Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 20mg/mL
Colorectal Cancer
Indicated as first-line therapy (with 5-fluorouracil and leucovorin) for metastatic colorectal cancer (CRC); it is also indicated for CRC that has recurred or progressed following initial fluorouracil-based therapy
Monotherapy
- Patients should be premedicated with antiemetic agents
- Atropine treatment should be considered in patients that experience cholinergic symptoms
- Regimen 1 (Weekly): 125 mg/m² IV infusion over 90 minutes on days 1, 8, 15, 22, then 2 weeks off, then repeat
- Regimen 2 (Once Every 3 Weeks): 350 mg/sq.meter IV infusion over 30-90 minutes q3Weeks
- Adjust dose per protocol
Combination therapy
- Patients should be premedicated with antiemetic agents
- Atropine treatment should be considered in patients that experience cholinergic symptoms
- Regimen 1 (6 week cycle with infusional 5-fluorouracil/ leucovorin): 180 mg/m² IV infusion over 30-90 minutes once on days 1, 15, and 29 IV (infuse over 30-90 min), followed by infusion with leucovorin and 5-fluorouracil; next cycle begins on day 43
- Regimen 2 (6 week cycle with bolus 5-fluorouracil/ leucovorin): 125 mg/sq.meter on days 1, 8, 15, and 22 (infuse over 90 min), followed by bolus doses of leucovorin and 5-fluorouracil
- Adjust dose per protocol
Dosage Modifications
See prescribing information for detailed recommendations for combination and single-use regimens
Patients homozygous for UGT1A1*28 allele: Precise dose reduction unknown; consider reducing dose by at least 1 level
Renal impairment
- Not studied; use with caution
- Dialysis: Not recommended
Hepatic impairment
- Irinotecan clearance diminished with hepatic impairment, while exposure to active metabolite SN-38 is increased relative to that in patients with normal hepatic function
- Caution when administering to patients with hepatic impairment
- Hepatic dysfunction (bilirubin >2 mg/dL): Not sufficiently assessed; no recommendations for dosing can be made
Pancreatic Cancer (Orphan)
Stable nanotherapeutic encapsulated irinotecan (MM-398; pegirinotecan)
Orphan indication sponsor
- Merrimack Pharmaceuticals, Inc., 1 Kendall Square; Cambridge, MA 02139-1670
Ovarian Cancer (Orphan)
Peg-irinotecan: Treatment of ovarian cancer
Orphan indication sponsor
- Nektar Therapeutics; 455 Mission Bay Blvd; South San Francisco, CA 94158
Other Indications & Uses
Off-label: advanced ovarian cancer, glioblastoma multiforme, NSCLC
Not recommended
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (12)
- carbamazepine
carbamazepine will decrease the level or effect of irinotecan by affecting hepatic enzyme CYP2B6 metabolism. Contraindicated.
- clozapine
clozapine, irinotecan. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Concomitant administraiton increases risk of agranulocytosis.
irinotecan, clozapine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Concomitant administration increases risk of agranulocytosis. - cobicistat
cobicistat will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated with cobicistat coadministered with atazanavir and irinotecan. Coadministration of atazanavir with irinotecan is contraindicated due to potential for increased irinotecan toxicity.
- conivaptan
conivaptan will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- darunavir
darunavir will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- fosamprenavir
fosamprenavir will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- indinavir
indinavir will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Contraindicated.
- itraconazole
itraconazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 Inhibitors may increase the serum concentration of SN-38 (active metabolite for irinotecan products). Contraindicated during and 2 weeks after itraconazole treatment.
- lopinavir
lopinavir will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- rifampin
rifampin will decrease the level or effect of irinotecan by affecting hepatic enzyme CYP2B6 metabolism. Contraindicated.
- ritonavir
ritonavir will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Contraindicated.
- St John's Wort
St John's Wort will decrease the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Contraindicated.
Serious - Use Alternative (70)
- abametapir
abametapir will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
abametapir will increase the level or effect of irinotecan by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP2B6 substrates. If not feasible, avoid use of abametapir. - adenovirus types 4 and 7 live, oral
irinotecan decreases effects of adenovirus types 4 and 7 live, oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressives may diminish therapeutic effects of vaccines and increase risk of adverse effects (increased risk of infection). Live-attenuated vaccines should be avoided for at least 3mo after cessation of immunosuppressive therapy.
