Irinocedal® is an anticancer medicine containing the active substance Irinotecan hydrochloride trihydrate.
Irinocedal® Injection is contraindicated in patients with a known hypersensitivity to the drug or its excipients. )Each milliliter of solution contains 20 mg of irinotecan hydrochloride (on the basis of the trihydrate salt), 45 mg of sorbitol, NF, and 0.9 mg of lactic acid, USP. The pH of the solution has been adjusted with sodium hydroxide.
Early diarrhea (occurring during or shortly after infusion of Irinocedal®) is usually transient and in frequently severe. It may be accompanied by cholinergic symptoms of rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing and intestinal hyperperistalsis that can cause abdominal cramping. Bradycardia may also occur. Early diarrhea and other cholinergic symptoms may be prevented or treated. Consider prophylactic or therapeutic administration of 0.25 mg to 1 mg of intravenous or subcutaneous atropine (unless clinically contraindicated). These symptoms are expected to occur more frequently with higher irinotecan doses.
Late diarrhea (generally occurring more than 24 hours after administration of Irinocedal®) can be life threatening since it may be prolonged and may lead to dehydration, electrolyte imbalance, or sepsis. Late diarrhea can be complicated by colitis, ulceration, bleeding, ileus, obstruction, and infection. Cases of megacolon and intestinal perforation have been reported. Patients should have loperamide readily available to begin treatment for late diarrhea. Begin loperamide at the first episode of poorly formed or loose stools or the earliest onset of bowel movements more frequent than normal. One dosage regimen for loperamide is 4 mg at the first onset of late diarrhea and then 2 mg every 2 hours until the patient is diarrhea-free for at least 12 hours. Loperamide is not recommended to be used for more than 48 consecutive hours at these doses, because of the risk of paralytic ileus. During the night, the patient may take 4 mg of loperamide every 4 hours. Monitor and replace fluid and electrolytes. Use antibiotic support for ileus, fever, or severe neutropenia. Subsequent weekly chemotherapy treatments should be delayed in patients until return of pretreatment bowel function for at least 24 hours without anti-diarrhea medication. Patients must not be treated with Irinocedal® until resolution of the bowel obstruction. If grade 2, 3, or 4 late diarrhea recurs, subsequent doses of Irinocedal® should be decreased.
Deaths due to sepsis following severe neutropenia have been reported in patients treated with Irinocedal®. Manage febrile neutropenia promptly with antibiotic support. Hold Irinocedal® if neutropenic fever occurs or if the absolute neutrophil count drops <1000/mm3. After recovery to an absolute neutrophil count ≥1000/mm3, subsequent doses of Irinocedal® should be reduced.
Patients who have previously received pelvic/abdominal irradiation are at increased risk of severe myelosuppression following the administration of Irinocedal®. Based on sparse available data, the concurrent administration of Irinocedal® with irradiation is not recommended.
Patients with baseline serum total bilirubin levels of 1.0 mg/dl or more also had a greater likelihood of experiencing first-cycle grade 3 or 4 neutropenia than those with bilirubin levels that were less than 1.0 mg/dl. Patients with deficient glucuronidation of bilirubin, such as those with Gilbert’s syndrome, may be at greater risk of myelosuppression when receiving therapy with Irinocedal®.
Individuals who are homozygous for the UGT1A1*28 allele (UGT1A1 7/7 genotype) are at increased risk for neutropenia following initiation of Irinocedal® treatment.
Hypersensitivity reactions including severe anaphylactic or anaphylactoid reactions have been observed. Discontinue Irinocedal® if anaphylactic reaction occurs.
Renal impairment and acute renal failure have been identified, usually in patients who became volume depleted from severe vomiting and/or diarrhea.
Interstitial Pulmonary Disease (IPD)-like events, including fatalities, have occurred in patients receiving irinotecan (in combination and as monotherapy). Risk factors include pre-existing lung disease, use of pneumotoxic drugs, radiation therapy, and colony stimulating factors.
Patients with risk factors should be closely monitored for respiratory symptoms before and during Irinocedal® therapy. New or progressive, dyspnea, cough, and fever should prompt interruption of chemotherapy, pending diagnostic evaluation. If IPD is diagnosed, Irinocedal® and other chemotherapy should be discontinued and appropriate treatment instituted as needed.
Irinocedal® Injection should not be used in combination with a regimen of 5-FU/LV administered for 4-5 consecutive days every 4 weeks because of reports of increased toxicity, including toxic deaths.
