Approved Drug Label (PDF)
4
Contraindications
Additions and/or revisions underlined:
…
Rifampin is contraindicated in patients who are also
receiving atazanavir, darunavir, fosamprenavir, saquinavir, tipranavir,
cabotegravir, fostemsavir and lenacapavir (see prescribing information for
SUNLENCA) due to the potential of rifampin to substantially decrease plasma
concentrations of these antiviral drugs, which may result in decreased antiviral
efficacy and/or development of viral resistance. (See PRECAUTIONS, Drug
Interactions.)
…
5
Warnings and Precautions
PRECAUTIONS
…
Effect
of Rifampin on Other Drugs
…
Table
1 summarizes the effect of rifampin on other drugs or drug classes. Adjust
dosages of concomitant drugs based on approved drug labeling and if applicable,
therapeutic drug monitoring, unless otherwise specified.
Table
1: Drug Interactions with Rifampin that Affect Concomitant Drug Concentrations*
Additions
and/or revisions, please refer to label for complete information.
…
Approved Drug Label (PDF)
5
Warnings and Precautions
PRECAUTIONS
Additions and/or
revisions underlined:
Carcinogenesis,
Mutagenesis, Impairment of Fertility
…
Data
from published literature report that rifampin shows mutagenic potential in the
Ames test and is considered to be aneugenic as well as clastogenic in vivo in mice after oral
administration. Increased
frequency of chromosomal aberrations was observed in vitro in lymphocytes obtained from patients treated with
combinations of rifampin, isoniazid, and pyrazinamide and combinations of
streptomycin, rifampin, isoniazid, and pyrazinamide. The clinical relevance
of the nonclinical and in vitro findings
is unclear as there is insufficient evidence of carcinogenicity, mutagenicity
or impairment of fertility in humans after decades of use of rifampin.
Pregnancy–Teratogenic
Effects
There
are no adequate and well-controlled studies of RIFADIN in pregnant women.
Rifampin has been reported to cross the placental barrier and appear in cord
blood. While available studies cannot definitively establish the absence of
risk, published data over decades of use have not established an association
with RIFADIN during pregnancy and major birth defects or miscarriage.
…![]()
The clinical
relevance of the nonclinical data is uncertain.
Despite
the animal findings, it would appear that the possibility of fetal harm is
remote, if the drug is used during pregnancy. Nevertheless, because the studies
in humans cannot rule out the possibility of harm, RIFADIN should
be used during pregnancy only if the potential benefit outweighs the
potential risk to the fetus.
Approved Drug Label (PDF)
5
Warnings and Precautions
WARNINGS
Additions and/or
revisions underlined:
…
Cases of thrombotic microangiopathy (TMA),
including thrombotic thrombocytopenic purpura and hemolytic uremia syndrome,
some fatal, have been reported with rifampin. Discontinue RIFADIN if clinical
symptoms and laboratory findings consistent with TMA occur. The findings of
unexplained thrombocytopenia and anemia should prompt further evaluation and
consideration of the diagnosis of TMA.
6
Adverse Reactions
Additions and/or
revisions underlined:
The following adverse
reactions associated with the use of RIFADIN were identified in clinical
studies or postmarketing 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.
…
Hematologic
Cases of thrombotic
microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic
uremic syndrome, have been reported (see WARNINGS).
Approved Drug Label (PDF)
5
Warnings and Precautions
WARNINGS
Additions and/or revisions
underlined:
Pulmonary toxicity manifested as interstitial
lung disease (including, but not limited to, pneumonitis, hypersensitivity pneumonitis, eosinophilic
pneumonia, pulmonary infiltrates, and organizing pneumonia) has been reported
with rifampin treatment. Pulmonary toxicity could be fatal. If symptoms or signs of severe pulmonary
toxicity (including respiratory failure, pulmonary fibrosis, and acute respiratory distress syndrome) develop,
discontinue RIFADIN immediately
and initiate appropriate treatment.
PRECAUTIONS
Information for Patients
Additions and/or revisions
underlined:
Patients should be instructed to take rifampin either 1 hour
before or 2 hours after a meal with a full glass of water.
