Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

COPIKTRA (NDA-211155)

(DUVELISIB)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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07/26/2024 (SUPPL-7)

Approved Drug Label (PDF)

Boxed Warning

Additions and revisions underlined:

WARNING: TREAMENT-RELATED MORTALITY AND SERIOUS TOXICITIES:

INFECTIONS, DIARRHEA OR COLITIS, CUTANEOUS REACTIONS, and

PNEUMONITIS

• Treatment-related mortality occurred in 15% of COPIKTRA-treated patients

5 Warnings and Precautions

5.1 Treatment-related Mortality

Newly added subsection:

In a randomized controlled study in patients with relapsed or refractory CLL or SLL, treatment with COPIKTRA caused increased treatment-related mortality [see Clinical Studies (14)]. With extended follow-up with a median of 63 months, treatment-related deaths occurred in 15% (23/158) of those patients in the overall population. In the indicated patient population, patients with relapsed or refractory CLL or SLL after at least two prior lines of systemic therapy, treatment- related deaths following treatment with COPIKTRA occurred in 14% (13/93) of patients. The most common cause of the treatment-related deaths were infections, which occurred in 9% and 11% of patients with relapsed or refractory CLL following at least one or two prior systemic therapies, respectively [see Adverse Reactions (6.1)]. COPIKTRA is not indicated and is not recommended for any patients in the initial or second-line treatment setting [see Indications and Usage (1)].

6 Adverse Reactions

Additions and revisions underlined:

The following adverse reactions have been associated with COPIKTRA in clinical trials and are discussed in greater detail in other sections of the prescribing information:

Treatment-related Mortality [see Warnings and Precautions (5.1)]

6.1 Clinical Trial Experience

Newly added information:

Long-Term Safety Follow-Up

The comparative safety data from the 5 year follow up in those treated with either COPIKTRA (n=158) or ofatumumab (n=155) were analyzed in adult patients with CLL or SLL as part of a randomized, open-label, actively controlled clinical trial (DUO) [see Clinical Studies (14)].

Fatal adverse reactions occurred in 15% (23/158) of patients treated with COPIKTRA and in 3% (5/155) of patients treated with ofatumumab. The most common fatal adverse reactions in the COPIKTRA arm were infections and respiratory adverse reactions, occurring in 9% and 3% of patients, respectively.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Newly added information:

Death due to treatment side effects. COPIKTRA can cause severe, life-threatening side effects that can lead to death. The serious side effects are listed below. Infections were the most common cause of death. If you develop any of these or any new or worsening side effects, tell your healthcare provider right away.
COPIKTRA should not be used as the first or second medicine to treat anyone, including people with CLL or
SLL because of an increased risk of death due to treatment side effects.

PATIENT COUNSELING INFORMATION

Newly added information:

Treatment-related Mortality

Advise patients that COPIKTRA has been associated with increased deaths due to side effects of therapy in a randomized study when compared to standard therapy. The main reason for death was infection [see Warnings and Precautions (5.1)].

09/22/2021 (SUPPL-3)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trial Experience

(Revision of table numbers; please refer to label)

7 Drug Interactions

7.1 Effects of Other Drugs on COPIKTRA

(Additions and/or revisions underlined)

Strong CYP3A4 Inhibitors

Coadministration with a strong CYP3A4 inhibitor increases duvelisib AUC [see Clinical Pharmacology (12.3)], which may increase the risk of COPIKTRA toxicities. Reduce COPIKTRA dosage when co-administered with a strong CYP3A4 inhibitor [see Dosage and Administration (2.4)].

Strong and Moderate CYP3A4 Inducers

Coadministration with a strong or moderate CYP3A4 inducer decreases duvelisib area under the curve (AUC) [see Clinical Pharmacology (12.3)], which may reduce COPIKTRA efficacy.

Avoid coadministration of strong or moderate CYP3A4 inducers with COPIKTRA. If coadministration with a moderate CYP3A4 inducer cannot be avoided, increase the COPIKTRA dose. [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)].

7.2 Effects of COPIKTRA on Other Drugs

(Additions and/or revisions underlined)

CYP3A4 Substrates

Coadministration with COPIKTRA increases AUC of a sensitive CYP3A4 substrate [see Clinical Pharmacology (12.3)] which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the co- administered sensitive CYP3A4 substrate.