is irinotecan hydrochloride effective

Precautions

Irinotecan Hydrochloride 1 Use in Cancer. Colorectal cancer that has metastasized (spread to other parts of the body), including metastatic cancer that has recurred (come back) or has not gotten better with other ... 2 More About Irinotecan Hydrochloride. ... 3 Clinical Trials Accepting Patients. ...

What are the uses of irinotecan hydrochloride?

After irinotecan was introduced for the treatment of metastatic colorectal cancer (CRC) at the end of the last century, survival has improved dramatically.

How effective is irinotecan for the treatment of metastatic colorectal cancer?

The most clinically significant adverse events for patients receiving Irinotecan-based therapy were diarrhea, nausea, vomiting, neutropenia, and alopecia. The most clinically significant adverse events for patients receiving 5-FU/LV therapy were diarrhea, neutropenia, neutropenic fever, and mucositis.

What are the side effects of irinotecan?

Based on findings from animal studies and its mechanism of action, Irinotecan hydrochloride injection can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ].

Is irinotecan hydrochloride safe during pregnancy?

What cancers does irinotecan treat?

Irinotecan is a type of chemotherapy. It is also known by its brand name Campto. It is a treatment for cancer that started in the bowel (bowel cancer). This includes the colon and back passage (rectum).

How many cycles of irinotecan can you have?

Each cycle of treatment lasts 2 weeks (14 days). Depending on your needs, you may have up to 12 cycles, taking up to 6 months in total. You have irinotecan through a drip into the bloodstream over 30 to 90 minutes (depending on which cycle you are having).

Is irinotecan better than oxaliplatin?

The response rate of oxaliplatin group was higher than that of irinotecan group (relative risk (RR) = 0.82, 95% confidence interval (95%CI) (0.70, 0.96), P = 0.01), and the median overall survival of oxaliplatin group was longer by 2.04 months than that of irinotecan group (95%CI (-3.54, -0.54), P = 0.008).

Is irinotecan an immunotherapy?

3 Discussion. In this study, we demonstrate that irinotecan is capable of triggering a chemo-immunotherapy response in an orthotopic KPC model. Not only is the response more robust during drug delivery by silicasome but considerably augmented in combination with an anti-PD-1 antibody.

How long does irinotecan stay in the body?

Use an effective form of birth control to keep from getting pregnant during treatment and for at least 6 months after your last dose. Males who are using this medicine, with female partners who can become pregnant must use effective birth control during and for at least 3 months after the last dose of this medicine.

Do you lose your hair with irinotecan?

Hair loss is fairly common with Irinotecan. This usually starts 3–4 weeks after the first dose of irinotecan, although it may happen earlier. Hair may completely fall out. You may also have thinning and loss of eyelashes, eyebrows and other body hair.

Why is oxaliplatin given before irinotecan?

Our study suggested that irinotecan followed by oxaliplatin-based regimens might be a better chemotherapy treatment option for metastatic colorectal cancer than the reverse sequence given the higher crossover rate and potential overall survival benefit.

Is Folfiri stronger than folfox?

In general, a doublet, oxaliplatin–5-fluorouracil/leucovorin (FOLFOX) or irinotecan–5-fluorouracil/leucovorin (FOLFIRI) is superior to FU alone in terms of OS, PFS and response rate (RR) [3., 4., 5., 6.]. However, they are also more toxic.

Is irinotecan cell cycle specific?

Irinotecan is cell cycle phase-specific (S-phase). Irinotecan inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex.

What is the cost of irinotecan?

The cost for irinotecan intravenous solution (20 mg/mL) is around $19 for a supply of 2 milliliters, depending on the pharmacy you visit....Intravenous Solution.QuantityPer unitPrice2 milliliters$9.34 – $122.12$18.68 – $244.235 milliliters$3.92$19.6015 milliliters$7.43 – $8.25$111.50 – $123.741 more row

Does irinotecan cause liver damage?

Likelihood score irinotecan: B (likely cause of clinically apparent liver injury). Topotecan is a less frequently used topoisomerase inhibitor and has been associated with serum enzyme elevations in up to 50% of patients, but these have been transient, mild and not associated with jaundice or symptoms.