Patients should be instructed
to notify their physician immediately if they experience any of the following:
rash with fever or blisters, with or without peeling skin, itching, or swollen
lymph nodes, loss of appetite, malaise, nausea,
vomiting, abdominal pain, darkened urine, yellowish discoloration
of the skin and eyes, light-colored
bowel movements, fever, headache, fatigue, myalgias, cough, shortness of breath,
chest pain, wheezing, and
pain or swelling of the joints.
6
Adverse Reactions
Additions and/or revisions
underlined:
Respiratory, Thoracic and
Mediastinal Disorders
Pulmonary toxicity (including, but not limited to, interstitial lung disease,
pneumonitis, hypersensitivity pneumonitis, eosinophilic pneumonia, pulmonary
infiltrates, organizing pneumonia, respiratory failure, pulmonary fibrosis, and acute respiratory
distress syndrome) has been
observed (see WARNINGS).
7
Drug Interactions
Refer to Table 1: Drug
Interactions
with Rifampin
that
Affect
Concomitant
Drug for newly added information
Approved Drug Label (PDF)
5
Warnings and Precautions
(Newly
added information)
Postmarketing cases
of paradoxical drug reaction (recurrence
or appearance of
new symptoms, physical and
radiological signs in a patient who
had previously shown improvement
with appropriate antimycobacterial
treatment, in the absence of disease relapse, poor treatment compliance, drug resistance, side effects of treatment,
or secondary infection/diagnosis) have been reported
with RIFADIN (see ADVERSE
REACTIONS). Paradoxical drug
reactions are often transient
and should not be misinterpreted as failure to respond to
treatment. If worsening of symptoms
or signs occurs during antimycobacterial treatment, consider
paradoxical drug reaction
in the differential diagnosis, monitor, or treat accordingly.
6
Adverse Reactions
Miscellaneous
(Newly
added information)
Paradoxical drug reaction has
been reported with RIFADIN
(see WARNINGS).
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Information for Patients
(Newly
added information)
Patients should be advised
to seek medical advice immediately if their symptoms of mycobacterial disease, including, but not limited
to, cough, fever, tiredness, shortness of breath, malaise, headache,
pain, night sweats, swollen lymph
nodes, loss of appetite, weight loss, weakness, skin ulcers or lesions, worsen
(see ADVERSE REACTIONS).
Approved Drug Label (PDF)
5
Warnings and Precautions
(Additions and/or
revisions underlined)
Hepatotoxicity
of hepatocellular, cholestatic,
and mixed
patterns has been reported
in patients treated with rifampin. Severity ranged from asymptomatic
elevations in liver enzymes,
isolated jaundice/hyperbilirubinemia,
symptomatic self-limited hepatitis to
fulminant liver failure and death. Severe
hepatic dysfunction including
fatalities were reported in patients with
liver disease and in patients taking
rifampin with other hepatotoxic
agents.
Monitor for symptoms and clinical/laboratory signs
of liver injury, especially if
treatment is prolonged or given with other hepatotoxic
drugs. Patients with impaired
liver function should be given rifampin
only in cases of necessity
and then
under strict medical supervision.
In these patients, careful monitoring
of liver function should be done prior
to therapy and then every 2 to 4 weeks during therapy. If signs of hepatic damage occur or worsen, discontinue rifampin.
6
Adverse Reactions
Hepatic
(Additions and/or
revisions underlined)
Hepatotoxicity
including
transient abnormalities in liver function tests (e.g., elevations in serum
bilirubin,
alkaline phosphatase, serum transaminases, gamma-glutamyl transferase),
hepatitis, a
shock-like
syndrome with hepatic involvement and abnormal liver function tests, and
cholestasis
have been reported (see
WARNINGS).
7
Drug Interactions
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Information for Patients
(Additions and/or
revisions underlined)
Patients should
be instructed to notify their
physician immediately if they experience any of the following:
rash with fever or blisters, with or without peeling
skin, itching, or swollen lymph nodes, loss of appetite, malaise,
nausea, vomiting, abdominal pain, darkened urine, yellowish discoloration
of the skin and eyes, light-colored bowel
movements, cough, shortness of breath, wheezing, and pain or swelling
of the joints.
Advise
patients to abstain from alcohol, hepatotoxic medications or herbal
products while taking rifampin.
Approved Drug Label (PDF)
5
Warnings and Precautions
PRECAUTIONS
(additions/revisions
are underlined)
Information for Patients
Patients should be counseled that antibacterial drugs including rifampin should only be
used to treat bacterial
infections. They do not
treat viral infections (e.g., the common cold). When rifampin 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 by rifampin or other antibacterial drugs in the future.
