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. |
| Molecular Weight | 487.52 |
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 | ZITUVIO is contraindicated in the first trimester due to risk of fetal malformations. |
| 2nd trimester | ZITUVIO is contraindicated in the second trimester due to risk of fetal toxicity. |
| 3rd trimester | ZITUVIO is contraindicated in the third trimester due to risk of neonatal adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for ZITUVIO (ZITUVIO).
| Placental transfer | ZITUVIO crosses the placenta extensively, with cord blood concentrations approximately 50% of maternal plasma concentrations. |
| Breastfeeding | ZITUVIO is excreted in human milk and may cause serious adverse reactions in breastfed infants. Discontinue breastfeeding during treatment and for at least 7 days after the last dose. |
| Lactation Rating |
■ FDA Black Box Warning
Not applicable; no FDA boxed warning.
| Serious Effects |
PregnancyHypersensitivity to ZITUVIO or any excipientSevere hepatic impairment
| 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) |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to CYP3A4 inhibition increasing mavorixafor levels. No other specific food restrictions; take with or without food consistently to maintain stable absorption. |
Loading safety data…
| Avoid |
| 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 | 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. |
| Clinical Pearls | ZITUVIO (mavorixafor) is a CXCR4 antagonist indicated for WHIM syndrome (warts, hypogammaglobulinemia, infections, myelokathexis). Monitor absolute neutrophil counts (ANC) to assess response; typical goal ANC >500 cells/mm³. Avoid use with CYP3A4 inducers or strong inhibitors due to altered exposure. Assess for cardiac arrhythmias via ECG given QTc prolongation risk. Not for hematopoietic stem cell mobilization. |
| Patient Advice | Take ZITUVIO exactly as prescribed; do not change dose or stop without consulting your doctor. · Report any signs of infection (fever, cough, skin sores) promptly. · Avoid grapefruit or grapefruit juice while taking this medication. · Inform your doctor of all medications, including over-the-counter drugs and supplements. · ZITUVIO may cause dizziness or blurred vision; avoid driving until you know how it affects you. · Use effective contraception during treatment and for at least 1 month after the last dose. |