Approved Drug Label (PDF)
5
Warnings and Precautions
5.3 Depression
Additions and/or revisions underlined:
Plaque Psoriasis: During the
16-week placebo-controlled period of the 3 controlled clinical trials in adult
subjects with moderate to severe plaque psoriasis, 1.3% (12/920) of subjects
treated with OTEZLA reported depression compared to 0.4% (2/506) treated with
placebo.
…
During the 16-week placebo-controlled period of the clinical
trial in adults with mild to moderate plaque psoriasis, the incidence of
subjects reporting depression was similar to what was observed in the adult
moderate to severe plaque psoriasis trials.
5.4 Weight Decrease
Additions and/or revisions underlined:
Weight loss may occur in adult or pediatric patients
treated with OTEZLA.
Regularly monitor the weight of patients treated
with OTEZLA. If unexplained or clinically significant weight loss occurs,
evaluate weight loss and consider discontinuation of OTEZLA [see Adverse Reactions (6.1)].
Weight Loss in Adult Patients
…
During the placebo-controlled period of the trials in
adults with moderate to severe plaque psoriasis, weight decrease between
5%-10% of body weight occurred in 12% (96/784) of subjects treated with OTEZLA compared
to 5% (19/382) treated with placebo.
…
During the placebo-controlled period of the clinical
trial in adults with mild to moderate plaque psoriasis, weight decrease was
similar to what was observed in the trials of adults with moderate to
severe plaque psoriasis.
…
Weight
Loss in Pediatric Patients
During
the placebo-controlled period of the clinical trial in pediatric subjects 6 to
17 years of age with moderate to severe plaque psoriasis, weight decrease
between 5%-10% of body weight occurred in 12% (19/163) of pediatric subjects
treated with OTEZLA compared to 2.5% (2/80) of pediatric subjects treated with
placebo. Weight decrease of greater than or equal to 10% of body weight occurred in 1% (1/163) of
pediatric subjects treated with OTEZLA twice daily compared to 0% (0/80) of
pediatric subjects treated with placebo.
Closely
monitor growth (height and weight) in OTEZLA-treated pediatric patients.
Pediatric patients who are not growing or gaining weight as expected may need
to have their treatment interrupted.
6
Adverse Reactions
6.1 Clinical
Trials Experience
Extensive changes
to table 3, table 4, and table 5 titles, please refer to label for complete
information.
Additions and/or
revisions underlined:
Moderate to Severe Plaque Psoriasis Clinical Trials
Adverse
Reactions from Clinical Trials in Adults
…
Adverse
Reactions from Clinical Trials in Pediatric Subjects 6 to 17 Years of Age
OTEZLA was evaluated in a Phase 3, multicenter,
randomized, placebo-controlled trial (PSOR-6) in pediatric subjects 6 to 17
years of age with moderate to severe plaque psoriasis [see Clinical Studies
(14.3)]. A total of 245 subjects were randomized to receive OTEZLA (163
subjects, at a dosage of 20 mg twice daily or 30 mg twice daily, based on body
weight) or placebo (82 subjects) twice daily during the 16-week
placebo-controlled phase of the trial. The trial also included a 36-week
extension phase during which all subjects received OTEZLA 20 mg or 30 mg twice
daily. Overall, the safety profile observed in pediatric subjects treated with
OTEZLA during the study was consistent with the safety profile established in
adult subjects with moderate to severe plaque psoriasis.
Mild to Moderate Plaque Psoriasis Clinical Trial in
Adults
…
8
Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
Plaque Psoriasis
The safety and effectiveness of OTEZLA have been
established in pediatric patients 6 years of age and older and weighing at
least 20 kg with moderate to severe plaque psoriasis who are candidates for
phototherapy or systemic therapy. Use of OTEZLA in these patients is supported
by evidence from a 52-week adequate and well-controlled clinical trial (PSOR-6)
in 245 pediatric subjects 6 to 17 years of age with moderate to severe plaque
psoriasis.
Weight loss in OTEZLA-treated pediatric subjects was
comparable to weight loss observed in adults. [see Warnings and Precautions (5.4), Adverse Reactions (6.1) and
Clinical Studies (14.3)].
