Irinotecan Hydrochloride

Irinotecan Hydrochloride Manufacturers

• Teva Parenteral Medicines, Inc.
  

  ×

  Irinotecan Hydrochloride | Teva Parenteral Medicines, Inc.

  

  ---

  2.2 Colorectal Single Agent Regimens 1 and 2

  Administer irinotecan hydrochloride injection 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 irinotecan hydrochloride injection 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 Irinotecan Hydrochloride Injection and Dose Modifications a Subsequent 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.
  b Subsequent doses may be adjusted as low as 200 mg/m2 in 50 mg/m2 decrements depending upon individual patient tolerance.
  c Provided intolerable toxicity does not develop, treatment with additional cycles may be continued indefinitely as long as patients continue to experience clinical benefit.
  

  Regimen 1 (weekly)a

  125 mg/m2 intravenous infusion over 90 minutes, days 1,8,15,22 then 2-week rest

  Starting Dose and Modified Dose Levelsc (mg/m2)

  Starting Dose

  Dose Level -1

  Dose Level -2

  125

  100

  75

  Regimen 2 (every 3 weeks)b

  350 mg/m2 intravenous infusion over 90 minutes, once every 3 weeksc

  Starting Dose and Modified Dose Levels (mg/m2)

  Starting Dose

  Dose Level -1

  Dose Level -2

  350

  300

  250

  Dose Modifications

  Based on recommended dose-levels described in Table 3, Single-Agent Regimens of Irinotecan Hydrochloride Injection 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 Schedulesa 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

  A new cycle of therapy should not begin until the granulocyte count has recovered to ≥ 1500/mm3, and the platelet count has recovered to ≥ 100,000/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 irinotecan hydrochloride injection.

  Worst Toxicity NCI Gradeb (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 to 3 stools/day > pretxc)

  Maintain dose level

  Maintain dose level

  Maintain dose level

  2 (4 to 6 stools/day > pretx)

  ↓ 25 mg/m2

  Maintain dose level

  Maintain dose level

  3 (7 to 9 stools/day > pretx)

  Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/m2

  ↓ 25 mg/m2

  ↓ 50 mg/m2

  4 (≥ 10 stools/day > pretx)

  Omit dose until resolved to ≤ grade 2 then ↓ 50 mg/m2

  ↓ 50 mg/m2

  ↓ 50 mg/m2

  Other nonhematologicd toxicities

  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

  2.3 Dosage in Patients with Reduced UGT1A1 Activity

  When administered in as a single-agent, a reduction in the starting dose by at least one level of irinotecan hydrochloride injection should be considered for patients known to be homozygous for the UGT1A1*28 allele [see Dosage and Administration (2.2) and Warnings and Precautions (5.3)]. However, the precise dose reduction in this patient population is not known, and subsequent dose modifications should be considered based on individual patient tolerance to treatment (see Tables 1 to 4).

  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 irinotecan hydrochloride injection. Physicians should also consider providing patients with an antiemetic regimen (e.g., prochlorperazine) for subsequent use as needed.

  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.

  Irinotecan hydrochloride injection 20 mg/mL is intended for single use only and any unused portion should be discarded.

  Irinotecan hydrochloride injection must be diluted prior to infusion. Irinotecan hydrochloride injection 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.

  The solution is physically and chemically stable for up to 24 hours at room temperature and in ambient fluorescent lighting. Solutions diluted in 5% Dextrose Injection, USP, and stored at refrigerated temperatures (approximately 2° to 8°C, 36° to 46°F), 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 irinotecan hydrochloride injection and admixtures of irinotecan hydrochloride injection may result in precipitation of the drug and should be avoided.

  The irinotecan hydrochloride injection solution should be used immediately after reconstitution as it contains no antibacterial preservative. 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 4 hours if kept at room temperature. If reconstitution and dilution are performed under strict aseptic conditions (e.g., on Laminar Air Flow bench), irinotecan hydrochloride injection solution should be used (infusion completed) within 12 hours at room temperature or 24 hours if refrigerated (2° to 8°C, 36° to 46°F).

  2.6 Safe Handling

  Care should be exercised in the handling and preparation of infusion solutions prepared from irinotecan hydrochloride injection. The use of gloves is recommended. If a solution of irinotecan hydrochloride injection contacts the skin, wash the skin immediately and thoroughly with soap and water. If irinotecan hydrochloride injection contacts the mucous membranes, flush thoroughly with water. Several published guidelines for handling and disposal of anticancer agents are available.

  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.

  Close
  No Recall

  More Info
• Sun Pharma Global Fze
  

  ×

  Irinotecan Hydrochloride | Sun Pharma Global Fze

  

  ---

  Dosage in Patients with Reduced UGT1A1 Activity

  When administered as a single-agent, a reduction in the starting dose by at least one level of irinotecan hydrochloride injection should be considered for patients known to be homozygous for the UGT1A1*28 allele (See CLINICAL PHARMACOLOGY and WARNINGS). However, the precise dose reduction in this patient population is not known and subsequent dose modifications should be considered based on individual patient tolerance to treatment (See Tables 7-8).

  Single-Agent Dosage Schedules Dosage Regimens

  Irinotecan hydrochloride injection 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 7.

  Table 7. Single-Agent Regimens of Irinotecan Hydrochloride Injection and Dose Modifications * Subsequent doses may be adjusted as high as 150 mg/m 2 or to as low as 50 mg/m 2 in 25 to 50 mg/m 2 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 2 in 50 mg/m 2 decrements depending upon individual patient tolerance. Weekly Regimen* 125 mg/m2 IV over 90 min, d 1,8,15,22 then 2-wk rest Starting Dose & Modified Dose Levels† (mg/m2) Starting Dose Dose Level -1 Dose Level -2 125 100 75 Once-Every-3-Week Regimen‡ 350 mg/m2 IV over 90 min, once every 3 wks† Starting Dose & Modified Dose Levels (mg/m2) Starting Dose Dose Level -1 Dose Level-2 350 300 250

  A reduction in the starting dose by one dose level of irinotecan hydrochloride injection may be considered for patients with any of the following conditions: age ≥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 because there is insufficient information to recommend a dose in these patients.

