Irinotecan

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Dosage 4 Pharmacokinetics 5 Monitor 6 Adverse-effects 7 Drug-interactions 8 Mechanism-of-action 9 More General Terms 10 Internet Database 11 References

Introduction

• Tradename: Camptosar

Indications

• metastatic carcinoma of the colon &/or rectum with failure of 5-fluorouracil treatment

Dosage

• 125 mg/m2 IV over 90 minutes once weekly for 4 weeks
• 2 weeks hiatus
• reinitiate therapy with dose increased 25-50 mg/m2 as tolerated
• prophylactic loperamide 2-4 mg PO, repeated as needed with each loose bowel movement
• avoid extravasation

• Injection: 20 mg/mL (5 mL)

Pharmacokinetics

• metabolized in liver
• 10% is eliminated in the urine
• 1/2life is of the parent drug is 6 hours
• active metabolite 1/2life is 10 hours
  

• elimination via liver
• elimination via kidney
• 1/2life = 6-10 hours

Monitor

• complete blood count with each dose

Adverse-effects

• common (> 10%)

• vasodilation
• insomnia
• dizziness
• fever (45%
• mild to moderate nausea (80%)/ vomiting (12%)
• moderate to severe diarrhea

• early diarrhea (50%)

• < 24 hours after treatment
• responds to atropine

• late diarrhea (88%)

• > 24 hours after treatment
• mean onset 11 days after treatment
• mean duration: 3-7 days

• myelosuppression: dose-limiting toxicity

• onset: 10 days
• nadir: 14-16 days
• recovery: 21-28 days

• neuromuscular & skeletal weakness (76%)
• dyspnea (22%)
• cough
• rhinitis
• diaphoresis

• less common (1-10%)

• thrombophlebitis

• other

• headache
• flu-like syndrome
• elevated liver function tests
• steatohepatitis (may effect mortality after hepatic resection for colorectal carcinoma metastases [4]

Drug-interactions

• increased incidence of akathisia with prochlorperazine
• diuretics (fluid & electrolyte balances due to diarrhea)

Mechanism-of-action

• inhibitor of topoisomerase 1
• down-regulation of PRMT7 confers increased sensitivity of Top1 to irinotecan

More General Terms

• alkaloid
• antineoplastic agent (chemotherapeutic agent)

Internet Database

PubChem: 60837
PubChem: 60838
PubChem: 3750
PubChem: 74990
PubChem: 357467
PubChem: 24360
PubChem: 72402

References

1. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
3. Irinotecan Plus 5-FU Boosts Survival in Advanced Colon Cancer [1]
4. Vauthey JN et al, Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 2006, 24:2065 PMID: [2]

irinotecan; camptothecin (Camptosar, Topotecin, CPT-11)