Miscellaneous immune disorders:
Indications for: IMBRUVICA ORAL SUSPENSION
Chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.
Study 1129 (ClinicalTrials.gov Identifier: NCT02195869)
- The safety and efficacy of Imbruvica in cGVHD were evaluated in an open-label, multicenter, single-arm trial of 42 patients with cGVHD after failure of first line corticosteroid therapy and requiring additional therapy.
- After receiving Imbruvica 420mg once daily, the overall response rate (ORR) was reported to be 67% (95% CI, 51-80).
- Median time to best response coinciding with the first scheduled response assessment was 12.3 weeks.
- Patient response was seen for all organs involved with cGVHD, including the skin, mouth, liver, and gastrointestinal tract.
- Nearly half of the patients (48%) had responses lasting ≥5 months.
iMAGINE (ClinicalTrials.gov Identifier: NCT03790332)
- The safety and efficacy of Imbruvica were evaluated in an open-label, multicenter, single-arm trial for the treatment of pediatric and young adult patients age 1 year to less than 22 years with moderate or severe cGVHD.
- Results showed an ORR (main efficacy outcome measure) of 60% (n=28; 95% CI, 44-74) through week 25, of which 4% (n=2) of patients achieved CR and 55% (n=26) achieved PR.
- Median duration of response was 5.3 months (95% CI, 2.8-8.8).
- Median time to first response was 0.9 month (range, 0.9-6.1 months), and the median time from first response to death or new systemic therapies for cGVHD was 14.8 months (95% CI, 4.6-not evaluable).
- 50% of patients 12 years of age and older showed at least a 7-point decrease in patient-reported symptom bother through week 25, as assessed by the Lee Symptom Scale overall summary score.
Use caps or tabs form. Swallow whole with water. Take at same time each day. ≥12yrs: 420mg once daily. Treat until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity; discontinue when treatment for cGVHD no longer required. Hepatic impairment (total bilirubin level >1.5–3×ULN [unless of non-hepatic origin or due to Gilbert’s syndrome]): 140mg once daily; (total bilirubin level >3×ULN [unless of non-hepatic origin or due to Gilbert’s syndrome]): avoid. Dose modifications for toxicities or concomitant CYP3A inhibitors (eg, voriconazole, posaconazole): see full labeling.
<1yr: not established. Can use caps/tabs or oral susp. Swallow caps/tabs whole with water. Take at same time each day. 1–<12yrs: 240mg/m2 once daily (based on BSA); max: up to 420mg once daily. Treat until disease progression, recurrence of an underlying malignancy, or unacceptable toxicity; discontinue when treatment for cGVHD no longer required. Hepatic impairment (total bilirubin level >1.5–3×ULN [unless of non-hepatic origin or due to Gilbert’s syndrome]): 80mg/m2 once daily; (total bilirubin level >3×ULN [unless of non-hepatic origin or due to Gilbert’s syndrome]): avoid. Recommended dose based on BSA, dose modifications for toxicities or concomitant CYP3A inhibitors (eg, voriconazole, posaconazole): see full labeling.
IMBRUVICA ORAL SUSPENSION Warnings/Precautions:
Risk of serious hemorrhagic events; consider the benefit/risk of withholding treatment for 3–7 days pre-and post-surgery. Monitor for fever and infections; evaluate promptly if occurs. Consider prophylaxis for opportunistic infections in high risk patients. Monitor for cytopenias; obtain CBCs monthly. Monitor for cardiac arrhythmias and cardiac function at baseline then periodically (esp. in those with cardiac risk factors, hypertension, diabetes, acute infections, history of cardiac arrhythmias); do ECG if arrhythmic symptoms, new onset dyspnea, or other cardiovascular concerns develop. Monitor for hypertension; initiate or adjust anti-hypertensives as appropriate. Risk of second primary malignancies (eg, non-melanoma skin cancer, others). Monitor for tumor lysis syndrome in patients at risk (eg, high tumor burden). Hepatic impairment (see Adult). Maintain adequate hydration. Embryo-fetal toxicity. Advise females of reproductive potential and males (w. female partners) to use effective contraception during and for 1 month after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 1 week after the last dose).
IMBRUVICA ORAL SUSPENSION Classification:
Bruton tyrosine kinase (BTK) inhibitor.
IMBRUVICA ORAL SUSPENSION Interactions:
Avoid concomitant strong CYP3A inhibitors (eg, ketoconazole); if short-term use (eg, anti-infectives for ≤7days), interrupt ibrutinib therapy. Concomitant posaconazole, voriconazole, and moderate CYP3A inhibitors (eg, erythromycin): adjust ibrutinib dose (see full labeling). Avoid grapefruit and Seville oranges during treatment. Avoid concomitant strong CYP3A inducers (eg, rifampin). Increased risk of hemorrhage with concomitant antiplatelets or anticoagulants; monitor.
Thrombocytopenia, diarrhea, fatigue, musculoskeletal pain, neutropenia, rash, anemia, bruising, muscle spasms, stomatitis, nausea, hemorrhage, pneumonia, pyrexia, stomatitis, abdominal pain, headache.
The half-life of ibrutinib is 4 hours to 6 hours. Eliminated primarily via feces.
Generic Drug Availability:
Caps 70mg—28; 140mg—90, 120; Tabs—28 (2×14 blister cards); Oral susp—108mL