How long does irinotecan diarrhea last?

The mean duration of symptoms is 30 minutes and they usually respond rapidly to atropine. Delayed-type diarrhea is defined as diarrhea occurring more than 24 hours after administration of irinotecan and is noncumulative and occurs at all dose levels.

Is irinotecan cell cycle specific?

Irinotecan is cell cycle phase-specific (S-phase). Irinotecan inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex.

Is irinotecan cytotoxic?

Drug type: Irinotecan is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. This medication is classified as a "plant alkaloid" and "topoisomerase I inhibitor." (For more detail, see "How this drug works" section below).

What is the cost of irinotecan?

The cost for irinotecan intravenous solution (20 mg/mL) is around $19 for a supply of 2 milliliters, depending on the pharmacy you visit....Intravenous Solution.QuantityPer unitPrice2 milliliters$9.34 – $122.12$18.68 – $244.235 milliliters$3.92$19.6015 milliliters$7.43 – $8.25$111.50 – $123.741 more row

Why does irinotecan cause diarrhea?

Irinotecan can cause acute diarrhea (immediately after drug administration) or delayed diarrhea. Immediate-onset diarrhea is caused by acute cholinergic properties and is often accompanied by other symptoms of cholinergic excess, including abdominal cramping, rhinitis, lacrimation, and salivation.

How to use irinotecan hydrochloride?

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.

How long does it take to administer irinotecan hydrochloride?

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

How much irinotecan is given?

In U.S. phase 1 trials, single doses of up to 345 mg/m 2 of Irinotecan were administered to patients with various cancers. Single doses of up to 750 mg/m 2 of Irinotecan have been given in non-U.S. trials. The adverse events in these patients were similar to those reported with the recommended dosage and regimen. There have been reports of overdosage at doses up to approximately twice the recommended therapeutic dose, which may be fatal. The most significant adverse reactions reported were severe neutropenia and severe diarrhea. There is no known antidote for overdosage of Irinotecan hydrochloride injection. Maximum supportive care should be instituted to prevent dehydration due to diarrhea and to treat any infectious complications.

What is irinotecan metabolized by?

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, [see Clinical Pharmacology (12.3) ]. Patients receiving concomitant ketoconazole, a CYP3A4 and UGT1A1 inhibitor, have increased exposure to Irinotecan and its active metabolite SN-38. Coadministration of Irinotecan hydrochloride injection 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 Irinotecan hydrochloride injection therapy. Do not administer strong CYP3A4 or UGT1A1 inhibitors with Irinotecan hydrochloride injection unless there are no therapeutic alternatives.

What enzymes convert irinotecan?

Irinotecan is subject to extensive metabolic conversion by various enzyme systems, including esterases to form the active metabolite SN-38, and UGT1A1 mediating glucuronidation of SN-38 to form the inactive glucuronide metabolite SN-38G. Irinotecan can also undergo CYP3A4-mediated oxidative metabolism to several inactive oxidation products, one of which can be hydrolyzed by carboxylesterase to release SN-38. In vitro studies indicate that Irinotecan, SN-38 and another metabolite aminopentane carboxylic acid (APC), do not inhibit cytochrome P-450 isozymes. UGT1A1 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity such as the UGT1A1*28 polymorphism. Approximately 10% of the North American population is homozygous for the UGT1A1*28 allele (also referred to as UGT1A1 7/7 genotype). In a prospective study, in which Irinotecan was administered as a single-agent (350 mg/m 2) on a once-every-3-week schedule, patients with the UGT1A1 7/7 genotype had a higher exposure to SN-38 than patients with the wild-type UGT1A1 allele (UGT1A1 6/6 genotype) [see Warnings and Precautions (5.3) and Dosage and Administration (2.3) ]. SN-38 glucuronide had 1/50 to 1/100 the activity of SN-38 in cytotoxicity assays using two cell lines in vitro.

How long does irinotecan stay in the body?

After intravenous infusion of Irinotecan in humans, Irinotecan plasma concentrations decline in a multiexponential manner, with a mean terminal elimination half-life of about 6 to 12 hours. The mean terminal elimination half-life of the active metabolite SN-38 is about 10 to 20 hours. The half-lives of the lactone (active) forms of Irinotecan and SN-38 are similar to those of total Irinotecan and SN-38, as the lactone and hydroxy acid forms are in equilibrium.