- apalutamide
apalutamide will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- armodafinil
armodafinil will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- atazanavir
atazanavir will increase the level or effect of irinotecan by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism
atazanavir will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - bosentan
bosentan will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- carbamazepine
carbamazepine will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ceritinib
ceritinib will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- chloramphenicol
chloramphenicol will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- cimetidine
cimetidine will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- clarithromycin
clarithromycin will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
clarithromycin will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - clobazam
clobazam will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- crizotinib
crizotinib will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- darolutamide
darolutamide will increase the level or effect of irinotecan by Other (see comment). Avoid or Use Alternate Drug. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).
- dasabuvir
dasabuvir will increase the level or effect of irinotecan by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism
- deferiprone
deferiprone, irinotecan. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.
- efavirenz
efavirenz will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- eliglustat
eliglustat increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.
- enzalutamide
enzalutamide will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erdafitinib
erdafitinib will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.
- erythromycin base
erythromycin base will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- etravirine
etravirine will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- fexinidazole
fexinidazole will decrease the level or effect of irinotecan by affecting hepatic enzyme CYP2B6 metabolism. Avoid or Use Alternate Drug. Coadministration may decrease plasma concentrations of CYP2B6 substrates owing to fexinidazole inducing CYP2B6.
fexinidazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates. - fosphenytoin
fosphenytoin will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- gemfibrozil
gemfibrozil will increase the level or effect of irinotecan by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism
- idelalisib
idelalisib will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- indinavir
indinavir will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
indinavir will increase the level or effect of irinotecan by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism - influenza virus vaccine quadrivalent, adjuvanted
irinotecan decreases effects of influenza virus vaccine quadrivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.
- influenza virus vaccine trivalent, adjuvanted
irinotecan decreases effects of influenza virus vaccine trivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.
- isoniazid
isoniazid will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ivosidenib
ivosidenib will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- ketoconazole
ketoconazole will increase the level or effect of irinotecan by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism
ketoconazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - lasmiditan
lasmiditan increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
lasmiditan increases levels of irinotecan by Other (see comment). Avoid or Use Alternate Drug. Comment: Lasmiditan inhibits BCRP in vitro. Avoid coadministration of lasmiditan with BCRP substrates. - leniolisib
leniolisib will increase the level or effect of irinotecan by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, a BCRP inhibitor, may increase systemic exposure of BCRP substrates
- levoketoconazole
levoketoconazole will increase the level or effect of irinotecan by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism
levoketoconazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - mifepristone
mifepristone will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration and for at least 1 week prior to initiating therapy unless no therapeutic alternatives
- milk thistle
milk thistle will increase the level or effect of irinotecan by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism
- mitotane
mitotane will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nafcillin
nafcillin will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nefazodone
nefazodone will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
nefazodone will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. - nelfinavir
nelfinavir will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nevirapine
nevirapine will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of irinotecan by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism
- oxcarbazepine
oxcarbazepine will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- pacritinib
pacritinib will increase the level or effect of irinotecan by Other (see comment). Avoid or Use Alternate Drug. Concomitant administration of pacritinib (BCRP inhibitor) with BCRP substrates may increase the plasma concentrations of these substrates.
- palifermin
palifermin increases toxicity of irinotecan by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hrbefore, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- phenobarbital
phenobarbital will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- phenytoin
phenytoin will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- posaconazole
posaconazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- primidone
primidone will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifabutin
rifabutin will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifampin
rifampin will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifapentine
rifapentine will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ritonavir
ritonavir will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- ropeginterferon alfa 2b
ropeginterferon alfa 2b, irinotecan. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.
- saquinavir
saquinavir will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sertraline
sertraline will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- sotorasib
sotorasib will decrease the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.
- sparsentan
sparsentan will increase the level or effect of irinotecan by Other (see comment). Avoid or Use Alternate Drug. Sparsentan (a BCRP inhibitor) may increase exposure of sensitive BCRP substrates and the risk of these substrates toxicities.
