Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

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.

SEPTRA (NDA-017376)

(SULFAMETHOXAZOLE; TRIMETHOPRIM)

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

Download Data

Expand all

02/21/2025 (SUPPL-68)

Approved Drug Label (PDF)

5 Warnings and Precautions

WARNINGS

Additions and/or revisions underlined:

…

Hemophagocytic Lymphohistiocytosis

Cases of hemophagocytic lymphohistiocytosis (HLH) have been reported in patients treated with trimethoprim-sulfamethoxazole. HLH is a life-threatening syndrome of pathologic immune activation characterized by clinical signs and symptoms of extreme systemic inflammation. Signs and symptoms of HLH may include fever, hepatosplenomegaly, rash, lymphadenopathy, neurologic symptoms, cytopenias, high serum ferritin, hypertriglyceridemia, and liver enzyme and coagulation abnormalities. If HLH is suspected, discontinue SEPTRA immediately and institute appropriate management.

…

6 Adverse Reactions

Additions and/or revisions underlined:

…

Allergic/Immune

…

Henoch-Schönlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria, and rash. In addition, periarteritis nodosa, hemophagocytic lymphohistiocytosis (HLH), and systemic lupus erythematosus have been reported (see WARNINGS).

…

06/24/2024 (SUPPL-66)

Approved Drug Label (PDF)

5 Warnings and Precautions

WARNINGS

Additions and/or revisions underlined:

…

Hypersensitivity Reactions of the Respiratory Tract

Cough, shortness of breath, and pulmonary infiltrates potentially representing hypersensitivity reactions of the respiratory tract have been reported in association with

trimethoprim-sulfamethoxazole treatment.

Respiratory Failure

Other severe pulmonary adverse reactions occurring within days to week of SEPTRA initiation and resulting in prolonged respiratory failure requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO), lung transplantation or death have also been reported in patients and otherwise healthy individuals treated with trimethoprim-sulfamethoxazole products.

Circulatory Shock

Circulatory shock with fever, severe hypotension, and confusion requiring intravenous fluid resuscitation and vasopressors has occurred within minutes to hours of re-challenge with trimethoprim-sulfamethoxazole in patients with history of recent (days to weeks) exposure to sulfamethoxazole-trimethoprim.

Management of Hypersensitivity and Other Serious Reactions

SEPTRA should be discontinued at the first appearance of skin rash or any sign of a serious adverse reaction. In rare instances, a skin rash may be followed by a more severe reaction, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, AGEP, or AFND, hepatic necrosis, and serious blood disorders (see PRECAUTIONS and ADVERSE REACTIONS).

Clinical signs, such as rash, pharyngitis, fever, cough, arthralgia, chest pain, dyspnea, pallor, purpura or jaundice may be early indications of serious reactions.

…

PRECAUTIONS

Additions and/or revisions underlined:

…

Information for Patients

Hypersensitivity and Other Serious Reactions

Advise patients to stop taking SEPTRA immediately if they experience any clinical signs such as rash, pharyngitis, fever, arthralgia, cough, chest pain, dyspnea, pallor, purpura or jaundice and to contact their healthcare provider as soon as possible (see WARNINGS and ADVERSE REACTIONS).

Antibacterial Resistance

Patients should be counseled that antibacterial drugs including SEPTRA should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When SEPTRA is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable with SEPTRA or other antibacterial drugs in the future.

Crystalluria and Stone Formation

Advise patients to maintain an adequate fluid intake in order to prevent crystalluria and stone formation.

Diarrhea

Advise patients that diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

…

11/18/2020 (SUPPL-62)

Approved Drug Label (PDF)

5 Warnings and Precautions

PRECAUTIONS

Additions and/or revisions underlined:

Use in the Treatment of and Prophylaxis for Pneumocystis jirovecii Pneumonia in Patients with Acquired Immunodeficiency Syndrome (AIDS)

… However, if a patient develops skin rash, fever, leukopenia, or any other sign of adverse reaction, therapy or re-challenge with SEPTRA should be re-evaluated (see WARNINGS) …

WARNINGS

Additions and/or revisions underlined:

Hypersensitivity and Other Serious or Fatal Reactions

Fatalities and serious adverse reactions, including severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) and acute febrile neutrophilic dermatosis (AFND), fulminant hepatic necrosis, agranulocytosis, aplastic anemia, other blood dyscrasias, acute and delayed lung injury, anaphylaxis, and circulatory shock have occurred with the administration of trimethoprim-sulfamethoxazole including SEPTRA (see PRECAUTIONS and ADVERSE REACTIONS).

Cough, shortness of breath, and pulmonary infiltrates potentially representing hypersensitivity reactions of the respiratory tract have been reported in association with trimethoprim-sulfamethoxazole treatment.

Clinical signs, such as rash, pharyngitis, fever, cough, arthralgia, chest pain, dyspnea, pallor, purpura or jaundice may be early indications of serious reactions.

