Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Hemorrhage
Newly
added information:
…
Conditions
associated with increased bleeding in pediatric patients include systemic lupus
erythematosus, Wilms tumor, antiphospholipid syndrome, antithrombin III
deficiency, Factor V Leiden, malignancy, pancytopenia, indwelling chest tubes,
thoracotomy, invasive infections, hypertensive encephalopathy, intestinal
lymphangiectasia and von Willebrand disease.
…
6
Adverse Reactions
6.1 Clinical
Trials Experience
Newly added information:
…
Clinical Trials Experience in Pediatric Patients
Safety data for use of ARIXTRA in the treatment of
VTE in pediatric patients aged 1 year or older is available from Study
FDPX-IJS-7001. In Study FDPX-IJS-7001 (n = 366), the median duration of
treatment with fondaparinux sodium injection, including ARIXTRA, was 85 days
(range 1 day to 3,768 days).
The incidence of major bleeding events, defined as
per the ISTH criteria, was the primary safety outcome of interest in Study
FDPX-IJS-7001. Seven patients (1.9%) had composite major bleeding events: 1
patient (0.3%) had clinically overt bleeding (associated with a decrease in
hemoglobin of at least 20 g/L (2 g/dL) in a 24-hour period), 3 patients (0.8%)
had bleeding that was retroperitoneal, pulmonary, intracranial, or otherwise
involved the central nervous system, and 3 patients (0.8%) had major bleeding that
required surgical intervention in an operating suite. Major bleeding events
resulted in the interruption of fondaparinux sodium injection treatment for 4
patients and the discontinuation of fondaparinux sodium injection for 3
patients. All major bleeding events were reported in patients between the ages
of greater than or equal to 2 years to less than 18 years.
Eleven patients (3%) had non-major bleeding events:
8 patients (2.2%) had overt bleeding for which a blood product was
administered, and which was not directly attributable to the patient’s
underlying medical condition and 4 patients (1.1%) had bleeding that required
medical or surgical intervention to restore hemostasis other than in an
operating room. All non-major bleeding events warranted either interruption or
withdrawal of fondaparinux sodium injection treatment except for 1 patient for
whom the action taken with fondaparinux was not reported. All non-major
bleeding events were reported in patients between the ages of greater than or
equal to 2 years to less than 18 years.
Overall, 65 patients (18%) had composite minor
bleeding events: 64 patients (18%) had overt or macroscopic evidence of
bleeding that did not fulfill the criteria for either major bleeding or
clinically relevant, non-major bleeding and two patients (0.5%) had non-major
menstrual bleeding which resulted in a medical consultation and/or
intervention.
Other Adverse Reactions
Other adverse reactions that occurred during
treatment with fondaparinux sodium injection in pediatric studies included:
anemia, thrombocytopenia, allergic reactions, generalized skin associated
events, abnormal liver function, hypokalemia, and hypotension.
6.2 Postmarketing
Experience
Additions and/or revisions underlined:
…
Elevations of hepatic transaminases have been reported
in pediatric patients with elevations greater than 10x ULN.
8
Use in Specific Populations
8.4 Pediatric Use
Newly added information:
The safety and effectiveness of ARIXTRA for the
treatment of venous thromboembolism have been established in pediatric patients
aged 1 year and older weighing at least 10 kg. Use of ARIXTRA for this
indication is supported by evidence from adequate and well-controlled studies
in adults with additional pharmacokinetic, pharmacodynamic, safety, and
efficacy data in pediatric patients aged 0.3 years and older [see Adverse Reactions (6.1), Clinical
Pharmacology (12.4), and Clinical Studies (14.8)]. The frequency, type, and
severity of adverse reactions observed were generally consistent with those
observed in adults.
The safety and effectiveness of ARIXTRA have not
been established in pediatric patients for the treatment of venous
thromboembolism who are younger than 1 year old, weigh less than 10 kg, or with
any category of renal or hepatic impairment.
The safety and effectiveness of ARIXTRA have not
been established in pediatric patients for the prophylaxis of DVT and treatment
of DVT or PE in conjunction with warfarin sodium.
