Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Thromboembolic Events
Additions and/or
revisions underlined:
HYMPAVZI is a tissue factor pathway inhibitor
(TFPI) antagonist, and may increase the risk of thromboembolic complications.
Venous and arterial thromboembolic events were reported in 0.8% of
patients (2/259) treated with HYMPAVZI in the open-label extension study
[see Adverse Reactions (6.1)].
Patients with independent risk factors for
thromboembolic events may be at increased risk of thromboembolic events with
use of HYMPAVZI.
HYMPAVZI has not been studied in patients with a
history of previous thromboembolic events [see Clinical Studies (14.1)].
Consider the benefit and risk of using HYMPAVZI in patients with known risk
factors for thromboembolism.
Interrupt HYMPAVZI prophylaxis if diagnostic
findings consistent with thromboembolism occur and manage as clinically
indicated.
If factor VIII or factor IX products or
bypassing agents are indicated in a patient receiving HYMPAVZI prophylaxis,
the minimum effective dose according to the product label is recommended [see
Dosage and Administration (2.5)].
Newly added
subsection:
5.4 Increased Laboratory Values of Fibrin D-dimer
and Prothrombin Fragment 1.2
Consistent with its mechanism of action and
hemostatic effect, HYMPAVZI causes an increase in fibrin D-dimer and
prothrombin fragment 1.2 [see Clinical Pharmacology (12.1, 12.2)].
Sporadic or transient increases in levels of these biomarkers above
physiological values were reported with no associated safety concerns [see
Clinical Pharmacology (12.2)]. Increased levels of fibrin D-dimer were seen
in 10 (8.1%) pediatric patients age 6 to less than 18 years and 6 (4.4%)
adults. Increased levels of prothrombin fragment 1.2 were seen in 13 (10.5%)
pediatric patients age 6 to less than 18 years and 6 (4.4%) adults. For
patients taking HYMPAVZI, these coagulation biomarkers may not be reliable
predictive markers for clinical decision-making with suspicion of thrombosis
such as deep vein thrombosis (DVT) and pulmonary embolism (PE).
6
Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or
revisions underlined:
Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a
drug cannot be directly compared to rates in the clinical trials of another
drug and may not reflect the rates observed in practice.
The safety of HYMPAVZI was evaluated in adults and pediatric
patients 6 years of age and older with severe hemophilia A (FVIII
<1%) or moderately severe to severe hemophilia B (FIX less
than or equal to 2%) with and without inhibitors enrolled in the BASIS and
BASIS KIDS studies. A total of 259 patients received the recommended
HYMPAVZI prophylaxis loading dose followed by a weekly maintenance dose
starting at Day 8 administered subcutaneously [see Clinical Studies (14.1,
14.2, 14.3)]. One-hundred-thirty-five (52%) were adults (18 years of age
and older), 56 (22%) were adolescents (12 to less than 18 years of age), and 68
(26%) were children (6 to less than 12 years of age). Among patients
receiving HYMPAVZI, 90% were exposed for 6 months or longer and 82%
were exposed for at least 1 year. The median duration of exposure across the
studies was 364 days (min, max: 14, 406 days).
Table 1 summarizes the adverse reactions reported
in greater than or equal to 2% of patients in all age groups who
received HYMPAVZI prophylaxis.
Table 1. Adverse Reactions
Reported in greater than or equal to 2% of Patients Treated with
HYMPAVZI* By Age Group
Extensive changes to table 1; please refer to label for complete
information.
8
Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
The safety and
effectiveness of HYMPAVZI to prevent or reduce the frequency of bleeding
episodes in hemophilia A or B with and without inhibitors have been
established in pediatric patients 6 years of age and older [see
Clinical Studies (14.1, 14.2, 14.3)]. Use of HYMPAVZI in pediatric
patients for this indication is supported by evidence from two
open-label, multi-center studies (BASIS and BASIS KIDS). These two studies
treated 56 adolescents (12 to less than 18 years of age). BASIS KIDS
treated 68 children (6 to less than 12 years of age). Efficacy and adverse
reaction profile were comparable between pediatric patients and adults [see
Adverse Reactions (6.1) and Clinical Studies (14.1, 14.2, 14.3)]. Differences
observed in steady-state pharmacokinetic (PK) exposures between pediatric
patients and adults were mostly accounted for by body weight [see
Clinical Pharmacology (12.3)].
