Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 iPLEDGE REMS
Subsection title revised
Additions and/or
revisions underlined:
Because of the risk of embryo-fetal toxicity, ABSORICA/ABSORICA LD are available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS) called the iPLEDGE REMS [see Warnings and Precautions (5.1)].
Notable requirements of the iPLEDGE REMS include the
following:
Assess the reproductive status of all patients prior to initiating treatment and during treatment.
Counsel patients who cannot get pregnant on the risk and REMS requirements prior
to initiating treatment.
Counsel patients who can get pregnant on the risk and REMS requirements prior to and during treatment.
Counsel patients
who can get pregnant on pregnancy prevention requirements prior to and during
treatment, or refer patients
who can get pregnant to an expert for such counseling.
Comply with the
pregnancy testing requirements.
Assess the pregnancy status for patients
who can get pregnant
by reviewing pregnancy tests and documenting a negative result prior to each
prescription.
Report all pregnancies to the REMS.
Patients who can get
pregnant must be enrolled in the REMS and must comply with the REMS
requirements, including the
following
Comply with the pregnancy testing and pregnancy prevention requirements [see Use in Specific
Populations (8.3)].
Demonstrate comprehension of the risk
and REMS requirements before each prescription is dispensed.
Obtain the prescription within the 7-day prescription window
(i.e., within 7 days of the pregnancy test collection).
Patients who cannot get pregnant must be enrolled
in the REMS
and must comply with the REMS requirements,
including to not share isotretinoin and not donate blood.
Wholesalers and distributors must be
registered in the REMS and must only distribute to certified pharmacies.
. . .
5.3 ABSORICA and
ABSORICA LD are Not Substitutable
Additions and/or
revisions underlined:
Given
that the bioavailability and the recommended dosage of ABSORICA and ABSORICA LD
are different, ABSORICA and ABSORICA LD are not substitutable on a mg per mg
basis. For example, ABSORICA and ABSORICA LD have a 20 mg strength;
however, these strengths have different bioavailability and are not
substitutable.
5.4 Psychiatric
Disorders
Additions and/or
revisions underlined:
Be
alert to the warning signs of psychiatric disorders to help ensure patients
receive the help they need (Prescribers should read the REMS educational
material on recognizing psychiatric disorders). Prior to
initiation of ABSORICA/ABSORICA LD treatment, ask patients and family
members about any history of psychiatric disorder, and at each visit during treatment
assess patients for symptoms of depression, mood disturbance, psychosis, or
aggression to determine if further evaluation is necessary.
If
a patient develops depression, mood disturbance, psychosis, or aggression,
instruct patients (or caregivers) to immediately stop ABSORICA/ABSORICA LD and
promptly contact their health care provider. Discontinuation ofABSORICA/ABSORICA
LD may be insufficient; further evaluation may be necessary such as a referral to
a mental healthcare professional.
5.12
Musculoskeletal Abnormalities
Additions and/or
revisions underlined:
Bone
Mineral Density Changes, Osteoporosis, and Fractures
Isotretinoin
may have a negative effect on bone mineral density (BMD) in some patients. In a
clinical trial of ABSORICA and another isotretinoin capsule product, 27/306
(9%) of pediatric subjects 12 years of age and older had BMD declines,
defined as greater than or equal to 4% lumbar spine or total hip, or greater
than or equal to 5% femoral neck, during the 20-week treatment period. Repeat
scans conducted within 2 to 3 months after the post-treatment scan showed no
recovery of BMD. Long-term data at 4 to 11 months showed that 3 out of 7
subjects had total hip and femoral neck BMD below pre-treatment baseline, and 2
others did not show the increase in BMD above baseline expected in this
pediatric population. Therefore, healthcare providers should use caution when
prescribing ABSORICA/ABSORICA LD to patients with a history of childhood
osteoporosis conditions, osteomalacia, or other disorders of bone metabolism or
patients diagnosed with anorexia nervosa [see
Use in Specific Populations (8.4)].
.
. .