8.5 Geriatric Use
Additions and/or revisions underlined:
Over 3,000 patients 65 years and older have received
ARIXTRA in randomized clinical trials for the treatment or prophylaxis of DVT
and PE. There were over 2,000 patients 65 years of age and older in the
orthopedic surgery clinical studies for prophylaxis of DVT and PE [see Clinical Studies (14)]. Of the
total number of ARIXTRA-treated patients in these orthopedic surgery studies,
1,111 (30.9%) were 65 years of age to 74 years of age, while 1,227 (34.2%) were
75 years of age and older. No overall differences in effectiveness of ARIXTRA
have been observed between patients 65 years of age and older and younger adult
patients. Serious adverse events were more frequent in patients 65 years of age
and older.
…
8.6
Renal Impairment
Additions and/or revisions underlined:
…
There
is no adequate data to support safe and effective use of ARIXTRA in pediatric
patients with renal impairment.
8.7 Hepatic Impairment
Additions and/or revisions underlined:
…
There
is no adequate data to support safe and effective use of ARIXTRA in pediatric
patients with hepatic impairment.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions
and/or revisions underlined:
…
If
patients must self-administer ARIXTRA or if administered by a caregiver, (e.g.,
if ARIXTRA is used at home), advise patients of the following:
- Advise
patients that ARIXTRA should be given by subcutaneous injection. Instruct
patients in the proper technique for administration.
- Instruct patients that if they miss a dose of ARIXTRA,
to inject the dose as soon as they remember. Advise patients not to inject two
doses at the same time.
…
PATIENT
INFORMATION
Extensive changes; please refer to label for complete
information
Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Hemorrhage
(Additions and/or revisions are underlined)
ARIXTRA
increases the risk of
hemorrhage in patients at risk for bleeding, including conditions such
as…
5.3 Renal Impairment and Bleeding Risk
(Additions and/or revisions are underlined)
In these patient
populations, the following is recommended:
- ARIXTRA may cause prolonged anticoagulation in patients
with CrCl 30 to 50 mL/min.
6
Adverse Reactions
(Additions and/or revisions are underlined)
The following
serious adverse reactions are described elsewhere in the labeling:
Spinal
or epidural hematomas
Hemorrhage
Renal
impairment and bleeding risk
Body
weight <50 Kg and bleeding risk
Thrombocytopenia
6.1 Clinical Trials Experience
(Additions and/or revisions are underlined)
Hemorrhage
Hip Fracture, Hip Replacement, and Knee Replacement
Surgery
The rates of major
bleeding events reported during 3 active-controlled peri-operative VTE prophylaxis
trials with enoxaparin sodium in hip fracture, hip replacement, or knee
replacement surgery (N = 3,616) and in an extended VTE prophylaxis trial (n
= 327) with ARIXTRA 2.5 mg are provided in Table 2.
Treatment of Deep Vein Thrombosis and Pulmonary Embolism
The rates of
bleeding events reported during a dose-response trial (n = 111) and an
active- controlled trial with enoxaparin sodium in DVT treatment (n
= 1,091) and an active-controlled trial with heparin in PE treatment (n =
1,092) with ARIXTRA are provided in Table 4.
6.3 Elevations of Serum Aminotransferases
(Additions and/or revisions are underlined)
…These elevations
are reversible and may be associated with increases in bilirubin…
8
Use in Specific Populations
8.1 Pregnancy
(Pregnancy and Lactation Labeling Rule (PLLR) Conversion;
additions and/or revisions are
underlined)
Risk Summary
Available data
from published literature and postmarketing reports have not reported a clear
association with fondaparinux sodium and adverse developmental outcomes.
Fondaparinux sodium plasma concentrations obtained
from four women
treated with ARIXTRA
during pregnancy and their newborn infants
demonstrated low placental transfer of fondaparinux sodium. There are
risks to the mother associated with untreated venous thromboembolism in
pregnancy and a risk of hemorrhage in the mother and fetus associated with use
of anticoagulants. In animal reproduction studies, there was no evidence
of adverse developmental outcomes when fondaparinux sodium was administered to
pregnant rats and rabbits during organogenesis at doses 32 and 65 times,
respectively, the recommended human dose based on body surface area.
The estimated
background risk of major birth defects and miscarriage for the indicated
population is unknown. All pregnancies
have a background risk of birth defect, loss, or other adverse outcomes. In the
U.S. general population, the estimated background risk of major birth defects
and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical
Considerations
Disease-associated maternal and/or embryo/fetal risk
Pregnancy
confers an increased risk for thromboembolism that is higher for women with
underlying thromboembolic disease and certain high-risk pregnancy conditions.
