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.

ORACEA (NDA-050805)

(DOXYCYCLINE)

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

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04/02/2025 (SUPPL-20)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.12 Fixed Drug Eruptions

New subsection added:

Fixed drug eruptions have occurred with doxycycline and have been associated with worsening severity upon subsequent administrations, including generalized bullous fixed drug eruption [see Adverse Reactions (6.2)]. If severe skin reactions occur, discontinue ORACEA immediately and initiate appropriate therapy.

6 Adverse Reactions

6.2 Postmarketing Experience

Additions and/or revisions underlined:

…

Skin: fixed drug eruption

Psychiatric: depression, anxiety, suicidal ideation, insomnia, abnormal dreams, hallucination

12/15/2021 (SUPPL-11)

Approved Drug Label (PDF)

5 Warnings and Precautions

5. 1 Inhibition of Bone Growth During Fetal and Pediatric Development

Subsection revised, additions and/or revisions underlined

Doxycycline, like other tetracycline-class drugs, may cause inhibition of bone growth when administered during the second and third trimesters of pregnancy, infancy, and childhood. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature human infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. If doxycycline is used during the second or third trimester of pregnancy, advise the patient of the potential risk to the fetus [see Use in Specific Populations (8.1)].

5.2 Tooth Discoloration During Fetal and Pediatric Development

New subsection added

The use of tetracycline class drugs orally during tooth development (last half of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drug but has been observed following repeated short- term courses. Enamel hypoplasia has also been reported.

Use of tetracycline drugs is not recommended during tooth development [see Use in Specific Populations (8.1)].

5.3 Clostridium difficile Associated Diarrhea (CDAD)

Subsection revised; additions underlined

Clostridium difficile associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including doxycycline, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

…

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion

Risk Summary

Doxycycline may cause reversible inhibition of bone growth and permanent discoloration of deciduous teeth when administered during the second and third trimesters of pregnancy [see Warnings and Precautions (5.1 and 5.2)]. Available data from published studies have not shown a difference in major birth defect risk with doxycycline exposure in the first trimester of pregnancy compared to unexposed pregnancies. Avoid use of ORECEA during the second and third trimester of pregnancy.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2– 4% and 15–20%, respectively.

Data

Human Data

Published studies, including epidemiological and observational studies, with use of doxycycline during the first trimester of pregnancy have not identified drug-related increases in major birth defects.

The use of tetracycline during tooth development (second and third trimester of pregnancy) may cause permanent discoloration of deciduous teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drug but has been observed following repeated short- term courses.

Animal Data

Results from animal studies indicate that doxycycline crosses the placenta and is found in fetal tissues.

8.2 Lactation

PLLR conversion

Risk Summary

Based on available published data, doxycycline is likely to be present in human breast milk but the specific concentration in breastmilk is not clear. There is no information on the effects of doxycycline on the breastfed infant or the effects on milk production. Because there are other antibacterial drug options available to treat rosacea in lactating women and because of the potential for serious adverse reactions, including tooth discoloration and inhibition of bone growth, advise patients that breastfeeding is not recommended during treatment with ORACEA and for 5 days after the last dose.

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

PATIENT COUNSELING INFORMATION

Additions underlined

…

Advise pregnant women that doxycycline, like other tetracycline-class drugs, may cause permanent discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimesters of pregnancy [see Warnings and Precautions (5.1 and 5.2) and Use in Specific Populations (8.1)].
Advise women not to breastfeed during treatment with ORACEA and for 5 days after the last dose [see Use in Specific Populations (8.2)].
Advise patients that use of tetracycline class drugs orally during tooth development (infancy and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown).
Advise patients that use of doxycycline, like other tetracycline-class drugs, may cause inhibition of bone growth when administered during infancy and childhood.
…