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 sulfamethoxazole-trimethoprim. 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 BACTRIM immediately and
institute appropriate management.
…
6
Adverse Reactions
Additions and/or
revisions underlined:
…
Allergic/Immune
Reactions: Stevens-Johnson syndrome, toxic epidermal
necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative
dermatitis, angioedema, drug fever, chills, Henoch-Schoenlein purpura, serum
sickness-like syndrome, generalized allergic reactions, generalized skin
eruptions, photosensitivity, conjunctival and scleral injection, pruritus,
urticaria, rash, periarteritis nodosa, hemophagocytic lymphohistiocytosis
(HLH), systemic lupus erythematosus, drug reaction with eosinophilia and
systemic symptoms (DRESS), acute generalized erythematous pustulosis (AGEP),
and acute febrile neutrophilic dermatosis (AFND) (see WARNINGS).
…
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 sulfamethoxazole and trimethoprim treatment.
Respiratory Failure
Other
severe pulmonary adverse reactions occurring within days to week of BACTRIM
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 sulfamethoxazole and trimethoprim
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 sulfamethoxazole and trimethoprim products,
including BACTRIM, in patients with history of recent (days to weeks) exposure to
sulfamethoxazole and trimethoprim.
Management of Hypersensitivity and Other Serious
Reactions
BACTRIM
should be discontinued at the first appearance of skin rash or any sign of a
serious adverse reaction. A skin rash may be followed by a more severe reaction,
such as Stevens-Johnson syndrome, toxic epidermal
necrolysis, DRESS, AFND, AGEP, hepatic necrosis, or serious blood disorders
(see PRECAUTIONS and ADVERSE REACTIONS).
Clinical signs, such as rash, pharyngitis, fever, arthralgia, cough, 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 BACTRIM 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 BACTRIM (sulfamethoxazole and trimethoprim) tablets should only be
used to treat bacterial infections. They do not treat viral infections (e.g.,
the common cold). When BACTRIM (sulfamethoxazole and trimethoprim) tablets are
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 by BACTRIM (sulfamethoxazole and trimethoprim) tablets 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.
…
Approved Drug Label (PDF)
4
Contraindications
(Additions and/or revisions underlined)
BACTRIM is contraindicated in the following situations:
known hypersensitivity to trimethoprim or sulfonamides
history of drug-induced immune thrombocytopenia with use of trimethoprim and/or
sulfonamides
documented megaloblastic anemia due to folate deficiency
pediatric
patients less than 2 months of age
marked
hepatic damage
severe renal insufficiency when renal function status cannot be monitored
concomitant administration with dofetilide (see PRECAUTIONS).
5
Warnings and Precautions
Electrolyte Abnormalities
(Additions and/or revisions underlined)
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 BACTRIM, 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, ensure adequate
fluid intake and urinary
output to prevent crystalluria. Patients who are “slow acetylators” may be more prone to idiosyncratic reactions to sulfonamides.
Folate Deficiency
(Additions and/or revisions underlined)
Avoid use of
BACTRIM in patients with impaired renal or hepatic
function, in those with possible folate deficiency (e.g., the elderly,
chronic alcoholics, patients receiving anticonvulsant therapy,
patients with malabsorption syndrome, and patients in malnutrition states) and in those with severe allergies
or bronchial asthma.
Hematological changes
indicative of folic acid deficiency may occur
in elderly patients
or in patients with preexisting folic acid deficiency or kidney failure.
These effects are reversible by folinic
acid therapy (see PRECAUTIONS, Geriatric
Use).
Hypersensitivity and Other Serious or Fatal Reactions
(Additions and/or revisions underlined)
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 febrile
neutrophilic dermatosis (AFND), acute generalized erythematous pustulosis (AGEP); fulminant hepatic
necrosis; agranulocytosis, aplastic anemia and other blood dyscrasias; acute and delayed
lung injury; anaphylaxis and circulatory shock have occurred with the administration of sulfamethoxazole and trimethoprim products, including
BACTRIM (see ADVERSE REACTIONS).
Cough, shortness of breath and pulmonary infiltrates potentially representing hypersensitivity reactions of the respiratory tract have been reported
in association with sulfamethoxazole and trimethoprim treatment.
Other severe
pulmonary adverse
reactions occurring within days to week of BACTRIM
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 sulfamethoxazole and trimethoprim products.
Circulatory shock with fever, severe hypotension, and confusion
requiring intravenous fluid resuscitation and vasopressors has occurred
within minutes to hours of re-challenge with sulfamethoxazole and trimethoprim products, including
BACTRIM, in patients
with history of recent (days to weeks) exposure to sulfamethoxazole and trimethoprim.
BACTRIM should be discontinued at the first appearance of skin rash or any sign of a serious
adverse reaction.
