Irinotecan (Adverse effects)

Irinotecan is an antineoplastic used in the treatment of various types of cancer such as colon, lung or pancreatic cancer. One of the adverse effects associated with the treatment is neutropenia, which can be associated with the presence of alleles in the UGT1A1 gene, involved in its metabolism.

Semi-synthetic antineoplastic derived from camptothecin alkaloid, specific inhibitor of topoisomerase I DNA. It induces lesions in single strands that block DNA replication and are responsible for cytotoxicity.

CONTRAINDICATIONS:

Hypersensitivity.

Chronic inflammatory disease and/or intestinal obstruction. Pregnancy and lactation. Hepatic insufficiency (bilirubin> 3 times the upper limit of normal), severe bone marrow insufficiency, patients with a WHO general state ≥ 2 and concomitant use with St. John's Wort.

PRECAUTIONS:

Renal insufficiency and hepatic impairment. Elderly and asthma.

Risk of late diarrhea (increased in patients with abdominal / pelvic irradiation, baseline hyperleukocytosis, or WHO overall status ≥ 2 and in women), acute cholinergic syndrome (atropine sulfate prophylaxis), patients with reduced uridyn diphosphate glucosyltransferase activity (Increased risk of haematological toxicity).

Prophylactic treatment with antiemetics, weekly haematological monitoring, contraceptive measures (during and at least 3 months after treatment) are recommended.

Avoid concomitant use of strong inhibitors (ketoconazole) or inducers (rifampicin, carbamazepine, phenobarbital, phenytoin or St. John's wort).

Not recommended for children.

SIDE EFFECTS:

Diarrhea (dose-limiting toxicity), nausea, vomiting.

Neutropenia (toxic effect dose limiting), anemia, thrombocytopenia. Acute cholinergic syndrome, alopecia, muscle contraction, cramps and paresthesia

PHARMACOLOGICAL INTERACTIONS:

Irinotecan may prolong the neuromuscular blocking effect of suxamethonium and antagonize the neuromuscular blockade of non-depolarizing myorelaxants.

Avoid joint use with CYP3A4 inhibitors (ketoconazole) or inducers (carbamazepine, phenobarbital, febitoin, rifampicin).

St John's wort may lower irinotecan levels, therefore it should be avoided.

BRAND NAME:

  • Campto ®
  • Irinotecan ®

Genes analyzed

UGT1A1

Bibliography

Atasilp C, Biswas M, Jinda P, et al.Association of UGT1A1*6, UGT1A1*28, or ABCC2 c.3972C>T genetic polymorphisms with irinotecan-induced toxicity in Asian cancer patients: Meta-analysis. Clin Transl Sci. 2022 Jul;15(7):1613-1633.

Cui C, Shu C, Cao D, et al.UGT1A1*6, UGT1A7*3 and UGT1A9*1b polymorphisms are predictive markers for severe toxicity in patients with metastatic gastrointestinal cancer treated with irinotecan-based regimens. Oncol Lett. 2016 Nov;12(5):4231-4237.

Hulshof EC, Deenen MJ, Nijenhuis M, et al . Dutch pharmacogenetics working group (DPWG) guideline for the gene-drug interaction between UGT1A1 and irinotecan. Eur J Hum Genet. 2023 Sep;31(9):982-987.

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