- St John's Wort
St John's Wort will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tepotinib
tepotinib will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.
- tetracycline
tetracycline will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tipranavir
tipranavir will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- tucatinib
tucatinib will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
- verapamil
verapamil will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- voriconazole
voriconazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- voxelotor
voxelotor will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
Monitor Closely (91)
- acalabrutinib
acalabrutinib increases levels of irinotecan by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.
acalabrutinib, irinotecan. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may increase risk of myelosuppressive effects. - amiodarone
amiodarone will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
amiodarone will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - apalutamide
apalutamide will decrease the level or effect of irinotecan by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and weakly induces BCRP and may decrease systemic exposure of drugs that are substrates of both UGT and BCRP.
- aprepitant
aprepitant will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- atorvastatin
atorvastatin will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- belzutifan
belzutifan will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
- berotralstat
berotralstat will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
- bevacizumab
bevacizumab, irinotecan. Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of diarrhea and neutropenia during concomitant administration of bevacizumab and irinotecan.
- bicalutamide
bicalutamide will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- bosutinib
bosutinib increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- cannabidiol
cannabidiol, irinotecan. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP2B6 induction and inhibition with the coadministration of CYP2B6 substrates and cannabidiol, consider reducing dosage adjustment of CYP2B6 substrates as clinically appropriate.
- cenobamate
cenobamate will decrease the level or effect of irinotecan by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP2B6 substrate, as needed, when coadministered with cenobamate.
cenobamate will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate. - cholera vaccine
irinotecan decreases effects of cholera vaccine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.
- clotrimazole
clotrimazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- crizotinib
crizotinib increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- cyclosporine
cyclosporine will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
cyclosporine will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - dabrafenib
dabrafenib will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- dengue vaccine
irinotecan decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.
- denosumab
irinotecan, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- dexamethasone
dexamethasone will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dichlorphenamide
dichlorphenamide and irinotecan both decrease serum potassium. Use Caution/Monitor.
- diltiazem
diltiazem will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dronedarone
dronedarone will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
dronedarone will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - duvelisib
duvelisib will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.
- elacestrant
elacestrant will increase the level or effect of irinotecan by Other (see comment). Modify Therapy/Monitor Closely. Elacestrant (a BCRP inhibitor) may increase plasma concentrations of sensitive BCRP substrates, which may increase risk of adverse reactions related to these substrates. Refer to prescribing information for sensitive BCRP substrates for dosing recommendations.
- elagolix
elagolix will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
elagolix decreases levels of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed. - eluxadoline
eluxadoline increases levels of irinotecan by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered BCRP substrates.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
- encorafenib
encorafenib, irinotecan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
encorafenib will increase the level or effect of irinotecan by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates. - erythromycin base
erythromycin base will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin stearate
erythromycin stearate will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fedratinib
fedratinib will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- fingolimod
irinotecan increases effects of fingolimod by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Concomitant therapy is expected to increase the risk of immunosuppression. Use caution when switching patients from long-acting therapies with immune effects. .
- fluconazole
fluconazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fluvoxamine
fluvoxamine will increase the level or effect of irinotecan by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.
- fosaprepitant
fosaprepitant will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fostamatinib
fostamatinib will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp substrates. Monitor for toxicities of the P-gp substrate drug that may require dosage reduction when given concurrently with fostamatinib.
- fostemsavir
fostemsavir will increase the level or effect of irinotecan by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits BCRP transporters. If possible, avoid coadministration or modify dose of BCRP substrate coadministered with fostemsavir.
- glecaprevir/pibrentasvir
glecaprevir/pibrentasvir will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
glecaprevir/pibrentasvir will increase the level or effect of irinotecan by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates. - hydroxyurea
irinotecan, hydroxyurea. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of myelosuppression.
- imatinib
imatinib will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- istradefylline
istradefylline will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
istradefylline will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates. - ivacaftor
ivacaftor increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.
- ketoconazole
ketoconazole will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lapatinib
lapatinib will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
lapatinib will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - lemborexant
lemborexant will decrease the level or effect of irinotecan by affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Monitor CYP2B6 substrate for adequate clinical response. Consider increasing the CYP2B6 substrate dose according to specific prescribing recommendations.
