IMBRUVICA*
Manufacturer DetailsPHARMACYCLICS INC.
PHARMACYCLICS INC
Compositions:
Ibrutinib- mg capsules,
Ibrutinib- mg capsules,
| Strength | Rate | Packing Style |
|---|---|---|
| mg | 0.00 | unit capsules |
List of Related Indications:
- To treat patients with Mantle Cell Lymphoma (MCL) a rare and aggressive type blood cancer
List Of Drugs:
- Ibrutinib - Imbruvica - @- (Nov 2013)-Chemotherapeutic Agents
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
CYP3A Inhibitors: Avoid co-administration with strong and moderate
CYP3A inhibitors.
If a moderate CYP3A inhibitor must be used, reduce IMBRUVICA dose
CYP3A Inducers: Avoid co-administration with strong CYP3A inducers
Indication:
MBRUVICA® (ibrutinib) capsules, for oral use
Initial U.S. Approval: 2013
RECENT MAJOR CHANGES
Indications and Usage (1.4) 01/15 Dosage and Administration (2.2, 2.3, 2.5) 01/15
Warnings and Precautions (5.1, 5.6) 01/15
Drug Name- Imbruvica
Active Ingredient - Ibrutinib
To treat patients with mantle cell lymphoma (MCL) a rare and aggressive
type blood cancer
Indication-
To treat patients with mantle cell lymphoma (MCL) a rare and aggressive
type blood cancer
Approved by FDA on 13-11-2013 (Ref- FDA approved List- 2013)
Proprietary Name- IMBRUVICA*
Established Name- Ibrutinib
Applicant- PHARMACYCLICS
Indication- For the treatment of patients with chronic lymphocytic leukemia(CLL)
who have received at least one prior therapy
Ibrutinib received acelrated aprroval on November 13, 2013 for
the treatment of patients with mantle cell lymphoma who have
received at least one prior therapy
Approval Date- 12/2/2014
Approved by U.S.FDA (Ref- FDA approved List- 2014)
Proprietary Name- IMBRUVICA-2*
Established Name- Ibrutinib
Applicant- PHARMACYCLICS
Indication- For the treatment of patients with Mantle Cell Lymphoma(MCL)
who have received at least one prior therapy
Approval Date- November 13,2013
Approved by U.S.FDA (Ref- FDA approved List- 2013)
SUBSEQUENT APPROVAL-
FDA approved Ibrutinib Capsules (IMBRIVICA Capsules, Pharmacyclics,Inc.)
for the treatment of patients with Waldenstroms Macroglobulinemia (WM).
Ibrutinib was initally approved in November 13, for the treatments with
Mantle Cell Lymphoma (MCL) who have received atleast one prior therapy.
Ibrutinib also received approval in February 2014 for the treatment of
Chronic Lymphocytic Leukemia(CLL) in patients who received at least one
prior therapy and in July 2014 for the treatment of CLL with 17p deletion
Approval date -January 29.2015
Approved by U.S.FDA as on 31-08-2015 (Ref- FDA approved List- 2015)
LIST OF APPROVED DRUG FROM 01-01-2015 To 31-12-2015
ISSUED BY NEW DRUG DIVISION - DRUG CONTROLLER GENERAL- INDIA
Sr.No Name of Drug Indication Date of Issue
13. Ibrutinib hard gelatin Capsule 07-10-2015
140mg
For the treatment of adult patients with
Mantle cell Lymphoma (MCL) who have
received at least one prior therapy.
Chronic Lymphocyte Leukemia (CLL)
who have received at least one prior
therapy - Chronic Lymphotic Leukemia
with 17p deletion
Approved by DCG INDIA (Ref- DCGI approved List- 01-01-2015 To 31-12-3015)
Adverse Reaction:
The most common adverse reactions (.25%) in patients with B-cell
malignancies (MCL, CLL, WM) were thrombocytopenia, neutropenia,
diarrhea, anemia, fatigue, musculoskeletal pain, bruising, nausea,
upper respiratory tract infection, and rash.
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
Hemorrhage: Monitor for bleeding .
Infections: Monitor patients for fever and infections and evaluate promptly
Cytopenias: Check complete blood counts monthly
Atrial Fibrillation: Monitor patients for atrial fibrillation
Second Primary Malignancies: Other malignancies have occurred in patients,
including skin cancers, and other carcinomas
.
Tumor Lysis Syndrome (TLS): Monitor patients at risk for TLS
(e.g. high tumor burden)
.
