WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA
VOYDEYA, a complement inhibitor, increases the risk of
serious
infections, especially those
caused by encapsulated bacteria, such as
Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type B [see Warnings and Precautions (5.1)]. Life-threatening and fatal infections with encapsulated
bacteria have occurred in patients treated with complement
inhibitors. These infections may become
rapidly life-threatening or fatal if not recognized and treated
early.
-
Complete or update vaccination for encapsulated bacteria
specifically, Neisseria meningitidis and
Streptococcus pneumoniae at least 2 weeks prior to the first dose of VOYDEYA, unless
the risks
of delaying therapy with VOYDEYA outweigh the
risk of developing a serious infection. Comply with the most
current Advisory Committee on Immunization Practices (ACIP)
recommendations for vaccinations against encapsulated bacteria
in patients receiving a complement inhibitor.
See Warnings and Precautions
(5.1) for additional guidance on the management of the risk of
serious infections caused by encapsulated bacteria.
-
Patients receiving VOYDEYA are at increased risk for
invasive disease
caused by encapsulated bacteria, even
if they develop antibodies following vaccination. Monitor patients
for early signs and symptoms
of
serious
infections and evaluate immediately if infection
is
suspected.
Because of the risk of serious infections caused by
encapsulated bacteria,
VOYDEYA is available only through
a restricted program under
a Risk Evaluation
and Mitigation Strategy (REMS) called the VOYDEYA REMS [see Warnings and Precautions (5.2)].
CONTRAINDICATIONS
Initiation in patients with unresolved serious infection caused
by encapsulated bacteria, including
Neisseria meningitidis, Streptococcus pneumoniae,
or Haemophilus influenzae type B.
WARNINGS AND PRECAUTIONS
Serious Infections Caused by Encapsulated Bacteria
VOYDEYA, a complement inhibitor, increases a patient’s
susceptibility to serious, life-threatening, or fatal infections
caused by encapsulated bacteria, including
Neisseria meningitidis (caused by any serogroup,
including non-groupable strains),
Streptococcus pneumoniae, and Haemophilus influenzae
type
B. Life-threatening and fatal infections with encapsulated
bacteria have occurred in both vaccinated and unvaccinated patients
treated with complement inhibitors.
Complete, update, or revaccinate patients in accordance with
ACIP recommendations considering the duration of VOYDEYA
therapy. Note that ACIP recommends an administration schedule in
patients receiving complement inhibitors that differs from the
administration schedule in the vaccine prescribing information.
If urgent VOYDEYA therapy is indicated in a patient who is not
up to date with vaccines against encapsulated bacteria according
to ACIP recommendations, provide antibacterial drug prophylaxis
and administer these vaccines as soon as possible. Various
durations and regimens of antibacterial drug prophylaxis have
been considered, but the optimal durations and drug regimens for
prophylaxis and their efficacy have
not
been studied in unvaccinated or vaccinated patients receiving complement
inhibitors, including VOYDEYA. The benefits and risks of treatment
with VOYDEYA, as well as those associated with antibacterial drug
prophylaxis in unvaccinated or vaccinated patients, must be considered
against the known risks for serious infections caused by encapsulated
bacteria.
Vaccination does not eliminate the risk of serious encapsulated
bacterial infections, despite development of antibodies
following vaccination. Closely monitor patients for early signs
and symptoms of serious infection and evaluate patients
immediately if an infection is suspected. Inform patients of
these signs and symptoms and instruct patients to seek immediate
medical care if they occur. Promptly treat known infections.
Serious infection may become rapidly life-threatening or fatal
if not recognized and treated early. Consider interruption of
VOYDEYA in patients who are undergoing treatment for serious
infections.
VOYDEYA REMS
Due to the risk of serious infections caused by encapsulated
bacteria, VOYDEYA is available only through a restricted program
called VOYDEYA
REMS. Per the REMS requirements:
Prescribers must enroll in the REMS, counsel patients about the
risk of serious infections caused by encapsulated bacteria,
provide patients with the REMS educational materials, assess
patient vaccination status for vaccines against encapsulated
bacteria, and vaccinate if needed according to current ACIP
recommendations 2 weeks prior to the first
dose of VOYDEYA.
Antibacterial drug prophylaxis must be prescribed if treatment must
be started urgently and the patient is not up to date with vaccines
against encapsulated bacteria according to current ACIP recommendations
at least 2 weeks prior to the first dose of VOYDEYA.
Pharmacies that dispense VOYDEYA must be certified in the
VOYDEYA REMS and must verify prescribers are certified.
Patients must receive counseling from the prescriber about the
need to
receive vaccinations against encapsulated
bacteria per ACIP recommendations, to take antibiotics as directed,
the early signs and symptoms of serious infection, and be instructed
to carry the Patient Safety Card at all times during and for 1 week
following the last dose of VOYDEYA.
Further information is available at www.voydeyarems.com or 1-888-765-4747.
Hepatic Enzyme Increases
Hepatic enzyme elevations have been observed in patients treated
with VOYDEYA. A total of
14% of patients receiving VOYDEYA
had elevations in serum alanine aminotransferase (ALT). ALT elevations
>3× the upper limit of normal (ULN) and ≤5× ULN occurred in 9% of
VOYDEYA-treated patients, and ALT elevations >5× ULN and ≤10× ULN
occurred in 5% of VOYDEYA-treated patients.
