INCASSIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INCASSIA (INCASSIA).
INCASSIA (bleomycin) is an antineoplastic antibiotic that causes DNA strand breaks through free radical generation, inhibiting DNA synthesis and cell division.
| Metabolism | Primarily metabolized by lung and liver microsomal enzymes; main metabolite is bleomycinic acid |
| Excretion | Renal excretion of unchanged drug accounts for approximately 60-70% of the administered dose, with biliary/fecal elimination contributing about 20-30%. Less than 10% is metabolized. |
| Half-life | Terminal elimination half-life is 8-12 hours in adults with normal renal function. This supports twice-daily dosing, though dose adjustment is required in renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 85-90% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.3-0.4 L/kg, indicating moderate distribution into total body water, with limited tissue binding and no significant accumulation in adipose tissue. |
| Bioavailability | Absolute oral bioavailability is 30-50% due to first-pass hepatic metabolism. Food does not significantly alter absorption. |
| Onset of Action | Oral: 1-2 hours to peak plasma concentration; clinical effect (e.g., blood pressure reduction) typically evident within 1-2 hours. Intravenous: onset within 5-10 minutes. |
| Duration of Action | Duration of antihypertensive effect is approximately 12-24 hours after oral dosing, allowing once or twice-daily administration. After IV, effect lasts 6-12 hours. |
1.5 mg orally once daily, administered with or without food.
| Dosage form | TABLET |
| Renal impairment | eGFR 30–89 mL/min/1.73 m²: no adjustment; eGFR 15–29 mL/min/1.73 m²: 1.5 mg every other day; eGFR <15 mL/min/1.73 m² or on dialysis: not recommended. |
| Liver impairment | Child-Pugh A: 1.5 mg once daily; Child-Pugh B or C: not recommended due to lack of data. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No dose adjustment required based on age alone; monitor renal function as elderly patients more likely to have decreased eGFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INCASSIA (INCASSIA).
| Breastfeeding | Contraindicated during breastfeeding. No human data on M/P ratio; drug and metabolites likely excreted into breast milk based on molecular weight. Potential for serious adverse effects in nursing infant. |
| Teratogenic Risk | Pregnancy Category X: contraindicated in pregnancy. First trimester exposure associated with increased risk of central nervous system and cardiovascular defects. Second and third trimester exposure may cause fetal growth restriction and oligohydramnios. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: Pulmonary fibrosis and pulmonary toxicity occur in up to 10% of patients, with a fatal outcome in approximately 1% of cases. Risk is dose- and age-related. Monitor pulmonary function. Discontinue immediately if pulmonary toxicity is suspected.
| Serious Effects |
Hypersensitivity to bleomycin or any component; severe pulmonary disease; history of significant bleomycin-induced pulmonary toxicity
| Precautions | Pulmonary fibrosis (dose- and age-related), renal impairment (reduce dose), hypersensitivity reactions (including anaphylaxis), cutaneous toxicity (stomatitis, alopecia, hyperpigmentation), and idiosyncratic reactions (fever, chills, hypotension). Monitor pulmonary function, renal function, and vital signs. |
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| Monitor maternal blood pressure, renal function, and liver enzymes. Perform fetal ultrasound for growth assessment and amniotic fluid volume. Monitor for signs of fetal distress. |
| Fertility Effects | May impair fertility in females by disrupting ovarian function; reversible upon discontinuation. In males, may cause decreased sperm count and motility. |