Irinotecan hydrochloride

Irinotecan hydrochloride is a derivative of camptothecin that specifically acts on topoisomerase I. Topoisomerase I unwinds DNA double strands by reversibly breaking single strands. Irinotecan hydrochloride and its active metabolite SN-38 bind to the topoisomerase I-DNA complex, preventing the broken single strands from rejoining. Current studies have shown that the cytotoxic effect of irinotecan hydrochloride is due to the damage of DNA double strands, which is caused by the interaction of replicase with the ternary complex composed of topoisomerase I, DNA, and irinotecan hydrochloride or SN-38 during DNA synthesis. Mammalian cells cannot effectively repair this double-strand damage. Irinotecan hydrochloride is a water-soluble precursor of the lipophilic metabolite SN-38, which has an inhibitory effect of 1000 times that of irinotecan hydrochloride on topoisomerase I purified from human or rodent tumor cell lines. However, the exact contribution of SN-38 to the activity of irinotecan hydrochloride is still unknown. Irinotecan hydrochloride and SN-38 both exist in an active lipoate form and an inactive hydroxy acid anion form. Acidic pH environments promote the formation of lipoate, whereas alkaline pH environments promote the formation of hydroxy acid anions. Irinotecan hydrochloride has anti-tumor activity against rodent and human malignant tumor cells of different tissue types implanted in mice.

The main ingredient of this product is irinotecan hydrochloride, and its chemical name is ()-(4S)-4,11-diethyl-4-hydroxy-9-(4-piperidinylpiperidinyl)carbonyl-1H-pyrano-3,4:6,7-indolizine-1,2b-quinoline-3,14-(4H,12H)-dione hydrochloride trihydrate.

For the treatment of adult metastatic colorectal cancer, this product can be used as a second-line treatment for patients who have failed chemotherapy containing 5-Fu.

It is recommended to give patients antiemetics for prevention. When patients develop cholinergic syndrome, consider the prophylactic or therapeutic administration of atropine (see Precautions). Combination Dosage Regimen: Irinotecan hydrochloride combined with 5-FU (5-fluorouracil) and LV (leucovorin) for two weeks: Irinotecan hydrochloride 180 mg/m2 intravenous infusion over 30 to 90 minutes on the first day; LV400 mg/m2 should be given 6 days after irinotecan hydrochloride infusion; LV400 mg/m2 should be given immediately after irinotecan hydrochloride infusion, with the same infusion time, on the first day; 5-FU400 mg/m2 intravenous push on the first day, then 1200 mg/m2/d×2 days continuous intravenous infusion (total 2400 mg/m2, infused for 46 to 48 hours). Repeat every 2 weeks. Dose Adjustment: Carefully monitor and evaluate patients for toxic reactions before each treatment, especially in the first cycle of treatment. The dose of irinotecan hydrochloride and 5-FU should be adjusted based on the individual patient's tolerance to treatment. Table 1 shows the recommended dose adjustment schedule for combined use. All dose adjustments should be based on the most severe toxic reaction that occurred previously. Patients should not start the next course of treatment until they have no diarrhea (return to pre-treatment bowel function) for at least 24 hours without the use of antidiarrheal medications. A new treatment cycle can be started when the toxic effects have recovered to NCI grade 1 or lower, the granulocyte count has recovered to ≥1.5×109/L, the platelet count has recovered to 100x109/L, and the treatment-related diarrhea has completely resolved. Treatment should be delayed for 1-2 weeks to allow for the recovery of related toxic reactions. If the patient still does not recover after a 2-week delay, chemotherapy should be discontinued. If no intolerable toxic reactions occur, the subsequent irinotecan hydrochloride/5-FU/LV regimen should be continued as long as the patient continues to have clinical benefit. Patients with renal impairment (monotherapy): No clinical studies have been conducted in patients with renal impairment. Therefore, special attention should be paid to monitoring patients with impaired renal function. This drug is not recommended for dialysis patients.