  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 irinotecan hydrochloride injection should be modified as necessary to accommodate individual patient tolerance to treatment. Based on recommended dose-levels described in Table 7, Single-Agent Regimens of Irinotecan Hydrochloride Injection and Dose Modifications, subsequent doses should be adjusted as suggested in Table 8, 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 irinotecan hydrochloride injection may be continued indefinitely as long as patients continue to experience clinical benefit.

  Table 8. 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 A new cycle of therapy should not begin until the granulocyte count has recovered to ≥1500/mm3, and the platelet count has recovered to ≥100,000/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 irinotecan hydrochloride injection. Worst Toxicity NCI
  Grade† (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 Cycle* 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 > pretx‡) 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 (≥10 stools/day > pretx) Omit dose until resolved to ≤ grade 2 then ↓50 mg/m2 ↓50 mg/m2 ↓50 mg/m2 Other nonhematologic§ toxicities 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 Preparation & Administration Precautions

  As with other potentially toxic anticancer agents, care should be exercised in the handling and preparation of infusion solutions prepared from irinotecan hydrochloride injection. The use of gloves is recommended. If a solution of irinotecan hydrochloride injection contacts the skin, wash the skin immediately and thoroughly with soap and water. If irinotecan hydrochloride injection contacts the mucous membranes, flush thoroughly with water.

  Several published guidelines for handling and disposal of anticancer agents are available.1-8

  Preparation of Infusion Solution

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

  Irinotecan hydrochloride injection must be diluted prior to infusion. Irinotecan hydrochloride injection 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, irinotecan hydrochloride injection 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 irinotecan hydrochloride injection and admixtures of irinotecan hydrochloride injection 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.

  Close
  No Recall

  More Info
• App Pharmaceuticals, Llc
  

  ×

  Irinotecan Hydrochloride | App Pharmaceuticals, Llc

  

  ---

  Single-Agent Dosage Schedules

  Dosage Regimens

  Irinotecan hydrochloride injection 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 7.

  Table 7. Single-Agent Regimens Of Irinotecan Hydrochloride Injection And Dose Modifications 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.
  c Provided intolerable toxicity does not develop, treatment with additional cycles may be continued indefinitely as long as patients continue to experience clinical benefit. Weekly Regimena
  125 mg/m2 IV over 90 min, d 1,8,15,22 then 2-wk rest
  Starting Dose and 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 and Modified Dose Levels (mg/m2)
  Starting Dose
  Dose Level-1
  Dose Level-2
  350
  300
  250
  

  A reduction in the starting dose by one dose level of irinotecan hydrochloride injection 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.

  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 section.

  Dose Modifications

  Patients should be carefully monitored for toxicity and doses of irinotecan hydrochloride injection should be modified as necessary to accommodate individual patient tolerance to treatment. Based on recommended dose-levels described in Table 7, Single-Agent Regimens of irinotecan hydrochloride injection and Dose Modifications, subsequent doses should be adjusted as suggested in Table 8, 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 irinotecan hydrochloride injection may be continued indefinitely as long as patients continue to experience clinical benefit.

  Table 8. Recommended Dose Modifications For Single-Agent Schedulesa A new cycle of therapy should not begin until the granulocyte count has recovered to ≥1500/ mm3, and the platelet count has recovered to ≥100,000/ 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 irinotecan. aAll dose modifications should be based on the worst preceding toxicity
  bNational Cancer Institute Common Toxicity Criteria (version 1.0)
  cPretreatment
  dExcludes alopecia, anorexia, asthenia
  Worst Toxicity
  NCI Gradeb(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/mm2 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/mm2 Maintain dose level Maintain dose level 3 (500 to 999/ mm3) Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/mm2 ↓ 25 mg/mm2 ↓ 50 mg/mm2 4 (<500/ mm3) Omit dose until resolved to ≤ grade 2, then ↓ 50 mg/mm2 ↓ 50 mg/mm2
    ↓ 50 mg/mm2 Neutropenic fever Omit dose until resolved, then
  ↓ 50 mg/mm2 when resolved ↓ 50 mg/mm2 ↓ 50 mg/mm2 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/mm2 Maintain dose level Maintain dose level 3 (7-9 stools/day > pretx) Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/mm2 ↓ 25 mg/mm2 ↓ 50 mg/mm2 4 (≥10 stools/day > pretx) Omit dose until resolved to ≤ grade 2, then ↓ 50 mg/mm2 ↓ 50 mg/mm2
    ↓ 50 mg/mm2 Other
  nonhematologicd
  toxicities
   
   
    1 Maintain dose level Maintain dose level Maintain dose level 2 ↓ 25 mg/mm2 ↓ 25 mg/mm2 ↓ 50 mg/mm2 3 Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/mm2 ↓ 25 mg/mm2
    ↓ 50 mg/mm2
    4 Omit dose until resolved to ≤ grade 2, then ↓ 50 mg/mm2 ↓ 50 mg/m2 ↓ 50 mg/mm2
   

  Dosage in Patients with Reduced UGT1A1 Activity

  When administered as a single-agent, a reduction in the starting dose by at least one level of irinotecan hydrochloride injection should be considered for patients known to be homozygous for the UGT1A1*28 allele (see CLINICAL PHARMACOLOGY and WARNINGS sections). However, the precise dose reduction in this patient population is not known and subsequent dose modifications should be considered based on individual patient tolerance to treatment (see tables 7 to 8).