A skin rash may be followed by a more severe
reaction, such as Stevens-Johnson syndrome, toxic epidermal
necrolysis, DRESS,
AFND, AGEP, hepatic
necrosis, or serious blood disorders
(see PRECAUTIONS and ADVERSE
REACTIONS).
Clinical signs, such as rash, pharyngitis, fever, arthralgia, cough, chest pain, dyspnea, pallor, purpura
or jaundice may be early indications of serious reactions.
Impaired Phenylalanine Metabolism
(Section
title updated)
(Additions and/or revisions underlined)
The trimethoprim component of BACTRIM has been noted to impair phenylalanine metabolism, but this is of no significance in phenylketonuric patients on appropriate dietary restriction.
Porphyria and Hypothyroidism
(Additions and/or revisions underlined)
Like other
drugs containing sulfonamides, BACTRIM can precipitate porphyria crisis
and hypothyroidism. Avoid use of BACTRIM in patients
with porphyria or thyroid dysfunction.
Potential Risk in the Treatment of Pneumocystis jirovecii Pneumonia in Patients with Acquired Immunodeficiency Syndrome (AIDS)
(Additions and/or revisions underlined)
AIDS patients
may not tolerate
or respond to BACTRIM in the same manner
as non-AIDS patients.
The incidence of adverse reactions, particularly rash, fever, leukopenia and elevated
aminotransferase (transaminase) values, with BACTRIM therapy
in AIDS patients who are being treated
for P. jirovecii
pneumonia has been reported to be increased compared with the incidence normally
associated with the use of BACTRIM
in non-AIDS patients.
If a patient develops skin rash, fever, leukopenia or any sign of adverse reaction, reevaluate benefit-risk of continuing therapy or re-challenge with BACTRIM (see WARNINGS).
Avoid coadministration of BACTRIM
and leucovorin during
treatment of
P. jirovecii pneumonia (see WARNINGS).
Thrombocytopenia
(Additions and/or revisions underlined)
BACTRIM-induced thrombocytopenia may be an immune-mediated disorder. Severe cases of thrombocytopenia that are fatal or life threatening have been reported. Thrombocytopenia usually resolves within a week upon discontinuation of BACTRIM.
Risk Associated with Concurrent Use of Leucovorin for Pneumocystis jirovecii Pneumonia Treatment failure and excess mortality
were observed when BACTRIM was used concomitantly with leucovorin for the treatment
of HIV positive
patients with P. jirovecii
pneumonia in a randomized placebo-controlled trial.4 Avoid coadministration of
BACTRIM and leucovorin during treatment
of P. jirovecii pneumonia.
6
Adverse Reactions
(Additions and/or revisions underlined)
The following
adverse reactions
associated with the use of BACTRIM
or sulfamethoxazole and trimethoprim were identified in clinical
trials, 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 reactions are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions
(such as rash and urticaria). 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 febrile neutrophilic dermatosis (AFND), acute generalized erythematous pustulosis (AGEP); fulminant hepatic necrosis; agranulocytosis, aplastic anemia and other blood dyscrasias; acute and delayed lung injury; anaphylaxis and circulatory shock have occurred with the administration of sulfamethoxazole and trimethoprim products, including BACTRIM (see WARNINGS).
Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia, thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura.
Allergic Reactions: Stevens-Johnson syndrome, toxic epidermal
necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever,
chills, Henoch- Schoenlein purpura,
serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral
injection, pruritus, urticaria, rash, periarteritis nodosa, systemic lupus erythematosus, drug reaction
with eosinophilia and systemic
symptoms (DRESS), acute
generalized erythematous pustulosis (AGEP), and acute febrile
neutrophilic dermatosis (AFND) (see WARNINGS).
Genitourinary: Renal failure, interstitial nephritis, BUN and serum creatinine elevation, renal insufficiency, oliguria and anuria,
crystalluria and nephrotoxicity in association with cyclosporine.
Metabolic and Nutritional: Hyperkalemia, hyponatremia (see PRECAUTIONS: Electrolyte Abnormalities), metabolic
acidosis.
Respiratory: Cough, shortness of breath
and pulmonary infiltrates, acute eosinophilic pneumonia, acute
and delayed lung injury, interstitial lung disease,
acute respiratory failure (see WARNINGS).
Cardiovascular System: QT prolongation resulting
in ventricular tachycardia and torsades de pointes, circulatory shock (see WARNINGS).
7
Drug Interactions
(Additions and/or revisions underlined)
Potential for BACTRIM to Affect Other Drugs
Trimethoprim is an inhibitor
of CYP2C8 as well as OCT2 transporter. Sulfamethoxazole is an inhibitor
of CYP2C9. Avoid coadministration of BACTRIM with drugs that are substrates of CYP2C8 and 2C9 or OCT2.
(Newly added table: Drug Interactions with BACTRIM)
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