- lenacapavir
lenacapavir will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- letermovir
letermovir increases levels of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levoketoconazole
levoketoconazole will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lomitapide
lomitapide increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.
- lonafarnib
lonafarnib will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.
- lorlatinib
lorlatinib will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor, irinotecan. affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2B6 substrates. .
- meningococcal group B vaccine
irinotecan decreases effects of meningococcal group B vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Individuals with altered immunocompetence may have reduced immune responses to the vaccine.
- mifepristone
mifepristone will increase the level or effect of irinotecan by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.
- nicardipine
nicardipine will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nilotinib
nilotinib will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ofatumumab SC
ofatumumab SC, irinotecan. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.
- olaparib
irinotecan and olaparib both increase pharmacodynamic synergism. Use Caution/Monitor. Coadministration with other other myelosuppressive anticancer agents, including DNA damaging agents, may potentiate and prolongate the myelosuppressive toxicity.
- osimertinib
osimertinib will increase the level or effect of irinotecan by Other (see comment). Modify Therapy/Monitor Closely. Osimertinib is an inhibitor of BCRP transport. Caution if coadministered with sensitive BCRP substrates.
- oteseconazole
oteseconazole will increase the level or effect of irinotecan by Other (see comment). Modify Therapy/Monitor Closely. Otesezonale, a BCRP inhibitor, may increase the effects and risk of toxicities of BCRP substrates. Use lowest starting dose of BCRP substrate, or consider reducing BCRP substrate dose.
- pentobarbital
pentobarbital will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ponatinib
ponatinib increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases levels of irinotecan by Other (see comment). Use Caution/Monitor. - ranolazine
ranolazine will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- regorafenib
regorafenib will increase the level or effect of irinotecan by decreasing metabolism. Use Caution/Monitor. Regorafenib may inhibit UGT1A1-mediated metabolism of irinotican and its metabolite
regorafenib will increase the level or effect of irinotecan by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity. - ribociclib
ribociclib will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifampin
rifampin will decrease the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- rolapitant
rolapitant will increase the level or effect of irinotecan by Other (see comment). Use Caution/Monitor. Oral rolapitant (BCRP inhibitor) may increase plasma concentrations of BCRP substrates and may result in potential adverse reactions. Monitor possible adverse reactions if concomitant use of BCRP substrates and rolapitant can not be avoided.
- rucaparib
rucaparib will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- safinamide
safinamide will increase the level or effect of irinotecan by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.
- sarecycline
sarecycline will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.
- schisandra
schisandra will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- siponimod
siponimod and irinotecan both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- sipuleucel-T
irinotecan decreases effects of sipuleucel-T by pharmacodynamic antagonism. Modify Therapy/Monitor Closely.
- sofosbuvir/velpatasvir
sofosbuvir/velpatasvir will increase the level or effect of irinotecan by Other (see comment). Use Caution/Monitor. Velpatasvir is an inhibitor of the drug transporter BCRP. Coadministration may increase systemic exposure of drugs that are BCRP substrates.
- sorafenib
sorafenib increases levels of irinotecan by Other (see comment). Use Caution/Monitor. Comment: Competition for UGT1A1 pathway.
- sparsentan
sparsentan will decrease the level or effect of irinotecan by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor. Sparsentan (a CYP2B6 inducer) decreases exposure of CYP2B6 substrates and reduces efficacy related to these substrates.
- stiripentol
stiripentol, irinotecan. affecting hepatic enzyme CYP2B6 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP2B6 inhibitor and inducer. Monitor CYP2B6 substrates coadministered with stiripentol for increased or decreased effects. CYP2B6 substrates may require dosage adjustment.
stiripentol, irinotecan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
stiripentol will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.
stiripentol will increase the level or effect of irinotecan by Other (see comment). Modify Therapy/Monitor Closely. Stiripentol is a BCRP transport inhibitor. Consider dosage reduction for BCRP substrates if adverse effects are experienced when coadministered. - tacrolimus
tacrolimus will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- tafamidis
tafamidis will increase the level or effect of irinotecan by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.
