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.

PANRETIN (NDA-020886)

(ALITRETINOIN)

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

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11/17/2025 (SUPPL-9)

Approved Drug Label (PDF)

4 Contraindications

PLR conversion; please refer to label for complete information.

5 Warnings and Precautions

5.1 Embryo-Fetal Toxicity

PLR conversion with additions and/or revisions underlined; please refer to label for complete information.

Based on data from animal studies and its mechanism of action, PANRETIN GEL can cause fetal harm when administered to a pregnant woman. Oral administration of alitretinoin to pregnant animals during the period of organogenesis was teratogenic and embryo-lethal at exposures 5 times the estimated daily human topical dose. Advise women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during treatment with PANRETIN GEL and for 1 week after the last dose [see Use in Specific Populations (8.1, 8.3)].

5.2 Photosensitivity

PLR conversion; please refer to label for complete information.

5.3 Toxicity with DEET-Containing Products

PLR conversion; please refer to label for complete information.

6 Adverse Reactions

PLR conversion with additions and/or revisions underlined; please refer to label for complete information.

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

Photosensitivity [see Warnings and Precautions (5.2)]

6.1 Clinical Trials Experience

PLR conversion with additions and/or revisions underlined; please refer to label for complete information.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of PANRETIN GEL was assessed in two multicenter, prospective, randomized, double-blind, vehicle-controlled trials (Trial 1 and Trial 2) in patients with cutaneous lesions of AIDS-related KS [see Clinical Studies (14.1)]. In a pooled analysis of both trials, the most common adverse reactions in greater than or equal to 5% of patients were rash, pain, paresthesia, pruritis, exfoliative dermatitis, edema, and skin disorder.

In Trial 1, severe local skin adverse reactions (erythema and edema with or without vesiculation) occurred in 10% of patients during the first 12 weeks of treatment (versus 0% in the vehicle control). Adverse reactions led to withdrawal from the study in 7% of patients.

In Trial 2, severe local skin adverse reactions (erythema and edema with or without vesiculation) occurred in 6% of patients during the first 12 weeks of treatment (versus 0% in the vehicle control) and 1 patient withdrew due to severe skin irritation.

Table 1 lists the most common application site adverse reactions that occurred in at least 5% of patients during the double-blind phase who received PANRETIN GEL in either of the two controlled studies.

Table 1 Adverse Reactions at Application Site in Trial 1 and 2 in greater than or equal to 5% of Patients Treated with PANRETIN GEL

. . .

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion:

Risk Summary

Based on findings in animal studies and its mechanism of action, PANRETIN GEL can cause fetal harm when administered to a pregnant woman. Oral administration of alitretinoin to pregnant animals during the period of organogenesis was teratogenic and embryo lethal at exposures at least 5 times the estimated daily human topical dose (see Data). There are no data on the use of PANRETIN GEL in pregnant women. Advise pregnant women of the potential risk to the fetus.

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

Oral administration of alitretinoin to pregnant rabbits during the period of organogenesis resulted in early resorptions, post-implantation loss, and fetal defects (limb, craniofacial, fused sternebrae) at doses greater than or equal to 0.5 mg/kg/day (approximately 5 times the estimated daily human topical dose based on body surface area, assuming complete systemic absorption of alitretinoin, when PANRETIN GEL is administered as a 60 g tube over 1 month in a 60 kg human). Early resorptions and post-implantation loss also occurred in rats administered oral alitretinoin at doses greater than or equal to 5 mg/kg/day (approximately 25 times the estimated daily human topical dose based on body surface area). Limb and craniofacial defects also occurred in mice administered oral alitretinoin on day 11 of gestation at single doses greater than or equal to 50 mg/kg (approximately 127 times the estimated daily human topical dose based on body surface area).

8.2 Lactation

PLLR conversion:

Risk Summary

It is not known whether alitretinoin or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions from PANRETIN GEL in the nursing child, advise patients that breastfeeding is not recommended during treatment with PANRETIN GEL and for 1 week after the last dose.

8.3 Females and Males of Reproductive Potential

PLLR conversion:

Pregnancy Testing

Verify pregnancy status of females of reproductive potential prior to initiating PANRETIN GEL.

Contraception

Females

PANRETIN GEL can cause embryo-fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with PANRETIN GEL and for 1 week after the last dose.

Males

Advise males with female partners of reproductive potential to use effective contraception during treatment with PANRETIN GEL and for 1 week after the last dose.

8.4 Pediatric Use

PLR conversion; please refer to label for complete information.

8.5 Geriatric Use

PLR conversion with additions and/or revisions underlined; please refer to label for complete information.

Clinical studies of PANRETIN GEL did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger adult patients.

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

PATIENT COUNSELING INFORMATION

New section added to comply with PLR:

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Embryo-Fetal Toxicity

Advise females to inform their healthcare provider if they are pregnant or become pregnant. Inform females of the risk to a fetus and potential loss of pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].

Advise females of reproductive potential to use effective contraception during treatment and for 1 week after the last dose of PANRETIN GEL [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].

Advise males with female partners of reproductive potential to use effective contraception during treatment and for 1 week following the last dose of PANRETIN GEL [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3)].

Lactation

Advise patients not to breastfeed during treatment with PANRETIN GEL and for 1 week after the last dose of PANRETIN GEL [see Use in Specific Populations (8.2)].

Photosensitivity

Advise patients that PANRETIN GEL can cause photosensitivity and to avoid sunlight and sunlamps and use measures such as protective clothing in PANRETIN-applied areas [see Warnings and Precautions (5.2)].

Toxicity with DEET-Containing Products

Advise patients to avoid DEET-containing products such as insect repellant while using PANRETIN GEL [see Warnings and Precautions (5.3)].

PATIENT INFORMATION

New section added to comply with PLR; please refer to label for complete information.

Other

Physician Labeling Rule (PLR) conversion