Irinotecan (Concentrate) Instructions for Use
ATC Code
L01CE02 (Irinotecan)
Active Substance
Irinotecan (Rec.INN registered by WHO)
Clinical-Pharmacological Group
Antineoplastic drug
Pharmacotherapeutic Group
Antineoplastic agents; plant alkaloids and other natural substances; topoisomerase I inhibitors
Pharmacological Action
Antineoplastic agent. The mechanism of action is associated with inhibition of the cellular enzyme topoisomerase I, which is involved in DNA synthesis. It has immunosuppressive activity.
It inhibits acetylcholinesterase.
Pharmacokinetics
Following intravenous infusion, Irinotecan is metabolized in the liver by the enzyme carboxylesterase to the active metabolite SN-38.
Plasma distribution is bi- or triphasic. The mean T1/2 in the initial phase is 12 min, in the second phase – 2.5 h, and in the terminal phase – 14.2 h. Cmax of irinotecan and SN-38 was reached by the end of the IV infusion at the recommended dose of 350 mg/m2. On average, 20% of unchanged irinotecan and 0.25% as the metabolite SN-38 are excreted by the kidneys within 24 hours. Approximately 30% of irinotecan is excreted in the bile – both unchanged and as the metabolite SN-38 glucuronide.
Plasma protein binding for irinotecan is approximately 65%, and for its active metabolite SN-38 – 95%.
Indications
Locally advanced or metastatic colorectal cancer (as part of mono- or combination therapy).
ICD codes
| ICD-10 code | Indication |
| C18 | Malignant neoplasm of colon |
| C19 | Malignant neoplasm of rectosigmoid junction |
| C20 | Malignant neoplasm of rectum |
| ICD-11 code | Indication |
| 2B90.Z | Malignant neoplasm of colon, unspecified |
| 2B91.Z | Malignant neoplasm of rectosigmoid junction, unspecified |
| 2B92.Z | Malignant neoplasm of rectum, unspecified |
Dosage Regimen
| The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen. |
Determine the dosage individually based on the therapeutic regimen, disease stage, and the patient’s hematological status.
Administer as an intravenous infusion over 30 to 90 minutes.
For monotherapy in metastatic colorectal cancer, a common initial dose is 350 mg/m², administered once every three weeks.
Adjust the dose based on tolerance and the severity of adverse reactions observed in the prior cycle.
Reduce the dose for severe neutropenia, febrile neutropenia, or severe diarrhea.
Withhold therapy if the absolute neutrophil count (ANC) is below 1500 cells/µL or if there is unresolved diarrhea.
For combination therapy, such as with 5-fluorouracil (5-FU) and leucovorin, use a lower dose, typically 180 mg/m² every two weeks.
Premedicate with antiemetics and consider intravenous atropine (0.25 to 1 mg) to prevent or treat acute cholinergic syndrome.
Initiate antidiarrheal therapy (loperamide) immediately at the first episode of late diarrhea, occurring more than 24 hours after infusion.
Monitor complete blood count with differential prior to each dose and liver function tests regularly.
Do not administer to patients with a serum bilirubin level exceeding 3 times the upper limit of normal (ULN).
Use with caution in patients over 65 years of age and in those with prior pelvic/abdominal radiotherapy due to increased risk of toxicity.
Adverse Reactions
From the hematopoietic system: very often – neutropenia, febrile neutropenia, leukopenia, anemia, thrombocytopenia.
From the digestive system: nausea, vomiting, diarrhea, abdominal pain, anorexia, mucositis, constipation, gastrointestinal candidiasis, hiccups, decreased appetite; rarely – pseudomembranous colitis, intestinal obstruction, gastrointestinal bleeding, intestinal perforation, increased activity of amylase or lipase. Diarrhea occurring later than 24 hours after irinotecan administration (delayed diarrhea) is its dose-limiting toxic effect.
Acute cholinergic syndrome: early diarrhea (within 8 hours after irinotecan administration), abdominal pain, conjunctivitis, rhinitis, decreased blood pressure, bradycardia, vasodilation, increased intestinal peristalsis, increased sweating, chills, malaise, dizziness, visual disturbance, miosis, lacrimation, salivation.
