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.

PEMAZYRE (NDA-213736)

(PEMIGATINIB)

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

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08/25/2022 (SUPPL-2)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Ocular Toxicity

Additions and or revisions underlined

…

Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, RPED occurred in 11% of patients, including Grade 3-4 RPED in 1.3%. The median time to first onset of RPED was 56 days. RPED led to dose interruption of PEMAZYRE in 3.1% of patients, and dose reduction and permanent discontinuation in 1.3% and in 0.2% of patients, respectively. RPED resolved or improved to Grade 1 levels in 76% of patients who required dosage modification of PEMAZYRE for RPED.

…

Dry Eye

Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, dry eye occurred in 31% of patients, including Grade 3-4 in 1.6% of patients. Treat patients with ocular demulcents as needed.

5.2 Hyperphosphatemia and Soft Tissue Mineralization

Additions and/or revisions underlined

635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, hyperphosphatemia was reported in 93% of patients based on laboratory values above the upper limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-169).

Phosphate lowering therapy was required in 33% of patients receiving PEMAZYRE.

…

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive additions and/or revisions; please refer to label for complete information.

8 Use in Specific Populations

8.5 Geriatric Use

Additions and/or revisions underlined

In FIGHT-202 in patients with cholangiocarcinoma, 32% of patients were 65 years and older, and 8% of patients were 75 years and older. In FIGHT-203 in patients with MLN with FGFR1 rearrangement, 44% of patients were 65 years and older, and 2.9% of patients were 75 years and older.

No overall differences in safety or effectiveness were observed between these patients and younger patients.

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

PATIENT INFORMATION

Additions and/or revisions underlined

What is PEMAZYRE?

PEMAZYRE is a prescription medicine that is used to treat adults with:

…

a type of blood cancer called myeloid/lymphoid neoplasms (MLNs):
- when it has come back or did not respond to treatment, and
- whose tumor has a certain type of abnormal FGFR1 gene.
  Your healthcare provider will test your cancer for certain types of abnormal FGFR1 or FGFR2 genes and make sure that PEMAZYRE is right for you.
  …
  How should I take PEMAZYRE?

Take PEMAZYRE exactly as your healthcare provider tells you.
For cholangiocarcinoma, PEMAZYRE is taken in cycles of 21 days. Take PEMAZYRE 1 time each day for 14 days, followed by 7 days off treatment, to complete a 21-day treatment cycle.
For myeloid/lymphoid neoplasms (MLNs), take PEMAZYRE 1 time each day.
…
What are the possible side effects of PEMAZYRE?
PEMAZYRE may cause serious side effects, including:
…
The most common side effects of PEMAZYRE for myeloid/lymphoid neoplasms (MLNs) include:

nails separate from the bed or poor formation of the nail
nose bleeds
disorder of the retina
hair loss
pain in feet or hands
mouth sores
decreased appetite
diarrhea
dry skin
dry eyes
indigestion
tiredness
back pain
anemia
nausea
stomach-area (abdominal) pain
blurry vision
rash
swelling in feet, legs, hands, or arms
constipation
dizziness
dry mouth
…

02/23/2021 (SUPPL-1)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Hyperphosphatemia and Soft Tissue Mineralization

(Subsection title revised; Additions and/or revisions underlined)

PEMAZYRE can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcification, calcinosis, and non-uremic calciphylaxis. Increases in phosphate levels are a pharmacodynamic effect of PEMAZYRE [see Clinical Pharmacology (12.2)]. Among 466 patients who received PEMAZYRE across clinical trials, hyperphosphatemia was reported in 92% of patients based on laboratory values above the upper limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-169). Phosphate lowering therapy was required in 29% of patients receiving PEMAZYRE.

Monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is > 5.5 mg/dL. For serum phosphate levels > 7 mg/dL, initiate phosphate lowering therapy and withhold, reduce the dose, or permanently discontinue PEMAZYRE based on duration and severity of hyperphosphatemia [see Dosage and Administration (2.3)].

6 Adverse Reactions

(Additions and/or revisions underlined)

The following adverse reactions are discussed elsewhere in the labeling:

Ocular Toxicity [see Warnings and Precautions (5.1)]
Hyperphosphatemia and Soft Tissue Mineralization [see Warnings and Precautions (5.2)]

6.1 Clinical Trials Experience

(Additions and/or revisions underlined)

…

Clinically relevant adverse reactions occurring in ? 10% of patients included fractures (2.1%). In all patients treated with pemigatinib, 1.3% experienced pathologic fractures (which included patients with and without cholangiocarcinoma [N=466]). Soft tissue mineralization, including cutaneous calcification, calcinosis, and non-uremic calciphylaxis associated with hyperphosphatemia were observed with PEMAZYRE treatment.

