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.

TOBRADEX ST (NDA-050818)

(DEXAMETHASONE; TOBRAMYCIN)

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

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03/17/2026 (SUPPL-10)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.10 Risk of Contamination

Additions and/or revisions underlined:

Do not touch the dropper tip of the bottle to the eye, eyelids or to any surface, as this may contaminate the contents.

5.5 Corneal and Scleral Melting

Newly added subsection:

Various ocular diseases and long-term use of topical corticosteroids have been known to cause corneal and scleral thinning. Use of topical corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation of the globe.

5.6 Bacterial Infections

Additions and/or revisions underlined:

Prolonged use of corticosteroids may suppress the host immune response and thus increase the hazard of secondary ocular infections. Acute purulent or parasitic infections of the eye may be masked or activity enhanced by the presence of corticosteroid medication. If signs and symptoms fail to improve after 2 days, the patient should be reevaluated.

5.7 Viral Infections

Additions and/or revisions underlined:

Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution; frequent slit lamp microscopy is recommended.

5.8 Fungal Infections

Additions and/or revisions underlined:

Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local corticosteroid application. Fungus invasion must be considered in any persistent corneal ulceration where a corticosteroid has been used or is in use. Fungal cultures should be taken when appropriate.

6 Adverse Reactions

Addition of the following bulleted line listing:

The following adverse reactions are described elsewhere in the labeling:

Viral, Mycobacterial, and Fungal Infections [see Contraindications (4.2)
Hypersensitivity [see Contraindications (4.3)]
Intraocular Pressure (IOP) Increase [see Warnings and Precautions (5.1)]
Aminoglycoside Sensitivity [see Warnings and Precautions (5.2)]
Cataracts [see Warnings and Precautions (5.3)]
Delayed Healing [see Warnings and Precautions (5.4)]
Corneal and Scleral Melting [see Warnings and Precautions (5.5)]
Bacterial Infections [see Warnings and Precautions (5.6)]
Viral Infections [see Warnings and Precautions (5.7)]
Fungal Infections [see Warnings and Precautions (5.8)]

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion:

Risk Summary

There are no adequate and well-controlled studies of TOBRADEX ST in pregnant women to inform a drug-associated risk. Developmental toxicity and teratogenicity were seen in animal studies with dexamethasone, both after systemic and ocular administration at therapeutically relevant dose levels (see Data).

Reproduction studies in rats and rabbits have not shown evidence to harm the fetus following subcutaneous administration of tobramycin at dose levels greater than 48-fold the maximum recommended ocular human dose (MROHD) of 0.288 mg/kg/day [based on body surface area (BSA)].

TOBRADEX ST should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies.

Data

Animal Data

Dexamethasone

In embryo-fetal development studies with dexamethasone in mice, rats and rabbits, a number of malformations, fetal growth retardation, and mortality were seen at maternal toxic doses following systemic administration (oral, subcutaneous, and intramuscular) during the period of organogenesis. The overall no-observed-effect level (NOEL) for developmental toxicity was derived from an oral rat study and was based on embryotoxicity (0.01 mg/kg/day). Dexamethasone has also been shown to be teratogenic in mice and rabbits following topical ophthalmic application. Based on the ratio of the rat, NOEL to the MROHD is less than 1.

Tobramycin

In embryo-fetal development studies in rats and rabbits, pregnant animals received subcutaneously tobramycin at doses up to 100 and 40 mg/kg/day, respectively, during organogenesis. There was no embryo-fetal toxicity in either species up to the maximum dose tested, corresponding to 60 and 48 times respectively, the MROHD, based on BSA.

In a peri- and postnatal development study in rats, subcutaneous administration of up to 100 mg/kg/day tobramycin during early gestation through lactation period did not adversely affect the offspring. Based on BSA, the ratio of the highest dose tested to the MROHD is 60.

8.2 Lactation

PLLR conversion:

Risk Summary

There are no data on the effects of topical ocular administration of tobramycin/dexamethasone on the breastfed infant or effects on milk production. It is not known if tobramycin or dexamethasone are present in human milk following topical ocular administration. It is not likely that the amount of tobramycin and dexamethasone would be detectable in human milk or be capable of producing clinical effects in the infant following topical use of the product. Limited published data in lactating women indicate that tobramycin was detected in the human milk following intramuscular administration. However, tobramycin was not detected in the human milk, following intravenous administration, with a detection limit of > 0.18mg/L.

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TOBRADEX ST and any potential adverse effects on the breast-fed child from TOBRADEX ST.

8.4 Pediatric Use

Additions and/or revisions underlined:

The safety and effectiveness of TOBRADEX ST have been established in pediatric patients aged 2 years and older. Use of TOBRADEX ST is supported by evidence from adequate and well-controlled studies in adults with additional safety data in pediatric patients aged 2 years and older.

…

08/16/2022 (SUPPL-7)

Approved Drug Label (PDF)

5 Warnings and Precautions

Newly added subsections:

5.8 Vision Blurred

Vision may be temporarily blurred following dosing with TOBRADEX ST. Care should be exercised in operating machinery or driving a motor vehicle.

5.9 Risk of Contamination

Do not touch the dropper tip of the bottle to any surface, as this may contaminate the contents.