In patients receiving either Irinotecan/5-FU/LV or 5-FU/LV in the clinical trials, higher rates of hospitalization, neutropenic fever, thromboembolism, first-cycle treatment discontinuation, and early deaths were observed in patients with a baseline performance status of 2 than in patients with a baseline performance status of 0 or 1.
Irinocedal® can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of irinotecan in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Irinocedal®.
The use of Irinocedal® in patients with significant hepatic impairment has not been established. In clinical trials of either dosing schedule, irinotecan was not administered to patients with serum bilirubin >2.0 mg/dL, or transaminase >3 times the upper limit of normal if no liver metastasis, or transaminase >5 times the upper limit of normal with liver metastasis. .patients with modestly elevated baseline serum total bilirubin levels (1.0 to 2.0 mg/dL) had a significantly greater likelihood of experiencing first-cycle, grade 3 or 4 neutropenia than those with bilirubin levels that were less than 1.0 mg/dL.
– Colorectal Cancer Combination Regimens 1 and 2
Administer Irinocedal® 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 Irinocedal® 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 Modificationsa
Regimen 1 6-wk cycle with bolus 5-FU/LV (next cycle begins on day 43) |
Irinocedal® LV 5-FU | 125 mg/m2 intravenous infusion over 90 minutes, days 1,8,15,22 20 mg/m2 intravenous injection bolus, days 1,8,15,22 500 mg/m2 intravenous injection bolus, days 1,8,15,22 |
Starting Dose & Modified Dose Levels (mg/m2) | ||
Starting Dose Dose Level -1 Dose Level -2 | ||
Irinocedal® LV 5-FU | 125 100 75 20 20 20 500 400 300 | |
Regimen 2 6-wk cycle with infusional 5-FU/LV (next cycle begins on day 43) |
Irinocedal® LV 5-FU Bolus 5-FU Infusionb |
180 mg/m2 intravenous infusion over 90 minutes, days 1,15,29 200 mg/m2 intravenous infusion over 2 hours, days 1,2,15,16,29,30 400 mg/m2 intravenous injection bolus, days 1,2,15,16,29,30 600 mg/m2 intravenous infusion over 22 hours, days 1,2,15,16,29,30 |
Starting Dose & Modified Dose Levels (mg/m2) | ||
Starting Dose Dose Level -1 Dose Level -2 | ||
Irinocedal® LV 5-FU Bolus 5-FU Infusionb | 180 150 120 200 200 200 400 320 240 600 480 360 |
a 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.
b 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.
Dose Modifications
Based on recommended dose levels described in Table 1, Combination Regimens of Irinocedal® 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
Irinocedal®/5-Fluorouracil (5-FU)/Leucovorin (LV) Combination Schedules
Patients should return to pre-treatment bowel function without requiring antidiarrhea medications for at least 24 hours before the next chemotherapy administration. A new cycle of therapy should not begin until the granulocyte count has recovered to 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 Grade a (Value) | During a Cycle of Therapy | At the Start of Subsequent Cycles of Therapy b |
No toxicity | Maintain dose level | Maintain dose level |
Neutropenia 1 (1500 to 1999/mm3) 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 > pretx c) 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 Toxicities d 1 2 3 4 |
Maintain dose level Omit dose until resolved to grade 1, then 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
For mucositis/stomatitis decrease only 5-FU, not Irinocedal® |
Maintain dose level Maintain dose level 1 dose level 2 dose levels For mucositis/stomatitis decrease only 5-FU, not Irinocedal® |
a National Cancer Institute Common Toxicity Criteria (version 1.0)
b Relative to the starting dose used in the previous cycle
c Pretreatment
d Excludes alopecia, anorexia, asthenia
– Colorectal Single Agent Regimens 1 and 2
Administer Irinocedal® 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 Irinocedal® 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 Irinocedal® and Dose Modifications
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 Levels c (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 weeks c |
Starting Dose and Modified Dose Levels (mg/m2) | |
Starting Dose Dose Level -1 Dose Level -2 | |
350 300 250 |
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.
Dose Modifications
Based on recommended dose-levels described in Table 3, Single-Agent Regimens of Irinocedal® 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
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 Irinocedal®.
Worst Toxicity NCI Grade b (Value) |
During a Cycle of Therapy | At the Start of the Next Cycles of Therapy (After Adequate Recovery), Compared with the Starting Dose in the Previous Cycle a | |
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 > pretx c) 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 Nonhematologic d 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 |
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
– 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 Irinocedal® should be considered for patients known to be homozygous for the UGT1A1*28 allele . However, the precise dose reduction in this patient populationis not known, and subsequent dose modifications should be considered based on individual patient tolerance to treatment (see Tables 1-4).
