Irinotecan Hydrochloride

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Overview

What is Irinotecan Hydrochloride?

Irinotecan hydrochloride injection, USP is an antineoplastic agent of the topoisomerase I inhibitor class.

Irinotecan Hydrochloride Injection, USP is supplied as a sterile, pale yellow, clear, aqueous solution. It is available in two single-dose sizes: 2 mL-fill vials contain 40 mg irinotecan hydrochloride USP (as trihydrate) and 5 mL-fill vials contain 100 mg irinotecan hydrochloride USP (as trihydrate). Each milliliter of solution contains 20 mg of irinotecan hydrochloride USP (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 NF and/or hydrochloric acid NF. Irinotecan hydrochloride injection, USP is intended for dilution with 5% Dextrose injection, USP (D5W), or 0.9% Sodium Chloride injection, USP, prior to intravenous infusion. The preferred diluent is 5% Dextrose injection, USP.

Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extract from plants such as or is chemically synthesized

The chemical name is -4,11-diethyl-3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo1 -pyrano[3',4':6,7]-indolizino[1,2-b]quinolin-9-yl-[1,4'bipiperidine]-1'-carboxylate, monohydrochloride, trihydrate. Its empirical formula is C33H38N4O6•HCl•3H2O and molecular weight is 677.19. It is slightly soluble in water and organic solvents.

Its structural formula is as follows:

What does Irinotecan Hydrochloride look like?

What are the available doses of Irinotecan Hydrochloride?

Irinotecan hydrochloride injection is available in two single-dose sizes:

What should I talk to my health care provider before I take Irinotecan Hydrochloride?

How should I use Irinotecan Hydrochloride?

Irinotecan is a topoisomerase inhibitor indicated for:

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.

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.

What interacts with Irinotecan Hydrochloride?

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What are the warnings of Irinotecan Hydrochloride?

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What are the precautions of Irinotecan Hydrochloride?

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What are the side effects of Irinotecan Hydrochloride?

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What should I look out for while using Irinotecan Hydrochloride?

Hypersensitivity to Irinotecan hydrochloride injection, USP or its excipients ()

What might happen if I take too much Irinotecan Hydrochloride?

In U.S. phase 1 trials, single doses of up to 345 mg/mof irinotecan were administered to patients with various cancers. Single doses of up to 750 mg/mof 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.

How should I store and handle Irinotecan Hydrochloride?

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Keep tightly closed (protect from moisture). Protect from light.Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Keep tightly closed (protect from moisture). Protect from light.Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Keep tightly closed (protect from moisture). Protect from light.Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.Each mL of Irinotecan Hydrochloride Injection, USP contains 20 mg irinotecan hydrochloride USP (on the basis of the trihydrate salt); 45 mg sorbitol NF; and 0.9 mg lactic acid USP. When necessary, pH has been adjusted to 3.5 (range, 3.0 to 3.8) with sodium hydroxide NF and/or hydrochloric acid NF.Irinotecan Hydrochloride Injection, USP is available in single-dose amber glass vials in the following package sizes:2 mL NDC 23155-179-315 mL NDC 23155-179-32Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].Protect from light. It is recommended that the vial should remain in the carton until the time of use.Inspect the vial for damage and visible signs of leaks before removing from the carton. If damaged, incinerate the unopened package. Each mL of Irinotecan Hydrochloride Injection, USP contains 20 mg irinotecan hydrochloride USP (on the basis of the trihydrate salt); 45 mg sorbitol NF; and 0.9 mg lactic acid USP. When necessary, pH has been adjusted to 3.5 (range, 3.0 to 3.8) with sodium hydroxide NF and/or hydrochloric acid NF.Irinotecan Hydrochloride Injection, USP is available in single-dose amber glass vials in the following package sizes:2 mL NDC 23155-179-315 mL NDC 23155-179-32Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].Protect from light. It is recommended that the vial should remain in the carton until the time of use.Inspect the vial for damage and visible signs of leaks before removing from the carton. If damaged, incinerate the unopened package. Each mL of Irinotecan Hydrochloride Injection, USP contains 20 mg irinotecan hydrochloride USP (on the basis of the trihydrate salt); 45 mg sorbitol NF; and 0.9 mg lactic acid USP. When necessary, pH has been adjusted to 3.5 (range, 3.0 to 3.8) with sodium hydroxide NF and/or hydrochloric acid NF.Irinotecan Hydrochloride Injection, USP is available in single-dose amber glass vials in the following package sizes:2 mL NDC 23155-179-315 mL NDC 23155-179-32Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].Protect from light. It is recommended that the vial should remain in the carton until the time of use.Inspect the vial for damage and visible signs of leaks before removing from the carton. If damaged, incinerate the unopened package. Each mL of Irinotecan Hydrochloride Injection, USP contains 20 mg irinotecan hydrochloride USP (on the basis of the trihydrate salt); 45 mg sorbitol NF; and 0.9 mg lactic acid USP. When necessary, pH has been adjusted to 3.5 (range, 3.0 to 3.8) with sodium hydroxide NF and/or hydrochloric acid NF.Irinotecan Hydrochloride Injection, USP is available in single-dose amber glass vials in the following package sizes:2 mL NDC 23155-179-315 mL NDC 23155-179-32Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].Protect from light. It is recommended that the vial should remain in the carton until the time of use.Inspect the vial for damage and visible signs of leaks before removing from the carton. If damaged, incinerate the unopened package. Each mL of Irinotecan Hydrochloride Injection, USP contains 20 mg irinotecan hydrochloride USP (on the basis of the trihydrate salt); 45 mg sorbitol NF; and 0.9 mg lactic acid USP. When necessary, pH has been adjusted to 3.5 (range, 3.0 to 3.8) with sodium hydroxide NF and/or hydrochloric acid NF.Irinotecan Hydrochloride Injection, USP is available in single-dose amber glass vials in the following package sizes:2 mL NDC 23155-179-315 mL NDC 23155-179-32Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].Protect from light. It is recommended that the vial should remain in the carton until the time of use.Inspect the vial for damage and visible signs of leaks before removing from the carton. If damaged, incinerate the unopened package. Each mL of Irinotecan Hydrochloride Injection, USP contains 20 mg irinotecan hydrochloride USP (on the basis of the trihydrate salt); 45 mg sorbitol NF; and 0.9 mg lactic acid USP. When necessary, pH has been adjusted to 3.5 (range, 3.0 to 3.8) with sodium hydroxide NF and/or hydrochloric acid NF.Irinotecan Hydrochloride Injection, USP is available in single-dose amber glass vials in the following package sizes:2 mL NDC 23155-179-315 mL NDC 23155-179-32Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].Protect from light. It is recommended that the vial should remain in the carton until the time of use.Inspect the vial for damage and visible signs of leaks before removing from the carton. If damaged, incinerate the unopened package. Each mL of Irinotecan Hydrochloride Injection, USP contains 20 mg irinotecan hydrochloride USP (on the basis of the trihydrate salt); 45 mg sorbitol NF; and 0.9 mg lactic acid USP. When necessary, pH has been adjusted to 3.5 (range, 3.0 to 3.8) with sodium hydroxide NF and/or hydrochloric acid NF.Irinotecan Hydrochloride Injection, USP is available in single-dose amber glass vials in the following package sizes:2 mL NDC 23155-179-315 mL NDC 23155-179-32Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].Protect from light. It is recommended that the vial should remain in the carton until the time of use.Inspect the vial for damage and visible signs of leaks before removing from the carton. If damaged, incinerate the unopened package.