1. Gastrointestinal (1) Delayed diarrhea: Diarrhea (occurring 24 hours after administration) is the dose-limiting toxic reaction of this drug. Severe diarrhea occurs in 20% of all patients who follow the advice on diarrhea treatment. The median time to the first loose stool is the fifth day after instillation of this drug. Pseudomembranous colitis has occurred in individual cases, one of which has been confirmed by bacteriology (Clostridium difficile). (2) Nausea and vomiting: Severe nausea and vomiting still occur in 10% of patients after the use of antiemetics. (3) Other gastrointestinal reactions: Diarrhea and/or vomiting accompanied by symptoms of dehydration have been reported. Less than 10% of patients experience constipation related to treatment with this drug. Reports of intestinal obstruction are rare. Other mild reactions include anorexia, abdominal pain and mucositis. 2. Hematology Neutrophils

1. It is contraindicated in patients with chronic enteritis and/or intestinal obstruction; 2. It is contraindicated in patients with a history of severe allergic reaction to irinotecan hydrochloride trihydrate or its excipients; 3. It is contraindicated in pregnant and lactating women; 4. It is contraindicated in patients with bilirubin exceeding 1.5 times the upper limit of normal; 5. It is contraindicated in patients with severe bone marrow failure; 6. It is contraindicated in patients with WHO performance status score 2.

Precautions for children: The safety or effectiveness of this product for children is uncertain. Precautions for pregnancy and lactation: Use with caution in pregnant women. Precautions for the elderly: No special pharmacokinetic studies have been conducted on the elderly. However, due to the high probability of decline in various physiological functions, especially liver function, in the elderly, caution should be exercised when selecting the dose.

1. Neuromuscular blockers: Interactions between irinotecan hydrochloride and neuromuscular blockers cannot be ruled out. Because irinotecan hydrochloride has cholinesterase inhibitor activity, drugs with cholinesterase inhibitory activity can prolong the neuromuscular blocking effect of succinylcholine chloride and can antagonize the neuromuscular blocking effect of non-depolarizing drugs. 2. Antineoplastic drugs: Adverse reactions of this product, such as bone marrow suppression and diarrhea, can be aggravated by other antineoplastic drugs with similar non-responsiveness. 3. Anticonvulsants: Concomitant use of CYP3A-inducing anticonvulsants (such as carbamazepine, phenobarbital or phenytoin) can cause reduced exposure to SN-38. For patients who require anticonvulsant treatment, consideration should be given to starting or switching to non-enzyme-inducing anticonvulsants at least one week before the first use of irinotecan hydrochloride. 4. Ketoconazole: Simultaneous treatment with ketoconazole can cause a significant decrease in the clearance of irinotecan hydrochloride, resulting in increased exposure to its active metabolite SN-38. Ketoconazole should be discontinued at least one week before starting irinotecan hydrochloride treatment, and it should not be administered with irinotecan hydrochloride. 5. St. John's Wort (Hypericum perforatum): Exposure to the active metabolite SN-38 is reduced in patients who are also treated with Hypericum perforatum. Discontinue Hypericum perforatum at least one week before the first use of irinotecan hydrochloride, and it should not be used simultaneously with irinotecan hydrochloride. 6. Atazanavir: Concomitant use of atazanavir, an inhibitor of CYP3A4 and UGTIA1, may increase SN-38 exposure. Physicians should take this into account when using these drugs simultaneously. 7. Dexamethasone: Lymphocytopenia has been reported in patients receiving irinotecan hydrochloride, and dexamethasone may aggravate this condition when used as an antiemetic. However, no serious opportunistic infections have been found, nor have any complications caused by lymphocytopenia been found. Hyperglycemia has been reported in patients receiving this product. This usually occurs in patients with a history of diabetes or impaired glucose tolerance prior to treatment with this drug. The increase in blood sugar in some patients may be caused by receiving dexamethasone. 8. Prochlorperazine: In clinical studies of a single weekly dosing regimen, the incidence of akathisia was higher in patients who were given prochlorperazine on the day of irinotecan hydrochloride treatment (8.5%, 4/47 patients), and lower when the two drugs were not given on the same day (1.3%, 1/80 patients). However, the 8.5% incidence of akathisia is still within the range reported for akathisia when prochlorperazine is used as a pre-chemotherapy drug with other drugs. 9. Laxatives: The use of laxatives while treating with this drug may increase the severity or incidence of diarrhea, but no studies have been conducted in this regard. 10. Diuretics: Due to the potential risk of secondary dehydration after vomiting and/or diarrhea, physicians should avoid using diuretics during irinotecan hydrochloride treatment, and of course, diuretics should not be used during diarrhea or vomiting. Physicians should avoid the use of diuretics during treatment with irinotecan hydrochloride because of the potential risk of dehydration secondary to vomiting and/or diarrhea, and certainly not during diarrhea or vomiting.

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Lianyungang Runzhong Pharmaceutical Co., Ltd.

• Founded in:

  2010-10-20

• Address:

  No. 16, Jinqiao Road, Dapu Industrial Zone, Lianyungang Economic and Technological Development Zone

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  913207005629851634

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  103.528805 yuan

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