Closely monitor growth (height and weight) in
OTEZLA-treated pediatric patients. Pediatric patients who are not growing or
gaining weight as expected may need to have their treatment interrupted.
The safety and effectiveness of OTEZLA have not been
established in pediatric patients below the age of 6 years or weighing less
than 20 kg with moderate to severe plaque psoriasis.
Psoriatic Arthritis and Behçet’s Disease
The safety and effectiveness of OTEZLA have not been
established in pediatric patients with psoriatic arthritis or oral ulcers
associated with Behçet’s Disease.
8.6 Renal Impairment
Additions and/or revisions underlined:
Apremilast pharmacokinetics were characterized in adult
subjects with mild, moderate, and severe renal impairment as defined by a
creatinine clearance of 60-89, 30-59, and less than 30 mL per minute,
respectively, by the Cockcroft–Gault equation. No dosage adjustment is needed
in patients with mild or moderate renal impairment. In adult patients with
severe renal impairment, reduce the maintenance dosage of OTEZLA to 30 mg
once daily. In pediatric patients 6 years of age and older and weighing at
least 20 kg with moderate to severe plaque psoriasis and severe renal
impairment, reduce the maintenance dosage of OTEZLA to 30 mg once daily for
pediatric patients weighing at least 50 kg and to 20 mg once daily for
pediatric patients weighing 20 kg to less than 50 kg [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions
and/or revisions underlined:
Administration Instructions
Instruct
patients to take OTEZLA only as prescribed [see
Dosage and Administration (2.1 and 2.2)]. Advise patients to take
OTEZLA with or without food. Instruct patients to swallow tablets whole
and not to crush, split, or chew prior to swallowing [see Dosage and Administration (2.3)].
…
Weight Decrease
Inform
patients that treatment with OTEZLA is associated with potential weight loss. Instruct
patients or caregivers to have their or their child’s weight
monitored regularly and, if unexplained or clinically significant weight loss
occurs, to contact their healthcare provider for evaluation of the weight loss [see Warnings and Precautions (5.4)].
Approved Drug Label (PDF)
6
Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or
revisions underlined:
…
OTEZLA was evaluated in a
Phase 3, multicenter, randomized, placebo-controlled trial (PSOR-5) in
adults with moderate to severe plaque psoriasis of the genital area [see Clinical Studies (14.2)]. A total
of 289 subjects were randomized to receive
OTEZLA 30 mg twice daily or placebo
twice daily. Overall,
the safety profile
observed in the OTEZLA group during the
placebo-controlled phase was consistent with the safety profile previously established in adult subjects
with moderate to severe plaque psoriasis.
Mild to Moderate
Plaque Psoriasis Clinical
Trial
OTEZLA was evaluated in a Phase
3, multicenter, randomized, placebo-controlled trial (PSOR-4)
in adult subjects with mild to moderate plaque
psoriasis [see Clinical Studies (14.3)].
A total of 595 subjects were randomized to receive OTEZLA 30 mg twice daily
(297 subjects) or placebo twice daily (298 subjects) during the
placebo-controlled phase of the trial. The trial also included an open-label extension phase during which all subjects received OTEZLA 30 mg twice
daily. Overall, the safety profile observed in the OTEZLA group during the placebo-controlled
phase was consistent with the safety profile previously established in adult
subjects with moderate to severe plaque psoriasis.
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Hypersensitivity
Newly added subsection:
Hypersensitivity reactions, including cases of angioedema and a naphylaxis, have been reported during post marketing surveillance.
Avoid theuse of OTEZLA in patients
with known hypersensitivity to apremilast or to any of the excipients in the formulation.
If signs or symptoms of serious
hypersensitivity reactions develop during treatment, discontinue OTEZLA and institute appropriate therapy.
5.4 Weight Decrease
Additions and/or revisions underlined:
During the placebo-controlled period of the trials in psoria tic arthritis (PsA), weight decrease
between 5%-10% of body weight was reported in 10% (49/497) of subjects treated with OTEZLA 30 mg twice daily compared to 3.3% (16/495) treated with placebo.