In
a 20-week clinical trial that included 289 pediatric subjects 12 years of
age and older on ABSORICA or another isotretinoin capsule product who had
hand radiographs taken to assess bone age, a total of 9 (3%) subjects had bone
age changes that were clinically significant and for which a drug-related
effect cannot be excluded.
5.14
Hypersensitivity Reactions
Additions and/or
revisions underlined:
Anaphylactic
reactions and other allergic reactions have been reported with isotretinoin
use. Cutaneous allergic reactions and serious cases of allergic vasculitis,
often with purpura (bruises and red patches) of the extremities and
extracutaneous involvement (including renal) have been reported. If a severe
allergic reaction occurs, discontinue ABSORICA/ABSORICA LD treatment and
initiate appropriate medical management.
.
. .
7
Drug Interactions
7.1 Vitamin A
Additions and/or
revisions underlined:
Avoid concomitant use of ABSORICA/ABSORICA LD with
supplements containing vitamin A.
. . .
7.3 Oral
Contraceptives
Newly added subsection
Isotretinoin
Capsules did not result in clinically significant changes in the
pharmacokinetics of norethindrone and ethinyl estradiol when used concomitantly
with a norethindrone and ethinyl estradiol oral contraceptive [see Clinical Pharmacology (12.3)]. It
is not known if there is an interaction with the concomitant use of
ABSORICA/ABSORICA LD with other oral contraceptives.
8
Use in Specific Populations
8.3 Females and
Males of Reproductive Potential
Additions and/or
revisions underlined:
All
patients who can get pregnant must comply with the iPLEDGE REMS requirements
[see Warnings and Precautions (5.2)].
Pregnancy
Testing
In
patients who can get pregnant, pregnancy testing is required prior to, during,
and after
ABSORICA/ABSORICA LD treatment.
Pregnancy Testing
Prior to Prescribing ABSORICA/ABSORICA LD: In patients who
can get pregnant, only
prescribe ABSORICA/ABSORICA LD after verification and documentation that
they are not pregnant:
Complete the first urine or serum pregnancy test (screening test) in a medical
setting (e.g., prescriber’s office, clinic, laboratory) and verify and document
that the test is negative, AND
For patients with:
Regular menstrual cycles, complete the second urine or serum pregnancy test
(confirmatory test) in a medical setting (1) at least 30 days after
the screening test and during the first five days of their menstrual
period immediately preceding the beginning of ABSORICA/ABSORICA LD treatment,
AND (2) after the patient has used their chosen pregnancy prevention methods
(i.e., two forms of contraception or committed to abstinence) for at least 30
days. Verify and document that the confirmatory test is negative, OR
Amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding, complete the second urine or serum pregnancy test (confirmatory test)
in a medical setting (1) at least 30 days after the screening test and
immediately preceding the beginning of ABSORICA/ABSORICA LD treatment,
AND
(2) after the patient
has used their chosen pregnancy prevention methods (i.e.,
two forms of contraception or committed to abstinence) for at least
30 days. Verify and document that the confirmatory test is negative.
If
a patient who can get pregnant has had negative screening and confirmatory
pregnancy tests but they missed the 7-day prescription window (the patient has
not obtained their ABSORICA/ABSORICA LD prescription within 7 days of the
pregnancy test collection) and has not started ABSORICA/ABSORICA LD treatment,
repeat the urine or serum pregnancy test in a medical setting and verify and
document that this repeat test is negative prior to prescribing
ABSORICA/ABSORICA LD. The confirmatory pregnancy test must be repeated, as
needed, until the patient receives ABSORICA/ABSORICA LD.
Pregnancy Testing
During Treatment with ABSORICA/ABSORICA LD: In patients who
can get pregnant who are being treated with ABSORICA/ABSORICA LD, within 7 days
before
each prescription, obtain a urine or serum pregnancy test in a
medical setting (e.g., prescriber’s office, laboratory, clinic) or instruct
patients to use a home pregnancy test.
If
the patient who can get pregnant missed the 7-day prescription window (the
patient has not obtained their ABSORICA/ABSORICA LD prescription within 7 days
of the pregnancy test collection), repeat the urine or serum pregnancy test
within 7 days before the next prescription in a medical setting or instruct
patients to use a home pregnancy test. Verify and document the negative
pregnancy test result prior to prescribing additional ABSORICA/ABSORICA LD
treatment.
