Approved Drug Label (PDF)
4
Contraindications
Additions and/or
revisions underlined:
Myfortic is
contraindicated in patients with a history of hypersensitivity, including
anaphylaxis, to mycophenolate sodium, mycophenolic acid (MPA),
mycophenolate mofetil, or to any of its excipients. [see Warnings and Precautions (5.9), Adverse
Reactions (6.2)].
5
Warnings and Precautions
5.9 Hypersensitivity Reactions
Newly
added subsection:
Postmarketing
cases of hypersensitivity reactions, including angioedema and anaphylaxis, have
been reported with Myfortic. These reactions generally occurred within hours to
the next day after initiating Myfortic. If signs or symptoms of a
hypersensitivity reaction occur, discontinue Myfortic; treat and monitor until
signs and symptoms resolve [see
Contraindications (4)].
6
Adverse Reactions
Addition of the
following to the bulleted line listing:
Hypersensitivity Reactions [see Warnings and
Precautions (5.9)]
6.2 Postmarketing
Experience
Additions
and/or revisions underlined:
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions
and/or revisions underlined:
…
Hypersensitivity
Reactions
Inform
patients of the potential risk of hypersensitivity reactions. Advise patients
to stop taking Myfortic and seek immediate medical attention if signs or
symptoms of a hypersensitivity reaction occur (such as swelling of face, lips,
tongue, or throat; difficulty breathing or swallowing) [see Warning and Precautions (5.9)].
…
MEDICATION GUIDE
Additions
and/or revisions underlined:
Who should not
take Myfortic?
Do
not take Myfortic if you have a history of allergic reactions to
mycophenolic acid (MPA), mycophenolate sodium, mycophenolate mofetil, or any of
the ingredients in Myfortic. See the end of this Medication Guide for a
complete list of ingredients in Myfortic.
…
What are the possible
side effects of Myfortic?
…
Allergic
(hypersensitivity) reactions. Allergic reactions, including a severe
allergic reaction called anaphylaxis, can happen after taking Myfortic. Stop
taking Myfortic and get emergency medical help right away if you have any of
the following symptoms of an allergic reaction:
swelling of the face, lips, tongue, or throat
trouble breathing or swallowing
rash, hives, or itching
fast heartbeat
fainting, dizziness, feeling lightheaded
chest pain
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.5 New or Reactivated Viral Infections
Additions and/or
revisions underlined:
Polyomavirus associated nephropathy (PVAN), JC
virus-associated progressive multifocal leukoencephalopathy (PML),
cytomegalovirus (CMV) infections, reactivation of hepatitis B (HBV) or
hepatitis C (HCV), SARS- CoV-2 infection, have been reported in patients
treated with immunosuppressants, including MPA derivatives Myfortic and MMF.
Reduction in immunosuppression should be considered for patients who develop
evidence of new or reactivated viral infections. Physicians should also
consider the risk that reduced immunosuppression represents to the functioning
allograft.
…
5.8 Acute Inflammatory Syndrome Associated with Mycophenolate Products
Newly added
subsection:
Acute inflammatory syndrome (AIS) has been reported
with the use of mycophenolate products, and some cases have resulted in
hospitalization. AIS is a paradoxical pro-inflammatory reaction characterized
by fever, arthralgias, arthritis, muscle pain and elevated inflammatory markers
including, C-reactive protein and erythrocyte sedimentation rate, without
evidence of infection or underlying disease recurrence. Symptoms occur within
weeks to months of initiation of treatment or a dose increase. After
discontinuation, improvement of symptoms and inflammatory markers are usually
observed within 24 to 48 hours.
Monitor patients for symptoms and laboratory
parameters of AIS when starting treatment with mycophenolate products or when
increasing the dosage. Discontinue treatment and consider other treatment
alternatives based on the risk and benefit for the patient.
6
Adverse Reactions
Addition of the
following to the bulleted line listing:
6.2 Postmarketing Experience
Additions and/or
revisions underlined:
…
The
following additional adverse reactions have been identified during
post-approval use of Myfortic: agranulocytosis, asthenia, osteomyelitis,
lymphadenopathy, lymphopenia, wheezing, dry mouth, gastritis, peritonitis,
anorexia, alopecia, pulmonary edema, Kaposi’s sarcoma, de novo purine synthesis inhibitors-associated acute
inflammatory syndrome.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or
revisions underlined:
…
…
What are the
possible side effects of Myfortic? Myfortic can cause serious side effects.