How much lactic acid is in a milliliter of irinotecan?

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 to 3.5 (range, 3.0 to 3.8) with sodium hydroxide or hydrochloric acid.

How is irinotecan given?

Your doctor may recommend a DNA test before your first dose. Some people are genetically more likely to have certain side effects from irinotecan.

What other drugs will affect irinotecan?

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Can irinotecan harm a baby?

Irinotecan can harm an unborn baby if the mother or the father is using irinotecan. If you are a woman, you may need to have a negative pregnancy test. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 6 months after your last dose.

Can you take irinotecan if you are allergic to it?

You should not use irinotecan if you are allergic to it. Tell your doctor if you have ever had: if you take a diuretic or "water pill.". Irinotecan can harm an unborn baby if the mother or the father is using irinotecan. If you are a woman, you may need to have a negative pregnancy test.

Can Irinotecan cause diarrhea?

If any of this medicine gets on your skin, wash right away with soap and water. Irinotecan can cause severe diarrhea, which can be life-threatening if it leads to dehydration. Your doctor may recommend keeping anti -diarrhea medicine on hand at all times (such as loperamide or Imodium ).

What is irinotecan hydrochloride?

Irinotecan hydrochloride is a camptothecin derivative that exerts antitumor activity against a variety of tumors. SN-38 produced in the body by carboxylesterase is the active metabolite of irinotecan. After irinotecan was introduced for the treatment ...

What is SN-38?

SN-38 produced in the body by car boxylesterase is the active metabolite of irinotecan. After irinotecan was introduced for the treatment of metastatic colorectal cancer (CRC) at the end of the last century, survival has improved dramatically. Irinotecan is now combined with 5-fluorouracil, oxaliplatin and several molecularly-targeted anticancer ...

What is irinotecan used for?

Contents. Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer, and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cisplatin. It is given by slow injection into a vein.

How does irinotecan work?

It works by blocking topoisomerase 1 which results in DNA damage and cell death. Irinotecan was approved for medical use in the United States in 1996. It is on the World Health Organization's List of Essential Medicines.

What enzyme converts irinotecan to SN-38?

Irinotecan is converted by an enzyme into its active metabolite SN-38, which is in turn inactivated by the enzyme UGT1A1 by glucuronidation.

What enzymes hydrolyze irinotecan?

About 2–5% of the pro-drug irinotecan is hydrolyzed into its active metabolite SN-38 in the liver by two carboxylesterase converting enzymes (CES1 and CES2) and in plasma by butyrylcholinesterase (hBChE). CES2 has a 12.5-fold higher affinity for irinotecan than CES1.

Which has a higher affinity for irinotecan than CES1?

CES2 has a 12.5-fold higher affinity for irinotecan than CES1. While, butyrylcholinesterase has a 6-fold higher activity for irinotecan than CES. After conversion, SN-38 is actively transported to the liver by the organic anion transporting polypeptide (OATP) 1B1 transporter.

What is SN-38?

In plasma, the majority of irinotecan and SN-38 are bound to albumin, which stabilizes their lactone forms. In blood, irinotecan and SN-38 are bound to platelets and red blood cells. Irinotecan has a linear pharmacokinetic.

What are the side effects of irinotecan?

Side effects. The most significant adverse effects of irinotecan include diarrhea, nausea and vomiting, neutropenia and fever, infections of blood or lungs (sepsis, pneumonia), shock, de hydration, kidney failure and thrombocytopenia (low levels of blood platelets).

What are the conditions for irinotecan hydrochloride injection?

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.

How much irinotecan is in USP?

Irinotecan hydrochloride injection, USP is supplied as a sterile, pale yellow, clear, aqueous solution. 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.

What medications can affect the removal of irinotecan?

Examples include azole antifungals (such as ketoconazole, itraconazole ), clarithromycin, gemfibrozil, nefazodone, HIV protease inhibitors (such as ritonavir, atazanavir ), rifamycins (such as rifabutin ), St. John's wort, drugs used to treat seizures (such as carbamazepine, phenytoin), telaprevir, among others.