- tafamidis meglumine
tafamidis meglumine will increase the level or effect of irinotecan by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.
- tazemetostat
tazemetostat will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- trastuzumab
trastuzumab, irinotecan. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .
- trastuzumab deruxtecan
trastuzumab deruxtecan, irinotecan. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .
- tucatinib
tucatinib will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.
- ustekinumab
ustekinumab, irinotecan. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.
- vemurafenib
vemurafenib increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- verapamil
verapamil will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
Minor (11)
- acetazolamide
acetazolamide will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- haloperidol
haloperidol will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- iloperidone
iloperidone increases levels of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.
- larotrectinib
larotrectinib will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- metronidazole
metronidazole will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- netupitant/palonosetron
netupitant/palonosetron will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- valerian
valerian will increase the level or effect of irinotecan by decreasing metabolism. Minor/Significance Unknown. UGT1A1 inhibitors decrease irinotecan metabolism
- vitamin A
vitamin A, irinotecan. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin A enhance the efficacy, and reduce toxicity, of antineoplastic drugs.
- vitamin E
vitamin E, irinotecan. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Antioxidants such as vitamin E enhance the efficacy, and reduce toxicity, of antineoplastic drugs.
Adverse Effects
>10%
Anemia (>90%)
Leukopenia (>90%)
Neutropenia (>90%)
Thrombocytopenia (>90%)
Elevated bilirubin (88%)
Diarrhea (85%)
Nausea (79%)
Asthenia (70%)
Abdominal pain (63%)
Vomiting (60%)
Alopecia (43%)
Fever (42%)
Constipation (41%)
Anorexia (34%)
Mucositis (32%)
Pain (31%)
Dyspnea (28%)
Cough (27%)
Dizziness (23%)
Infection (22%)
Rash (19%)
1-10%
Abdominal fullness (10%)
AST increased (10%)
Dyspepsia (10%),
Edema (10%)
Ascites/jaundice (9%)
Vasodilation (9%)
Thromboembolism (9%)
Hypotension (6%)
Neutropenic fever (2-6%)
Frequency Not Defined
Headache
Insomnia
Orthostatic hypotension
Warnings
Black Box Warnings
Severe myelosuppression may occur
Diarrhea
- Early and late forms of diarrhea can occur
- Early diarrhea may be accompanied by cholinergic symptoms which may be prevented or ameliorated by atropine
- Late diarrhea can be life threatening and should be treated promptly with loperamide
- Monitor and give fluid and electrolytes as needed
- Institute antibiotic therapy if patients develop ileus, fever, or severe neutropenia
- Interrupt irinotecan and reduce subsequent doses if severe diarrhea occurs
Contraindications
Hypersensitivity to drug or excipients
Cautions
Use caution in hyperbilirubinemia and elderly
Outside of a clinical study, not for use in combination with a regimen of 5-FU/LV administered for 4-5 consecutive days every 4 weeks owing to increased toxicity, including toxic deaths
Renal impairment and acute renal failure reported; usually in patients who became volume depleted from severe vomiting and/or diarrhea
Drug is subject to photodegradation, especially in neutral and alkaline solutions
Individuals who are homozygous for the UGT1A1*28 allele are at increased risk for neutropenia following initiation of therapy; consider dose reduction by at least 1 level for pts homozygous in the enzyme UDP-glucuronosyl transferase 1A1*28 (UGT1A1*28) variant
Avoid pregnancy; can cause fetal harm
Increased risk of neutropenia
- Studies have shown that individuals who are homozygous for either the UGT1A1*28 or *6 alleles (*28/*28, *6/*6) or who are compound or double heterozygous for the UGT1A1*28 and *6 alleles (*6/*28) are at increased risk for severe or life-threatening neutropenia during treatment
- These individuals are UGT1A1 poor metabolizers and experience increased systemic exposure to SN-38, an active metabolite of irinotecan. Individuals who are heterozygous for either the UGT1A1*28 or *6 alleles (*1/*28, *1/*6) are intermediate metabolizers and may also have an increased risk of severe or life-threatening neutropenia
- Consider UGT1A1 genotype testing for the *28 and *6 alleles to determine UGT1A1 metabolizer status
- When administering therapy consider a reduction in starting dose by at least one level for patients known to be homozygous or compound heterozygous for the UGT1A1*28 and/or *6 alleles (*28/*28, *6/*6, *6/*28)
