Approved Drug Label (PDF)
5
Warnings and Precautions
5.8 Potential
Risks Related to JAK Inhibition
Additions and/or
revisions underlined:
It is not known whether TYK2 inhibition may be associated with the observed
or potential adverse reactions of Janus Kinase (JAK) inhibition.
In
a large, randomized, postmarketing safety trial of
a JAK inhibitor in
rheumatoid arthritis (RA), patients
50 years of age and older with at least one cardiovascular risk factor, higher
rates of all-cause mortality, including sudden cardiovascular death, major
adverse cardiovascular events, overall thrombosis, deep venous thrombosis,
pulmonary embolism, and malignancies (excluding non-melanoma skin cancer) were observed in patients treated
with the JAK inhibitor compared
to those treated with TNF blockers. SOTYKTU is not approved for use in
RA.
Hypoglycemia,
including severe hypoglycemia, has been reported following initiation of JAK
inhibitors in patients with diabetes. Advise diabetic patients to notify their
healthcare provider(s) if they develop signs or symptoms of hypoglycemia.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or
revisions underlined:
…
Before taking
SOTYKTU, tell your healthcare provider
about all of your medical
conditions, including if you:
…
…
What are the possible side effects of
SOTYKTU? SOTYKTU may cause
serious side effects,
including:
…
…
PATIENT COUNSELING INFORMATION
Additions and/or
revisions underlined:
…
Potential Risks Related to JAK
Inhibition
Hypoglycemia,
including severe hypoglycemia, has been reported in patients with diabetes
after starting JAK inhibitors. Advise diabetic patients to notify their
healthcare provider(s) if they develop signs or symptoms of hypoglycemia [see Warnings and Precautions (5.8)].
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1
Hypersensitivity Reactions
Subsection
title revised
Hypersensitivity
reactions, such as angioedema, have been reported in subjects receiving
SOTYKTU. If a clinically significant hypersensitivity reaction occurs,
institute appropriate therapy and discontinue SOTYKTU [see Contraindications (4)].
5.2
Infections
Additions
and/or revisions underlined:
.
. .
Consider
the risks and benefits of SOTYKTU prior to initiating treatment
in patients:
- with
chronic or recurrent infection
- who
have been exposed to tuberculosis
- with
a history of a serious or an opportunistic infection
- with
underlying conditions that may predispose them to infection.
Closely
monitor patients for the development of signs and symptoms of infection during
and after treatment with SOTYKTU. Patients who develops a new infection during
treatment with SOTYKTU should undergo prompt and complete diagnostic testing, have
appropriate antimicrobial therapy be initiated, and be closely monitored.
Interrupt SOTYKTU if a serious infection occurs. Do not resume SOTYKTU
until the infection resolves or is adequately treated.
Viral
Reactivation
Herpes
virus reactivation (e.g., herpes zoster, herpes simplex) was reported in
clinical trials with SOTYKTU [see Adverse
Reactions (6.1)]. In the 16-week placebo-controlled period of Trials
PSO-1 and PSO-2, herpes simplex infections were reported in 17 subjects
(6.8 per 100 patient-years) treated with SOTYKTU, and 1 subject (0.8 per 100
patient-years) treated with placebo. Multidermatomal herpes zoster was reported
in an immunocompetent subject who received SOTYKTU.
The
clinical implications of SOTYKTU on viral hepatitis reactivation are
unknown. Subjects with positive screening tests for hepatitis B or C, or
chronic hepatitis B, or untreated hepatitis C were excluded from clinical
trials or closely monitored for evidence of reactivation. Consider viral
hepatitis screening and monitoring for reactivation in accordance with clinical
guidelines before starting therapy and during therapy with SOTYKTU. If signs of
reactivation occur, consult a hepatitis specialist. SOTYKTU is not recommended
for use in patients with active hepatitis B or hepatitis C.
5.3
Tuberculosis
Additions
and/or revisions underlined:
In
Trials PSO-1 and PSO-2, of 4 subjects with latent tuberculosis (TB) who
were treated with SOTYKTU and received appropriate TB prophylaxis, no subjects
developed active TB (during the mean follow-up of 34 weeks). One subject, who
did not have latent TB, developed active TB after receiving 54 weeks of
SOTYKTU.
.
. .
5.6
Laboratory Abnormalities
Additions
and/or revisions underlined:
.
. .
Liver
Enzyme Elevations
- Treatment with SOTYKTU has been associated with liver enzyme
elevation. Liver serum transaminase elevations greater than or equal to 3 times the ULN have been
reported in subjects treated with SOTYKTU [see
Adverse Reactions (6.1)]. Evaluate liver enzymes at baseline and during
treatment SOTYKTU in patients with known or suspected liver disease
according to routine patient management. If increases in liver enzymes occur
and drug-induced liver injury is suspected, interrupt SOTYKTU until a diagnosis
of liver injury is excluded.
5.7
Immunizations
Additions
and/or revisions underlined:
Prior
to initiating therapy with SOTYKTU, complete all age-appropriate
immunizations according to current immunization guidelines including
prophylactic herpes zoster vaccination. Avoid use of live vaccines in patients
treated with SOTYKTU. The response to live or non-live vaccines has not been
evaluated.