5.10 Contact Lens Use

TOBRADEX ST contains benzalkonium chloride, an antimicrobial preservative, that may be absorbed by soft contact lenses. Contact lenses should not be worn during the use of TOBRADEX ST.

6 Adverse Reactions

6.1 Clinical Trials Experience

Newly added 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.

Newly added to end of subsection:

The following additional adverse reactions have been reported with the individual components below:

Aminoglycosides: Neurotoxicity, ototoxicity, and nephrotoxicity have occurred in patients receiving systemic aminoglycoside therapy. Aminoglycosides may aggravate muscle weakness in patients with known or suspected neuromuscular disorders, such as myasthenia gravis or Parkinson’s disease, because of their potential effect on neuromuscular function.

Dexamethasone: Cushing’s syndrome and adrenal suppression may occur after use of dexamethasone in excess of the listed dosing instructions in predisposed patients, including children and patients treated with CYP3A4 inhibitors.

Newly added subsection:

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of TOBRADEX ST. 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.

Additional adverse reactions identified from postapproval use include, anaphylactic reaction, and erythema multiforme.

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:
There are no adequate and well-controlled studies in pregnant women. However, prolonged or repeated corticoid use during pregnancy has been associated with an increased risk of intra-uterine growth retardation. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be observed carefully for signs of hypoadrenalism. TOBRADEX ST Ophthalmic Suspension should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus [see Nonclinical Toxicology (13.1)].

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Storage and Handling

Instruct the patient to store the bottle upright and away from light. Shake well before using [see Dosage and Administration (2.1) and How Supplied/Storage and Handling (16)].

Avoid Contamination

Instruct the patient not to touch dropper tip to any surface, as this may contaminate the contents [see Warnings and Precautions (5.9)].

Contact Lens Wear

Advise the patient that contact lenses should not be worn during the use of this product [see Warnings and Precautions (5.10)].

Newly added information:

Ability to Drive and Use Machines

Advise the patient that vision may be temporarily blurred following dosing with TOBRADEX ST. Care should be exercised in operating machinery or driving a motor vehicle [see Warnings and Precautions (5.8)].

08/16/2022 (SUPPL-8)

Approved Drug Label (PDF)

5 Warnings and Precautions

Newly added subsections:

5.8 Vision Blurred

Vision may be temporarily blurred following dosing with TOBRADEX ST. Care should be exercised in operating machinery or driving a motor vehicle.

5.9 Risk of Contamination

Do not touch the dropper tip of the bottle to any surface, as this may contaminate the contents.

5.10 Contact Lens Use

TOBRADEX ST contains benzalkonium chloride, an antimicrobial preservative, that may be absorbed by soft contact lenses. Contact lenses should not be worn during the use of TOBRADEX ST.

6 Adverse Reactions

6.1 Clinical Trials Experience

Newly added information:

Newly added to end of subsection:

The following additional adverse reactions have been reported with the individual components below:

Newly added subsection:

6.2 Postmarketing Experience

Additional adverse reactions identified from postapproval use include, anaphylactic reaction, and erythema multiforme.

8 Use in Specific Populations

8.1 Pregnancy

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Storage and Handling

Instruct the patient to store the bottle upright and away from light. Shake well before using [see Dosage and Administration (2.1) and How Supplied/Storage and Handling (16)].

Avoid Contamination

Instruct the patient not to touch dropper tip to any surface, as this may contaminate the contents [see Warnings and Precautions (5.9)].

Contact Lens Wear

Advise the patient that contact lenses should not be worn during the use of this product [see Warnings and Precautions (5.10)].

Newly added information:

Ability to Drive and Use Machines

08/16/2022 (SUPPL-9)

Approved Drug Label (PDF)

5 Warnings and Precautions

Newly added subsections:

5.8 Vision Blurred

Vision may be temporarily blurred following dosing with TOBRADEX ST. Care should be exercised in operating machinery or driving a motor vehicle.

5.9 Risk of Contamination

Do not touch the dropper tip of the bottle to any surface, as this may contaminate the contents.

5.10 Contact Lens Use

TOBRADEX ST contains benzalkonium chloride, an antimicrobial preservative, that may be absorbed by soft contact lenses. Contact lenses should not be worn during the use of TOBRADEX ST.

6 Adverse Reactions

6.1 Clinical Trials Experience

Newly added information:

Newly added to end of subsection:

The following additional adverse reactions have been reported with the individual components below:

Newly added subsection:

6.2 Postmarketing Experience

Additional adverse reactions identified from postapproval use include, anaphylactic reaction, and erythema multiforme.

8 Use in Specific Populations

8.1 Pregnancy

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Storage and Handling

Instruct the patient to store the bottle upright and away from light. Shake well before using [see Dosage and Administration (2.1) and How Supplied/Storage and Handling (16)].

Avoid Contamination

Instruct the patient not to touch dropper tip to any surface, as this may contaminate the contents [see Warnings and Precautions (5.9)].

Contact Lens Wear

Advise the patient that contact lenses should not be worn during the use of this product [see Warnings and Precautions (5.10)].

Newly added information:

Ability to Drive and Use Machines