Embryo-Fetal Toxicity: Can cause fetal harm. Advise women of the
potential risk to a fetus and to avoid pregnancy while taking the drug
Dosages/ Overdosage Etc:
Indication- For the treatment of patients with Mantle Cell Lymphoma(MCL)
who have received at least one prior therapy
SUBSEQUENT APPROVAL-
FDA approved Ibrutinib Capsules (IMBRIVICA Capsules, Pharmacyclics,Inc.)
for the treatment of patients with Waldenstroms Macroglobulinemia (WM).
Ibrutinib was initally approved in November 13, for the treatments with
Mantle Cell Lymphoma (MCL) who have received atleast one prior therapy.
Ibrutinib also received approval in February 2014 for the treatment of
Chronic Lymphocytic Leukemia(CLL) in patients who received at least one
prior therapy and in July 2014 for the treatment of CLL with 17p deletion
INDICATIONS AND USAGE
IMBRUVICA is a kinase inhibitor indicated for the treatment of patients with:
Mantle cell lymphoma (MCL) who have received at least one prior
therapy
Accelerated approval was granted for this indication based on overall
response rate. Continued approval for this indication may be contingent
upon verification of clinical benefit in confirmatory trials.
Chronic lymphocytic leukemia (CLL) who have received at least one prior therapy
Chronic lymphocytic leukemia with 17p deletion
Waldenström’s macroglobulinemia (WM)
DOSAGE AND ADMINISTRATION
MCL:560 mg taken orally once daily (four 140 mg capsules
once daily)
CLL and WM: 420 mg taken orally once daily (three 140 mg capsules
once daily)
Capsules should be taken orally with a glass of water.
Do not open, break, or chew the capsules
DOSAGE FORMS AND STRENGTHS
Capsule:140 mg
Patient Information:
PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Patient Information).
Hemorrhage: Inform patients of the possibility of bleeding, and to report any signs
or symptoms (blood in stools or urine, prolonged or uncontrolled bleeding)
. Inform the patient that IMBRUVICA may need to be interrupted for medical
or dental procedures
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
Second primary malignancies: Inform patients that other malignancies
have occurred in patients who have been treated with IMBRUVICA,
including skin cancers and other carcinomas
Tumor lysis syndrome: Inform patients of the potential risk of tumor lysis
syndrome and report any signs and symptoms associated with this event
to their healthcare provider for evaluation
Embryo-fetal toxicity: Advise women of the potential hazard to a fetus and
to avoid becoming pregnant .
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 .
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
Advise patients of the common side effects associated with IMBRUVICA
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 .
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.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Ibrutinib is a small-molecule inhibitor of BTK. Ibrutinib forms a covalent bond with a
cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic
activity.
BTK is a signaling molecule of the B-cell antigen receptor (BCR) and
cytokine receptor pathways. BTK’s role in signaling through the B-cell surface
receptors results in activation of pathways necessary for B-cell trafficking,
chemotaxis, and adhesion.
Nonclinical studies show that ibrutinib inhibits malignant B-cell proliferation
and survival in vivo as well as cell migration and substrate adhesion in vitro
2. Pharmacokinetics
Absorption
Ibrutinib is absorbed after oral administration with a median Tmax of 1 to 2 hours
. Ibrutinib exposure increases with doses up to 840 mg.
The steady-state AUC (mean ± standard deviation) observed in patients
at 560 mg is 953 ± 705 ng·h/mL and in patients at 420 mg is 680 ± 517 ng·h/mL.
Administration with food increased ibrutinib Cmax and AUC by approximately
2 to 4-and 2-fold, respectively, compared with administration of ibrutinib
after overnight fasting
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category D
Risk Summary
Based on findings in animals, IMBRUVICA can cause fetal harm when administered
to a pregnant woman. If IMBRUVICA is used during pregnancy or if the patient becomes
pregnant while taking IMBRUVICA, the patient should be apprised of the potential
hazard to the fetus.
2. Nursing Mothers
It is not known whether ibrutinib is excreted in human milk. Because many drugs are
excreted in human milk and because of the potential for serious adverse reactions
in nursing infants from IMBRUVICA, a decision should be made whether to discontinue
nursing or to discontinue the drug, taking into account the importance of the drug
to the mother.
3. Pediatric Use
The safety and effectiveness of IMBRUVICA in pediatric patients has not been
established.
4.Geriatric Use
Of the 111 patients treated for MCL, 63% were 65 years of age or older. No overall
differences in effectiveness were observed between these patients and younger
patients.
Cardiac adverse events (atrial fibrillation and hypertension), infections
(pneumonia and cellulitis) and gastrointestinal events (diarrhea and dehydration)
occurred more frequently among elderly patients