– Premedication
It is recommended that patients receive premedication with antiemetic agents. In 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 Irinocedal®. 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 Irinocedal® in combination therapy.
Prophylactic or therapeutic administration of atropine should be considered in patient experiencing cholinergic symptoms.
– Irinocedal® is a sterile, pale yellow, clear, aqueous solution. Do not use if any discoloration or visible particles are observed.
– Irinocedal® Injection 20 mg/mL is intended for single use only and any unused portion should be discarded according to the standard procedures for disposal of cytotoxic waste.
– Irinocedal® Injection must be diluted prior to infusion. Irinocedal® 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.
– Irinocedal® is injected into a vein through an intravenous route (IV). Irinocedal® must be given slowly, and the IV infusion can take up to 90 minutes to complete.
– Freezing Irinocedal® and admixtures of Irinocedal® may result in precipitation of the drug and should be avoided.
– Care should be taken to avoid extravasation, and the infusion site should be monitored for signs of inflammation. If extravasation occur, flushing the site with sterile water and applications of ice are recommended.
Like all medicines, this medicine can cause side effects, although not everybody gets them. Side effects with Irinocedal® may include:
Cardiovascular: Vasodilation (9% to 11%)
Central nervous system: Cholinergic toxicity (47% – includes rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing and intestinal hyperperistalsis); fever (44% to 45%), pain (23% to 24%), dizziness (15% to 21%), insomnia (19%), headache (17%), chills (14%)
Dermatologic: Alopecia (46% to 72%), rash (13% to 14%)
Endocrine & metabolic: Dehydration (15%)
Gastrointestinal: Diarrhea, late (83% to 88%; grade 3/4: 14% to 31%), diarrhea, early (43% to 51%; grade 3/4: 7% to 22%), nausea (70% to 86%), abdominal pain (57% to 68%), vomiting (62% to 67%), cramps (57%), anorexia (44% to 55%), constipation (30% to 32%), mucositis (30%), weight loss (30%), flatulence (12%), stomatitis (12%)
Hematologic: Anemia (60% to 97%; grades 3/4: 5% to 7%), leukopenia (63% to 96%, grades 3/4: 14% to 28%), thrombocytopenia (96%, grades 3/4: 1% to 4%), neutropenia (30% to 96%; grades 3/4: 14% to 31%)
Hepatic: Bilirubin increased (84%), alkaline phosphatase increased (13%)
Neuromuscular & skeletal: Weakness (69% to 76%), back pain (14%)
Respiratory: Dyspnea (22%), cough (17% to 20%), rhinitis (16%)
Miscellaneous: Diaphoresis (16%), infection (14%)
Cardiovascular: Edema (10%), hypotension (6%), thromboembolic events (5%)
Central nervous system: Somnolence (9%), confusion (3%)
Gastrointestinal: Abdominal fullness (10%), dyspepsia (10%)
Hematologic: Neutropenic fever (grades 3/4: 2% to 6%), hemorrhage (grades 3/4: 1% to 5%), neutropenic infection (grades 3/4: 1% to 2%)
Hepatic: AST increased (10%), ascites and/or jaundice (grades 3/4: 9%)
Respiratory: Pneumonia (4%)
<1%, postmarketing, and/or case reports: ALT increased, amylase increased, anaphylactoid reaction, anaphylaxis, angina, arterial thrombosis, bleeding, bradycardia, cardiac arrest, cerebral infarct, cerebrovascular accident, circulatory failure, colitis, dysrhythmia, embolus, gastrointestinal bleeding, gastrointestinal obstruction, hepatomegaly, hyperglycemia, hypersensitivity, hyponatremia, ileus, interstitial pulmonary disease (IPD), intestinal perforation, ischemic colitis, lipase increased, lymphocytopenia, megacolon, MI, myocardial ischemia, neutropenic.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Please report any adverse drug reactions via contacting Cedal Nano.(1)
OVERDOSAGE:
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 Irinocedal®. Maximum supportive care should be instituted to prevent dehydration due to diarrhea and to treat any infectious complications.
In a study involving irinotecan, 5-fluorouracil (5-FU), and leucovorin (LV) in 26 patients with solid tumors, the disposition of irinotecan was not substantially altered when the drugs were co-administered. Although the Cmax and AUC0-24 of SN-38, the active metabolite, were reduced (by 14% and 8%, respectively) when irinotecan was followed by 5-FU and LV administration compared with when irinotecan was given alone, this sequence of administration was used in the combination trials and is recommended .