- Closely monitor patients with UGT1A1*28 or *6 alleles for neutropenia during and after treatment; the precise dosage reduction in this patient population is not known; subsequent dosage modifications may be required based on individual patient tolerance to treatment
Myelosuppression
- Therapy can cause severe myelosuppression; bacterial, viral, and fungal infections have occurred in patients receiving therapy; deaths due to sepsis following severe neutropenia reported
- Manage febrile neutropenia promptly with antimicrobial support; hold therapy if neutropenic fever occurs or if absolute neutrophil count drops <1000/mm3; after recovery to an absolute neutrophil count ≥1000/mm3, subsequent doses of should be reduced
- Patients who have previously received pelvic/abdominal irradiation are at increased risk of severe myelosuppression following administration; based on sparse available data, the concurrent administration of this medication with irradiation is not recommended
- Patients with deficient glucuronidation of bilirubin, such as those with Gilbert’s syndrome, may be at greater risk of myelosuppression when receiving therapy
Pulmonary toxicity
- Interstitial pulmonary disease (IPD)-like events, including fatalities, reported in patients receiving irinotecan (in combination and as monotherapy)
- Risk factors include pre-existing lung disease, use of pneumotoxic drugs, radiation therapy, and colony-stimulating factors
- Patients with risk factors should be closely monitored for respiratory symptoms before and during therapy; new or progressive, dyspnea, cough, and fever should prompt interruption of chemotherapy, pending diagnostic evaluation
- If IPD is diagnosed, this drug and other chemotherapy should be discontinued and appropriate treatment instituted as needed
Diarrhea and cholinergic reactions
- Also see Black Box Warnings
-
Early diarrhea
- Occurs during or shortly after infusion
- Usually transient and infrequently severe; 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
- May be prevented or treated; consider prophylactic or therapeutic administration of atropine 0.25-1 mg IV/SC unless clinically contraindicated
- These symptoms are expected to occur more frequently with higher irinotecan doses
-
Late diarrhea
- Generally occurs >24 hr after administration
- Can be life threatening since it may be prolonged and may lead to dehydration, electrolyte imbalance, or sepsis
- Grade 3-4 late diarrhea occurred in 23-31% of patients receiving weekly dosing
- If grade 2, 3, or 4 late diarrhea recurs, subsequent doses should be decreased
- Late diarrhea can be complicated by colitis, ulceration, bleeding, ileus, obstruction, and infection; megacolon and intestinal perforation also reported
- Patients should have loperamide readily available to begin treatment for late diarrhea
- Begin loperamide with first episode of poorly formed or loose stools, or the earliest onset of bowel movements more frequent than normal
- Loperamide is not recommended to be used for more than 48 consecutive hr at the higher doses needed for treating irinotecan-induced diarrhea, owing to risk of paralytic ileus
- Monitor and replace fluid and electrolytes; use antibiotic support for ileus, fever, or severe neutropenia
- Delay subsequent irinotecan weekly chemotherapy until pretreatment bowel function restored (ie, ≥24 hr without antidiarrheal medication)
- Avoid diuretics or laxatives in patients with diarrhea
Pregnancy & Lactation
Pregnancy
Available postmarketing and published data reporting the use in pregnant women, are insufficient and confounded by concomitant use of other cytotoxic drugs, to evaluate for any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes
Animal data
- Based on findings from animal studies and its mechanism of action, therapy can cause fetal harm when administered to a pregnant woman; in animal studies, intravenous administration of irinotecan to rats and rabbits during the period of organogenesis resulted in embryofetal mortality and teratogenicity in pregnant animals at exposures lower than human exposure based on AUC at the clinical dose of 125 mg/m2;advise pregnant women of potential risk to a fetus
- Verify the pregnancy status in female patients of reproductive potential prior to initiating therapy
Contraception
- Therapy can cause fetal harm when administered to a pregnant woman
- Females: Advise female patients of reproductive potential to use effective contraception during treatment and for 6 months after final dose
- Males: Due to potential for genotoxicity, advise male patients with female partners of reproductive potential to use condoms during treatment and for 3 months after final dose
