VITUZ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VITUZ (VITUZ).
Vituz is an epidermal growth factor receptor (EGFR) inhibitor that binds to the tyrosine kinase domain, blocking downstream signaling pathways involved in cell proliferation and survival.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP2D6 and CYP1A2. |
| Excretion | VITUZ (vitluzolamide) is primarily excreted via renal elimination as unchanged drug (45-55%) and as the major inactive metabolite M1 (20-30%). Biliary/fecal excretion accounts for 15-20%, primarily as M1. Less than 5% is eliminated via other routes. |
| Half-life | The terminal elimination half-life is 12-15 hours in patients with normal renal function, allowing twice-daily dosing. In moderate renal impairment (CrCl 30-50 mL/min), half-life extends to 20-28 hours; in severe impairment (CrCl <30 mL/min), it exceeds 40 hours. |
| Protein binding | Approximately 92-95% bound to serum albumin, with minor binding to alpha-1-acid glycoprotein. Binding is saturable at concentrations above 50 mcg/mL. |
| Volume of Distribution | Volume of distribution is 0.25-0.35 L/kg, indicating distribution primarily into extracellular fluid and limited tissue penetration. In obese patients (BMI >30), Vd increases to 0.4-0.5 L/kg. |
| Bioavailability | Oral bioavailability is 85-92% (mean 88%) with minimal first-pass metabolism. Food reduces bioavailability by 15-20% (take on empty stomach). Extended-release formulation has bioavailability of 75-85% relative to immediate-release. |
| Onset of Action | Oral: Peak plasma concentration achieved in 1-2 hours; clinical effect begins within 2-4 hours. Intravenous: Onset within 15-30 minutes. |
| Duration of Action | Oral: Duration of action is 12-15 hours based on trough plasma levels above therapeutic threshold (2 mcg/mL). Extended-release formulation provides coverage for 18-24 hours. Intravenous: Duration is 6-8 hours after a single dose, but maintenance therapy is typically continuous infusion. |
400 mg orally every 8 hours for 5 days; initiate within 48 hours of symptom onset.
| Dosage form | SOLUTION |
| Renal impairment | CrCl ≥30 mL/min: no adjustment; CrCl 15-29 mL/min: 400 mg every 12 hours; CrCl <15 mL/min: 400 mg every 24 hours; on hemodialysis: 400 mg every 24 hours, give after dialysis. |
| Liver impairment | Child-Pugh A or B: no adjustment; Child-Pugh C: 400 mg every 12 hours. |
| Pediatric use | Not approved for patients <18 years old. |
| Geriatric use | No specific dose adjustment; monitor renal function and adjust dose based on CrCl as per renal adjustment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VITUZ (VITUZ).
| Breastfeeding | Excreted in breast milk; M/P ratio 0.15. Consider risk of infant bleeding; avoid use in nursing mothers unless essential. |
| Teratogenic Risk | First trimester: Human data limited; animal studies show increased risk of skeletal malformations at high doses. Second and third trimesters: Risk of fetal hemorrhage and premature closure of ductus arteriosus with chronic use; avoid after 30 weeks. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Severe hypersensitivity to vituz or any excipients","Concurrent use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine)"]
| Precautions | ["Interstitial lung disease (ILD)","Hepatotoxicity","Diarrhea and dehydration","Dermatologic reactions (rash, dry skin)","Ocular disorders (keratitis, conjunctivitis)"] |
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| Monitor maternal CBC, liver function, and renal function. Fetal ultrasound for growth and amniotic fluid index. Doppler assessment of ductus arteriosus if used in third trimester. |
| Fertility Effects | Reversible inhibition of prostaglandin synthesis may impair implantation; use with caution in women attempting conception. |