Published data describe that women with a previous history of venous thrombosis
are at high risk for recurrence during pregnancy.
Fetal/Neonatal adverse reactions
Fondaparinux
sodium has been demonstrated to cross the placenta in humans (see Data). Use
of anticoagulants, including fondaparinux sodium, may increase the risk of
bleeding in the fetus and neonate. Monitor neonates for bleeding.
Labor or delivery
All patients
receiving anticoagulants, including pregnant women, are at risk for bleeding.
Fondaparinux sodium use during labor or delivery in women who are receiving
neuraxial anesthesia may result in epidural or spinal hematomas. Pregnant women
receiving fondaparinux sodium should be carefully monitored for evidence of
bleeding or unexpected changes in coagulation parameters. Consideration for use
of a shorter acting anticoagulant should be specifically addressed as delivery
approaches.
Data
Human Data
In a study of
five pregnant women treated with fondaparinux sodium during the third trimester
of pregnancy at a dose of 2.5 mg/day, four of the women had elevated
anti-factor Xa activity noted in the cord blood. Anti-factor Xa clotting times
in these four cases were between 37.5 and 50.9 seconds. The patient who did not
have elevated anti-factor Xa activity had received only one dose of
fondaparinux sodium 22 hours prior to delivery. The concentration of
fondaparinux sodium in umbilical cord plasma was approximately 1/10th the level
of fondaparinux sodium in maternal plasma. None of the infants experienced adverse
effects.
Animal Data
Embryo-fetal
development studies have been conducted with fondaparinux sodium in pregnant rats at subcutaneous doses up
to 10 mg/kg/day (about 32 times the recommended human dose based on body
surface area) administered from days 6 to 17 of gestation and pregnant
rabbits at subcutaneous doses up to 10 mg/kg/day (about 65 times the
recommended human dose based on body surface area) administered from days 6
to 18 of gestation. These studies have revealed no evidence of adverse
developmental outcomes when fondaparinux sodium was administered to
pregnant rats and rabbits during organogenesis. Additionally, there were no
effects on pre and postnatal development in a study conducted
in rats at subcutaneous doses up to 10 mg/kg/day (about 32 times the
recommended human dose based on body surface area).
8.2 Lactation
(Pregnancy and Lactation Labeling Rule (PLLR) Conversion;
additions and/or revisions are
underlined)
Risk Summary
There are no
data on the presence of fondaparinux sodium in human milk, or the effects on
milk production. Limited clinical data during lactation preclude a clear
determination of the risk of ARIXTRA to an infant during lactation; therefore,
the developmental and health benefits of breastfeeding should be considered
along with the mother’s clinical need for ARIXTRA and any potential adverse
effects on the breastfed infant from ARIXTRA or from the underlying maternal
condition.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
(Additions and/or revisions are underlined)
What is the most
important information I should know about ARIXTRA?
ARIXTRA may
cause serious side effects, including:
…
What should I
tell my doctor before taking ARIXTRA?
Before taking
ARIXTRA, tell your doctor about all of your medical conditions, including if
you:
- have kidney or liver problems
- are pregnant or plan to become pregnant. ARIXTRA may
harm your unborn baby. If you are pregnant, talk to your doctor about
the best way for you to prevent or treat blood clots.
- are breastfeeding or plan to breastfeed. It is not known if
ARIXTRA passes into breast milk. You and your doctor should decide if
you will breastfeed during treatment with ARIXTRA.
What are possible side effects of ARIXTRA?
- Increased bleeding risk in people undergoing certain surgeries
who weigh less than 110 pounds (50Kg).
The most
common side effects of ARIXTRA include:
- bleeding problems
- bleeding, rash, and itching at the injection site (injection site
reactions)
- sleep problems (insomnia)
- low red blood cell count (anemia)
- increased wound drainage
- low potassium in your blood (hypokalemia)
- dizziness
- purplish spots on skin (purpura)
- low blood pressure (hypotension)
- confusion
- fluid-filled blisters (bullous eruption)
- blood clots (hematoma)
- severe bleeding after surgery (post-operative hemorrhage)
General information about the safe and
effective use of ARIXTRA
…
Get Email Alerts |
Guide