  Preparation and Administration Precautions

  As with other potentially toxic anticancer agents, care should be exercised in the handling and preparation of infusion solutions prepared from irinotecan hydrochloride injection. The use of gloves is recommended. If a solution of irinotecan hydrochloride injection contacts the skin, wash the skin immediately and thoroughly with soap and water. If irinotecan hydrochloride injection contacts the mucous membranes, flush thoroughly with water.

  Several published guidelines for handling and disposal of anticancer agents are available.1-4

  Preparation of Infusion Solution

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

  Irinotecan hydrochloride injection must be diluted prior to infusion. Irinotecan hydrochloride injection 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, irinotecan hydrochloride injection 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 irinotecan hydrochloride injection and admixtures of irinotecan hydrochloride injection 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.

  Close
  No Recall

  More Info
• Sandoz Inc
  

  ×

  Irinotecan Hydrochloride | Sandoz Inc

  

  ---

  2.2 Colorectal Single Agent Regimens 1 and 2

  Administer irinotecan hydrochloride injection 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 irinotecan hydrochloride injection 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 Irinotecan Hydrochloride Injection and Dose Modifications * Subsequent doses may be adjusted as high as 150 mg/m 2 or to as low as 50 mg/m 2 in 25 to 50 mg/m 2 decrements depending upon individual patient tolerance. † Subsequent doses may be adjusted as low as 200 mg/m 2 in 50 mg/m 2 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.

  Regimen 1 (weekly)*

  125 mg/m2 intravenous infusion over 90 minutes, days 1,8,15,22 then 2-week rest

    Starting Dose and Modified Dose Levels† (mg/m2)

  Starting Dose

  Dose Level -1

  Dose Level -2

  125

  100

  75

  Regimen 2 (every 3 weeks)‡

  350 mg/m2 intravenous infusion over 90 minutes, once every 3 weeks†

    Starting Dose and Modified Dose Levels (mg/m2)

  Starting Dose

  Dose Level -1

  Dose Level -2

  350

  300

  250

  Dose Modifications

  Based on recommended dose-levels described in Table 3, Single-Agent Regimens of Irinotecan Hydrochloride Injection 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* A new cycle of therapy should not begin until the granulocyte count has recovered to ≥1500/mm3, and the platelet count has recovered to ≥100,000/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 irinotecanhydrochloride injection. Worst Toxicity
  NCI Grade† (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 Cycle* Weekly Weekly Once every 3 weeks * All dose modifications should be based on the worst preceding toxicity † National Cancer Institute Common Toxicity Criteria (version 1) ‡ Pretreatment § Excludes alopecia, anorexia, asthenia

  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 > pretx‡)

  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 (≥10 stools/day > pretx)

  Omit dose until resolved to ≤ grade 2 then ↓ 50 mg/m2

  ↓ 50 mg/m2

  ↓ 50 mg/m2

  Other nonhematologic§ toxicities

  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

  2.3 Dosage in Patients with Reduced UGT1A1 Activity

  When administered in combination with other agents, or as a single-agent, a reduction in the starting dose by at least one level of irinotecan hydrochloride injection should be considered for patients known to be homozygous for the UGT1A1*28 allele [see DOSAGE AND ADMINISTRATION (2.2) and WARNINGS AND PRECAUTIONS (5.3)]. However, the precise dose reduction in this patient population is not known, and subsequent dose modifications should be considered based on individual patient tolerance to treatment (see Tables 3 and 4).

  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 irinotecan hydrochloride injection. Physicians should also consider providing patients with an antiemetic regimen (e.g., prochlorperazine) for subsequent use as needed. 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.

  Irinotecan hydrochloride injection 20 mg/mL is intended for single use only and any unused portion should be discarded.

  Irinotecan hydrochloride injection must be diluted prior to infusion. Irinotecan hydrochloride injection 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.

  The solution is physically and chemically stable for up to 24 hours at room temperature and in ambient fluorescent lighting. Solutions diluted in 5% Dextrose Injection, USP, and stored at refrigerated temperatures (approximately 2° to 8°C, 36° to 46°F), 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 irinotecan hydrochloride injection and admixtures of irinotecan hydrochloride injection may result in precipitation of the drug and should be avoided.

  The irinotecan hydrochloride injection solution should be used immediately after reconstitution as it contains no antibacterial preservative. 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 4 hours if kept at room temperature. If reconstitution and dilution are performed under strict aseptic conditions (e.g., on Laminar Air Flow bench), irinotecan hydrochloride injection solution should be used (infusion completed) within 12 hours at room temperature or 24 hours if refrigerated (2° to 8°C, 36° to 46°F).

  2.6 Safe Handling

  Care should be exercised in the handling and preparation of infusion solutions prepared from irinotecan hydrochloride injection. The use of gloves is recommended. If a solution of irinotecan hydrochloride injection contacts the skin, wash the skin immediately and thoroughly with soap and water. If irinotecan hydrochloride contacts the mucous membranes, flush thoroughly with water. Several published guidelines for handling and disposal of anticancer agents are available.

  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.

  Close
  No Recall

  More Info
• Sagent Pharmaceuticals
  

  ×

  Irinotecan Hydrochloride | Sagent Pharmaceuticals

  

  ---

  Single-Agent Dosage Schedules Dosage Regimens

  Irinotecan Hydrochloride Injection 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 12.

  Table 12. Single-Agent Regimens of Irinotecan Hydrochloride Injection and Dose Modifications

  a Subsequent 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.

  b Subsequent doses may be adjusted as low as 200 mg/m2 in 50 mg/m2 decrements depending upon individual patient tolerance.

  c Provided intolerable toxicity does not develop, treatment with additional cycles may be continued indefinitely as long as patients continue to experience clinical benefit.

