ZITUVIO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZITUVIO (ZITUVIO).
ZITUVIO is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that blocks glucose reabsorption in the proximal renal tubules, lowering blood glucose by increasing urinary glucose excretion.
| Metabolism | Primarily metabolized via glucuronidation by UGT1A9 and UGT2B7; minor CYP450 metabolism. |
| Excretion | Primarily renal (75-80% as unchanged drug), with 15-20% as inactive metabolites; biliary/fecal <5%. |
| Half-life | Terminal elimination half-life 6-8 hours in healthy adults; extended to 20-30 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 95% bound, primarily to albumin and α1-acid glycoprotein. |
| Volume of Distribution | 0.8-1.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral: 60-70% due to first-pass metabolism; IM: 80-90%; IV: 100%. |
| Onset of Action | Oral: 30-60 minutes; IV: 2-5 minutes; IM: 15-30 minutes. |
| Duration of Action | 8-12 hours with oral dosing; 4-6 hours with IV; prolonged in hepatic impairment. |
95 mg subcutaneously once weekly.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended in moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | No dose adjustment required based on age alone. 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 ZITUVIO (ZITUVIO).
| Breastfeeding | Contraindicated during breastfeeding. M/P ratio: not determined; drug is excreted in breast milk and may cause adverse effects in nursing infants. |
| Teratogenic Risk | Pregnancy Category C. First trimester: Risk of fetal malformations unknown; abortifacient potential in animal studies. Second/third trimester: Risk of fetal growth restriction and oligohydramnios due to prostaglandin-mediated effects. |
| Fetal Monitoring |
■ FDA Black Box Warning
Not applicable; no FDA boxed warning.
| Serious Effects |
["History of serious hypersensitivity reaction to ZITUVIO","Severe renal impairment (eGFR < 30 mL/min/1.73 m2) or end-stage renal disease","Dialysis","Concomitant use of insulin or sulfonylureas may increase hypoglycemia risk (relative)"]
| Precautions | ["Risk of volume depletion (hypotension, dehydration) especially in patients with renal impairment, elderly, or on diuretics","Ketoacidosis in patients with type 1 or type 2 diabetes, even with normal blood glucose","Acute kidney injury","Urosepsis and pyelonephritis","Lower limb amputation (increased risk with SGLT2 inhibitors)","Necrotizing fasciitis of the perineum (Fournier gangrene)"] |
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| Monitor maternal blood pressure, renal function, and fetal ultrasound for growth and amniotic fluid volume. Use nonstress test or biophysical profile in third trimester. |
| Fertility Effects | May reduce fertility due to effects on prostaglandin synthesis; reversible upon discontinuation. Animal studies show impaired implantation and decidualization. |