BRYNOVIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BRYNOVIN (BRYNOVIN).
Brynoxin is a potent and selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2), reducing renal glucose reabsorption and lowering blood glucose levels independently of insulin.
| Metabolism | Primarily metabolized via glucuronidation by UGT1A9 and UGT2B7; minor metabolism by CYP3A4. |
| Excretion | Renal excretion accounts for 70% of the administered dose as unchanged drug; biliary/fecal excretion accounts for 30%. |
| Half-life | Terminal elimination half-life is 12 hours in patients with normal renal function; prolonged to 24-48 hours in moderate to severe renal impairment (CrCl < 30 mL/min). |
| Protein binding | 85% bound primarily to albumin; minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | 1.5 L/kg, indicating extensive tissue distribution and penetration into peripheral compartments. |
| Bioavailability | Oral: 75% (range: 60-90%) with minimal first-pass metabolism; intravenous: 100%. |
| Onset of Action | Intravenous: 2-5 minutes; oral: 30-60 minutes. |
| Duration of Action | Intravenous: 4-6 hours; oral: 8-12 hours (dose-dependent). Clinical effect may persist longer in hepatic impairment. |
Adult: 150 mg orally twice daily.
| Dosage form | SOLUTION |
| Renal impairment | CrCl 30-59 mL/min: 75 mg twice daily; CrCl 15-29 mL/min: 50 mg twice daily; CrCl <15 mL/min or dialysis: 25 mg once daily. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 75 mg twice daily; Child-Pugh C: 50 mg twice daily. |
| Pediatric use | Children ≥12 years and ≥40 kg: 150 mg twice daily; <40 kg: 5 mg/kg/dose twice daily (max 150 mg/dose). |
| Geriatric use | No specific dose adjustment, but monitor renal function; start at lower end of dosing range if renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BRYNOVIN (BRYNOVIN).
| Breastfeeding | Excreted in breast milk in low amounts (M/P ratio 0.2–0.4). Considered compatible with breastfeeding; monitor infant for sedation or gastrointestinal effects. |
| Teratogenic Risk | First trimester: Human data limited; animal studies show embryotoxicity at supra-therapeutic doses. Avoid unless benefit outweighs risk. Second trimester: No specific malformation signal; monitor fetal growth. Third trimester: Risk of neonatal adaptation syndrome (irritability, feeding difficulties) at delivery if used near term. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease on dialysis","History of serious hypersensitivity reaction to brynoxin or any excipient in the formulation"]
| Precautions | ["Ketoacidosis: Monitor for signs of ketoacidosis, including euglycemic ketoacidosis","Lower limb amputation: Consider risk factors prior to initiation; monitor for signs of infection or ulceration"] |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to CYP3A4 inhibition. Avoid alcohol as it may increase hepatotoxicity risk. Take with food to reduce gastrointestinal upset. |
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| Fetal Monitoring |
| Maternal: liver function tests (ALT/AST) every 4 weeks, renal function (creatinine, BUN) monthly, complete blood count (CBC) every 8 weeks. Fetal: ultrasound for growth assessment every 4 weeks from 24 weeks gestation; nonstress test or biophysical profile weekly from 32 weeks if prolonged use. |
| Fertility Effects | In female rats, decreased implantation rates at high doses. Human data insufficient to exclude reversible impairment of spermatogenesis (oligospermia) and menstrual cycle irregularities. Discontinuation may restore baseline fertility. |
| Clinical Pearls |
| Monitor renal function and electrolytes before and during therapy. Use with caution in patients with pre-existing cardiac disease due to risk of QT prolongation. Adjust dose in hepatic impairment (Child-Pugh B or C). Contraindicated with strong CYP3A4 inducers. |
| Patient Advice | Take exactly as prescribed; do not skip doses or double up. · Avoid grapefruit and grapefruit juice during treatment. · Report any signs of infection, unusual bruising, or yellowing of skin or eyes. · Use effective contraception during treatment and for 3 months after last dose. · Do not drive if you experience dizziness or blurred vision. |