From the nervous system: involuntary muscle contractions or cramps, paresthesia, asthenia; very rarely – transient speech disorders.
From the cardiovascular system: sometimes – decreased blood pressure, hypovolemic shock due to dehydration; rarely – increased blood pressure during or after infusion.
From the respiratory system: sometimes – dyspnea, fever, pulmonary infiltrates.
From the skin and subcutaneous tissues: very often – reversible alopecia; sometimes – skin reactions.
From laboratory parameters: very often – transient increase in serum transaminase activity, alkaline phosphatase or bilirubin concentration (combination therapy); often – transient increase in serum transaminase activity, alkaline phosphatase or bilirubin concentration (monotherapy), increased serum creatinine concentration; rarely – hypokalemia and hyponatremia; very rarely – increased serum amylase and/or lipase activity.
Allergic reactions: rarely – skin rash; very rarely – development of anaphylactic shock.
Other: increased fatigue, secondary infections, increased body temperature, local reactions.
Contraindications
Hypersensitivity to irinotecan; chronic inflammatory bowel diseases and/or intestinal obstruction; severe bone marrow suppression; serum bilirubin concentration more than 3 times the upper limit of normal (ULN); general condition of patients assessed by the ECOG (Eastern Cooperative Oncology Group) scale >2; pregnancy, breastfeeding period; childhood (data on safety and efficacy in children are lacking), renal failure (data on safety are lacking).
With caution radiotherapy (in history) to the abdominal or pelvic area (high risk of myelosuppression), leukocytosis, female patients (increased risk of diarrhea), hypovolemia, increased risk of venous thromboembolic complications, elderly age.
Use in Pregnancy and Lactation
Contraindicated during pregnancy and lactation (breastfeeding).
Patients of reproductive potential should use reliable methods of contraception during treatment and for 3 months after its completion.
Use in Hepatic Impairment
If the serum bilirubin concentration exceeds the ULN by no more than 1.5 times, blood counts should be carefully monitored due to the increased risk of severe neutropenia. If the bilirubin concentration increases more than 3 times, irinotecan therapy should be discontinued.
Use in Renal Impairment
Contraindicated in patients with renal failure. Irinotecan is not recommended for use in patients with impaired renal function.
Pediatric Use
Use of irinotecan in children is contraindicated.
Geriatric Use
Should be prescribed with caution to patients over 65 years of age due to the increased risk of early diarrhea in this category of patients.
Special Precautions
Treatment with irinotecan should be carried out in specialized chemotherapy departments under the supervision of a physician experienced in working with anticancer drugs.
In patients receiving Irinotecan, a complete blood count should be performed weekly and liver function should be monitored.
The patient should be warned in advance about the possibility of developing delayed diarrhea. Patients should immediately inform their doctor about the onset of diarrhea and immediately begin appropriate treatment.
When the first episode of diarrhea develops, measures should be taken immediately to correct it. The duration of neutropenia is most often 8 days, with complete recovery of neutrophils observed by day 22. Acute cholinergic syndrome is observed in approximately 83% of patients, occurring during administration or within 24 hours after administration.
Inadequate treatment of diarrhea can lead to a life-threatening condition, especially if diarrhea develops against the background of neutropenia.
If neutropenia, nausea, vomiting, or diarrhea develop during treatment, dose regimen adjustment is required. Do not use until the neutrophil count in the peripheral blood is restored (>1500/µl).
Patients of reproductive potential should use reliable methods of contraception during treatment and for 3 months after its completion.
Effect on ability to drive vehicles and operate machinery
During treatment with irinotecan, especially within 24 hours after its administration, it is not recommended to engage in potentially hazardous activities that require concentration and high speed of psychomotor reactions.
Drug Interactions
Due to the anticholinesterase activity of irinotecan, it is possible to increase the duration of neuromuscular blockade caused by suxamethonium chloride; antagonistic interaction in relation to neuromuscular blockade caused by non-depolarizing muscle relaxants.
When irinotecan is used concomitantly with myelosuppressive drugs and radiotherapy, the toxic effect on the bone marrow (leukopenia, thrombocytopenia) is enhanced.