The safety and effectiveness of HYMPAVZI have not
been established in pediatric patients younger than 6 years of age.
8.5 Geriatric Use
Additions and/or
revisions underlined:
Two patients 65 years of age and older were enrolled
in the clinical studies for hemophilia A or B with or without inhibitors
[see Clinical Studies (14.1, 14.2)]. Clinical studies of HYMPAVZI did
not include sufficient numbers of subjects 65 years of age and over to
determine whether they respond differently from younger subjects.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
Additions and/or
revisions underlined:
Important information:
- Before you start using HYMPAVZI, it is very important to talk to your
healthcare provider about using factor VIII and factor IX products or
bypassing agents (products that help blood clot but work in a different
way than HYMPAVZI).
- Your
healthcare provider may prescribe factor VIII, factor IX
medicines, or bypassing agents to treat episodes of breakthrough
bleeding during your treatment with HYMPAVZI. Carefully follow your
healthcare provider’s instructions regarding when to use these medicines
and the prescribed dose during your treatment with HYMPAVZI. Do not use additional doses of HYMPAVZI
to treat breakthrough bleeds.
What is HYMPAVZI?
HYMPAVZI is a
prescription medicine used regularly to prevent or reduce the frequency of
bleeding episodes in adults and children 6 years of age and older with:
- hemophilia A with or without factor VIII
inhibitors, or
- hemophilia B with or without factor IX
inhibitors.
It is not known if
HYMPAVZI is safe and effective in people receiving ongoing Immune Tolerance
Induction (ITI). It is not known if
HYMPAVZI is safe and effective in children younger than 6 years of
age.
. . .
How should I use HYMPAVZI?
See the detailed “Instructions for Use” that comes with your HYMPAVZI
for information on how to inject a dose of HYMPAVZI, and how to properly throw
away (dispose of) used HYMPAVZI prefilled syringe or HYMPAVZI prefilled pen.
- Use
HYMPAVZI exactly as prescribed by your healthcare provider.
- Your
healthcare provider will provide instructions for stopping (discontinuing) your
current treatment when switching from factor- or non-factor-based medicines or
bypassing agents to HYMPAVZI.
- HYMPAVZI
comes in two different strengths in a single-dose prefilled syringe or
single-dose prefilled pen.
- HYMPAVZI
is given as an injection under your skin (subcutaneous injection) by you or
your caregiver.
- People
12 years of age and older, or their caregiver may inject HYMPAVZI if your
healthcare provider decides that it is appropriate. Your
healthcare provider should show you or your caregiver how to inject HYMPAVZI
before the first injection.
- Do not
inject yourself or someone else until you have been shown how to inject
HYMPAVZI.
- Inject
HYMPAVZI 1 time a week on the same day each week. Inject HYMPAVZI at any time
of day.
- Dosing for adults and children 12 years of age and
older:
- Your
first dose (loading dose) of HYMPAVZI is 300 mg (two 150 mg injections). Then
you will inject a weekly (maintenance) dose as prescribed by your healthcare
provider.
- If you
miss a maintenance dose of 150 mg of HYMPAVZI:
- Give the
dose as soon as possible before the day of your next scheduled dose, and
then continue with your usual weekly dosing schedule. You may inject your next
dose at your regularly scheduled time or continue dosing based on the new day
you injected your missed dose. In case you are not sure when to inject
HYMPAVZI, call your healthcare provider.
- If more
than 13 days have passed since your last dose was given, you will need to
restart with a loading dose. Call your healthcare provider right away for
dosing instructions.
- If you
miss 1 or more doses of maintenance dose of 300 mg of HYMPAVZI:
- Give a
dose as soon as possible, and then continue with your usual weekly
dosing schedule. You may inject your next dose at your regularly scheduled time
or continue dosing based on the new day you injected your missed dose. In case
you are not sure when to inject HYMPAVZI, call your healthcare provider.
- Dosing for children 6 years to less than 12 years
of age:
- Your
first dose (loading dose) of HYMPAVZI is 150 mg (one 150 mg injection or two 75
mg injections) as prescribed by your healthcare provider. Then you will inject
a weekly (maintenance) dose as prescribed by your healthcare provider.