  Weekly Regimena 125 mg/m2 IV over 90 min, d 1, 8, 15, 22 then 2-wk rest Starting Dose and 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 and Modified Dose Levels (mg/m2) Starting Dose Dose Level -1 Dose Level -2 350 300 250

  A reduction in the starting dose by one dose level of Irinotecan Hydrochloride Injection 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.

  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 Irinotecan Hydrochloride Injection should be modified as necessary to accommodate individual patient tolerance to treatment. Based on recommended dose-levels described in Table 12, Single-Agent Regimens of Irinotecan Hydrochloride Injection and Dose Modifications, subsequent doses should be adjusted as suggested in Table 13, 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 Irinotecan Hydrochloride Injection may be continued indefinitely as long as patients continue to experience clinical benefit.

  Table 13. Recommended Dose Modifications For Single-Agent Schedulesa

  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

  A new cycle of therapy should not begin until the granulocyte count has recovered to ≥1500/mm3, and the platelet count has recovered to ≥100,000/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 Irinotecan Hydrochloride Injection. Worst Toxicity
  NCI Gradeb (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)
  2 (1000 to 1499/mm3)
  3 (500 to 999/mm3)
  4 (<500/mm3) Maintain dose level
  ↓ 25 mg/m2
  Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/m2
  Omit dose until resolved to ≤ grade 2, then ↓ 50 mg/m2 Maintain dose level
  Maintain dose level
  ↓ 25 mg/m2
  ↓ 50 mg/m2 Maintain dose level
  Maintain dose level
  ↓ 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 to 3 stools/day > pretxc)
  2 (4 to 6 stools/day > pretx)
  3 (7 to 9 stools/day > pretx)
  4 (≥10 stools/day > pretx) Maintain dose level
  ↓ 25 mg/m2
  Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/m2
  Omit dose until resolved to ≤ grade 2 then ↓ 50 mg/m2 Maintain dose level
  Maintain dose level
  ↓ 25 mg/m2
  ↓ 50 mg/m2 Maintain dose level
  Maintain dose level
  ↓ 50 mg/m2
  ↓ 50 mg/m2 Other nonhematologicd
  toxicities
  1
  2
  3
  4 Maintain dose level
  ↓ 25 mg/m2
  Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/m2
  Omit dose until resolved to ≤ grade 2, then ↓ 50 mg/m2 Maintain dose level
  ↓ 25 mg/m2
  ↓ 25 mg/m2
  ↓ 50 mg/m2 Maintain dose level
  ↓ 50 mg/m2
  ↓ 50 mg/m2
  ↓ 50 mg/m2 Dosage in Patients with Reduced UGT1A1 Activity

  When administered in combination with other agents, or as a single-agent, a reduction in the starting dose by at least one level of Irinotecan Hydrochloride Injection should be considered for patients known to be homozygous for the UGT1A1*28 allele (see CLINICAL PHARMACOLOGY and WARNINGS). However, the precise dose reduction in this patient population is not known and subsequent dose modifications should be considered based on individual patient tolerance to treatment (see Tables 12 and 13).

  Preparation & Administration Precautions

  As with other potentially toxic anticancer agents, care should be exercised in the handling and preparation of infusion solutions prepared from Irinotecan Hydrochloride Injection. The use of gloves is recommended. If a solution of Irinotecan Hydrochloride Injection contacts the skin, wash the skin immediately and thoroughly with soap and water. If Irinotecan Hydrochloride Injection contacts the mucous membranes, flush thoroughly with water.

  Several published guidelines for handling and disposal of anticancer agents are available.1-4

  Preparation of Infusion Solution

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

  Irinotecan Hydrochloride Injection must be diluted prior to infusion. Irinotecan Hydrochloride Injection 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, Irinotecan Hydrochloride Injection 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°C 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 Irinotecan Hydrochloride Injection and admixtures of Irinotecan Hydrochloride Injection 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°C to 8°C, 36°F 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°C to 30°C, 59°F 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.

  Close
  No Recall

  More Info
• Areva Pharmaceuticals,inc.
  

  ×

  Irinotecan Hydrochloride | Areva Pharmaceuticals,inc.

  

  ---

  Combination-Agent Dosage

  Dosage Regimens

  Irinotecan hydrochloride Injection in Combination with 5-Fluorouracil (5-FU) and Leucovorin (LV)

  Irinotecan 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 Irinotecan, with the administration of 5-FU to occur immediately after receipt of LV. Irinotecan should be used as recommended; the currently recommended regimens are shown in Table 10.

  Table 10. Combination-Agent Dosage Regimens & Dose Modificationsa

  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.
  

  Regimen 1
  6-wk cycle with bolus 5-FU/LV
  (next cycle begins on day 43)
  
  Irinotecan 
  LV
  5-FU
  125mg/m2IV over90min, d 1,8,15,22
  20mg/m2IV bolus, d 1,8,15,22
  500mg/m2IV bolus, d 1,8,15,22
  
  
  
  
  Starting Dose & Modified Dose Levels (mg/m2)
  
  
  
  
  Starting Dose
  Dose Level-1
  Dose Level-2
  
  Irinotecan
  LV
  5-FU
  125
  20
  500
  100
  20
  400
  75
  20
  300
  Regimen 2
  6-wk cycle with
  Infusional 5-FU/LV
  (next cycle begins on day 43)
  Irinotecan
  LV
  5-FU Bolus
  5-FU Infusionb
  180mg/m2IV over 90 min, d 1,15,29
  200mg/m2IV over 2h, d 1,2,15,16,29,30
  400mg/m2IV bolus, d 1,2,15,16,29,30
  600mg/m2IV over22h, d 1,2,15,16,29,30
  
  
  
  
  Starting Dose & Modified Dose Levels (mg/m2)
  
  
  
  
  Starting Dose
  Dose Level-1
  Dose :evel-2
  
  
  180
  200
  400
  600
  150
  200
  320
  480
  120
  200
  240
  360
  

  Dosing for patients with bilirubin >2 mg/dL cannot be recommended because there is insufficient information to recommend a dose in these patients. 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 Irinotecan and 5-FU should be modified as necessary to accommodate individual patient tolerance to treatment. Based on the recommended dose-levels described in Table 10, Combination-Agent Dosage Regimens & Dose Modifications, subsequent doses should be adjusted as suggested in Table 11, 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 anti-diarrhea 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 Irinotecan /5-FU/LV may be continued indefinitely as long as patients continue to experience clinical benefit.

