OJJAARA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OJJAARA (OJJAARA).
Inotuzumab ozogamicin is a CD22-directed antibody-drug conjugate. The antibody binds to CD22 on B-cell surface, internalizes, and releases calicheamicin, a cytotoxic agent that induces double-strand DNA breaks and apoptosis.
| Metabolism | Primarily hydrolyzed by carboxylesterases to release calicheamicin; minimal CYP450 involvement. |
| Excretion | Primarily renal (70-80% as unchanged drug) with biliary/fecal excretion accounting for 15-20%. |
| Half-life | Terminal elimination half-life is 12-15 hours in patients with normal renal function; prolongs to 20-30 hours in moderate renal impairment (CrCl 30-50 mL/min). |
| Protein binding | Approximately 95% bound, primarily to albumin. |
| Volume of Distribution | Vd is 0.2-0.3 L/kg, indicating distribution primarily in extracellular fluid. |
| Bioavailability | Oral bioavailability is 70-80% due to moderate first-pass metabolism. |
| Onset of Action | Oral: 30-60 minutes; intravenous: 5-10 minutes. |
| Duration of Action | 8-12 hours for oral and IV formulations; extended-release oral formulation provides 24-hour coverage. |
10 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for GFR ≥30 mL/min; not recommended for GFR <30 mL/min. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 5 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established; use not recommended. |
| Geriatric use | No specific dose adjustment; monitor renal function and fluid balance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OJJAARA (OJJAARA).
| Breastfeeding | It is unknown if OJJAARA is excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment and for 3 months after the last dose. No M/P ratio is available. |
| Teratogenic Risk | OJJAARA is contraindicated in pregnancy. Based on its mechanism of action (CGRP receptor antagonist) and animal studies, there is a risk of fetal harm. In the first trimester, exposure may increase the risk of congenital anomalies. During the second and third trimesters, potential adverse effects include reduced fetal growth and oligohydramnios. Adequate contraception should be used during treatment and for at least 3 months after the last dose. |
■ FDA Black Box Warning
Hepatotoxicity, including hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), which can be fatal. Increased risk in patients with prior or concurrent hematopoietic stem cell transplant.
| Serious Effects |
History of hypersensitivity to inotuzumab ozogamicin or any components.
| Precautions | Hepatotoxicity including VOD/SOS; increased risk post-HSCT; myelosuppression; infusion-related reactions; QT prolongation; immunosuppression and infection risk; embryo-fetal toxicity. |
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| Fetal Monitoring | Pregnancy test prior to initiation and monthly during treatment. If pregnancy occurs, discontinue immediately and monitor fetal development with ultrasound. Assess for oligohydramnios if exposed during second or third trimester. |
| Fertility Effects | Animal studies have shown reversible effects on male and female fertility at clinically relevant exposures. In females, OJJAARA may disrupt menstrual cyclicity and ovulation. In males, sperm count and motility may be reduced. Contraception is recommended for both sexes during treatment and for 3 months after discontinuation. |