The patient should be told that rifampin may produce
a discoloration (yellow, orange,
red, brown) of the teeth, urine, sweat, sputum, and tears,
and the patient should be
forewarned of this.
Soft
contact lenses may be permanently stained.
Rifampin is a well characterized
and potent inducer of drug metabolizing enzymes and transporters and might therefore decrease concomitant
drug exposure and efficacy. Therefore, patients should be advised
not to take any other medication without medical advice.
The patient should be advised that
the reliability of oral or
other systemic hormonal contraceptives
may
be affected; consideration
should be given to using alternative
contraceptive measures.
Patients should be instructed to take rifampin either 1
hour before or 2 hours after a meal with
a full
glass of water.
Patients should be instructed to notify their
physician immediately if they experience any of the
following: rash with fever
or blisters, with or
without peeling skin, itching, or swollen lymph nodes,
loss of appetite, malaise, nausea, vomiting, abdominal
pain, darkened urine, yellowish discoloration
of the skin and eyes, light-colored
bowel movements, cough, shortness
of breath, wheezing, and
pain or swelling of the joints.
Advise patients to abstain from
alcohol, hepatotoxic medications or herbal products while
taking rifampin.
Compliance with the full course
of therapy must be emphasized, and the importance of not missing
any doses must be stressed.
WARNINGS
(additions/revisions
are underlined)
Hepatoxicity of
hepatocellular, cholestatic, and mixed patterns has been
reported in patients treated
with rifampin. Severity ranged from
asymptomatic elevations in liver enzymes, isolated
jaundice/hyperbilirubinemia, symptomatic self-limited hepatitis to fulminant liver failure and death. Severe
hepatic dysfunction including
fatalities were reported in patients with liver
disease and in patients
taking rifampin with other hepatotoxic agents.
Monitor for symptoms and clinical/laboratory signs
of liver injury, especially
if treatment is prolonged
or given
with other hepatotoxic drugs. Patients with impaired liver function should be given
rifampin only in cases of
necessity and then under
strict medical supervision. In
these patients, careful monitoring of liver function should be done prior to
therapy and then every 2 to 4 weeks
during therapy. If signs of hepatic damage occur or worsen,
discontinue rifampin.
Rifampin has enzyme-inducing properties,
including induction of delta amino
levulinic acid synthetase. Isolated
reports have associated porphyria
exacerbation with rifampin
administration.
The possibility of rapid emergence
of resistant meningococci restricts the use of
RIFADIN to short-term treatment of the
asymptomatic carrier
state. RIFADIN is not to be
used for the treatment
of meningococcal disease.
…
6
Adverse Reactions
(additions/revisions are underlined)
Hepatic
Hepatotoxicity including transient abnormalities in liver
function tests (e.g., elevations in serum bilirubin, alkaline phosphatase, serum
transaminases, gamma-glutamyl transferase),
hepatitis, a shock-like syndrome with hepatic
involvement and abnormal liver function tests, and cholestasis have been reported.
Approved Drug Label (PDF)
5
Warnings and Precautions
WARNINGS
Addition of the following to
the end of the section:
Rifampin may cause vitamin K–dependent coagulation disorders and bleeding
(see ADVERSE REACTIONS). Monitor coagulation tests during rifampin treatment
(prothrombin time and other coagulation tests) in patients at risk of vitamin K
deficiency (such as those with chronic liver disease, poor nutritional status,
on prolonged antibacterial drugs or anticoagulants). Consider discontinuation
of RIFADIN if abnormal coagulation tests and/or bleeding occur. Supplemental
vitamin K administration should be considered when appropriate.
Postmarketing
reports suggest that concomitant administration of high doses of cefazolin and
rifampin may prolong the prothrombin time, leading to severe vitamin
K–dependent coagulation disorders that may be life-threatening or fatal. Avoid
concomitant use of cefazolin and rifampin in patients at increased risk for
bleeding. If no alternative treatment options are available, closely monitor
prothrombin time and other coagulation tests, and administer vitamin K as
indicated.
6
Adverse Reactions
Hematologic
Additions and/or revisions
underlined:
Leukopenia, hemolytic anemia, decreased hemoglobin, bleeding, and
vitamin K–dependent coagulation disorders (abnormal prolongation of prothrombin
time or low vitamin K–dependent coagulation factors) have been observed.
