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. |
| Molecular Weight | 625.7 |
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 | Avoid use in first trimester due to potential embryotoxicity. There are no adequate and well-controlled studies in pregnant women. |
| 2nd trimester | Avoid use in second trimester unless benefit clearly outweighs risk. Fetal development may be affected. |
| 3rd trimester | Avoid use in third trimester due to risk of fetal harm, including potential for neonatal toxicity. |
Clinical note
Comprehensive clinical and safety monograph for UKONIQ (UKONIQ).
| Placental transfer | Evidence suggests placental transfer in animals. No human data. Molecular weight and properties imply potential for human placental crossing. |
| Breastfeeding | No data on presence in human milk. Due to potential serious adverse effects in nursing infants, advise patients not to breastfeed 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 |
Known hypersensitivity to ukoniq or any excipientsPregnancySevere hepatic impairment (Child-Pugh C)
| 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. |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| 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. |
| Avoid grapefruit and grapefruit juice. No other specific food restrictions known. |
| Clinical Pearls | Monitor for infusion-related reactions; pre-medicate with antihistamines and acetaminophen. Check hepatic function before and during treatment due to risk of hepatotoxicity. Assess for tumor lysis syndrome in patients with high tumor burden; institute prophylaxis with allopurinol or rasburicase. Do not co-administer with strong CYP3A4 inducers or inhibitors; adjust dose accordingly. |
| Patient Advice | Umbralisib may cause diarrhea; if severe, contact your doctor immediately. · Report any signs of liver problems such as yellowing of skin or eyes, dark urine, or abdominal pain. · Avoid grapefruit and grapefruit juice during treatment as they may increase drug levels. · Use effective contraception during and for at least 1 month after last dose. · Do not take St. John's wort or other herbal supplements without consulting your doctor. |