Imbruvica Oral Suspension Generic Name & Formulations
Caps 70mg—28; 140mg—90, 120; Tabs—28 (2×14 blister cards); Oral susp—108mL
- 70mg/mL, white to off-white suspension.
The oral suspension bottle is provided in a carton with two 3mL reusable oral dosing syringes.
Store bottle at 2°C to 25°C (36°F to 77°F). Do not freeze. Dispense in the original sealed container. Discard any unused Imbruvica oral suspension remaining 60 days after first opening the bottle.
Imbruvica Oral Suspension Indications
Imbruvica Oral Suspension Dosage and Administration
Prior to Treatment Evaluations
Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function.
Verify pregnancy status prior to initiating treatment.
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 Contraindications
Imbruvica Oral Suspension Boxed Warnings
Imbruvica Oral Suspension Warnings/Precautions
- Fatal bleeding events have occurred in patients receiving Imbruvica; the mechanism of bleeding events is not well understood.
- Use of anticoagulant/antiplatelet agents concomitantly increases the risk of major hemorrhage; consider the risks/benefits of concomitant anticoagulant/antiplatelet therapy.
- Monitor for signs/symptoms of bleeding.
- Consider the benefit-risk of withholding Imbruvica for at least 3-7 days pre- and post-surgery depending on the type of surgery and the risk of bleeding.
- Bacterial, viral and fungal infections have occurred with Imbruvica therapy.
- Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have been reported.
- In patients at risk of opportunistic infections: consider prophylaxis according to standard of care.
- Monitor and evaluate patients for fever and infections and treat appropriately.
Cardiac Arrhythmias, Cardiac Failure, and Sudden Death
- Fatal and serious cardiac arrhythmias and cardiac failure have occurred with Imbruvica.
- Patients with cardiac abnormalities may be at greater risk.
- Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function.
- For patients who develop symptoms of arrhythmia, new onset dyspnea, or other cardiovascular concerns: obtain further evaluation (eg, ECG, echocardiogram) as indicated.
- Manage cardiac arrhythmias and cardiac failure appropriately; refer to dose modification guidelines and consider the benefits/risks of continued treatment.
- Median time to onset of hypertension was observed to be 5.9 months (range, 0.03 to 24 months).
- Monitor BP, initiate or adjust antihypertensive medication throughout treatment with Imbruvica.
- Follow dosage modification guidelines for grade 3 or higher hypertension.
- Neutropenia, thrombocytopenia, and anemia reported in clinical trials.
- Monitor CBC monthly.
Second Primary Malignancies
- Other malignancies, including non-skin carcinomas, occurred among patients who received Imbruvica in clinical trials.
- The most frequent second primary malignancy was non-melanoma skin cancer.
Tumor Lysis Syndrome
- Infrequently reported with Imbruvica.
- Assess baseline risk and take appropriate precautions.
- Monitor closely and treat as appropriate.
Can cause fetal harm when administered to a pregnant woman. Verify pregnancy status prior to initiating treatment.
Nursing Mother Considerations
There is no information regarding the presence of ibrutinib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Women should not breastfeed during treatment and for 1 week after the last dose.
Safety and effectiveness of Imbruvica have been established for treatment of cGVHD after failure of 1 or more lines of systemic therapy in pediatric patients 1 year of age and older. Use for this indication is supported by evidence from the iMAGINE study.
Safety and effectiveness have not been established for this indication in pediatric patients less than 1 year of age.
No overall differences in effectiveness were observed between younger and older patients. Anemia, pneumonia, thrombocytopenia, hypertension, and atrial fibrillation occurred more frequently among older patients treated with Imbruvica.
Renal Impairment Considerations
Mild or moderate renal impairment: no influence on the exposure of ibrutinib
Severe renal impairment: no data available
Hepatic Impairment Considerations
See Dosing and Administration.
Total bilirubin level >1.5 to 3x upper limit of normal (ULN) (unless of nonhepatic origin or due to Gilbert syndrome): reduce dose
Total bilirubin level >3x ULN (unless of nonhepatic origin or due to Gilbert syndrome): avoid use
Other Considerations for Specific Populations
Females of reproductive potential: use effective contraception during treatment and for 1 month after the last dose. Verify pregnancy status prior to initiating treatment.
Males with female partners of reproductive age: use effective contraception during treatment and for 1 month after the last dose.
Imbruvica Oral Suspension Pharmacokinetics
Ibrutinib is absorbed after oral administration with a median Tmax of 1 hour to 2 hours.
Reversible binding of ibrutinib to human plasma protein in vitro was 97.3%
The half-life of ibrutinib is 4 hours to 6 hours. Eliminated primarily via feces.
Imbruvica Oral Suspension Interactions
Imbruvica Oral Suspension Adverse Reactions
Imbruvica Oral Suspension 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.
Imbruvica Oral Suspension Note
Imbruvica Oral Suspension Patient Counseling
The medication should be taken at approximately the same time each day. Take a missed dose as soon as possible on the same day and return to normal schedule the following day; do not take extra doses to make up for the missed dose.
Inform patients of common side effects as well as potentially serious adverse events: hemorrhage; infections; cardiac arrhythmias, cardiac failure and sudden death; hypertension, secondary primary malignancies, tumor lysis syndrome, embryo-fetal toxicity.
Use effective contraception during treatment and for 1 month after the last dose.
Avoid breastfeeding during treatment and for 1 week after the last dose.
Patients may experience loose stools or diarrhea; maintain adequate hydration. Report persistent diarrhea.