UKONIQ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for UKONIQ (UKONIQ).
Phosphatidylinositol-3-kinase (PI3K) inhibitor; specifically inhibits the PI3Kδ isoform, blocking downstream signaling pathways (e.g., AKT/mTOR), leading to apoptosis and reduced proliferation of malignant B-cells.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP3A5 and CYP2C8. |
| Excretion | Primarily fecal (80%) as unchanged drug; renal excretion accounts for <1% of the dose. |
| Half-life | Terminal elimination half-life is approximately 5.3 hours (range 3.4–7.7 hours). Steady-state is achieved within 2–3 days of once-daily dosing. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Mean apparent volume of distribution (Vd/F) is 346 L (approximately 4.9 L/kg for a 70 kg adult), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 18% (range 11–29%) due to first-pass metabolism. |
| Onset of Action | Oral administration: clinical effect (improvement in plaque psoriasis) observed within 2–4 weeks, with maximum response by 8–16 weeks. |
| Duration of Action | Duration of action for psoriasis control is maintained with continued once-daily dosing. Upon discontinuation, recurrence of lesions typically occurs within months. |
60 mg/m2 intravenously over 1 hour on days 1, 8, and 15 of a 28-day cycle.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not evaluated in severe renal impairment (CrCl <30 mL/min) or dialysis. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose to 45 mg/m2. Child-Pugh Class C: Not recommended. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. No specific dosing guidelines available. |
| Geriatric use | No specific dose modification recommended. Monitor for increased toxicity (e.g., diarrhea, neutropenia) as elderly patients may have decreased organ function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for UKONIQ (UKONIQ).
| Breastfeeding | No data are available on the presence of umbralisib in human milk, its effects on the breastfed infant, or its effects on milk production. Because of the potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for at least 1 month after the last dose. |
| Teratogenic Risk | Based on its mechanism of action as a PI3Kδ inhibitor, Ukoniq (umbralisib) has potential for fetal harm. There are no adequate and well-controlled studies in pregnant women. In animal studies, PI3Kδ inhibition caused embryo-fetal toxicity. Ukoniq should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women of reproductive potential should use effective contraception during treatment and for at least 1 month after the last dose. |
■ FDA Black Box Warning
WARNING: FATAL AND SERIOUS TOXICITIES INCLUDING INFECTIONS, HEMATOLOGIC TOXICITY, HEPATOTOXICITY, AND PNEUMONITIS. UKONIQ should only be used when the patient's disease has progressed after at least two prior systemic therapies.
| Serious Effects |
None
| Precautions | ["Infections: Fatal and serious infections, including opportunistic infections, have occurred. Monitor for signs and symptoms; withhold or discontinue if infection develops.","Hematologic toxicity: Severe neutropenia, thrombocytopenia, and anemia may occur. Monitor blood counts regularly.","Hepatotoxicity: Elevations in hepatic enzymes and bilirubin; monitor liver function periodically.","Pneumonitis: Severe and fatal pneumonitis/interstitial lung disease can occur; monitor pulmonary symptoms.","Diarrhea: Severe diarrhea occurs, manage with antidiarrheals, fluids, and electrolyte replacement.","Embryo-fetal toxicity: Can cause fetal harm; advise patients of reproductive potential to use effective contraception."] |
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| Fetal Monitoring | Monitor complete blood counts (CBCs) monthly during treatment due to risk of neutropenia. Monitor liver function tests (LFTs) monthly; interrupt or reduce dose for Grade 3 or higher transaminase elevation. Monitor for signs and symptoms of infection, including opportunistic infections. Perform pregnancy testing in women of reproductive potential prior to initiation of therapy. |
| Fertility Effects | Based on animal studies, Ukoniq may impair fertility in males and females. In rats, umbralisib caused reduced fertility and testicular toxicity. The effects on human fertility are unknown. |