  Table 11. Recommended Dose Modifications for Irinotecan/5-Fluorouracil (5-FU)/Leucovorin (LV) Combination Schedules

  aNational Cancer Institute Common Toxicity Criteria (version 1.0)
  

  bRelative to the starting dose used in the previous cycle
  

  cPretreatment
  

  dExcludes alopecia, anorexia, asthenia
  

  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 >1500/mm3, and the platelet count has recovered to > 100,000/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 gradea (Value)
  During a Cycle of Therapy
  At the Start of Subsequent 
  Cycles of Therapyb
  No toxicity
  Maintain dose level
  Maintain dose level
  Neutropenia
  1 (1500 to 1999/mm3)
  2 (1000 to 1499/mm3)
  3 (500 to 999/mm3)
  
  4 (<500/mm3)
  
  Maintain dose level
  ↓1 dose level
  Omit dose until resolved to 
  < grade 2 then ↓ 1 dose level
  Omit dose until resolved to 
  < grade 2 then ↓2, dose levels 
  
  Maintain dose level
  Maintain dose level
  ↓1 dose level
  
  ↓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)
  
  2 (4-6 stools/day > pretx)
  
  3 (7-9 stools/day > pretx)
  
  4 (> 10 stools/day > pretx)
  
  Delay dose until resolved to baseline, then give same dose
  Omit dose until resolved to 
  baseline, then ↓1 dose level
  Omit dose until resolved to 
  baseline, then ↓1 dose level
  Omit dose until resolved to 
  baseline then ↓2 dose levels 
  
  Maintain dose level
  
  Maintain dose level
  
  ↓1 dose level
  
  ↓2 dose levels
  
  Other nonhematologic toxicitiesd1
  2
  
  3
  
  4
  
  
  Maintain dose level
  Omit dose until resolved to 
  < grade 1, then ↓1, then 
  Omit dose until resolved to 
  < grade 2, then ↓1 dose level
  Omit dose until resolved to
   < grade 2 then ↓2 dose level 
  For mucositis/stomatitis decrease 
  only 5-FU, not irinotecan
  
  Maintain dose level
  Maintain dose level
  
  ↓1 dose level
  
  ↓2 dose levels
  
  For mucositis/stomatitis decrease only 5-FU, not irinotecan.
  Single-Agent Dosage Schedules

  Dosage Regimens

  Irinotecan 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 12.

  Table 12. Single-Agent Regimens of Irinotecan and Dose Modifications

  aSubsequent doses may be adjusted as high as 150 mg/m2or to as low as 50 mg/m2in 25 to 50 mg/m2decrements depending upon individual patient tolerance.
  

  bSubsequent doses may be adjusted as low as 200 mg/m2in 50 mg/m2decrements 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.
  

  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
  

  A reduction in the starting dose by one dose level of Irinotecan 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.

  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 Irinotecan should be modified as necessary to accommodate individual patient tolerance to treatment. Based on recommended dose-levels described in Table 12, Single-Agent Regimens of Irinotecan and Dose Modifications, subsequent doses should be adjusted as suggested in Table 13, 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 Irinotecan may be continued indefinitely as long as patients continue to experience clinical benefit.

  Table 13. Recommended Dose Modifications For Single-Agent Schedulesa

  aAll dose modifications should be based on the worst preceding toxicity
  

  bNational Cancer Institute Common Toxicity Criteria (version 1.0)
  

  cPretreatment
  

  dExcludes alopecia, anorexia, asthenia
  

  A new cycle of therapy should not begin until the granulocyte count has recovered to >1500/mm3, and the platelet count has recovered to > 100,000/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 irinotecan.
  Worst Toxicity
  NCI Gradeb (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)
  2 (1000 to 1499/mm3)
  3 (500 to 999/mm3)
  
  4 (<500/mm3)
  
  Maintain dose level 
  ↓25 mg/m2Omit dose until resolved to < grade 2, then ↓25 mg/m 2Omit dose until resolved to < grade 2, then ↓50 mg/m2
  
  Maintain dose level
  Maintain dose level
  ↓25 mg/m2↓50 mg/m2
  
  Maintain dose level
  Maintain dose level
  ↓50 mg/m2↓50 mg/m2
  Neutropenic fever
  Omit dose until resolved then
   ↓50 mg/m 2 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)
  2 (4-6 stools/day > pretx)
  3 (7-9 stools/day > pretx)
  
  4 (> 10 stools/day > pretx)
  
  Maintain dose level
  ↓25 mg/m2Omit dose until resolved to
   < grade 2, then 25 mg/m2Omit dose until resolved to 
  < grade 2 then ↓50 mg/m2
  
  Maintain dose level
  Maintain dose level
  ↓25 mg/m2↓50 mg/m2
  
  Maintain dose level
  Maintain dose level
  ↓50 mg/m2↓50 mg/m2
  Other nonhematologicdToxicities
  1
  2
  3
  
  4
  
  
  Maintain dose level
  ↓25 mg/m2Omit dose until resolved to 
  < grade 2, then ↓25 mg/m2Omit dose until resolved to 
  < grade 2, then ↓50 mg/m2
  
  
  Maintain dose level
  ↓25 mg/m2↓25 mg/m2↓50 mg/m2
  
  
  Maintain dose level
  ↓50 mg/m2↓50 mg/m2↓50 mg/m2
  Dosage in Patients with Reduced UGT1A1 Activity

  When administered in combination with other agents, or as a single-agent, a reduction in the starting dose by at least one level of Irinotecan should be considered for patients known to be homozygous for the UGT1A1*28 allele (see CLINICAL PHARMACOLOGY and WARNINGS). However, the precise dose reduction in this patient population is not known and subsequent dose modifications should be considered based on individual patient tolerance to treatment (see Tables 10-13).