Risk of Failure and Excess Mortality with Leucovorin Use for Pneumocystis jirovecii Pneumonia Treatment

Treatment failure and excess mortality were observed …

6 Adverse Reactions

Additions and/or revisions underlined:

The following adverse reactions associated with the use of SEPTRA or trimethoprim-sulfamethoxazole were identified in clinical studies, postmarketing or published reports. Because some of these reactions were 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.

The most common adverse effects are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash and urticaria). Fatalities associated with the administration of sulfonamides have occurred due to severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS), fulminant hepatic necrosis, agranulocytosis, aplastic anemia, other blood dyscrasias, acute and delayed lung injury, anaphylaxis, and circulatory shock (see WARNINGS).

Hematologic

Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura.

Allergic

Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, acute generalized exanthematous pustulosis (AGEP), acute febrile neutrophilic dermatosis (AFND), anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills Henoch-Schönlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria, and rash. In addition, periarteritis nodosa and systemic lupus erythematosus have been reported.

Respiratory System

Cough, shortness of breath, pulmonary infiltrates, acute eosinophilic pneumonia, acute and delayed lung injury, interstitial lung disease, and acute respiratory failure (see WARNINGS).

Cardiovascular System

QT prolongation resulting in ventricular tachycardia and torsade de pointes, circulatory shock.

08/10/2020 (SUPPL-63)

Approved Drug Label (PDF)

4 Contraindications

(Additions underlined)

…

concomitant administration with dofetilide (see PRECAUTIONS)

5 Warnings and Precautions

(Additions underlined)

WARNINGS

…

Hypersensitivity and Other Serious or Fatal Reactions

Fatalities associated with the administration of sulfonamides, although rare, have occurred due to severe reactions, including severe cutaneous adverse reactions (SCARs), including Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) and acute febrile neutrophilic dermatosis (AFND), fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias (see PRECAUTIONS and ADVERSE REACTIONS).

… In rare instances, a skin rash may be followed by a more severe reaction, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, AGEP, or AFND, hepatic necrosis, and serious blood disorders (see PRECAUTIONS and ADVERSE REACTIONS). Clinical signs, such as rash, sore throat, fever, arthralgia, pallor, purpura or jaundice may be early indications of serious reactions.

…

Risk of Failure and Excess Mortality with Adjunctive Treatment with Leucovorin for

Pneumocystis jirovecii Pneumonia

Treatment failure and excess mortality were observed when trimethoprim-sulfamethoxazole was used concomitantly with leucovorin for the treatment of HIV positive patients with Pneumocystis jirovecii pneumonia in a randomized placebo controlled trial.4 Co-administration oftrimethoprim-sulfamethoxazole and leucovorin during treatment of Pneumocystis jirovecii

pneumonia should be avoided.

…

PRECAUTIONS

…

Hyperkalemia

High dosage of trimethoprim, as used in patients with P. jirovecii pneumonia, induces a progressive but reversible increase of serum potassium concentrations in a substantial number of patients. Even treatment with recommended doses may cause hyperkalemia when trimethoprim is administered to patients with underlying disorders of potassium metabolism, with renal insufficiency, or if drugs known to induce hyperkalemia are given concomitantly. Close monitoring of serum potassium is warranted in these patients.

Hyponatremia

Severe and symptomatic hyponatremia can occur in patients receiving sulfamethoxazole/trimethoprim, particularly for the treatment of P. jirovecii pneumonia. Evaluation for hyponatremia and appropriate correction is necessary in symptomatic patients to prevent life-threatening complications.

Crystalluria

During treatment, adequate fluid intake and urinary output should be ensured to prevent crystalluria. Patients who are “slow acetylators” may be more prone to idiosyncratic reactions to sulfonamides.

6 Adverse Reactions

(Additions underlined)

The most common adverse effects are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash and urticaria). FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE, HAVE OCCURRED DUE TO SEVERE CUTANEOUS ADVERSE REACTIONS (SCARs), INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, AND DRESS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC ANEMIA, OTHER BLOOD DYSCRASIAS, AND HYPERSENSITIVITY OF THE RESPIRATORY TRACT (SEE WARNINGS).

…

6.2 Postmarketing Experience

(additions underlined)

…

Drug reaction with eosinophilia and systemic symptoms (DRESS)
Acute generalized exanthematous pustulosis (AGEP)
Acute febrile neutrophilic dermatosis (AFND)

08/10/2020 (SUPPL-64)

Approved Drug Label (PDF)

4 Contraindications

(Additions underlined)

…

concomitant administration with dofetilide (see PRECAUTIONS)

5 Warnings and Precautions

(Additions underlined)

WARNINGS

…

Hypersensitivity and Other Serious or Fatal Reactions

…

Risk of Failure and Excess Mortality with Adjunctive Treatment with Leucovorin for

Pneumocystis jirovecii Pneumonia

pneumonia should be avoided.

…

PRECAUTIONS

…

Hyperkalemia

Hyponatremia

Crystalluria

6 Adverse Reactions

(Additions underlined)

…

6.2 Postmarketing Experience

(additions underlined)

…

Drug reaction with eosinophilia and systemic symptoms (DRESS)
Acute generalized exanthematous pustulosis (AGEP)
Acute febrile neutrophilic dermatosis (AFND)