Formal in vivo or in vitro drug interaction studies to evaluate the influence of irinotecan on the disposition of 5-FU and LV have not been conducted.
Exposure to irinotecan or its active metabolite SN-38 is substantially reduced in adult and pediatric patients concomitantly receiving the CYP3A4 enzyme-inducing anticonvulsants phenytoin, phenobarbital, carbamazepine, or St. John’s wort. The appropriate starting dose for patients taking these or other strong inducers such as rifampin and rifabutin has not been defined. Consider substituting non-enzyme inducing therapies at least 2 weeks prior to initiation of Irinocedal® therapy. Do not administer strong CYP3A4 inducers with Irinocedal® unless there are no therapeutic alternatives.
Irinotecan and its active metabolite, SN-38, are metabolized via the human cytochrome P450 3A4 isoenzyme (CYP3A4) and uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1), respectively. Patients receiving concomitant ketoconazole, a CYP3A4 and UGT1A1 inhibitor, have increased exposure to irinotecan and its active metabolite SN-38. Coadministration of Irinocedal® with other inhibitors of CYP3A4 (e.g., clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) or UGT1A1 (e.g., atazanavir, gemfibrozil, indinavir) may increase systemic exposure to irinotecan or SN-38. Discontinue strong CYP3A4 inhibitors at least 1 week prior to starting Irinocedal® therapy. Do not administer strong CYP3A4 or UGT1A1 inhibitors with Irinocedal® unless there are no therapeutic alternatives.
Pregnancy Category D There are no adequate and well-controlled studies of irinotecan in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Irinocedal®.
Radioactivity appeared in rat milk within 5 minutes of intravenous administration of radiolabeled irinotecan and was concentrated up to 65-fold at 4 hours after administration relative to plasma concentrations. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Irinocedal®, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
The effectiveness of irinotecan in pediatric patients has not been established.
Patients greater than 65 years of age should be closely monitored because of a greater risk of early and late diarrhea in this population The starting dose of Irinocedal® in patients 70 years and older for the once-every-3-week-dosage schedule should be 300 mg/m2 .\
The frequency of grade 3 and 4 late diarrhea by age was significantly greater in patients≥65 years than in patients <65 years (40% [53/133] versus 23% [40/171]; p=0.002). In another study of 183 patients treated on the weekly schedule, the frequency of grade 3 or 4 late diarrhea in patients 65 years of age was 28.6% [26/91] and in patients <65 years of age was23.9% [22/92].
The influence of renal impairment on the pharmacokinetics of irinotecan has not been evaluated. Therefore, use caution in patients with impaired renal function. Irinocedal® is not recommended for use in patients on dialysis.
Irinotecan clearance is diminished in patients with hepatic impairment while exposure to the active metabolite SN-38 is increased relative to that in patients with normal hepatic function. The magnitude of these effects is proportional to the degree of liver impairment as measured by elevations in total bilirubin and transaminase concentrations. Therefore, use caution when administering Irinocedal® to patients with hepatic impairment. The tolerability of irinotecan in patients with hepatic dysfunction (bilirubin greater than 2 mg/dl) has not been assessed sufficiently, and no recommendations for dosing can be made.
How supplied
Irinocedal® is provided as one vial containing irinotecan hydrochloride trihydrate equivalent to 100 mg or 300 mg (20 mg/ml) as concentrate for solution for infusion with a leaflet in a box.
Handling and disposal
Care should be exercised in the handling and preparation of infusion solutions prepared from Irinocedal® Injection. The use of gloves is recommended. If a solution of Irinocedal® contacts the skin, wash the skin immediately and thoroughly with soap and water. If Irinocedal® contacts the mucous membranes, flush thoroughly with water. Several published guidelines for handling and disposal of anticancer agents are available. Storage
– Store Irinocedal® concentrate for solution for infusion at controlled room temperature 15° to 30°C.
– In order to protect from light, keep the vial in the original package.
– Protect from freezing .
– Keep the medicine out of the reach of children.
– From a microbiological point of view the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and diluted solution of Irinocedal® prepared in 5% dextrose injection are physically and chemically stable for up to 24 hours if refregirated or within 4 hours if maintained at room temperature. Diluted solution prepared in sodium chloride injection should not be refrigerated but should be stored at room temperature and used within 4 hours.