See "What is
the most important information I should know about Myfortic?"
Stomach
and intestinal bleeding can happen in people who take Myfortic. Bleeding can be
severe and you may have to be hospitalized for treatment.
Some
people taking Myfortic may have an inflammatory reaction with fever, joint
stiffness, joint pain, and muscle pain. Some of these reactions may require
hospitalization. This reaction could happen within weeks to months after you
start treatment with Myfortic or if your dose is increased. Call your doctor
right away if you experience these symptoms.
…
PATIENT COUNSELING INFORMATION
Additions and/or
revisions underlined:
…
…
Acute
Inflammatory Syndrome
Inform
patients that acute inflammatory reactions have been reported in some patients
who received mycophenolate products. Some reactions were severe, requiring
hospitalization. Advise patients to contact their physician if they develop
fever, joint stiffness, joint pain or muscle pains [see Warnings and Precautions (5.8)].
Approved Drug Label (PDF)
Boxed Warning
(additions
underlined)
WARNING: EMBRYO-FETAL TOXICITY, MALIGNANCIES, AND
SERIOUS INFECTIONS
…
5
Warnings and Precautions
5.1 Embryo-Fetal Toxicity
(additions underlined)
Use
of Myfortic during pregnancy is associated with an increased risk of first trimester
pregnancy loss and an increased risk of congenital malformations, especially external
ear and other facial abnormalities, including cleft lip and palate, and anomalies
of the distal limbs, heart, esophagus, kidney, and nervous system. Females
of reproductive potential must be aware of these risks and must be counseled
regarding pregnancy prevention and planning. Avoid use of Myfortic during
pregnancy if safer treatment options are available.
5.10 Blood Donation
(new subsection added)
Patients should not donate blood during therapy and
for at least 6 weeks following discontinuation of Myfortic because their blood
or blood products might be administered to a female of reproductive potential
or a pregnant woman.
5.11 Semen Donation
(new subsection
added)
Based
on animal data, men should not donate semen during therapy and for 90 days
following discontinuation of Myfortic.
5.8 Immunizations
(additions
underlined)
During
treatment with Myfortic, the use of live attenuated vaccines should be
avoided and patients should be advised that vaccinations may be less
effective. Advise patients to discuss with the physician before seeking
any immunizations.
8
Use in Specific Populations
8.1 Pregnancy
(PLLR conversion)
Pregnancy
Exposure Registry
There
is a pregnancy exposure registry that monitors pregnancy outcomes in women
exposed to mycophenolate during pregnancy and those becoming pregnant within 6
weeks of discontinuing Myfortic treatment. To report a pregnancy or obtain
information about the registry, visit www.mycophenolateREMS.com or call
1-800-617-8191.
Risk
Summary
Following
oral or intravenous (IV) administration, MMF is metabolized to mycophenolic
acid (MPA), the active ingredient in Myfortic and the active form of the drug.
Use of MMF during pregnancy is associated with an increased risk of first
trimester pregnancy loss and an increased risk of multiple congenital malformations
in multiple organ systems (see Human
Data). Oral administration of mycophenolate to rats and rabbits during the
period of organogenesis produced congenital malformations and pregnancy loss at
doses less than the recommended clinical dose (0.05 and 1.1 times exposure at
the recommended clinical doses in kidney transplant patients for rats and
rabbits, respectively) [see Animal Data].
Risks
and benefits of Myfortic should be discussed with the patient. When
appropriate, consider alternative immunosuppressants with less potential for
embryo-fetal toxicity.
The
estimated background risk of pregnancy loss and congenital malformations in
organ transplant populations is not clear. In the U.S. general population, the
estimated background risk of major birth defects and miscarriage in clinically
recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Human Data
A
spectrum of congenital malformations (including multiple malformations in
individual newborns) has been reported in 23% to 27% of live births in MMF
exposed pregnancies, based on published data from pregnancy registries.