During the placebo-controlled period of the trials in moderate to severe plaque psoriasis, weight decrease between 5%-10% of body weight occurred in 12% (96/784)
of subjects treated with OTEZLA
compared to 5% (19/382) treated with placebo. Weight decrease of greater than or equal to 10% of body weight
occurred in 2% (16/784) of subjects
treated with OTEZLA 30 mg twice daily compared to 1% (3/382) subjects treated with placebo.
During the placebo-controlled period of the mild to moderate plaque
psoriasis clinical
trial, weight decrease was similar to wha t was observed in the moderate to severe plaque psoriasis trials.
During the placebo-controlled period of the phase
3 trial in Behçet’s Disease, weight decrease >5%
of body weight was reported in 4.9% (5/103)
of subjects treated with OTEZLA 30 mg twice daily compared to 3.9% (4/102) subjects treated with placebo.
6
Adverse Reactions
6.1
Clinical Trials Experience
Extensive changes; please refer to
label
8
Use in Specific Populations
8.5 Geriatric Use
Additions and/or revisions underlined:
Of the 1493 patients who enrolled in Tria ls PsA-1, PsA-2, and PsA-3, a total of 146 psoriatic arthritis patients were 65 years of age and older, including 19 patients 75 years and older. No overall differences were observed in the safety profile of geriatric patients
greater than or equal to 65 years of age and younger adult patients
< 65 years of age in the clinical trials.
Of the 1257 subjects who enrolled in two placebo-controlled plaque psoriasis trials (PSOR 1 and PSOR 2), a totalof 108 plaque psoriasis patients were 65 years of age andolder, including 9 patients who were
75 years of age and older. No overall differences were observed in
the safety or effectiveness in geriatric patients greater than or equal to 65 years of age and younger adult patients < 65 years of age in the clinical trials.
Because patients 65 years of age or older may be at a higher risk of complications such as volume depletion or hypotension from severe diarrhea,
nausea, or vomiting, monitor geriatric patients closely for such complications [see Warning and Precautions (5.2)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING
INFORMATION
Additions and/or revisions underlined:
- Administration Instructions
Instruct patients to take OTEZLA
only as prescribed.
Advise patients that OTEZLAcan be taken with or without food,
and that the tablets should not be crushed,
split, or chewed [see Dosage and Administration(2.1)].
Inform patients that hypersensitivity reactions can occur following administration of OTEZLA. Instruct patients to contact their healthcare provider
if they experience symptoms of an allergic reaction [see Warnings and Precautions (5.1)].
- Diarrhea, Nausea,
and Vomiting
Advise patients of the potential complications of severe diarrhea, nausea, or vomitingand instruct them to contact their healthcare provider
if they experience these
adverse reactions, especially if the patient
is 65 years of age or older [see Warnings and Precautions (5.2)].
Inform patients that treatment with OTEZLA is associated with
an increased incidence of depression.
Patients, their caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal thoughts or other mood changes,
and if such changes
occur to contact their healthcare provider [see Warnings and Precautions (5.3)].
Instruct patients to have their weight monitored regularly and,
if unexplained or clinica lly significant weight loss occurs, to contact their healthcare provider for evaluation of the weight loss.
Approved Drug Label (PDF)
6
Adverse Reactions
(Newly added information)
OTEZLA was evaluated in a
Phase 3, multicenter, randomized, placebo-controlled study (PSOR-3) in adults with moderate to
severe psoriasis of the scalp [see Clinical
Studies (14.2)]. A total
of 302
subjects were randomized to receive OTEZLA
30 mg twice daily or placebo
twice daily. The most
commonly reported adverse reactions that occurred
at a higher rate in the OTEZLA group than in the
placebo group were: diarrhea (31%
vs. 11%), nausea (22% vs. 6%), headache (12% vs. 5%), and vomiting (6% vs. 2%).
The proportion of subjects who discontinued treatment
because of any adverse reaction during the 16
-week placebo-controlled period of the study was 6% for
subjects who received OTEZLA
30 mg twice daily and 3% for subjects who received
placebo. Gastrointestinal adverse reactions that led
to discontinuation of treatment were diarrhea (3% vs 0%), nausea
(1.5% vs 1%), and vomiting (1.5%
vs 0 %) in the OTEZLA group compared to placebo.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Depression
(additions underlined)
…
![]()
Behçet’s disease: During the
placebo-controlled period of the phase 3 study, 1% (1/104) of patients treated
with OTEZLA reported depression/depressed mood compared to 1% (1/103) treated
with placebo. None of these reports of depression was serious or led to study
discontinuation. No instances of suicidal ideation or behavior were reported
during the placebo-controlled period of the phase 3 study in patients treated
with OTEZLA (0/104) or treated with placebo (0/103).
