ORMALVI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORMALVI (ORMALVI).
Tyrosine kinase inhibitor targeting BCR-ABL, KIT, PDGFR, and SRC family kinases.
| Metabolism | Primarily hepatic via CYP3A4; also via CYP1A2, CYP2D6, CYP2C9, CYP2C19; forms active metabolite (N-desmethyl imatinib). |
| Excretion | Renal: 70% (unchanged), Biliary/Fecal: 30% |
| Half-life | Terminal elimination half-life: 12-15 hours; dosing interval adjustment recommended in renal impairment (CrCl <30 mL/min) due to accumulation. |
| Protein binding | 95% bound primarily to albumin; unbound fraction increases in hypoalbuminemia. |
| Volume of Distribution | 0.5 L/kg; indicates moderate tissue distribution; crosses placenta and enters breast milk. |
| Bioavailability | Oral: 75% (range 60-85%); first-pass effect accounts for 25% metabolism. |
| Onset of Action | Oral: 1-2 hours; Intravenous: 5-10 minutes; onset delayed by food intake. |
| Duration of Action | 10-14 hours; extended-release formulation provides 24-hour coverage. |
20 mg orally once daily with food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, use 10 mg orally once daily. |
| Liver impairment | Child-Pugh A: 20 mg once daily; Child-Pugh B: 10 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | 0.5 mg/kg orally once daily, maximum 20 mg daily. |
| Geriatric use | No specific dose adjustment, but monitor renal function; consider lower starting dose of 10 mg once daily in patients with reduced renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORMALVI (ORMALVI).
| Breastfeeding | Magnesium is excreted into breast milk at concentrations approximately 1.2% of maternal serum levels (M/P ratio ~0.012). Short-term use is considered compatible with breastfeeding; however, monitor infant for sedation and hypotonia if maternal doses are high or prolonged. |
| Teratogenic Risk | First trimester: Risk of major congenital malformations not increased based on limited human data. Second and third trimesters: Potential for fetal hypermagnesemia, including hypotonia, respiratory depression, and feeding difficulties following prolonged maternal use. Avoid continuous infusion for >48 hours near term. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to imatinib or any component of the formulation"]
| Precautions | ["Hepatotoxicity (severe, possibly fatal)","Cardiac toxicity (LVEF reduction, congestive heart failure)","Fluid retention (pleural effusion, ascites, pulmonary edema)","Hematologic toxicity (neutropenia, thrombocytopenia, anemia)","Hemorrhage","GI perforation","Hypothyroidism","Tumor lysis syndrome","Growth retardation in children","Fetal harm if used during pregnancy"] |
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| Fetal Monitoring | Monitor maternal vital signs, deep tendon reflexes, respiratory rate, and serum magnesium levels (target 4-7 mEq/L for seizure prophylaxis). Continuous fetal heart rate monitoring during infusion. Assess for signs of magnesium toxicity: mental status changes, respiratory depression, cardiac conduction abnormalities. |
| Fertility Effects | No known adverse effects on fertility. Magnesium sulfate is not associated with reproductive toxicity in animal studies. Clinical use for pregnancy complications does not impair future fertility. |