ICOTYDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ICOTYDE (ICOTYDE).
ICOTYDE (trifluridine/tipiracil) is a combination of trifluridine, a thymidine-based nucleoside analog that incorporates into DNA and inhibits cell proliferation, and tipiracil, a thymidine phosphorylase inhibitor that increases the systemic exposure of trifluridine by inhibiting its degradation.
| Metabolism | Trifluridine is metabolized by thymidine phosphorylase to an inactive metabolite; tipiracil inhibits thymidine phosphorylase, reducing trifluridine metabolism. Neither is significantly metabolized by CYP450 enzymes. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 70% of elimination, with biliary/fecal elimination contributing the remaining 30%. |
| Half-life | Terminal elimination half-life is 12-15 hours in adults with normal renal function; may be prolonged in renal impairment. |
| Protein binding | Approximately 95% bound primarily to albumin. |
| Volume of Distribution | Volume of distribution is 0.3-0.5 L/kg, indicating moderate tissue distribution. |
| Bioavailability | Oral bioavailability is 60-70% due to first-pass metabolism. |
| Onset of Action | Oral: 1-2 hours; Intravenous: within 5-10 minutes. |
| Duration of Action | Oral: 12-24 hours; Intravenous: 6-12 hours, depending on dose and renal function. |
Intravenous: 1000 mg administered over 90 minutes on days 1 and 15 of a 28-day cycle.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-89 mL/min: No adjustment. For GFR <30 mL/min or dialysis: Not recommended due to lack of data. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose to 750 mg. Child-Pugh Class C: Contraindicated. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific adjustment required; monitor renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ICOTYDE (ICOTYDE).
| Breastfeeding | Contraindicated due to high milk-to-plasma ratio (M/P ~0.24-0.67). Excreted into breast milk; potential for infant toxicity. Alternatives recommended. |
| Teratogenic Risk | Pregnancy category D. First trimester: risk of Ebstein's anomaly and other cardiovascular defects. Second/third trimester: risk of neonatal lithium toxicity (hypotonia, cyanosis, poor suck reflex). |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
None
| Precautions | Myelosuppression (neutropenia, anemia, thrombocytopenia), severe diarrhea, hepatotoxicity, embryo-fetal toxicity, and increased risk of infections. |
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| Monitor serum lithium levels monthly, renal function (serum creatinine), thyroid function (TSH), and ECG for arrhythmias. Fetal echocardiography at 16-20 weeks. Neonatal: assess for hypotonia, feeding difficulties, and cyanosis at birth. |
| Fertility Effects | May reduce fertility due to hormonal disruptions (thyroid, prolactin). Reversible upon discontinuation. |