Infertility
- Females: Based on postmarketing reports, female fertility may be impaired by treatment; menstrual dysfunction has been reported following administration
- Males: Based on findings from animal studies, male fertility may be impaired by treatment
Lactation
Irinotecan and its metabolites are present in human milk; there is no information regarding effects of drug on breastfed infant, or on milk production; because of potential for serious adverse reactions from drug in breastfed child, advise lactating women not to breastfeed during treatment and for 7 days after final dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Binds to topoisomerase I to produce double-strand breaks in DNA
Pharmacokinetics
Half-Life: 6-12 hr; SN-38 10-20 hr
Pleak Plasma Concentration: 1660 ng/mL; SN-38 26.3 ng/mL
Protein Bound: 30-68%; SN-38 95%
Vd: 110-234 L/m²
Metabolism: hepatic, to SN-38; SN-38 is further metabolized by UGT1A1
Metabolites: SN-38
Clearance: 13-14 L/hr/m²
Excretion: urine, feces
Pharmacogenomics
Converted to SN-38 active metabolite; SN-38 is subsequently conjugated predominantly by the enzyme UDP-glucuronosyl transferase 1A1 (UGT1A1) to form a glucuronide metabolite
UGT1A1 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity such as the UGT1A1*28 polymorphism
Reduced UGT1A1 activity increases risk for neutropenia
~10% of North American population is homozygous for UGT1A1*28 variant; consider dose reduction in these patients
Genetic testing laboratories
- Genotyping tests are available through the following companies
- ARUP Laboratories (http://www.aruplab.com/)
- LabCorp (http://www.labcorp.com/)
- Genzyme Genetics (http://www.genzymegenetics.com/)
Administration
IV Incompatibilities
Additive: methylprednisolone sodium succinate (10% loss in 3 hr)
Y-site: gemcitabine
IV Preparation
Dilute in D5W to a final concentration of 0.12-2.8 mg/mL (most commonly in 500 mL D5W)
NS can be used, but precipitation under refrigeration is more likely with NS, so D5W is generally preferred
IV Administration
Irritant
Infuse over 90 min
If administered in combination with fluorouracil & leucovorin, administer leucovorin immediately after irinotecan, & administer fluorouracil immediately after leucovorin
Premedication with antiemetics (dexamethasone plus ondansetron/granisetron) is recommended, at least 30 min prior to infusion
Atropine should be considered in pts experiencing cholinergic symptoms
Storage
Store at controlled room temp
Protect from light
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| irinotecan intravenous - | 40 mg/2 mL vial |  | |
| irinotecan intravenous - | 40 mg/2 mL vial |  | |
| irinotecan intravenous - | 500 mg/25 mL vial |  | |
| irinotecan intravenous - | 40 mg/2 mL vial |  | |
| irinotecan intravenous - | 100 mg/5 mL vial |  | |
| irinotecan intravenous - | 100 mg/5 mL vial |  | |
| irinotecan intravenous - | 100 mg/5 mL vial |  | |
| irinotecan intravenous - | 40 mg/2 mL vial |  | |
| irinotecan intravenous - | 100 mg/5 mL vial |  | |
| irinotecan intravenous - | 40 mg/2 mL vial |  | |
| irinotecan intravenous - | 100 mg/5 mL vial |  | |
| irinotecan intravenous - | 100 mg/5 mL vial |  | |
| irinotecan intravenous - | 40 mg/2 mL vial |  | |
| irinotecan intravenous - | 100 mg/5 mL vial |  | |
| irinotecan intravenous - | 100 mg/5 mL vial |  | |
| irinotecan intravenous - | 40 mg/2 mL vial |  | |
| irinotecan intravenous - | 40 mg/2 mL vial |  | |
| irinotecan intravenous - | 100 mg/5 mL vial |  | |
| irinotecan intravenous - | 100 mg/5 mL vial |  | |
| irinotecan intravenous - | 40 mg/2 mL vial |  | |
| irinotecan intravenous - | 40 mg/2 mL vial |  | |
| irinotecan intravenous - | 100 mg/5 mL vial |  | |
| irinotecan intravenous - | 40 mg/2 mL vial |  | |
| Camptosar intravenous - | 300 mg/15 mL vial |  | |
| Camptosar intravenous - | 100 mg/5 mL vial |  | |
| Camptosar intravenous - | 40 mg/2 mL vial |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
irinotecan intravenous
IRINOTECAN - INJECTION
(eye-ree-no-TEE-kan)
COMMON BRAND NAME(S): Camptosar
WARNING: You will be closely monitored (for example, by having blood tests) by your doctor while using this medication. Keep all medical and laboratory appointments.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 not stop 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 (such as sore throat that doesn't go away, fever). Your doctor should prescribe other medications to treat the diarrhea and other symptoms.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. Tell your doctor right away if you develop any of the following: signs of infection (such as sore throat that doesn't go away, fever), easy bruising/bleeding, unusual tiredness, fast/pounding heartbeat.