…

7 Drug Interactions

7.1 Effect of Other Drugs on PEMAZYRE

(Additions and/or revisions underlined)

Strong and Moderate CYP3A Inducers

Concomitant use of PEMAZYRE with a strong or moderate CYP3A inducer decreases pemigatinib plasma concentrations, [see Clinical Pharmacology (12.3)] which may reduce the efficacy of PEMAZYRE. Avoid concomitant use of strong and moderate CYP3A inducers with PEMAZYRE.

Strong and Moderate CYP3A Inhibitors

Concomitant use of a strong or moderate CYP3A inhibitor with PEMAZYRE increases pemigatinib plasma concentrations, [see Clinical Pharmacology (12.3)] which may increase the incidence and severity of adverse reactions. Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. Reduce PEMAZYRE dosage if concomitant use of strong and moderate CYP3A inhibitors cannot be avoided [see Dosage and Administration (2.2)].

8 Use in Specific Populations

8.6 Renal Impairment

(Additions and/or revisions underlined)

Reduce the recommended dosage of PEMAZYRE for patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2, estimated by Modification of Diet in Renal Disease [MDRD] equation) [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].

No dosage adjustment is recommended for patients with mild or moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m2). No dosage adjustment is recommended for patients with end- stage renal disease (eGFR < 15 mL/min/1.73 m2) who are receiving intermittent hemodialysis. [see Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

(Additions and/or revisions underlined)

Reduce the recommended dosage of PEMAZYRE for patients with severe hepatic impairment (total bilirubin > 3 × ULN with any AST) [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3)].

No dosage adjustment is recommended for patients with mild (total bilirubin > upper limit of normal [ULN] to 1.5 × ULN or AST > ULN) or moderate (total bilirubin >1.5–3 × ULN with any AST) hepatic impairment [see Clinical Pharmacology (12.3)].

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

PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

…

Hyperphosphatemia and Soft Tissue Mineralization

Inform patients that they may experience increase in phosphate levels and of the need to monitor serum phosphate levels. Advise patients to immediately inform their healthcare provider of any symptoms related to acute change in phosphate levels such as muscle cramps, numbness, or tingling around the mouth [see Warnings and Precautions 5.2)].

PATIENT INFORMATION

(Additions and/or revisions underlined)

…

Before you take PEMAZYRE, tell your healthcare provider about all of your medical conditions, including if you:

have vision or eye problems
have kidney problems
have liver problems

are pregnant or plan to become pregnant. PEMAZYRE can harm your unborn baby or cause loss of your pregnancy (miscarriage). You should not become pregnant during treatment with PEMAZYRE.

…

are breastfeeding or plan to breastfeed. It is not known if PEMAZYRE passes into your breast milk. Do not breastfeed during treatment and for 1 week after your final dose of PEMAZYRE.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

…

What are the possible side effects of PEMAZYRE? PEMAZYRE may cause serious side effects, including:

Eye problems. Certain eye problems are common with PEMAZYRE but can also be serious. Eye problems include dry eye or inflamed eyes, inflamed cornea (front part of the eye), increased tears, and a disorder of the retina (an internal part of the eye). You will need to see an eye specialist for a complete eye exam before you begin treatment with PEMAZYRE, every 2 months for the first 6 months, and then every 3 months during treatment with PEMAZYRE.
- You should use artificial tears or substitutes, hydrating or lubricating eye gels as needed, to help prevent or treat dry eyes.
- Tell your healthcare provider right away if you develop any changes in your vision during treatment with PEMAZYRE, including: blurred vision, flashes of light, or see black spots. You may need to see an eye specialist right away.
High phosphate levels in your blood (hyperphosphatemia) and buildup of minerals in different tissues in your body. Hyperphosphatemia is common with PEMAZYRE but can also be serious. High levels of phosphate in your blood may lead to buildup of minerals such as calcium, in different tissues in your body. Your healthcare provider will check your blood phosphate levels during treatment with PEMAZYRE.

Your healthcare provider may prescribe changes in your diet or phosphate lowering therapy, or change, interrupt or stop PEMAZYRE if needed.
Tell your healthcare provider right away if you develop any muscle cramps, or numbness or tingling around your mouth.

…