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Clinical Information

Chemical Structure

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Clinical Pharmacology

Irinotecan is a derivative of camptothecin. Camptothecins interact specifically with the enzyme topoisomerase I, which relieves torsional strain in DNA by inducing reversible single-strand breaks. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I -DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks.

Non-Clinical Toxicology

Hypersensitivity to Irinotecan hydrochloride injection, USP or its excipients ()

Clonidine may potentiate the CNS-depressive effects of alcohol, barbiturates or other sedating drugs. If a patient receiving clonidine hydrochloride is also taking tricyclic antidepressants, the hypotensive effect of clonidine may be reduced, necessitating an increase in the clonidine dose. If a patient receiving clonidine is also taking neuroleptics, orthostatic regulation disturbances (e.g., orthostatic hypotension, dizziness, fatigue) may be induced or exacerbated. Monitor heart rate in patients receiving clonidine concomitantly with agents known to affect sinus node function or AV nodal conduction, e.g. digitalis, calcium channel blockers and beta-blockers. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concomitantly with diltiazem or verapamil. Amitriptyline in combination with clonidine enhances the manifestation of corneal lesions in rats (see ). Based on observations in patients in a state of alcoholic delirium it has been suggested that high intravenous doses of clonidine may increase the arrhythmogenic potential (QT-prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. Causal relationship and relevance for clonidine oral tablets have not been established. In several studies with oral clonidine hydrochloride, a dose-dependent increase in the incidence and severity of spontaneous retinal degeneration was seen in albino rats treated for six months or longer. Tissue distribution studies in dogs and monkeys showed a concentration of clonidine in the choroid. In view of the retinal degeneration seen in rats, eye examinations were performed during clinical trials in 908 patients before, and periodically after, the start of clonidine therapy. In 353 of these 908 patients, the eye examinations were carried out over periods of 24 months or longer. Except for some dryness of the eyes, no drug-related abnormal ophthalmological findings were recorded and, according to specialized tests such as electroretinography and macular dazzle, retinal function was unchanged. In combination with amitriptyline, clonidine hydrochloride administration led to the development of corneal lesions in rats within 5 days.

Early diarrhea (occurring during or shortly after infusion of irinotecan hydrochloride injection) is usually transient and infrequently 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 irinotecan hydrochloride injection) can be life threatening since it may be prolonged and may lead to dehydration, electrolyte imbalance, or sepsis. Grade 3 to 4 late diarrhea occurred in 23 to 31% of patients receiving weekly dosing. In the clinical studies, the median time to the onset of late diarrhea was 5 days with 3-week dosing and 11 days with weekly dosing. 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 irinotecan until resolution of the bowel obstruction. If grade 2, 3, or 4 late diarrhea recurs, subsequent doses of irinotecan hydrochloride injection should be decreased . Avoid diuretics or laxatives in patients with diarrhea.

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Reference

This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"

While we update our database periodically, we cannot guarantee it is always updated to the latest version.

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