Pregnancy Testing
in Patients Who Have Completed ABSORICA/ABSORICA LD Treatment: In patients who
can get pregnant who have completed ABSORICA/ABSORICA LD treatment, complete
a urine or serum pregnancy test in a medical setting (e.g., prescriber’s
office, laboratory, clinic) or instruct patients to use a home pregnancy test:
At
the end of the entire course of ABSORICA/ABSORICA LD treatment, AND
1
month after the discontinuation of ABSORICA/ABSORICA LD.
.
. .
8.4 Pediatric Use
Additions and/or
revisions underlined:
The
safety and effectiveness of ABSORICA/ABSORICA LD for the treatment of severe
recalcitrant nodular acne have been established in non-pregnant pediatric
patients 12 years of age and older with multiple inflammatory nodules with a
diameter of 5 mm or greater who are unresponsive to conventional therapy,
including systemic antibiotics. Use
of ABSORICA/ABSORICA LD in this age group for this indication is supported by
evidence from a clinical trial (Study 1) that compared the use ABSORICA to
another isotretinoin capsule product in 397 pediatric subjects 12 years of
age and older [see Clinical Studies
(14)] and pharmacokinetic data in pediatric subjects [see Clinical Pharmacology (12.3)].
.
. .
In
an open-label clinical trial (N=217) of a single course of treatment with
isotretinoin capsules for pediatric subjects 12 years of age and older with
severe recalcitrant nodular acne, BMD at several skeletal sites were not
significantly decreased (lumbar spine change >-4% and total hip change
>-5%) or were increased in the majority of subjects. One subject had a
decrease in lumbar spine BMD >4% based on unadjusted data. Sixteen (8%)
subjects had decreases in lumbar spine BMD >4%, and all the other subjects
(92%) did not have significant decreases or had increases (adjusted for body
mass index). Nine subjects (5%) had a decrease in total hip BMD >5% based on
unadjusted data. Twenty-one (11%) subjects had decreases in total hip BMD. .
.
Epiphyseal
Closure
There
are reports of premature epiphyseal closure in acne patients who used
isotretinoin at recommended doses. The effect of multiple courses of
isotretinoin on epiphyseal closure is unknown. In a 20-week clinical trial that
included 289 pediatric subjects 12 years of age and older who had hand
radiographs taken to assess bone age, a total of 9 subjects had bone age changes that were clinically significant and
for which an isotretinoin-related effect cannot be excluded [see Warnings and Precautions (5.12)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions and/or
revisions underlined:
.
. .
iPLEDGE
REMS
ABSORICA
and ABSORICA LD are available only through a restricted program called the
iPLEDGE REMS [see Warnings and
Precautions (5.2)]. Inform patients who can get pregnant of the following
notable requirements. These patients must:
Inform patients who cannot get pregnant of the following
notable requirements. These patients must enroll in the REMS and comply with the REMS
requirements.
.
. .
MEDICATION GUIDE
Extensive changes;
please refer to label for complete information
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Embryo-Fetal Toxicity
Additions and/or
revisions underlined:
ABSORICA/ABSORICA
LD is contraindicated in pregnancy [see
Contraindications (4.1)]. Based on human data, ABSORICA/ABSORICA LD can
cause fetal harm when administered to a pregnant patient. There is an extremely
high risk that life-threatening birth defects will result if pregnancy
occurs while taking any amount of ABSORICA/ABSORICA LD even for short periods
of time.
…
6
Adverse Reactions
Additions and/or
revisions underlined:
…
Reproductive
System
Abnormal
menses and sexual dysfunction, including erectile dysfunction, decreased
libido, decreased vaginal lubrication, and vaginal
dryness.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
Advise
the patient to read the FDA-approved patient labeling (Medication Guide).
Embryo-Fetal
Toxicity
There
is an extremely high risk of life-threatening birth defects when
ABSORICA/ABSORICA LD is used in pregnancy [see
Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].
…
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