- If you
miss a maintenance dose of 75 mg of HYMPAVZI:
- Give the
dose as soon as possible before the day of your next scheduled dose, and then
continue with your usual weekly dosing schedule. You may inject your next dose
at your regularly scheduled time or continue dosing based on the new day you
injected your missed dose. In case you are not sure when to inject HYMPAVZI,
call your healthcare provider.
- If more
than 13 days have passed since your last dose was given, you will need to
restart with a loading dose. Call your healthcare provider right away for
dosing instructions.
- If you miss 1 or more doses of maintenance dose of
150 mg of HYMPAVZI:
- Give a dose as soon as possible, and then continue
with your usual weekly dosing schedule. You may inject your next dose at your
regularly scheduled time or continue dosing based on the new day you injected
your missed dose. In case you are not sure when to inject HYMPAVZI, call your
healthcare provider.
- If you inject too much HYMPAVZI, call your
healthcare provider or the Poison Help Line at 1-800-222-1222 or go to the
nearest hospital emergency room right away.
What are the possible side effects of HYMPAVZI?
HYMPAVZI may cause serious side effects, including:
. . .
The most common side effects of HYMPAVZI include:
- swelling,
hardening, redness, bruising, bleeding, and pain at injection site
- joint
pain
- diarrhea
- headache
- itching
- fever
- rash
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Thromboembolic
Events
Additions and/or
revisions underlined:
HYMPAVZI is a tissue factor pathway inhibitor
(TFPI) antagonist, and may increase the risk of thromboembolic complications.
Venous thrombotic events were reported in clinical studies with HYMPAVZI [see
Adverse Reactions (6.1)].
Patients with independent risk factors for
thromboembolic events may be at increased risk of thromboembolic events with
use of HYMPAVZI.
HYMPAVZI has not been studied in patients with a
history of previous thromboembolic events [see Clinical Studies (14.1)].
Consider the benefit and risk of using HYMPAVZI in patients with known risk
factors for thromboembolism.
. . .
6
Adverse Reactions
6.1 Clinical
Trials Experience
Additions and/or
revisions underlined:
. . .
A serious adverse reaction of venous thrombosis
occurred in 0.9% of patients (1/116) treated with HYMPAVZI in the open-label
extension study [see Clinical Studies
(14.1)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions and/or
revisions underlined:
.
. .
Thromboembolic
Events
Inform
patients and/or caregivers that HYMPAVZI increases coagulation potential.
Discuss the appropriate dosing of concomitant agents such as FVIII or FIX with
the patient prior to starting on HYMPAVZI prophylaxis [see Warnings and Precautions (5.1)]. Advise the patient to
discontinue HYMPAVZI and seek immediate medical attention if any signs or
symptoms of thromboembolism occur.
.
. .
PATIENT
INFORMATION
Additions and/or
revisions underlined:
. . .
What
is HYMPAVZI?
HYMPAVZI is a prescription medicine used
regularly to prevent or reduce the frequency of bleeding episodes in adults
and children 12 years of age and older with hemophilia A without factor VIII
inhibitors or hemophilia B without factor IX inhibitors.
It is not known if HYMPAVZI is safe and effective in
children younger than 12 years old.
. . .
Before
using HYMPAVZI, tell your healthcare provider about all of your medical
conditions, including if you:
have a planned surgery. Your healthcare provider may
stop treatment with HYMPAVZI before your surgery. Talk to your healthcare
provider about when to stop using HYMPAVZI and when to start it again if you
have a planned surgery.
have a severe short-term (acute) illness such as an
infection or injury.
- have been told that you have
a risk for blood clots.
. . .
What
are the possible side effects of HYMPAVZI? HYMPAVZI may cause serious side
effects, including:
- blood clots (thromboembolic events). HYMPAVZI may increase the risk for your blood to clot in blood vessels in
your arm, leg, lung, or head and can be life-threatening. Blood clots have
happened in people using HYMPAVZI. You may have an increased risk of blood
clots if you have certain risk factors. Stop using HYMPAVZI and get medical
help right away if you develop any of these signs or symptoms of blood clots:
. . .
The
most common side effects of HYMPAVZI include:
. . .
headache
swelling, hardening, redness, bruising, and pain at
injection site
. . .
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