Irinotecan

Irinotecan is a topoisomerase inhibitor (a type of chemotherapy that disrupts cancer cell DNA) used intravenously for two main cancer types, with approved uses that vary by product:

• Camptosar and irinotecan hydrochloride injection products are approved as first-line treatment for metastatic carcinoma of the colon or rectum, used in combination with 5-fluorouracil (5-FU) and leucovorin
• Camptosar and irinotecan hydrochloride injection products are approved for metastatic colorectal cancer that has come back or progressed after initial fluorouracil-based therapy — in these cases they may be used as a single agent
• Onivyde (a liposomal formulation) is approved for first-line treatment of metastatic pancreatic adenocarcinoma in combination with oxaliplatin, fluorouracil, and leucovorin
• Onivyde is also approved for metastatic pancreatic adenocarcinoma in patients whose disease progressed on gemcitabine-based therapy, used in combination with fluorouracil and leucovorin
• Onivyde is not approved as a single agent for pancreatic cancer — it must be used as part of a combination regimen

Irinotecan works by interfering with an enzyme called topoisomerase I, which cancer cells rely on to unwind and repair their DNA during cell division. When irinotecan (and especially its active metabolite SN-38) binds to this enzyme, it prevents broken DNA strands from being resealed. This creates permanent double-strand DNA breaks that cancer cells cannot fix, ultimately stopping them from multiplying.

Irinotecan itself is a prodrug — meaning your body must convert it into SN-38 to unlock its full power. SN-38 is roughly 1,000 times more potent than irinotecan as a topoisomerase I inhibitor. People with certain genetic variations (specifically in an enzyme called UGT1A1) clear SN-38 more slowly, which raises their risk of serious side effects.

Irinotecan is always given intravenously by a healthcare professional — never taken by mouth at home. It is infused over 90 minutes, and the schedule depends on which product you are receiving, which cancer is being treated, and which regimen your oncologist has chosen.

• Camptosar and irinotecan hydrochloride injections follow colorectal cancer regimens that may involve weekly dosing or dosing every 3 weeks, always paired with other chemotherapy agents when used in first-line treatment
• Onivyde is given every two weeks for pancreatic cancer, in combination with other chemotherapy medicines; it must be given before oxaliplatin, fluorouracil, and leucovorin in the first-line regimen
• Do not substitute Onivyde for other irinotecan products — they are different formulations with different dosing

Your care team will monitor your blood counts and side effects and may pause or adjust your dose. Always follow your oncologist's instructions.

Irinotecan causes side effects in most patients; knowing what to expect helps you respond quickly when it matters:

• Diarrhea — both early (during/right after infusion) and late (24+ hours later); late diarrhea can be severe
• Nausea and vomiting
• Loss of appetite
• Abdominal pain and cramping
• Neutropenia (low white blood cell counts), which raises infection risk
• Anemia (low red blood cells), causing fatigue
• Hair loss (alopecia)
• Weakness and fatigue (asthenia)
• Fever and increased risk of infection

Seek immediate medical attention for late diarrhea that won't stop, any fever (especially with low blood counts), signs of severe infection, new breathing problems, or symptoms of a serious allergic reaction such as hives, swelling, or difficulty breathing.

• Life-threatening diarrhea: Late diarrhea (starting more than 24 hours after infusion) can rapidly lead to dehydration, dangerous electrolyte loss, and life-threatening infection. Treat immediately with loperamide and contact your care team at the first sign of loose stools.
• Severe bone marrow suppression (myelosuppression): Irinotecan can dangerously reduce white blood cell counts, increasing the risk of serious or fatal infections, including neutropenic fever and sepsis. Blood counts must be monitored regularly.
• UGT1A1 genetic risk: People who are homozygous for the UGT1A1*28 allele (a common genetic variant) have a higher exposure to SN-38 and a greater risk of severe neutropenia. Genetic testing may be considered before treatment.
• Lung inflammation (interstitial pulmonary disease): Serious and sometimes fatal lung inflammation has been reported. Report any new shortness of breath, cough, or fever right away.
• Kidney problems: Rare cases of acute kidney failure have occurred, usually in patients who became severely dehydrated from diarrhea or vomiting.
• Embryo-fetal toxicity: Irinotecan can cause serious harm to an unborn baby. Effective contraception is required during and after treatment.

Irinotecan is processed by liver enzymes (CYP3A4 and UGT1A1), so medicines that affect these enzymes can significantly change how much irinotecan or its active metabolite SN-38 is in your body:

• Strong CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin, St. John's Wort) — speed up breakdown of irinotecan, potentially making it less effective; switch to a non-inducing alternative at least 2 weeks before starting irinotecan if possible
• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, itraconazole, ritonavir, voriconazole, nefazodone, telaprevir, and others) — slow breakdown of irinotecan, raising drug levels and the risk of severe side effects; stop these at least 1 week before starting irinotecan if possible
• Strong UGT1A1 inhibitors (atazanavir, gemfibrozil, indinavir) — slow breakdown of the active metabolite SN-38, increasing toxicity risk
• Diuretics and laxatives — can worsen dehydration during episodes of diarrhea and should be avoided

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Tell your oncologist and pharmacist about every medication, supplement, vitamin, and herbal product you take — especially anti-seizure drugs, antibiotics, antifungals, HIV medicines, and St. John's Wort
• Patients with elevated bilirubin or significant liver impairment may not be able to receive standard doses — discuss your liver function with your care team
• Patients with kidney impairment should be used with caution; irinotecan should not be used in patients on dialysis
• Ask your doctor about UGT1A1 genetic testing — a common variant (UGT1A1*28) increases your risk of severe low white blood cell counts
• Women who are pregnant or could become pregnant: irinotecan can harm a developing baby; use effective contraception during treatment and for 6 months after the last dose; confirm pregnancy status before starting
• Men whose partners could become pregnant should use condoms during treatment and for 3 months after the last dose
• Do not breastfeed during treatment or for 7 days after the final dose
• Older adults (over 65) face a higher risk of severe diarrhea and require closer monitoring; patients 70 and older on the once-every-3-week schedule may receive a lower starting dose
• The effectiveness of irinotecan in children has not been established
• Irinotecan may impair fertility in both men and women; discuss this with your doctor before starting treatment if this is a concern

Overdoses of irinotecan have been reported at approximately twice the recommended dose and may be fatal. The most serious consequences are severe neutropenia (dangerously low white blood cells) and severe diarrhea. There is no specific antidote; treatment focuses on preventing dehydration from diarrhea and managing any resulting infections with supportive care.

After irinotecan is converted to SN-38 in the body, SN-38 is approximately 1,000 times more potent than irinotecan at blocking topoisomerase I. By trapping topoisomerase I bound to DNA, it causes double-strand DNA breaks that cancer cells cannot efficiently repair, stopping them from dividing. Both irinotecan and SN-38 exist in an active form (lactone) and an inactive form; an acidic environment favors the active form, while a more basic environment shifts the balance toward the inactive form.

After a 90-minute intravenous infusion, irinotecan is cleared from the bloodstream with a half-life of about 6 to 12 hours; its active metabolite SN-38 has a longer half-life of roughly 10 to 20 hours. SN-38 reaches its peak concentration in the blood within about 1 hour after the end of the infusion. Irinotecan is moderately bound to blood proteins (30–68%), while SN-38 is very tightly bound (about 95%). The drug is broken down primarily in the liver — by an enzyme called UGT1A1, which deactivates SN-38, and by CYP3A4 — and is eliminated through urine and other routes.

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F). Protect from freezing. Protect from light.