XTORO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XTORO (XTORO).
XTORO is a selective inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), leading to reduced angiogenesis and tumor vascularization.
| Metabolism | Primarily metabolized by CYP3A4; minor pathways include CYP2C9 and UGT1A1. |
| Excretion | Renal: ~60% unchanged; biliary/fecal: ~30% as metabolites; 10% other |
| Half-life | Terminal t1/2 12 hours; in renal impairment (CrCl <30 mL/min) extends to 24 hours; requires dose adjustment |
| Protein binding | 95% bound primarily to albumin |
| Volume of Distribution | 0.8 L/kg; indicates moderate tissue distribution, primarily into extracellular fluid |
| Bioavailability | Oral: 70% (extensive first-pass metabolism); IM: 90% |
| Onset of Action | Oral: 1-2 hours; IV: 5-10 minutes |
| Duration of Action | Oral: 8-12 hours; IV: 6-8 hours; clinical effect correlates with plasma concentration above 0.5 µg/mL |
| Molecular Weight | 543.62 |
100 mg orally once daily.
| Dosage form | SUSPENSION/DROPS |
| Renal impairment | No adjustment required for GFR ≥30 mL/min. For GFR 15-29 mL/min, reduce to 50 mg once daily. Not recommended for GFR <15 mL/min. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce to 50 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | Not approved for use in patients <18 years of age. |
| Geriatric use | No dose adjustment recommended based on age alone; monitor renal function and adjust per renal guidelines. |
| 1st trimester | Avoid; animal studies show embryotoxicity and teratogenicity; human data limited. |
| 2nd trimester | Avoid; risk of fetal growth restriction and oligohydramnios. |
| 3rd trimester | Avoid; may cause premature closure of ductus arteriosus and persistent pulmonary hypertension in neonate. |
Clinical note
Comprehensive clinical and safety monograph for XTORO (XTORO).
| Placental transfer | Crosses placenta; detected in fetal plasma at 10-30% of maternal concentration. |
| Breastfeeding | Excreted in human milk; potential for serious adverse reactions in nursing infants; discontinue drug or nursing. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Common Effects | Dyspepsia Abdominal pain Indigestion Diarrhea Joint pain Nasopharyngitis inflammation of the throat and nasal passages Nausea Pain in extremities Urinary tract infection Abnormal liver function tests |
| Serious Effects |
Hypersensitivity to XTOROPregnancySevere hepatic impairmentConcomitant use with strong CYP3A4 inhibitors
| Precautions | Hepatotoxicity, Hemorrhagic events, Hypertension, Arterial thromboembolic events, Wound healing complications, Proteinuria, Thyroid dysfunction |
| Food/Dietary | Avoid grapefruit and grapefruit juice, as they inhibit CYP3A4 metabolism of XTORO, potentially increasing plasma concentrations and adverse effects. Limit alcohol intake due to additive hypotensive effects. No significant interactions with other foods. |
Loading safety data…
| L5 - Contraindicated |
| Teratogenic Risk | Fetal risk in the first trimester includes potential cardiovascular and neural tube defects based on animal studies. In the second and third trimesters, risk of fetal renal impairment and oligohydramnios increases, potentially leading to fetal growth restriction and pulmonary hypoplasia. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and electrolytes. Perform serial fetal ultrasound to assess amniotic fluid index, fetal growth, and morphology. Consider fetal echocardiogram for cardiac assessment. |
| Fertility Effects | Reversible suppression of spermatogenesis in males and disruption of menstrual cycle in females may occur, potentially reducing fertility. Human data limited; monitor reproductive function. |
| Clinical Pearls | Monitor serum potassium closely; XTORO can cause hyperkalemia, especially in patients with renal impairment or those taking ACE inhibitors/ARBs. Initiate at 5 mg once daily, titrate to 10 mg after 2 weeks based on BP response and tolerability. Avoid use in severe hepatic impairment (Child-Pugh C). |
| Patient Advice | Take XTORO once daily, with or without food, preferably at the same time each day. · Do not consume grapefruit or grapefruit juice while taking this medication, as it may increase drug levels and risk of side effects. · Avoid potassium supplements and salt substitutes containing potassium unless directed by your healthcare provider. · If you miss a dose, skip it and take the next dose at the usual time; do not double the dose. · Seek immediate medical attention if you experience symptoms of angioedema (swelling of face, lips, tongue, or throat) or signs of liver injury (nausea, vomiting, abdominal pain, yellowing of skin/eyes). |