IMBRUVICA ® ( ibrutinib ) capsules
All pregnancies have a background risk of birth defect , loss , or other adverse outcomes . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown . In the U . S . general population , the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4 % and 15-20 %, respectively .
Animal Data : Ibrutinib was administered orally to pregnant rats during the period of organogenesis at doses of 10 , 40 and 80 mg / kg / day . Ibrutinib at a dose of 80 mg / kg / day was associated with visceral malformations ( heart and major vessels ) and increased resorptions and post-implantation loss . The dose of 80 mg / kg / day in rats is approximately 14 times the exposure ( AUC ) in patients with MCL or MZL and 20 times the exposure in patients with CLL / SLL or WM administered the dose of 560 mg daily and 420 mg daily , respectively . Ibrutinib at doses of 40 mg / kg / day or greater was associated with decreased fetal weights . The dose of 40 mg / kg / day in rats is approximately 6 times the exposure ( AUC ) in patients with MCL administered the dose of 560 mg daily . Ibrutinib was also administered orally to pregnant rabbits during the period of organogenesis at doses of 5 , 15 , and 45 mg / kg / day . Ibrutinib at a dose of 15 mg / kg / day or greater was associated with skeletal variations ( fused sternebrae ) and ibrutinib at a dose of 45 mg / kg / day was associated with increased resorptions and post-implantation loss . The dose of 15 mg / kg / day in rabbits is approximately 2.0 times the exposure ( AUC ) in patients with MCL and 2.8 times the exposure in patients with CLL / SLL or WM administered the dose of 560 and 420 mg daily , respectively .
Lactation : Risk Summary : There is no information regarding the presence of ibrutinib or its metabolites in human milk , the effects on the breastfed infant , or the effects on milk production . The development and health benefits of breastfeeding should be considered along with the mother ’ s clinical need for IMBRUVICA and any potential adverse effects on the breastfed child from IMBRUVICA or from the underlying maternal condition .
Females and Males of Reproductive Potential : Pregnancy Testing : Verify the pregnancy status of females of reproductive potential prior to initiating IMBRUVICA therapy .
Contraception Females : Advise females of reproductive potential to avoid pregnancy while taking IMBRUVICA and for up to 1 month after ending treatment . If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug , the patient should be informed of the potential hazard to a fetus .
Males : Advise men to avoid fathering a child while receiving IMBRUVICA , and for 1 month following the last dose of IMBRUVICA .
Pediatric Use : The safety and effectiveness of IMBRUVICA in pediatric patients has not been established . Geriatric Use : Of the 905 patients in clinical studies of IMBRUVICA , 62 % were ≥ 65 years of age , while 21 % were ≥75 years of age . No overall differences in effectiveness were observed between younger and older patients . Anemia ( all grades ) and Grade 3 or higher pneumonia occurred more frequently among older patients treated with IMBRUVICA . Hepatic Impairment : Avoid use of IMBRUVICA in patients with moderate or severe hepatic impairment ( Child-Pugh class B and C ). The safety of IMBRUVICA has not been evaluated in patients with mild to severe hepatic impairment by Child-Pugh criteria . Monitor patients for adverse reactions of IMBRUVICA and follow dose modification guidance as needed . [ see Dosage and Administration ( 2.5 ) and Clinical Pharmacology ( 12.3 ) in Full Prescribing Information ].
Plasmapheresis : Management of hyperviscosity in WM patients may include plasmapheresis before and during treatment with IMBRUVICA .
Modifications to IMBRUVICA dosing are not required .
PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information ).
• Hemorrhage : Inform patients of the possibility of bleeding , and to report any signs or symptoms ( severe headache , blood in stools or urine , prolonged or uncontrolled bleeding ). Inform the patient that IMBRUVICA may need to be interrupted for medical or dental procedures [ see Warnings and Precautions ].
• Infections : Inform patients of the possibility of serious infection , and to report any signs or symptoms ( fever , chills , weakness , confusion ) suggestive of infection [ see Warnings and Precautions ].
• Atrial fibrillation : Counsel patients to report any signs of palpitations , lightheadedness , dizziness , fainting , shortness of breath , and chest discomfort [ see Warnings and Precautions ].
• Hypertension : Inform patients that high blood pressure has occurred in patients taking IMBRUVICA , which may require treatment with anti-hypertensive therapy [ see Warnings and Precautions ].
• Second primary malignancies : Inform patients that other malignancies have occurred in patients who have been treated with IMBRUVICA , including skin cancers and other carcinomas [ see Warnings and Precautions ].
• Tumor lysis syndrome : Inform patients of the potential risk of tumor lysis syndrome and to report any signs and symptoms associated with this event to their healthcare provider for evaluation [ see Warnings and Precautions ].
• Embryo-fetal toxicity : Advise women of the potential hazard to a fetus and to avoid becoming pregnant during treatment and for 1 month after the last dose of IMBRUVICA [ see Warnings and Precautions ].
• Inform patients to take IMBRUVICA orally once daily according to their physician ’ s instructions and that the capsules should be swallowed whole with a glass of water without being opened , broken , or chewed at approximately the same time each day [ see Dosage and Administration ( 2.1 ) in Full Prescribing Information ].
• Advise patients that in the event of a missed daily dose of IMBRUVICA , it should be taken as soon as possible on the same day with a return to the normal schedule the following day . Patients should not take extra capsules to make up the missed dose [ see Dosage and Administration ( 2.6 ) in Full Prescribing Information ].
• Advise patients of the common side effects associated with IMBRUVICA [ see Adverse Reactions ]. Direct the patient to a complete list of adverse drug reactions in PATIENT INFORMATION .
• Advise patients to inform their health care providers of all concomitant medications , including prescription medicines , over-the-counter drugs , vitamins , and herbal products [ see Drug Interactions ].
• Advise patients that they may experience loose stools or diarrhea , and should contact their doctor if their diarrhea persists . Advise patients to maintain adequate hydration [ see Adverse Reactions ].
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Active ingredient made in China .
Distributed and Marketed by : Pharmacyclics LLC Sunnyvale , CA USA 94085 and Marketed by : Janssen Biotech , Inc . Horsham , PA USA 19044
Patent http :// www . imbruvica . com IMBRUVICA ® is a registered trademark owned by Pharmacyclics LLC
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