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.

PHOTOFRIN (NDA-020451)

(PORFIMER SODIUM)

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

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01/01/2020 (SUPPL-29)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.10 Risk of Prolonged Duration of Photosensitivity in Patients with Hepatic and Renal Impairment

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

Hepatic or renal impairment will likely prolong the elimination of porfimer sodium leading to higher rates of toxicity. Inform patients with severe renal impairment or mild to severe hepatic impairment that the period requiring the precautionary measures for photosensitivity may be longer than 90 days.

5.12 Embryo-Fetal Toxicity

(Newly added subsection)

Based on animal studies, PHOTOFRIN may cause embryo-fetal toxicity when administered to a pregnant woman. Intravenous administration of porfimer sodium to pregnant rats and rabbits during the period of organogenesis at dose levels approximately 0.64 times the recommended human dose of PHOTOFRIN based on body surface area (BSA) resulted in increased fetal resorptions, decreased litter size, and reduced fetal weight but did not cause fetal malformations. Advise pregnant women of the potential risk to fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with PHOTOFRIN and for 5 months after the final dose.

5.2 Pulmonary and Gastroesophageal Hemorrhage

(Additions and/or revisions underlined)

Patients with large, centrally located tumors, cavitating tumors, or extensive tumors extrinsic to the bronchus are at high risk for fatal massive hemoptysis. Assess patients for tumors eroding into a pulmonary blood vessel and esophageal varices. Do not administer light directly to an area with esophageal varices because of the high risk of hemorrhage.

5.3 High-Grade Dysplasia (HGD) in Barrett’s Esophagus (BE)

(Additions and/or revisions underlined)

The long-term effect of PDT on HGD in BE is unknown. There is always a risk of cancer or abnormal epithelium that is invisible to the endoscopist beneath the new squamous cell epithelium; these facts emphasize the risk of overlooking cancer in such patients and the need for rigorous continuing surveillance despite the endoscopic appearance of complete squamous cell reepithelialization. Conduct endoscopic biopsy surveillance every 3 months, until 4 consecutive negative evaluations for HGD have been recorded; further follow-up may be scheduled every 6 to 12 months, as per judgment of healthcare providers. The follow-up period of the randomized study at the time of analysis was a minimum of 2 years (range 2 to 5.6 years).

5.6 Use Before or After Radiotherapy

(Additions and/or revisions underlined)

If PDT is to be used before or after radiotherapy, allot sufficient time between the two therapies to ensure that the inflammatory response produced by the first treatment has subsided before commencing the second treatment. The inflammatory response from PDT will depend on tumor size and extent of surrounding normal tissue that receives light. Allow 2 to 4 weeks after PDT before commencing radiotherapy.

The acute inflammatory reaction from radiotherapy usually subsides within 4 weeks after completing radiotherapy. Allow 4 weeks after completing radiotherapy before commencing PDT.

6 Adverse Reactions

(Addition of the following information)

The following clinically significant adverse reactions are described elsewhere in the labeling:

Gastroesophageal Fistula and Perforation
Pulmonary and Gastroesophageal Hemorrhage
High-Grade Dysplasia (HGD) in Barrett’s Esophagus (BE)
Photosensitivity
Ocular Sensitivity
Use Before or After Radiotherapy
Chest Pain
Airway Obstruction and Respiratory Distress
Esophageal Strictures
Thromboembolism

6.2 Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified during post-approval use of PHOTOFRIN with PDT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Infusion reactions: Infusion reactions including urticaria, bradycardia, hypotension, dizziness, and hypertension.

7 Drug Interactions

7.1 Use with Other Photosensitizing Agents

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

PHOTOFRIN can cause photosensitivity. The concomitant use of PHOTOFRIN with other photosensitizing agents (e.g., tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, thiazide diuretics, griseofulvin, and fluoroquinolones) may increase the risk of a photosensitivity reaction. Avoid the concomitant use of PHOTOFRIN with other products known to cause photosensitivity.

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

Based on animal studies, PHOTOFRIN may cause embryo-fetal toxicity when administered to a pregnant woman. There are no available data on PHOTOFRIN use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Intraveneous administration of porfimer sodium to pregnant rats and rabbits during the period of organogenesis at dose levels approximately

0.64 times the recommended human dose of PHOTOFRIN based on body surface area (BSA) resulted in increased fetal resorptions, decreased litter size, and reduced fetal weight, but did not cause fetal malformations.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20% respectively.

Data

Animal Data

Intravenous administration of porfimer sodium to pregnant rats for 10 days during the period of organogenesis at dose levels 0.64 times the recommended human dose of PHOTOFRIN based on BSA resulted in maternal and embryo-fetal toxicity resulting in increased resorptions, decreased litter size, delayed ossification, and reduced fetal weight but did not cause major fetal malformations. Intravenous administration of porfimer sodium to pregnant rabbits for 13 days during the period of organogenesis at dose levels 0.65 times the recommended human dose of PHOTOFRIN based on BSA caused maternal toxicity resulting in increased resorptions, decreased litter size, and reduced fetal body weight but did not cause major fetal malformations. Intravenous administration of porfimer sodium to rats for at least 42 days during late pregnancy (post- organogenesis, GD17-PND21) through lactation at dose levels 0.32 times the recommended human dose of PHOTOFRIN based on BSA caused a reversible decrease in growth of offspring. Parturition was unaffected.

8.2 Lactation

(PLLR conversion)

Risk Summary

There are no data on the presence of porfimer sodium in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise patients that breastfeeding is not recommended during treatment with PHOTOFRIN and for 5 months after the last dose.

8.3 Females and Males of Reproductive Potential

(PLLR conversion)

Pregnancy Testing

Verify pregnancy status in females of reproductive potential prior to the initiation of PHOTOFRIN therapy.

Contraception

PHOTOFRIN may cause fetal harm when administered to a pregnant woman.

Females

Advise females of reproductive potential to use effective contraception during treatment with PHOTOFRIN and for 5 months after the final dose.

Males

Advise male patients with female partners of reproductive potential to use condoms during treatment with PHOTOFRIN and for 5 months following the final dose.

8.4 Pediatric Use

(Newly added subsection)

Safety and effectiveness in pediatrics have not been established.

8.5 Geriatric Use

(Additions and/or revisions underlined)

Approximately 70% of the patients treated with PDT using PHOTOFRIN in clinical trials were over 60 years of age. No overall differences in safety or effectiveness were observed between these patients compared to younger patients.