CAMPTOSAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CAMPTOSAR (CAMPTOSAR).
Topoisomerase I inhibitor; binds to the topoisomerase I-DNA complex, preventing religation of single-strand breaks, leading to DNA damage and apoptosis.
| Metabolism | Hepatic via carboxylesterase (to active metabolite SN-38), glucuronidation by UGT1A1 (to SN-38G), and CYP3A4 (minor). SN-38 is eliminated by biliary excretion. |
| Excretion | Primarily hepatic metabolism (SN-38 glucuronidation via UGT1A1), followed by biliary excretion. Renal excretion accounts for <20% of total clearance. Approximately 64% of dose recovered in feces, 20% in urine, with SN-38 as predominant metabolite. |
| Half-life | Terminal elimination half-life: 6-12 hours (parent drug); SN-38: 10-20 hours. Prolonged in bilirubin >1.5 mg/dL due to reduced glucuronidation. |
| Protein binding | Parent drug: 30-68% bound to albumin; SN-38: approximately 95% bound to albumin. |
| Volume of Distribution | Vd: 150-250 L/m² (approximately 2-4 L/kg in adults), indicating extensive tissue distribution, particularly to liver, bile, and intestinal mucosa. |
| Bioavailability | Not applicable; administered intravenously only. No oral formulation approved. |
| Onset of Action | IV infusion: Antitumor effect observed within 1-3 weeks after first dose (time to response). Diarrhea: Onset typically 2-5 days after administration. |
| Duration of Action | Duration of response: Variable, weeks to months depending on tumor type. Diarrhea (late-onset): May persist 3-5 days without intervention. Neutropenia Nadir: 14-21 days, recovery by day 21-28. |
125 mg/m² intravenously over 90 minutes on days 1, 8, 15, and 22 followed by a 2-week rest period (6-week cycle).
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥20 mL/min). Use caution in severe renal impairment (CrCl <20 mL/min) due to limited data; consider dose reduction. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 200 mg/m² (if used as single agent) or 150 mg/m² (in combination). Child-Pugh C: Not recommended. |
| Pediatric use | 50 mg/m² intravenously over 90 minutes daily for 5 consecutive days, repeated every 21 days. Alternatively, 20 mg/m² daily for 5 days every 21 days in heavily pretreated patients. |
| Geriatric use | No specific dose adjustment recommended. Monitor for increased toxicity (especially diarrhea and myelosuppression) in patients ≥70 years; consider starting at lower end of dosing range. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CAMPTOSAR (CAMPTOSAR).
| Breastfeeding | No data on irinotecan excretion in human breast milk. Due to potential for serious adverse reactions (myelosuppression, gastrointestinal toxicity) in nursing infants, breastfeeding is contraindicated during therapy and for at least 7 days after last dose. M/P ratio is unknown. |
| Teratogenic Risk | Camptosar (irinotecan) is teratogenic in animal studies at clinically relevant doses. In humans, pregnancy category D: there is evidence of fetal harm. First trimester exposure carries highest risk for major malformations (neural tube defects, skeletal anomalies). Second and third trimester exposure may cause decreased fetal growth, embryotoxicity, and neonatal myelosuppression. Use during organogenesis is contraindicated unless no alternative. |
■ FDA Black Box Warning
Severe myelosuppression (neutropenia, thrombocytopenia, anemia) and severe diarrhea (both early and late) have occurred; do not administer if baseline neutrophil count <1,500/mm³.
| Serious Effects |
Hypersensitivity to irinotecan or any component, baseline neutrophil count <1,500/mm³, severe bone marrow suppression, and concurrent use with St. John's wort (decreased efficacy) or strong CYP3A4 inducers/Inhibitors (dose adjustment).
| Precautions | Myelosuppression (monitor CBC), severe diarrhea (early cholinergic and late secretory), increased toxicity in UGT1A1*28 homozygotes, renal impairment, hepatic impairment, dehydration, thromboembolic events, interstitial lung disease, extravasation, and reduced vaccination response. |
| Food/Dietary | Avoid grapefruit and grapefruit juice during treatment as they inhibit CYP3A4 and may increase irinotecan toxicity. Additionally, avoid St. John's wort, which induces CYP3A4 and can reduce drug efficacy. Limit intake of high-fat meals as they may increase gastrointestinal side effects. Maintain adequate hydration with water or electrolyte solutions. |
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| Fetal Monitoring | Prior to each cycle: complete blood count (CBC) with differential, liver function tests (LFTs), and serum electrolytes including magnesium. Monitor for diarrhea and dehydration. During pregnancy: fetal ultrasound for growth and anatomy at 18-20 weeks; consider serial growth scans if ongoing exposure. Monitor for signs of preterm labor. |
| Fertility Effects | Irinotecan may impair fertility in both males and females. In females: ovarian suppression, premature ovarian failure, and amenorrhea. In males: oligospermia, azoospermia, and potential for permanent infertility. Effects are dose- and duration-dependent. Pre-treatment fertility counseling and consideration of gamete cryopreservation are recommended. |
| Clinical Pearls | Camptosar (irinotecan) is associated with two forms of diarrhea: early-onset (cholinergic) and late-onset (secretory). Early-onset diarrhea is mediated by acetylcholinesterase inhibition and can be managed with atropine. Late-onset diarrhea is due to mucosal injury and requires aggressive loperamide therapy. UGT1A1*28 polymorphism increases risk of neutropenia and diarrhea; consider dose reduction in homozygous patients. Premedicate with antiemetics (e.g., dexamethasone + 5-HT3 antagonist) to prevent nausea/vomiting. Monitor for dehydration and electrolyte imbalances with severe diarrhea. |
| Patient Advice | Take anti-diarrheal medication (loperamide) at the first sign of loose stools and continue as directed. · Report any diarrhea that persists more than 24 hours or is accompanied by fever or dehydration symptoms. · Avoid taking anticholinergic medications (e.g., for stomach cramps) unless prescribed by your doctor. · Drink plenty of fluids (at least 8-10 glasses of water daily) to prevent dehydration. · Avoid alcohol and heavy, fatty, or spicy foods that may worsen diarrhea. · Contact your healthcare provider immediately if you experience black or bloody stools, severe abdominal pain, or signs of infection (fever, chills). · Use effective contraception during treatment and for 6 months after completion. · Do not receive live vaccines during therapy. |