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IMBRUVICA™ (ibrutinib) capsules

2014-02-13 20:23:47 来源: 作者: 【大中小】浏览:398次评论:0条

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 (1).

This indication is based on overall response rate. An improvement in survival or disease-related symptoms has not been established (14.1).

DOSAGE AND ADMINISTRATION
560 mg taken orally once daily (four 140 mg capsules once daily) (2.2).

Capsules should be taken orally with a glass of water. Do not open, break, or chew the capsules (2.1).
DOSAGE FORMS AND STRENGTHS
Capsule: 140 mg (3)

CONTRAINDICATIONS
None (4)

WARNINGS AND PRECAUTIONS
Hemorrhage: Monitor for bleeding (5.1).
Infections: Monitor patients for fever and infections and eva luate promptly. (5.2).
Myelosuppression: Check complete blood counts monthly (5.3).
Renal Toxicity: Monitor renal function and maintain hydration (5.4).
Second Primary Malignancies: Other malignancies have occurred in patients, including skin cancers, and other carcinomas (5.5).
Embryo-Fetal Toxicity: Can cause fetal harm. Advise women of the potential risk to a fetus and to avoid pregnancy while taking the drug (5.6).
ADVERSE REACTIONS
The most common adverse reactions (≥20%) in patients with MCL were thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, peripheral edema, upper respiratory tract infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting and decreased appetite (6).

To report SUSPECTED ADVERSE REACTIONS, contact Pharmacyclics at 1-877-877-3536 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DRUG INTERACTIONS
CYP3A Inhibitors: Avoid co-administration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce IMBRUVICA dose (2.4, 7.1).

CYP3A Inducers: Avoid co-administration with strong CYP3A inducers (7.2).
USE IN SPECIFIC POPULATIONS
Hepatic Impairment: Avoid use of IMBRUVICA in patients with baseline hepatic impairment (8.7).
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 11/2013
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FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Dosing Guidelines
2.2 Dosage for Mantle Cell Lymphoma
2.3 Dose Modifications for Adverse Reactions
2.4 Dose Modifications for Use with CYP3A Inhibitors
2.5 Missed Dose
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Hemorrhage
5.2 Infections
5.3 Myelosuppression
5.4 Renal Toxicity
5.5 Second Primary Malignancies
5.6 Embryo-Fetal Toxicity
6 ADVERSE REACTIONS
7 DRUG INTERACTIONS
7.1 CYP3A Inhibitors
7.2 CYP3A Inducers
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
8.8 Females and Males of Reproductive Potential
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
14.1 Mantle Cell Lymphoma
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
PRINCIPAL DISPLAY PANEL - 90 Capsule Bottle Carton
*
Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

IMBRUVICA is indicated for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. This indication is based on overall response rate. An improvement in survival or disease-related symptoms has not been established [see Clinical Studies (14.1)].

2 DOSAGE AND ADMINISTRATION

2.1 Dosing Guidelines

Administer IMBRUVICA orally once daily at approximately the same time each day. Swallow the capsules whole with water. Do not open, break, or chew the capsules.

2.2 Dosage for Mantle Cell Lymphoma

The recommended dose of IMBRUVICA for MCL is 560 mg (four 140 mg capsules) orally once daily.

2.3 Dose Modifications for Adverse Reactions

Interrupt IMBRUVICA therapy for any Grade 3 or greater non-hematological, Grade 3 or greater neutropenia with infection or fever, or Grade 4 hematological toxicities. Once the symptoms of the toxicity have resolved to Grade 1 or baseline (recovery), IMBRUVICA therapy may be reinitiated at the starting dose. If the toxicity reoccurs, reduce dose by one capsule (140 mg per day). A second reduction of dose by 140 mg may be considered as needed. If these toxicities persist or recur following two dose reductions, discontinue IMBRUVICA.

Recommended dose modifications for these toxicities are described below:

Toxicity Occurrence	MCL Dose Modification After Recovery Starting Dose = 560 mg
First	Restart at 560 mg daily
Second	Restart at 420 mg daily
Third	Restart at 280 mg daily
Fourth	Discontinue IMBRUVICA

2.4 Dose Modifications for Use with CYP3A Inhibitors

Avoid co-administration with strong or moderate CYP3A inhibitors and consider alternative agents with less CYP3A inhibition.

Concomitant use of strong CYP3A inhibitors which would be taken chronically (e.g., ritonavir, indinavir, nelfinavir, saquinavir, boceprevir, telaprevir, nefazodone) is not recommended. For short-term use (treatment for 7 days or less) of strong CYP3A inhibitors (e.g., antifungals and antibiotics) consider interrupting IMBRUVICA therapy until the CYP3A inhibitor is no longer needed [see Drug Interactions (7.1)].

Reduce IMBRUVICA dose to 140 mg if a moderate CYP3A inhibitor must be used (e.g., fluconazole, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir, fosamprevir, crizotinib, imatinib, verapamil, grapefruit products and ciprofloxacin) [see Drug Interactions (7.1)].