5.3 Weight Decrease
(additions underlined)
![]()
…
During the controlled period of the
phase 3 study in Behçet’s disease, weight decrease >5% of body weight was
reported in 4.9% (5/103) of subjects treated with OTEZLA 30 mg twice daily
compared to 3.9% (4/102) patients treated with placebo.
…
6
Adverse Reactions
(section updated, additions underlined)
The
following adverse reactions are described elsewhere in the labeling:
6.1 Clinical Trials Experience
(additions
underlined)
…
Behçet’s
Disease Clinical Trials
OTEZLA
was evaluated in a Phase 3, multicenter, randomized, placebo-controlled study
(BCT-002) in adult patients with Behçet’s Disease (BD) with active oral ulcers.
A total of 207 patients were randomized to receive OTEZLA 30 mg twice daily or
placebo twice daily. Titration was used over the first 5 days . After Week 12, all patients received
treatment with OTEZLA 30 mg twice daily. Patients ranged in age from 19 to 72, with
a mean age of 40 years.
Diarrhea,
nausea, headache, and upper respiratory tract infection were the most commonly
reported adverse reactions. The proportion of patients with BD who discontinued
treatment due to any adverse reaction during the placebo-controlled period of
the study, was 2.9% for patients treated with OTEZLA 30 mg twice daily and 4.9%
for placebo-treated patients.
Table
4: Adverse Reactions Reported in greater than or equal to5% of Patients on
OTEZLA and with at least 1% Greater Frequency than Patients on Placebo; up to
Week 12
(please
refer to label to view Table 4)
8
Use in Specific Populations
8.1 Pregnancy
(PLLR
conversion, please refer to label for more information)
8.2 Lactation
(PLLR
conversion)
Risk
Summary
There
are no data on the presence of apremilast in human milk, the effects on the
breastfed infant, or the effects on milk production. However, apremilast was
detected in the milk of lactating mice. When a drug is present in animal milk,
it is likely that the drug will be present in human milk. The developmental and
health benefits of breastfeeding should be considered along with the mother’s
clinical need for OTEZLA and any potential adverse effects on the breastfed
infant from OTEZLA or from the underlying maternal condition.
Data
In
mice, following a single oral administration of 10 mg/kg to dams on postpartum
day 13, apremilast concentrations in milk were approximately 1.5-times that of
simultaneously collected blood samples.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
(addition
underlined)
…
Inform patients that there is a
pregnancy registry for pregnant women who have taken OTEZLA during pregnancy.
Advise patients to contact the registry at 1-877-311-8972 to enroll or visit https://mothertobaby.org/ongoing-study/otezla.
Advise pregnant women and females of reproductive potential of the potential
risk to a fetus. Advise females to inform their prescriber of a known or
suspected pregnancy.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Diarrhea, Nausea, and Vomiting
(new subsection added)
There have been postmarketing reports of severe
diarrhea, nausea, and vomiting associated with the use of OTEZLA. Most
events occurred within the first
few weeks of treatment. In some cases patients were
hospitalized. Patients
65 years of age or older and patients taking medications that can
lead to volume depletion or
hypotension may be at
a higher risk of complications from severe diarrhea, nausea,
or vomiting. Monitor patients who are more
susceptible to complications of diarrhea or vomiting.
Patients who reduced dosage or discontinued
OTEZLA generally improved quickly. Consider
OTEZLA dose reduction or suspension
if patients develop severe diarrhea,
nausea, or vomiting.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
(additions
underlined)
Diarrhea, Nausea,
and
Vomiting
![]()
![]()
Instruct patients to contact their healthcare provider if they experience severe diarrhea, nausea, or vomiting. Prescribers should advise patients of the potential complications of severe diarrhea,
nausea, or vomiting.
Consider OTEZLA dose reduction
or suspension if patients
develop severe
diarrhea, nausea, or
vomiting.
…
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