When irinotecan is used concomitantly with corticosteroids (e.g., dexamethasone), the risk of hyperglycemia (especially in patients with diabetes mellitus or reduced glucose tolerance) and lymphocytopenia increases.
Concomitant use of irinotecan with diuretics may worsen dehydration caused by diarrhea and vomiting. Concomitant use of laxatives during irinotecan therapy may worsen the frequency or severity of diarrhea.
Concomitant administration of irinotecan and prochlorperazine increases the likelihood of signs of akathisia.
When irinotecan is used concomitantly with herbal preparations based on St. John’s wort (Hypericum perforatum), as well as with anticonvulsant drugs – inducers of the CYP3A isoenzyme (carbamazepine, phenobarbital and phenytoin), the plasma concentration of the active metabolite SN-38 decreases. The possibility of taking anticonvulsant drugs that do not induce isoenzymes, or switching to them, should be assessed at least 1 week before starting irinotecan therapy in patients requiring treatment with anticonvulsant drugs. St. John’s wort should not be taken concomitantly with irinotecan; it should be discontinued at least 1 week before starting irinotecan therapy.
Irinotecan and the active metabolite SN-38 are metabolized via the CYP3A4 isoenzyme and UGT1A1. Concomitant use of irinotecan and inhibitors of the CYP3A4 isoenzyme and/or UGT1A1 may lead to increased systemic exposure to irinotecan and the active metabolite SN-38.
Concomitant use of irinotecan with atazanavir, an inhibitor of the CYP3A4 and UGT1A1 isoenzymes, as well as with ketoconazole, may cause an increase in the plasma concentration of the active metabolite SN-38. Ketoconazole should be discontinued at least 1 week before starting therapy and should not be taken during irinotecan therapy.
Irinotecan should not be mixed with other drugs in the same vial.
Administration of a live or attenuated vaccine to patients undergoing a course of treatment with anticancer agents, including Irinotecan, may lead to serious or fatal infections. Vaccination with a live vaccine should be avoided in patients receiving Irinotecan. A killed or inactivated vaccine may be administered, but the response to such a vaccine may be weakened.
When irinotecan is used concomitantly with phenytoin, there is a risk of seizure exacerbation due to decreased absorption of phenytoin in the gastrointestinal tract against the background of concomitant use with anticancer drugs or an increased risk of increased toxicity due to more active metabolism in the liver induced by phenytoin.
When irinotecan is used concomitantly with cyclosporine, tacrolimus, significant immunosuppression with a risk of lymphoproliferation is possible.
Storage Conditions
Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.
Dispensing Status
Rx Only
Important Safety Information
This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.
Medical DisclaimerBrand (or Active Substance), Marketing Authorisation Holder, Dosage Form
Concentrate for solution for infusion 20 mg/1 ml: vial 2 ml or 5 ml 1 pc.
Marketing Authorization Holder
Belmedpreparaty RUP (Republic of Belarus)
Dosage Form
 |
Irinotecan | Concentrate for solution for infusion 20 mg/1 ml: vial 2 ml or 5 ml 1 pc. |
Dosage Form, Packaging, and Composition
Concentrate for solution for infusion as a clear, colorless with a yellowish tint to light yellow or light greenish-yellow solution.
| 1 ml | |
| Irinotecan hydrochloride trihydrate | 20 mg |
Excipients: sorbitol, lactic acid, sodium hydroxide 1M solution, water for injections.
2 ml – dark glass vials with a capacity of 5 ml (1) – cardboard boxes.
5 ml – dark glass vials with a capacity of 5 ml (1) – cardboard boxes.
Concentrate for solution for infusion 20 mg/ml
Marketing Authorization Holder
Belmedpreparaty RUP (Republic of Belarus)
Dosage Form
|
Irinotecan | Concentrate for solution for infusion 20 mg/ml |
Dosage Form, Packaging, and Composition
Concentrate for solution for infusion
| 1 ml | |
| Irinotecan | 20 mg |
2 ml – vials – cardboard packs – By prescription
2 ml – vials (20 pcs.) – cardboard boxes – for hospitals
5 ml – vials – cardboard packs – By prescription
5 ml – vials (20 pcs.) – cardboard boxes – for hospitals
Concentrate for solution for infusion 20 mg/ml: 2 ml or 5 ml vial 1 pc.