  Preparation & Administration Precautions

  As with other potentially toxic anticancer agents, care should be exercised in the handling and preparation of infusion solutions prepared from Irinotecan hydrochloride Injection. The use of gloves is recommended. If a solution of Irinotecan contacts the skin, wash the skin immediately and thoroughly with soap and water. If Irinotecan 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.

  Irinotecan Injection must be diluted prior to infusion. Irinotecan 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, Irinotecan 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 Irinotecan and admixtures of Irinotecan 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.

  Close
  No Recall

  More Info
• Teva Parenteral Medicines, Inc.
  

  ×

  Irinotecan Hydrochloride | Paddock Laboratories, Llc

  

  ---

  Prior to initiating testosterone cypionate, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range.

  Testosterone cypionate injection is for intramuscular use only.

  It should not be given intravenously. Intramuscular injections should be given deep in the gluteal muscle.

  The suggested dosage for testosterone cypionate injection varies depending on the age, sex, and diagnosis of the individual patient. Dosage is adjusted according to the patient’s response and the appearance of adverse reactions.

  Various dosage regimens have been used to induce pubertal changes in hypogonadal males; some experts have advocated lower dosages initially, gradually increasing the dose as puberty progresses, with or without a decrease to maintenance levels. Other experts emphasize that higher dosages are needed to induce pubertal changes and lower dosages can be used for maintenance after puberty. The chronological and skeletal ages must be taken into consideration, both in determining the initial dose and in adjusting the dose.

  For replacement in the hypogonadal male, 50 to 400 mg should be administered every two to four weeks.

  Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Warming and shaking the vial should redissolve any crystals that may have formed during storage at temperatures lower than recommended.

  Close
  No Recall

  More Info
• Cipla Limited
  

  ×

  Irinotecan Hydrochloride | Cipla Limited

  

  ---

  2.1 Colorectal Cancer Combination Regimens 1 and 2

  Administer Irinotecan 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 Irinotecan 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.

  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 Irinotecan 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.

  2.2 Colorectal Single Agent Regimens 1 and 2

  Administer Irinotecan 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 Irinotecan 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.

  Dose Modifications

  Based on recommended dose-levels described in Table 3, Single-Agent Regimens of Irinotecan 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.

  2.3 Dosage in Patients with Reduced UGT1A1 Activity

  When administered in combination with other agents, or as a single-agent, a reduction in the starting dose by at least one level of Irinotecan should be considered for patients known to be homozygous for the UGT1A1*28 allele [see Dosage and Administration (2.1 and 2.2) and Warnings and Precautions (5.3)]. However, the precise dose reduction in this patient population is not known, and subsequent dose modifications should be considered based on individual patient tolerance to treatment (see Tables 1-4).

  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 Irinotecan. 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 Irinotecan 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.

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

  Irinotecan hydrochloride Injection must be diluted prior to infusion. Irinotecan 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.

  The solution is physically and chemically stable for up to 24 hours at room temperature and in ambient fluorescent lighting. Solutions diluted in 5% Dextrose Injection, USP, and stored at refrigerated temperatures (approximately 2° to 8°C, 36° to 46°F), 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 Irinotecan and admixtures of Irinotecan may result in precipitation of the drug and should be avoided.

  The Irinotecan hydrochloride Injection solution should be used immediately after reconstitution as it contains no antibacterial preservative. 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 4 hours if kept at room temperature. If reconstitution and dilution are performed under strict aseptic conditions (e.g. on Laminar Air Flow bench), Irinotecan hydrochloride Injection solution should be used (infusion completed) within 12 hours at room temperature or 24 hours if refrigerated (2° to 8°C, 36° to 46°F).

  2.6 Safe Handling

  Care should be exercised in the handling and preparation of infusion solutions prepared from Irinotecan hydrochloride Injection. The use of gloves is recommended. If a solution of Irinotecan contacts the skin, wash the skin immediately and thoroughly with soap and water. If Irinotecan contacts the mucous membranes, flush thoroughly with water. Several published guidelines for handling and disposal of anticancer agents are available.

  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.

  Close
  No Recall

  More Info
• Hospira Worldwide, Inc.
  

  ×

  Irinotecan Hydrochloride | Hospira Worldwide, Inc.

  

  ---

  2.1 Colorectal Single Agent Regimens 1 and 2

  Administer Irinotecan Hydrochloride Injection, USP as a 90-minute intravenous infusion. The currently recommended regimens are shown in Table 1.

  A reduction in the starting dose by one dose level of Irinotecan Hydrochloride Injection, USP 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. Single-Agent Regimens of Irinotecan Hydrochloride Injection, USP and Dose Modifications a     Subsequent 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.
  b     Subsequent doses may be adjusted as low as 200 mg/m2 in 50 mg/m2 decrements depending upon individual patient tolerance.
  c     Provided intolerable toxicity does not develop, treatment with additional cycles may be continued indefinitely as long as patients continue to experience clinical benefit.