Malformations
that have been documented include external ear, eye, and other facial
abnormalities, including cleft lip and palate, and anomalies of the distal
limbs, heart, esophagus, kidney, and nervous system. Based on published data
from pregnancy registries, the risk of first trimester pregnancy loss has been
reported at 45% to 49% following MMF exposure. Animal Data
In
animal reproductive toxicology studies, congenital malformations and pregnancy
loss occurred when pregnant rats and rabbits received mycophenolate at dose
multiples equivalent to and less than the recommended human dose. Oral
administration of mycophenolate sodium to pregnant rats from Gestational Day 7
to Day 16 at a dose as low as 1 mg per kg resulted in malformations including
anophthalmia, exencephaly, and umbilical hernia. The systemic exposure at this
dose represents 0.05 times the clinical exposure at the human dose of 1440 mg
per day Myfortic. Oral administration of mycophenolate to pregnant rabbits from
Gestational Day 7 to Day 19 resulted in embryofetal lethality and malformations
including ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical
hernia at doses equal to or greater than 80 mg per kg per day, in the absence
of maternal toxicity. This corresponds to about 1.1 times the recommended
clinical dose based on BSA.
8.2 Lactation
(PLLR conversion)
Risk
Summary
There
are no data on the presence of mycophenolate in human milk, or the effects on
milk production. There are limited data in the National Transplantation
Pregnancy Registry on the effects of mycophenolate on a breastfed child [see Data]. Studies in rats treated with
MMF have shown mycophenolic acid to be present in milk. Because available data
are limited, it is not possible to exclude potential risks to a breastfeeding
infant.
The
developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for Myfortic and any potential adverse effects
on the breastfed infant from Myfortic or from the underlying maternal
condition. Because available data are limited, it is not possible to exclude
potential risks to a breastfeeding infant.
Data
Limited
information is available from the National Transplantation Pregnancy Registry.
Of seven infants reported by the National Transplantation Pregnancy Registry to
have been breastfed while the mother was taking mycophenolate, all were born at
34 to 40 weeks gestation and breastfed for up to 14 months. No adverse events
were reported.
8.3 Females and Males of Reproductive Potential
(PLLR conversion,
please refer to label for complete information)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
(revisions to the
Medication Guide to reflect the changes to the Prescribing Information
pertinent to the PLLR related sections, please refer to label for complete
information)
…
PATIENT COUNSELING INFORMATION
(additions
underlined)
…
Embryo-Fetal
Toxicity
Pregnancy loss and
malformations
Inform
pregnant women and females of reproductive potential that use of Myfortic in
pregnancy is associated with an increased risk of first trimester pregnancy
loss and an increased risk of congenital malformations. Advise patients that
they must use an acceptable form of contraception.
Encourage
pregnant women to enroll in the Mycophenolate Pregnancy Registry
(1-800-617-8191). This registry monitors pregnancy outcomes in women exposed
to mycophenolate
Contraception
Discuss
pregnancy testing, pregnancy prevention and planning with females of
reproductive potential.
Females
of reproductive potential must use acceptable form of birth control during the
entire Myfortic therapy and for 6 weeks after stopping Myfortic, unless the
patient chooses to avoid heterosexual sexual intercourse completely
(abstinence). Myfortic may reduce effectiveness of oral contraceptives. Use
of additional barrier contraceptive methods is recommended.
For
patients who are considering pregnancy, discuss appropriate alternative
immunosuppressants with less potential for embryo-fetal toxicity. Risks and
benefits of Myfortic should be discussed with the patient.
Development
of Lymphoma and Other Malignancies
…
Increased
Risk of Infection
Inform
patients they are at increased risk of developing a variety of infections,
including opportunistic infections, due to immunosuppression and to contact
their physician if they develop any symptoms of infection as explained in
the Medication Guide.
…
Immunizations
Inform
patients that Myfortic can interfere with the usual response to immunizations
and that they should avoid live vaccines. Before seeking vaccines on their
own, advise patients to discuss first with their physician.
…
Blood
Donation
Advise
patients not to donate blood during therapy and for at least 6 weeks following
discontinuation of Myfortic.
Semen
Donation
Advise
males of childbearing potential not to donate semen during therapy and for 90
days following discontinuation of Myfortic.
Get Email Alerts |
Guide