Marketing Authorization Holder
Biocad, JSC (Russia)
Dosage Form
|
Irinotecan | Concentrate for solution for infusion 20 mg/ml: 2 ml or 5 ml vial 1 pc. |
Dosage Form, Packaging, and Composition
| Concentrate for solution for infusion | 1 ml |
| Irinotecan hydrochloride trihydrate | 20 mg |
2 ml – vials (1) – contour cell packaging (1) – cardboard boxes.
5 ml – vials (1) – cardboard boxes.
Concentrate for solution for infusion 20 mg/1 ml: vial 2 ml, 5 ml, 7.5 ml, 11.5 ml or 15 ml 1, 5 or 10 pcs.
Marketing Authorization Holder
Pharmera LLC (Russia)
Dosage Form
|
Irinotecan | Concentrate for solution for infusion 20 mg/1 ml: vial 2 ml, 5 ml, 7.5 ml, 11.5 ml or 15 ml 1, 5 or 10 pcs. |
Dosage Form, Packaging, and Composition
Concentrate for solution for infusion clear, light yellow in color.
| 1 ml | |
| Irinotecan hydrochloride trihydrate | 20 mg |
Excipients: sorbitol – 45 mg, lactic acid – 0.9 mg, sodium hydroxide 0.1M solution – to pH 3.0 to 4.0, water for injections – up to 1 ml.
2 ml – dark glass vials (1) – cardboard boxes.
2 ml – dark glass vials (5) – cardboard boxes.
2 ml – dark glass vials (10) – cardboard boxes.
5 ml – dark glass vials (1) – cardboard boxes.
5 ml – dark glass vials (5) – cardboard boxes.
5 ml – dark glass vials (10) – cardboard boxes.
7.5 ml – dark glass vials (1) – cardboard boxes.
7.5 ml – dark glass vials (5) – cardboard boxes.
7.5 ml – dark glass vials (10) – cardboard boxes.
11.5 ml – dark glass vials (1) – cardboard boxes.
11.5 ml – dark glass vials (5) – cardboard boxes.
11.5 ml – dark glass vials (10) – cardboard boxes.
15 ml – dark glass vials (1) – cardboard boxes.
15 ml – dark glass vials (5) – cardboard boxes.
15 ml – dark glass vials (10) – cardboard boxes.
Concentrate for solution for infusion 20 mg/1 ml: fl. 2 ml, 5 ml or 15 ml 1 pc.
Marketing Authorization Holder
Medac, GmbH (Germany)
Manufactured By
Fresenius Kabi Oncology, Limited (India)
Labeled By
Medac, GmbH (Germany)
Dosage Form
|
Irinotecan Medac | Concentrate for solution for infusion 20 mg/1 ml: fl. 2 ml, 5 ml or 15 ml 1 pc. |
Dosage Form, Packaging, and Composition
| Concentrate for solution for infusion | 1 ml |
| Irinotecan hydrochloride trihydrate | 20 mg |
2 ml – vials (1) – cardboard boxes.
5 ml – vials (1) – cardboard boxes.
15 ml – vials (1) – cardboard boxes.
Concentrate for solution for infusion 20 mg/1 ml: fl. 2 ml, 5 ml or 15 ml 1 pc.
Marketing Authorization Holder
Medac, GmbH (Germany)
Manufactured By
Oncotec Pharma Produktion, GmbH (Germany)
Secondary Packaging
Medac, GmbH (Germany)
Dosage Form
|
Irinotecan Medak | Concentrate for solution for infusion 20 mg/1 ml: fl. 2 ml, 5 ml or 15 ml 1 pc. |
Dosage Form, Packaging, and Composition
Concentrate for solution for infusion as a clear yellow liquid.
| 1 ml | |
| Irinotecan hydrochloride trihydrate | 20 mg |
Excipients: lactic acid – 0.9 mg, sodium hydroxide – 0-0.25 mg (to pH 3.5±0.2), sorbitol – 45 mg, water for injections – to 1 ml.
2 ml – dark glass vials (1) – cardboard packs.
5 ml – dark glass vials (1) – cardboard packs.
15 ml – dark glass vials (1) – cardboard packs.