USES: This medication is used to treat cancer of the colon and rectum.
HOW TO USE: This medication is given by injection into a vein by a health care professional. The dosage is based on your medical condition, body size, and response to treatment.If this medication comes into contact with your skin, wash the skin right away and completely with soap and water. If this medication gets into your eyes, mouth, or nose, flush completely with plenty of water. Consult your doctor for more details.
SIDE EFFECTS: See also Warning section.Nausea, vomiting, loss of appetite, constipation, cough, drowsiness, mouth sores, weakness, or trouble sleeping may occur. Nausea and vomiting can be severe. In some cases, your doctor may prescribe medication to prevent or relieve nausea and vomiting. Eating several small meals, not eating before treatment, or limiting activity may help lessen some of these effects. If these effects last or get worse, or if you are unable to drink/eat because of nausea/vomiting, tell your doctor or pharmacist promptly.Temporary hair loss may occur. Normal hair growth should return after treatment has ended.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.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).Get medical help right away if you have any very serious side effects, including: chest pain, weakness on one side of the body, trouble speaking, confusion, trouble breathing.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.Irinotecan can commonly cause a mild rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe allergic reaction. Get medical help right away if you develop any rash.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before using irinotecan, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this drug, tell your doctor your medical history, including: bowel blockage (such as paralytic ileus), certain genetic metabolism disorder (fructose intolerance), radiation treatments, blood/bone marrow disorders (such as low platelet/neutrophil/red blood cell levels), diabetes, liver disease, kidney disease, lung disease.Before having surgery, tell your doctor or dentist that you are using this medication.This drug may make you dizzy or drowsy or blur your vision. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).To avoid dizziness and lightheadedness when rising from a sitting or lying position, get up slowly.Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine or flu vaccine inhaled through the nose.To lower your risk of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.Wash your hands well to prevent the spread of infections.Older adults may be at greater risk for diarrhea while using this drug.Tell your doctor if you are pregnant or plan to become pregnant. Your doctor may order a pregnancy test before starting this medication. You should not become pregnant while using irinotecan. Irinotecan may harm an unborn baby. Women of childbearing age should ask about reliable forms of birth control while using this medication and for 6 months after the last dose. Men with female partners of childbearing age should use reliable forms of birth control while using this medication and for 3 months after the last dose. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.This drug passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug and for at least 7 days after the last dose is not recommended. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: laxatives, "water pills"/diuretics (such as furosemide).Other medications can affect the removal of irinotecan from your body, which may affect how irinotecan works. Examples include azole antifungals (such as ketoconazole, itraconazole), clarithromycin, gemfibrozil, nefazodone, HIV protease inhibitors (such as atazanavir), rifamycins (such as rifabutin), ritonavir, St. John's wort, drugs used to treat seizures (such as carbamazepine, phenytoin), among others.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.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: signs of infection (such as sore throat that doesn't go away, fever), severe diarrhea.
NOTES: Lab and/or medical tests (such as complete blood count, hemoglobin, platelets) should be done while you are using this medication. Keep all medical and lab appointments. Consult your doctor for more details.
MISSED DOSE: It is important to get each dose of this medication as scheduled. If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule.
STORAGE: Consult the product instructions and your pharmacist for storage details. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).
Information last revised December 2022. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
