PROTOSTAT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROTOSTAT (PROTOSTAT).
Proto-oncogene tyrosine-protein kinase Src inhibitor; inhibits cell proliferation and induces apoptosis in cancer cells overexpressing Src.
| Metabolism | Primarily hepatic via CYP3A4; also undergoes glucuronidation by UGT1A1. |
| Excretion | Renal: 70% as unchanged drug; biliary/fecal: 15% as metabolites; 15% other. |
| Half-life | 8 hours (range 6-10 h); in renal impairment, half-life prolonged up to 20 hours; dose adjustment required for CrCl < 30 mL/min. |
| Protein binding | 99% bound to albumin, with minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.6 L/kg (0.5-0.7 L/kg); indicates distribution into total body water with some tissue binding. |
| Bioavailability | Oral: 80-90% (with extensive first-pass metabolism to active metabolite). |
| Onset of Action | Oral: 30-60 minutes; IV: immediate. |
| Duration of Action | 8-12 hours; sustained-release formulation extends to 24 hours. |
250 mg orally three times daily after meals for 7-10 days; alternatively, 500 mg twice daily for 7 days.
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: administer every 12-18 hours; GFR <10 mL/min: administer every 24 hours. |
| Liver impairment | Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: use with caution, reduce dose by 75%. |
| Pediatric use | 15-30 mg/kg/day orally divided every 8 hours; maximum 1.5 g/day. |
| Geriatric use | No specific dose adjustment; monitor renal function and adjust accordingly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROTOSTAT (PROTOSTAT).
| Breastfeeding | ProtoStat is excreted into human breast milk. The M/P ratio is approximately 0.85. It may interfere with lactation and could cause hormonal effects in the infant; thus, breastfeeding is not recommended during treatment. |
| Teratogenic Risk | ProtoStat (protostat) is a synthetic progestin with potential teratogenic effects. In the first trimester, there is an increased risk of neural tube defects, cardiovascular anomalies, and hypospadias. In the second and third trimesters, exposure may be associated with masculinization of female fetuses and pseudobermaphroditism. Risk is dose-dependent and highest with high-dose therapy. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to PROTOSTAT or its components"]
| Precautions | ["Hepatotoxicity (elevated transaminases, bilirubin)","Myelosuppression (neutropenia, thrombocytopenia, anemia)","Hemorrhage (including severe bleeding)","Fluid retention (pleural or pericardial effusion)","QT prolongation","Pancreatitis","Fatal infections"] |
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| Fetal Monitoring | Monitor maternal blood glucose, blood pressure, and liver function tests. Perform serial fetal ultrasound for growth and anatomy, and consider amniocentesis in high-risk cases. Monitor for signs of thromboembolism and fluid retention. |
| Fertility Effects | ProtoStat suppresses ovulation via progestogenic activity, impairing fertility during use. After discontinuation, ovulation resumes within 2–3 cycles in most women, although long-term use may result in a delayed return to fertility. |