What are the side effects of a syringe?

Tell your doctor right away if you have any serious side effects, including: pain/redness/swelling at the injection site or arms/legs, numbness/tingling/burning of arms/legs, black/ bloody stools, signs of kidney problems (such as change in the amount of urine), lung problems (such as shortness of breath, cough ).

Can you eat curcumin while taking irinotecan?

Avoid eating foods or taking products containing tumeric (curcumin) while being treated with irinotecan. It may decrease this medication's effects. Consult your doctor or pharmacist for more details.

Can a syringe cause anemia?

This medication may cause very serious (possibly fatal) blood disorders (decreased bone marrow function leading to low number of blood cells such as white cells, red cells, and platelets). This effect can decrease your body's ability to fight an infection, cause your body to bruise or bleed easier, or cause anemia.

Can irinotecan cause diarrhea?

Irinotecan may cause severe diarrhea, which can occur during or right after you receive this medication and/or more than 24 hours afterward. If the diarrhea starts right away, you may also have other side effects such as runny nose, increased saliva, watery eyes, sweating, stomach cramps, or flushing. If the diarrhea starts later, it could be a different type that may be persistent and can cause serious (possibly fatal) loss of too much body water ( dehydration ), mineral imbalance, or serious infection ( sepsis ). Tell your doctor right away if you have diarrhea and/or any of the symptoms that occur with the early form of diarrhea. Also tell your doctor if you have stomach / abdominal pain, extreme thirst, very dry mouth, muscle cramps / weakness, fast/slow/irregular heartbeat, fainting, dizziness, lightheadedness, or signs of infection (e.g., fever, persistent sore throat ). Your doctor should prescribe other medications to treat the diarrhea and other symptoms.

What is the best treatment for CPT-11 diarrhea?

Several emerging and existing therapies such as herbal formulas, plant extractions, and phytochemicals have been proven effective for the treatment and prevention of CPT-11-related diarrhea in preclinical and clinical studies.

What is the mechanism of action of herbal medicines for delayed onset diarrhea?

The proposed mechanisms of action of herbal medicines for treatment of delayed-onset diarrhea are diverse, mainly acting on metabolism of CPT-11, which occurs through a number of enzymes, metabolites, and transporters.

What is sairei to used for?

Sairei-to, a traditional Japanese herbal medicine used to treat severe diarrhea and various inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematodes, and nephrotic syndrome, is made from a combined formulation of twelve medicinal herbs ( Ito et al., 2002; Kato et al., 2015 ). In a preclinical study conducted on male Wistar rats, co-administration of Sairei-to (1 g/kg; b.i.d.) alleviated CPT-11-induced delayed-onset diarrhea. The probable mechanism of action was related to the inhibition of bacterial β-glucuronidase ( Takasuna et al., 1995b ). Recently, Satoh et al. (2018) investigated the inhibitory effects of β-glucuronidase-treated or untreated Sairei-to on SN-38 glucuronidation in human liver microsomes. They reported that β-glucuronidase-treated Sairei-to remarkably increased baicalein, which was the key ingredient responsible for inhibition of UGT activity. Baicalein, the deglycosylation product of baicalin derived from Sairei-to, could be a pharmacokinetic regulating factor associated with SN-38-induced late-onset diarrhea in vitro. Similarly, Kato et al. (2015) demonstrated that Sairei-to (100, 300, or 1000 mg/kg; b.i.d.) dose-dependently attenuated 5-FU-induced diarrhea in mice during chemotherapy via suppression of up-regulation of inflammatory cytokines such as TNF-α, IL-1β, and TGF-β.

Is loperamide good for diarrhea?

High-dose loperamide and octreotide are generally recommended for treatment of CPT-11-induced diarrhea. However, in clinical practice, loperamide is associated with a significant failure rate and the beneficial effects of octreotide are controversial.

Indications and Usage

Dosage and Administration

Contraindications

Warnings and Precautions

Adverse Reactions

Drug Interactions

Use in Specific Populations

Overdosage

Irinotecan Description

Irinotecan - Clinical Pharmacology