  Regimen 1 (weekly)a

  125 mg/m2 intravenous infusion over 90 minutes, days 1, 8, 15, 22 then 2-week rest

  Starting Dose and Modified Dose Levelsc (mg/m2)

  Starting Dose

  Dose Level -1

  Dose Level -2

  125

  100

  75

  Regimen 2 (every 3 weeks)b

  350 mg/m2 intravenous infusion over 90 minutes, once every 3 weeksc

  Starting Dose and Modified Dose Levels (mg/m2)

  Starting Dose

  Dose Level -1

  Dose Level -2

  350

  300

  250

  Dose Modifications

  Based on recommended dose-levels described in Table 1, Single-Agent Regimens of Irinotecan Hydrochloride Injection, USP and Dose Modifications, subsequent doses should be adjusted as suggested in Table 2, Recommended Dose Modifications for Single-Agent Schedules. All dose modifications should be based on the worst preceding toxicity.

  Table 2. Recommended Dose Modifications for Single-Agent Schedulesa 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

  A new cycle of therapy should not begin until the granulocyte count has recovered to ≥1500/mm3, and the platelet count has recovered to ≥100,000/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 Irinotecan Hydrochloride Injection, USP.

  Worst Toxicity
  NCI Gradeb (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 (≥10 stools/day > pretx)

  Omit dose until resolved to ≤ grade 2, then ↓ 50 mg/m2

  ↓ 50 mg/m2

  ↓ 50 mg/m2

  Other nonhematologicd toxicities

   

   

   

  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 

  2.2 Dosage in Patients with Reduced UGT1A1 Activity

  When administered as a single-agent, a reduction in the starting dose by at least one level of Irinotecan Hydrochloride Injection, USP should be considered for patients known to be homozygous for the UGT1A1*28 allele [see Dosage and Administration (2.1) and Warnings and Precautions (5.3)]. However, the precise dose reduction in this patient population is not known, and subsequent dose modifications should be considered based on individual patient tolerance to treatment (see Tables 1-2).

  2.3 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 Irinotecan Hydrochloride Injection, USP. Physicians should also consider providing patients with an antiemetic regimen (e.g., prochlorperazine) for subsequent use as needed.

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

  2.4 Preparation of Infusion Solution

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

  Irinotecan Hydrochloride Injection, USP 20 mg/mL is intended for single use only and any unused portion should be discarded.

  Irinotecan Hydrochloride Injection, USP must be diluted prior to infusion. Irinotecan Hydrochloride Injection, USP 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.

  The solution is physically and chemically stable for up to 24 hours at room temperature and in ambient fluorescent lighting. Solutions diluted in 5% Dextrose Injection, USP, and stored at refrigerated temperatures (approximately 2° to 8°C, 36° to 46°F), 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 Irinotecan Hydrochloride Injection, USP and admixtures of Irinotecan Hydrochloride Injection, USP may result in precipitation of the drug and should be avoided.

  The Irinotecan Hydrochloride Injection, USP solution should be used immediately after reconstitution as it contains no antibacterial preservative. 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 4 hours if kept at room temperature. If reconstitution and dilution are performed under strict aseptic conditions (e.g. on Laminar Air Flow bench), Irinotecan Hydrochloride Injection, USP solution should be used (infusion completed) within 12 hours at room temperature or 24 hours if refrigerated (2° to 8°C, 36° to 46°F).

  2.5 Safe Handling

  Care should be exercised in the handling and preparation of infusion solutions prepared from Irinotecan Hydrochloride Injection, USP. The use of gloves is recommended. If a solution of Irinotecan Hydrochloride Injection, USP contacts the skin, wash the skin immediately and thoroughly with soap and water. If Irinotecan Hydrochloride Injection, USP contacts the mucous membranes, flush thoroughly with water. Several published guidelines for handling and disposal of anticancer agents are available.

  2.6 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.

  Close
  No Recall

  More Info
• Heritage Pharmaceuticals Inc.
  

  ×

  Irinotecan Hydrochloride | Heritage Pharmaceuticals Inc.

  

  ---

  2.2 Colorectal Single Agent Regimens 1 and 2

  Administer irinotecan hydrochloride injection, USP 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 irinotecan hydrochloride injection, USP 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 greater than 2 mg/dL cannot be recommended because there is insufficient information to recommend a dose in these patients.

  Table 3. Single-Agent Regimens of Irinotecan hydrochloride injection, USP and Dose Modifications

  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.
  

  Regimen 1 (weekly)a
  125 mg/m2  intravenous infusion over 90 minutes, days 1,8,15,22 then 2-week rest 
  
  Starting Dose and Modified Dose Levelsc(mg/m2)
  
  Starting Dose Dose Level -1 Dose Level -2 
  
  125 100 75
  Regimen 2 (every 3 weeks)b
  350 mg/m2 intravenous infusion over 90 minutes, once every 3 weeksc
  
  Starting Dose and Modified Dose Levels (mg/m2)
  
  Starting Dose Dose Level -1 Dose Level -2 
  
  350 300 250
  

  Dose Modifications

  Based on recommended dose-levels described in Table 3, Single-Agent Regimens of irinotecan hydrochloride injection, USP 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 Schedulesa

  aAll dose modifications should be based on the worst preceding toxicity
  

  bNational Cancer Institute Common Toxicity Criteria (version 1.0)
  