Assess liver enzyme test results prior to the initiation of
VOYDEYA and periodically during treatment. Consider treatment
interruption or discontinuation if elevations are clinically
significant or if the patient becomes symptomatic. VOYDEYA has
not been studied in patients with severe hepatic impairment.
Monitoring of PNH Manifestations After VOYDEYA
Discontinuation
After discontinuing treatment with VOYDEYA, closely monitor
patients for at least 2 weeks after the last dose for signs and
symptoms of hemolysis. If discontinuation of VOYDEYA is
necessary, continue background treatment
with ravulizumab or eculizumab or consider alternative therapy
if necessary. The signs and symptoms of hemolysis may include sudden
decrease in hemoglobin or fatigue.
If hemolysis occurs after discontinuation of VOYDEYA, consider
restarting treatment with VOYDEYA, if appropriate.
Hyperlipidemia
VOYDEYA increases total cholesterol and LDL-cholesterol. Of the
50
VOYDEYA-treated
patients who
had a normal total cholesterol
level at baseline, 30% developed Grade 1 hypercholesterolemia. Of
the 6 VOYDEYA-treated patients who had Grade 1 hypercholesterolemia
at baseline, 1 patient experienced increased total cholesterol that
worsened to Grade 2. Of the 54 VOYDEYA-treated patients who had LDL-cholesterol
≤130 mg/dL at baseline, 13% developed LDL-cholesterol >130-160 mg/dL,
and 9% developed LDL-cholesterol >160-190 mg/dL.
Some patients required cholesterol-lowering medications. Monitor
serum lipid parameters periodically during treatment with
VOYDEYA
and initiate cholesterol-lowering medication, if indicated.
ADVERSE REACTIONS
The most common adverse reaction reported in ≥10% of patients
treated with VOYDEYA was headache. Serious adverse reactions
were reported in 5% of patients who received VOYDEYA and
included pancreatitis, cholecystitis, and increased blood
bilirubin. No specific serious adverse reaction was reported in
more than 1 patient treated with VOYDEYA. Adverse reactions
reported in ≥5% of patients treated with VOYDEYA and greater
than placebo in the randomized, controlled period included
vomiting, pyrexia, increased alanine aminotransferase,
hypertension, and pain in the extremities. Clinically relevant
adverse reactions in <5% of patients included increased serum
triglycerides.
DRUG INTERACTIONS
BCRP Substrates
Danicopan is a Breast Cancer Resistance Protein (BCRP)
inhibitor.
Concomitant use of VOYDEYA
with a BCRP substrate increases the plasma concentrations of the
BCRP substrate, which may increase the risk for adverse reactions
associated with the BCRP substrate.
If used together, monitor
patients more frequently for adverse reactions, associated
with the BCRP substrate and consider dose reduction of the BCRP substrate
according to
its prescribing information.
Rosuvastatin
Danicopan significantly increased rosuvastatin exposure. The
dose of rosuvastatin should not exceed 10mg once daily when
concomitantly used
with VOYDEYA.
P-glycoprotein Substrates
Danicopan is an inhibitor of P-glycoprotein (P-gp). Concomitant
administration of VOYDEYA with P-gp substrates may increase the
plasma concentrations of the P-gp substrates. Dose adjustment
might be necessary for P-gp substrates where minimal
concentration changes may lead to serious adverse reactions.
USE IN SPECIFIC POPULATIONS
Pregnancy
There are no available data on VOYDEYA use in pregnant
individuals to
evaluate for a drug-associated
risk of major birth defects, miscarriage, or adverse maternal or
fetal outcomes. There are risks to the mother and fetus associated
with untreated PNH in pregnancy. The use of VOYDEYA in pregnant women
or women planning to become pregnant may be considered following
an assessment of the risks and benefits.
Lactation
There are no data on the presence of VOYDEYA in human milk, the
effects on the breastfed
child, or the effect on milk production.
VOYDEYA is present in animal milk. When a
drug is present
in animal milk, it is likely that the drug will be present in human
milk.
Because of the potential for
serious adverse reactions in the breastfed child, including serious
infections with encapsulated bacteria and liver enzyme increases,
advise patients not to breastfeed during treatment with VOYDEYA and
for 3 days after the last dose.
Hepatic Impairment
No dose adjustment is required in patients with mild to moderate
hepatic impairment. Studies have not been conducted in patients
with severe hepatic impairment, therefore, avoid use of VOYDEYA
in this patient population.
INDICATION
VOYDEYA is indicated as an add-on therapy to ravulizumab or
eculizumab for the treatment of extravascular hemolysis (EVH) in
adults with paroxysmal nocturnal hemoglobinuria (PNH).
Limitation of Use:
VOYDEYA has not been shown to be effective
as monotherapy and
should only be prescribed
as an add-on to ravulizumab or eculizumab.
To report SUSPECTED ADVERSE REACTIONS, contact Alexion
Pharmaceuticals, Inc. at
1-844-259-6783 or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information for VOYDEYA, including Boxed WARNING
regarding serious
and life-threatening or
fatal infections.