Miscellaneous immune disorders:

Indications for: IMBRUVICA ORAL SUSPENSION

Chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.

Clinical Trials:

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.

Adult Dosage:

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.

Children Dosage:

<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).

See Also:

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.

Adverse Reactions:

Thrombocytopenia, diarrhea, fatigue, musculoskeletal pain, neutropenia, rash, anemia, bruising, muscle spasms, stomatitis, nausea, hemorrhage, pneumonia, pyrexia, stomatitis, abdominal pain, headache.

Metabolism:

Ibrutinib is metabolized to several metabolites primarily by cytochrome P450 (CYP)3A and to a minor extent by CYP2D6.

Drug Elimination:

The half-life of ibrutinib is 4 hours to 6 hours. Eliminated primarily via feces.

Generic Drug Availability:

NO

How Supplied:

Caps 70mg—28; 140mg—90, 120; Tabs—28 (2×14 blister cards); Oral susp—108mL