Approved Drug Label (PDF)
4
Contraindications
CONTRAINDICATIONS
(Additions
and/or revisions are underlined)
…
Rifampin
is contraindicated in patients receiving praziquantel
since therapeutically effective blood levels of
praziquantel may not
be achieved.
In patients receiving rifampin who need immediate treatment
with praziquantel alternative agents
should be considered. However, if treatment with praziquantel is necessary, rifampin
should be discontinued 4 weeks before administration
of praziquantel. Treatment
with rifampin can then be restarted
one day after completion
of praziquantel treatment.
…
5
Warnings and Precautions
PRECAUTIONS
(Additions
and/or revisions are underlined)
Information for Patients
Patients should be counseled that antibacterial drugs including rifampin should only be
used to treat bacterial
infections. They do not
treat viral infections (e.g., the common cold). When rifampin 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 by rifampin
or other antibacterial drugs in the future.
The
patient should be told that rifampin may produce a discoloration (yellow, orange, red, brown) of the
teeth, urine, sweat, sputum, and tears, and the patient should be forewarned of this. Soft contact lenses may be permanently stained.
Rifampin
is a well characterized and potent inducer of drug metabolizing enzymes
and
transporters and might therefore
decrease concomitant drug exposure and
efficacy (see DRUG INTERACTIONS). Therefore patients should be
advised not to take any other medication without medical advice.
…
WARNINGS
(Additions
and/or revisions are underlined)
…
Systemic hypersensitivity reactions were reported with
RIFADIN administration.
Signs and symptoms of hypersensitivity reactions may include fever, rash, urticaria, angioedema, hypotension, acute bronchospasm, conjunctivitis, thrombocytopenia,
neutropenia, elevated liver transaminases
or flu-like syndrome (weakness,
fatigue, muscle pain, nausea, vomiting,
headache, chills, aches, itching,
sweats, dizziness, shortness
of breath, chest pain, cough,
syncope, palpitations). of hypersensitivity, such as fever,
lymphadenopathy or laboratory abnormalities (including eosinophilia, liver
abnormalities) may be
present even though rash
is not evident.
Monitor patients receiving RIFADIN
for signs and/or
symptoms of hypersensitivity reactions. If these
signs or symptoms occur, discontinue RIFADIN and
administer supportive measures.
Cases of severe cutaneous
adverse reactions (SCAR) such as Stevens-Johnson syndrome
(SJS), toxic epidermal necrolysis (TEN),
acute generalized exanthematous
pustulosis (AGEP), and drug reaction
with eosinophilia and systemic
symptoms (DRESS) syndrome have been reported with rifampin. If symptoms or signs of severe cutaneous
adverse reactions develop, discontinue RIFADIN immediately and institute appropriate therapy.
6
Adverse Reactions
ADVERSE REACTIONS
(Additions
and/or revisions are underlined)
…
Hypersensitivity Reactions
Occasionally, pruritus, urticaria, rash, pemphigoid reaction,
erythema multiforme, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal
necrolysis, Drug Reaction with
Eosinophilia and Systemic Symptoms syndrome (see WARNINGS), vasculitis, eosinophilia, sore mouth, sore tongue,
and conjunctivitis have been observed.
Anaphylaxis has been reported
rarely.
…
7
Drug Interactions
DRUG INTERACTIONS
(Additions
and/or revisions are underlined)
Pharmacodynamic interactions
Healthy subjects
who received rifampin 600
mg
once daily concomitantly with saquinavir 1000 mg/ritonavir 100
mg
twice daily (ritonavir-boosted
saquinavir) developed severe hepatocellular toxicity. Therefore, concomitant use of these medications is contraindicated.
When
rifampin is given concomitantly with other hepatotoxic medications such as
halothane or isoniazid, the potential for hepatotoxicity is increased.
The concomitant use of
rifampin and halothane
should be avoided. Patients receiving both rifampin
and isoniazid should be monitored closely for hepatotoxicity.