Concentrate for solution for infusion 20 mg/ml: 2 ml, 5 ml, 7.5 ml, 11.5 ml or 15 ml vial 1 pc.
Marketing Authorization Holder
Amedart LLC (Russia)
Dosage Form
|
Irinotecan-Amedart | Concentrate for solution for infusion 20 mg/ml: 2 ml, 5 ml, 7.5 ml, 11.5 ml or 15 ml vial 1 pc. |
Dosage Form, Packaging, and Composition
Concentrate for solution for infusion clear from light yellow to yellow.
| 1 ml | |
| Irinotecan | 20 mg |
Excipients: sorbitol, lactic acid, 1M sodium hydroxide solution (for pH adjustment), 1M hydrochloric acid solution (for pH adjustment), water for injections.
2 ml – dark glass vials (1) – cardboard packs.
5 ml – dark glass vials (1) – cardboard packs.
7.5 ml – dark glass vials (1) – cardboard packs.
11.5 ml – dark glass vials (1) – cardboard packs.
15 ml – dark glass vials (1) – cardboard packs.
Concentrate for solution for infusion 20 mg/ml: 2 ml or 5 ml vial 1 pc.
Marketing Authorization Holder
Jodas Expoim, LLC (Russia)
Manufactured By
Jodas Expoim, Pvt. Ltd. (India)
Dosage Form
|
Irinotecan-J | Concentrate for solution for infusion 20 mg/ml: 2 ml or 5 ml vial 1 pc. |
Dosage Form, Packaging, and Composition
Concentrate for solution for infusion from light yellow to yellow, clear.
| 1 ml | |
| Irinotecan hydrochloride trihydrate | 20 mg |
Excipients: sorbitol – 45 mg, lactic acid – 0.9 mg, sodium hydroxide – q.s. to pH 3.5, water for injections – to 1 ml.
2 ml – vials (1) – cardboard packs.
2 ml – vials (5) – cardboard boxes (for hospitals).
2 ml – vials (10) – cardboard boxes (for hospitals).
5 ml – vials (1) – cardboard packs.
5 ml – vials (5) – cardboard boxes (for hospitals).
5 ml – vials (10) – cardboard boxes (for hospitals).
Concentrate for solution for infusion 20 mg/ml: vial 2 ml, 5 ml, 7.5 ml, 11.5 ml or 15 ml 1, 5, 10, 50, 85 or 100 pcs.
Marketing Authorization Holder
Promomed Rus LLC (Russia)
Manufactured By
Biokhimik, JSC (Russia)
Dosage Form
|
Irinotecan-Promomed | Concentrate for solution for infusion 20 mg/ml: vial 2 ml, 5 ml, 7.5 ml, 11.5 ml or 15 ml 1, 5, 10, 50, 85 or 100 pcs. |
Dosage Form, Packaging, and Composition
Concentrate for solution for infusion as a clear colorless or light yellow, yellow or light greenish-yellow liquid.
| 1 ml | |
| Irinotecan | 20 mg |
Excipients: sorbitol, lactic acid, sodium hydroxide or hydrochloric acid (for pH adjustment), water for injections.
2 ml – type I dark glass vials (1, 5 or 10) – cardboard packs.
2 ml – type I dark glass vials (50, 85 or 100) – cardboard packs (for hospitals).
5 ml – dark glass vials (1, 5 or 10) – cardboard packs.
5 ml – dark glass vials (50, 85 or 100) – cardboard packs (for hospitals).
7.5 ml – dark glass vials (1, 5 or 10) – cardboard packs.
7.5 ml – dark glass vials (50, 85 or 100) – cardboard packs (for hospitals).
11.5 ml – type I dark glass vials (1, 5 or 10) – cardboard packs.
11.5 ml – type I dark glass vials (50, 85 or 100) – cardboard packs (for hospitals).
15 ml – type I dark glass vials (1, 5 or 10) – cardboard packs.
15 ml – type I dark glass vials (50, 85 or 100) – cardboard packs (for hospitals).
![Irinotecan [Concentrate] 1](https://www.medixlife.com/wp-content/uploads/Medixlife_favi_512.png "Irinotecan [Concentrate] 2")