g., prochlorperazine) for subsequent use as needed. A similar antiemetic regimen should be used with CAMPTOSAR in combination therapy.

Prophylactic or therapeutic administration of atropine should be considered in patients experiencing cholinergic symptoms.

2.5 Preparation of Infusion Solution

Inspect vial contents for particulate matter and discoloration and repeat inspection when drug product is withdrawn from vial into syringe.

CAMPTOSAR Injection 20 mg/mL is intended for single use only and any unused portion should be discarded.

CAMPTOSAR Injection must be diluted prior to infusion using aseptic technique. 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 mg/mL to 2.8 mg/mL. Other drugs should not be added to the infusion solution.

Prepare the infusion solution immediately prior to use and commence infusion as soon as possible after preparation. If visible particulates are present in the infusion solution discard. If it is not possible to use the infusion solution immediately, the infusion solution may be stored for up to 24 hours at 2 °C to 8 °C or discarded.

2.6 Safe Handling

CAMPTOSAR is a hazardous drug. Follow applicable special handling and disposal procedures. ¹

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.

2.7 Extravasation

Care should be taken to avoid extravasation, and the infusion site should be monitored for signs of inflammation. Should extravasation occur, flushing the site with sterile water and applications of ice are recommended.

In U.S. phase 1 trials, single doses of up to 345 mg/m² of irinotecan were administered to patients with various cancers. Single doses of up to 750 mg/m² of irinotecan have been given in non-U.S. trials. The adverse events in these patients were similar to those reported with the recommended dosage and regimen. There have been reports of overdosage at doses up to approximately twice the recommended therapeutic dose, which may be fatal. The most significant adverse reactions reported were severe neutropenia and severe diarrhea. There is no known antidote for overdosage of CAMPTOSAR. Maximum supportive care should be instituted to prevent dehydration due to diarrhea and to treat any infectious complications.

Store at controlled room temperature 15°C to 30°C (59° to 86°F). Protect from light. Keep the vial in the carton until the time of use.

Inspect the vial for damage and visible signs of leaks before removing from the carton. If damaged, incinerate the unopened package.

CAMPTOSAR is a hazardous drug. Follow special handling and disposal procedures.¹