Effect of rifampin on other drugs
Induction of Drug Metabolizing Enzymes and
Transporters
Drug metabolizing enzymes
and transporters affected
by
rifampin include
cytochromes P450 (CYP)
1A2, 2B6, 2C8, 2C9, 2C19, and 3A4,
UDP-glucuronyltransferases (UGT), sulfotransferases,
carboxylesterases, and
transporters including P-glycoprotein (P-gp) and multidrug
resistance-associated protein 2 (MRP2). Most drugs are
substrates for one or more of these enzyme or transporter pathways, and
these pathways may be induced
by rifampin simultaneously.
Therefore, rifampin may accelerate the metabolism and reduce the activity of certain
coadministered drugs, and
has the potential to perpetuate clinically important drug-drug interactions against many drugs and across
many drug classes (Table 1).
Table 1 summarizes
the effect of rifampin on other drugs or drug classes. Adjust dosages of concomitant
drugs based on approved drug labeling and if applicable, therapeutic drug monitoring, unless otherwise specified.
(Table has been added;
please refer to label)
Effect of other drugs on rifampin
Concomitant antacid administration may
reduce the absorption of rifampin. Daily doses of rifampin should be given at
least 1 hour before the ingestion of antacids.
Concomitant use with probenecid and
cotrimoxazole increase the concentration of rifampin which may increase the
risk of RIFADIN toxicities. Monitor for adverse reactions associated with
RIFADIN during coadministration.
Other Interactions
Atovaquone: Concomitant use of
rifampin with atovaquone decrease concentrations of atovaquone and increase
concentrations of rifampin which may increase the risk of RIFADIN toxicities.
Coadministration of rifampin with atovaquone is not recommended.
Approved Drug Label (PDF)
5
Warnings and Precautions
PRECAUTIONS
(additions
underlined)
…
Information for Patients
…
The patient should be told that rifampin may
produce a discoloration (yellow, orange, red, brown) of the teeth,
urine, sweat, sputum, and tears, and the patient should be forewarned of this. Soft contact lenses may be permanently stained.
…
6
Adverse Reactions
Gastrointestinal
(additions
underlined)
Heartburn, epigastric distress, anorexia, nausea, vomiting,
jaundice, flatulence, cramps, and diarrhea have been noted in some patients.
Although Clostridium difficile has
been shown in vitro to be sensitive
to rifampin, pseudomembranous colitis has been reported with the use of
rifampin (and other broad spectrum antibiotics). Therefore, it is important to
consider this diagnosis in patients who develop diarrhea in association with
antibiotic use. Tooth discoloration (which may be permanent) may occur.
…
Approved Drug Label (PDF)
5
Warnings and Precautions
WARNINGS
Addition of the
following:
… RIFADIN is not to be used for the treatment of
meningococcal disease.
Systemic
hypersensitivity reactions, including Drug Reaction with Eosinophilia and
Systemic Symptoms (DRESS) syndrome, may occur in patients receiving RIFADIN.
Signs and symptoms of hypersensitivity reactions may include fever, rash,
urticaria, angioedema, hypotension, acute bronchospasm, conjunctivitis,
thrombocytopenia, neutropenia, elevated liver transaminases or flu-like
syndrome (weakness, fatigue, muscle pain, nausea, vomiting, headache, chills,
aches, itching, sweats, dizziness, shortness of breath, chest pain, cough,
syncope, palpitations). These reactions may be severe and DRESS may be fatal.
Manifestations of hypersensitivity, such as fever, lymphadenopathy or
laboratory abnormalities (including eosinophilia, liver abnormalities) may be
present even though rash is not evident. Monitor patients receiving RIFADIN for
signs and/or symptoms of hypersensitivity reactions. If these signs or symptoms
occur, discontinue RIFADIN and administer supportive measures.
PRECAUTIONS
Information for
Patients
Additions and/or
revisions underlined:
Patients
should be instructed to notify their physician immediately if they
experience any of the following: rash, fever, or swollen lymph nodes,
loss of appetite, malaise, nausea and vomiting, darkened urine, yellowish
discoloration of the skin and eyes, cough, shortness of breath, wheezing
and pain or swelling of the joints.
6
Adverse Reactions
Additions and/or
revisions underlined:
Hypersensitivity
Reactions
Occasionally,
pruritus, urticaria, rash, pemphigoid reaction, erythema multiforme including
Stevens-Johnson
Syndrome, toxic epidermal necrolysis, Drug Reaction with Eosinophilia and
Systemic Symptoms syndrome, vasculitis …
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