Important
Safety Information
WARNING:
EMBRYO-FETAL TOXICITY
VANRAFIA is contraindicated for use in pregnant patients; it may
cause major birth defects, based on animal data. Exclude
pregnancy prior to initiation of treatment with VANRAFIA. Advise
use of effective contraception before the initiation of
treatment, during treatment, and for 2 weeks after
discontinuation of treatment with VANRAFIA. Stop VANRAFIA as soon
as possible if the patient becomes pregnant.
CONTRAINDICATIONS
Pregnancy
Use of
VANRAFIA is contraindicated in patients who are pregnant.
Hypersensitivity
VANRAFIA
is contraindicated in patients with a history of a
hypersensitivity reaction to atrasentan or any component of the
product.
WARNINGS
AND PRECAUTIONS
Embryo-Fetal
Toxicity
Based
on data from animal reproduction studies, VANRAFIA may cause
fetal harm when administered to a pregnant patient and is
contraindicated during pregnancy. The available human data for
endothelin receptor antagonists (ERAs) do not establish the
presence or absence of major birth defects related to the use of
VANRAFIA. Counsel patients who can become pregnant of the
potential risk to a fetus. Exclude pregnancy prior to initiation
of treatment with VANRAFIA. Advise patients to use effective
contraception prior to initiation of treatment, during treatment,
and for 2 weeks after discontinuation of treatment with VANRAFIA.
When pregnancy is detected, discontinue VANRAFIA as soon as
possible.
Hepatotoxicity
Some
ERAs have caused elevations of aminotransferases, hepatotoxicity,
and liver failure. Asymptomatic and transient transaminase
elevations have been observed with VANRAFIA. Obtain liver enzyme
testing before initiating VANRAFIA, and repeat during treatment
as clinically indicated. In patients with elevated
aminotransferases at baseline (>3 × upper limit of normal [ULN]),
consider periodic liver test monitoring. Do not initiate VANRAFIA
in patients with severe hepatic impairment.
Advise patients to report symptoms suggesting hepatic injury (eg,
nausea, vomiting, right upper quadrant pain, fatigue, anorexia,
jaundice, dark urine, fever, or itching). If clinically relevant
aminotransferase elevations occur, or if elevations are
accompanied by an increase in bilirubin >2 × ULN, or by clinical
symptoms of hepatotoxicity, discontinue VANRAFIA. Consider
reinitiation of VANRAFIA when hepatic enzyme levels normalize in
patients who have not experienced clinical symptoms of
hepatotoxicity or jaundice.
Fluid
Retention
Fluid retention may occur with ERAs and has been observed in
clinical studies with VANRAFIA. VANRAFIA has not been evaluated
in IgAN patients with heart failure. If clinically significant
fluid retention develops, consider initiating or increasing
diuretic treatment and interrupting VANRAFIA treatment.
Decreased
Sperm Counts
VANRAFIA, similar to other ERAs, may have an adverse effect on
spermatogenesis. Counsel men about the potential effects on
fertility.
ADVERSE
REACTIONS
The
most common adverse reactions (incidence ≥5%) with VANRAFIA were
peripheral edema and anemia.
EFFECT
OF OTHER DRUGS ON VANRAFIA
Strong or Moderate
CYP3A Inducers: Avoid concomitant use with a strong or moderate
CYP3A inducer. Atrasentan is a CYP3A substrate. Concomitant use
with a strong and moderate CYP3A inducer is expected to decrease
atrasentan exposure, which may reduce VANRAFIA efficacy.
OATP1B1/1B3
Inhibitors: Avoid concomitant use with organic anion
transporting polypeptides (OATP) 1B1/1B3 (OATP1B1/1B3)
inhibitors. Atrasentan is an OATP1B1/1B3 substrate. Concomitant
use with an OATP1B1/1B3 inhibitor increases atrasentan exposure,
which may increase the risk of VANRAFIA adverse reactions.
Please see full
Prescribing Information,
including Boxed WARNING and Medication
Guide.