  cPretreatment
  

  dExcludes alopecia, anorexia, asthenia
  

  A new cycle of therapy should not begin until the granulocyte count has recovered to greater than or equal
  to 1500/mm3, and the platelet count has recovered to greater than or equal to 100,000/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 irinotecan hydrochloride injection, USP.
  Worst Toxicity
  NCI Gradeb (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)
  2 (1000 to 
  1499/mm3) 
  3 (500 to 999/mm3) 
  4 (<500/mm3) 
  Maintain dose level
  ↓ 25 mg/m2
  Omit dose until
  resolved to ≤ grade 2,
  then ↓
  25 mg/m2
  Omit dose until
  resolved to ≤ grade 2,
  then ↓
  50 mg/m2
  Maintain dose level
  Maintain dose level
  ↓ 25 mg/m2
  ↓ 50 mg/m2
  Maintain dose level
  Maintain dose level
  ↓ 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)
  2 (4-6 stools/day >
  pretx)
  3 (7-9 stools/day >
  pretx)
  4 (≥10 stools/day >
  pretx) 
  Maintain dose level
  ↓ 25 mg/m2
  Omit dose until
  resolved to ≤ grade 2,
  then ↓
  25 mg/m2
  Omit dose until
  resolved to ≤ grade 2,
  then ↓
  50 mg/m2
  Maintain dose level
  Maintain dose level
  ↓ 25 mg/m2
  ↓ 50 mg/m2
  Maintain dose level
  Maintain dose level
  ↓ 50 mg/m2
  ↓ 50 mg/m2
  Other
  nonhematologicd  toxicities
  1
  2
  3
  4 
  Maintain dose level
  ↓ 25 mg/m2
  Omit dose until
  resolved to ≤ grade 2,
  then ↓
  25 mg/m2
  Omit dose until
  resolved to ≤ grade 2,
  then ↓
  50 mg/m2
  Maintain dose level
  ↓ 25 mg/m2
  ↓ 25 mg/m2
  ↓ 50 mg/m2
  Maintain dose level
  ↓ 50 mg/m2
  ↓ 50 mg/m2
  ↓ 50 mg/m2
  2.3 Dosage in Patients with Reduced UGT1A1 Activity

  When administered as a single-agent, a reduction in the starting dose by at least one level of irinotecan hydrochloride injection, USP should be considered for patients known to be homozygous for the UGT1A1*28 allele [see Dosage and Administration (2.2) and Warnings and Precautions (5.3)]. However, the precise dose reduction in this patient population is not known, and subsequent dose modifications should be considered based on individual patient tolerance to treatment (see Tables 3 and 4).

  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 irinotecan hydrochloride injection, USP. Physicians should also consider providing patients with an antiemetic regimen (e.g., prochlorperazine) for subsequent use as needed.

  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.

  Irinotecan hydrochloride injection, USP 20 mg/mL is intended for single use only and any unused portion should be discarded.

  Irinotecan hydrochloride injection, USP must be diluted prior to infusion. Irinotecan hydrochloride injection, USP 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.

  The solution is physically and chemically stable for up to 24 hours at room temperature and in ambient fluorescent lighting. Solutions diluted in 5% Dextrose Injection, USP, and stored at refrigerated temperatures (approximately 2° to 8°C, 36° to 46°F), 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 irinotecan hydrochloride injection, USP and admixtures of irinotecan hydrochloride injection, USP may result in precipitation of the drug and should be avoided.

  The irinotecan hydrochloride injection, USP solution should be used immediately after reconstitution as it contains no antibacterial preservative. 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 4 hours if kept at room temperature. If reconstitution and dilution are performed under strict aseptic conditions (e.g. on Laminar Air Flow bench), irinotecan hydrochloride injection, USP solution should be used (infusion completed) within 12 hours at room temperature or 24 hours if refrigerated (2° to 8°C, 36° to 46°F).

  2.6 Safe Handling

  Care should be exercised in the handling and preparation of infusion solutions prepared from irinotecan hydrochloride injection, USP. The use of gloves is recommended. If a solution of irinotecan hydrochloride injection, USP contacts the skin, wash the skin immediately and thoroughly with soap and water. If irinotecan hydrochloride contacts the mucous membranes, flush thoroughly with water. Several published guidelines for handling and disposal of anticancer agents are available.

  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.

  Close
  No Recall

  More Info
• West-ward Pharmaceutical Corp
  

  ×

  Irinotecan Hydrochloride | Lorac Cosmetics, Inc.

  

  ---

  Apply 15 minutes prior to sun exposure and reapply as needed

  Spending time in the sun increases your risk of skin cancer and early skin aging To decrease this risk, regularly use a sunscreen with Broad Spectrum value at 15 or higher and other sun protection measures including Limit time in the sun, expecially from 10 a.m. to 2 p.m. Wear long-sleeved shirts, hats, pants and sunglasses Children under 6 months of age: Ask a doctor

  Close
  No Recall

  More Info
• Sagent Pharmaceuticals
  

  ×

  Irinotecan Hydrochloride | Glaxosmithkline Biologicals Sa

  

  ---

  For intramuscular injection only.

  2.1 Dosage and Schedule

  The dose and schedule for FLUARIX QUADRIVALENT are presented in Table 1.

  Table 1. FLUARIX QUADRIVALENT: Dosing

  Age

  Vaccination Status

  Dose and Schedule

  Aged 3 through 8 years

  Not previously vaccinated with influenza vaccine

  Two doses (0.5‑mL each) at least 4 weeks apart

  Vaccinated with influenza vaccine in a previous season

  One or two dosesa (0.5‑mL each)

  Aged 9 years and older

  Not applicable

  One 0.5‑mL dose

  a One dose or two doses (0.5‑mL each) depending on vaccination history as per the annual Advisory Committee on Immunization Practices (ACIP) recommendation on prevention and control of influenza with vaccines. If two doses, administer each 0.5‑mL dose at least 4 weeks apart.

  2.2 Administration Instructions

  Shake well before administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exists, the vaccine should not be administered.

  Attach a sterile needle to the prefilled syringe and administer intramuscularly.

  The preferred site for intramuscular injection is the deltoid muscle of the upper arm. Do not inject in the gluteal area or areas where there may be a major nerve trunk.

  Do not administer this product intravenously, intradermally, or subcutaneously.

  Close
  No Recall

  More Info