6
Adverse Reactions
Additions
and/or revisions underlined:
The
following adverse reactions are discussed in greater detail in other sections
of labeling:
.
. .
- Elevated
CPK [see Warnings and Precautions (5.5)]
.
. .
6.1
Clinical Trials Experience
Additions
and/or revisions underlined:
.
. .
Plaque Psoriasis Clinical Trials
The
safety of SOTYKTU was evaluated in two placebo- and active-controlled trials
(Trial PSO-1 and Trial PSO-2) and an open-label extension trial in which
subjects who completed Trial PSO-1 or Trial PSO-2 could enroll [see Clinical Studies (14.1)]. In these
clinical trials, a total of 1,519 subjects with moderate-to-severe plaque
psoriasis who were candidates for systemic therapy or phototherapy received
SOTYKTU 6 mg orally once daily. Of these, 1,141 subjects were exposed to
SOTYKTU for at least one year.
In
Trials PSO-1 and PSO-2, 1,681 subjects were randomized to receive SOTYKTU 6 mg once
daily (840 subjects), placebo (419 subjects), or apremilast 30 mg twice daily
(422 subjects). All subjects randomized to placebo switched to SOTYKTU at Week
16. All other subjects remained in
their original treatment group until Week 24, at which point subjects could
have continued on the same treatment or be switched to SOTYKTU or placebo. The
mean age of subjects was 47 years. The majority of subjects were White (87%)
and male (67%).
.
. .
Specific
Adverse Reactions
Exposure
adjusted incidence rates are reported for all the adverse reactions presented
below.
Infections
In
the 16-week placebo-controlled period, infections occurred in 29% of subjects
in the SOTYKTU group (116 events per 100 patient-years) compared to
22% of subjects in the placebo group (83.7 events per 100 patient-years).
The majority of infections were non-serious and mild to moderate in severity
and did not lead to discontinuation of SOTYKTU.
.
. .
Psoriatic Arthritis Clinical Trials
The
safety of SOTYKTU was evaluated in two placebo-controlled clinical trials in
adults with active psoriatic arthritis, Trials PsA-1 and PsA-2 [see Clinical Studies (14.2)].
The
overall safety profile of SOTYKTU observed in subjects with active psoriatic
arthritis was generally consistent with the safety profile observed in subjects
with plaque psoriasis.
8
Use in Specific Populations
8.1
Pregnancy
Additions
and/or revisions underlined:
Risk
Summary
.
. .
In
animal reproduction studies, no effects on embryo-fetal development were
observed with oral administration of deucravacitinib to rats and rabbits during
organogenesis at doses that were at least 72 times the maximum
recommended human dose (MRHD) of 6 mg once daily (see Data).
.
. .
Data
Animal data
Deucravacitinib
was administered orally during the period of organogenesis at doses of 5, 15,
or 75 mg/kg/day in rats and 1, 3, or 10 mg/kg/day in rabbits. Deucravacitinib
was not associated with embryo-fetal lethality or fetal malformations in either
species. These doses resulted in maternal exposures (AUC) that were 211
times (rat) or 72 times (rabbit) the exposure at the MRHD.
In
a pre- and post-natal development study in rats, deucravacitinib was
administered orally from gestation day 6 through lactation day 20, at doses of
5, 15, or 50 mg/kg/day. At 50 mg/kg/day, F1 offspring had reduced body weight
gains during the pre-weaning period. After weaning, body weights of affected F1
offspring gradually normalized to control levels. No maternal effects were
observed at 50 mg/kg/day (87 times the MRHD based on AUC comparison). No
deucravacitinib-related
effects on postnatal developmental, neurobehavioral, or reproductive
performance of offspring were noted at doses up to 15 mg/kg/day (15
times the MRHD based on AUC comparison).
8.5
Geriatric Use
Additions
and/or revisions underlined:
Plaque
Psoriasis
In
clinical trials of SOTYKTU
in adults with moderate to severe plaque psoriasis, of the 1,519
subjects, 152 (10%) subjects were 65 years or older and 21 (1.4%) subjects were
75 years or older.
During
the Week 0-16 period of the clinical trials 80 subjects greater than or equal to 65 years old,
including 12 subjects greater than or equal to 75 years old, who received SOTYKTU without switching
treatment arms, had a higher incidence of overall serious adverse
reactions, including serious infections, and discontinuations due to adverse
reactions compared with younger adult subjects.
No
overall differences in effectiveness of SOTYKTU have been observed between
patients 65 years of age and older and younger adult patients.
Psoriatic
Arthritis
In
clinical trials of SOTYKTU in adults with active psoriatric arthritis, of the
1312 subjects treated with SOTYKTU, 171 (13%) patients were 65 years or older
and 22 (1.7%) subjects were 75 years or older. No overall differences safety or
effectiveness of SOTYKTU or exposure of deucravacitinib were observed between
subjects 65 years of age and older and younger adult subjects.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION
GUIDE
Additions
and/or revisions underlined:
.
. .
What is SOTYKTU?
SOTYKTU
is a prescription medicine used to treat:
- adults
with moderate to severe plaque psoriasis who may benefit from taking injections
or pills (systemic therapy) or treatment using ultraviolet or UV light
(phototherapy)
- adults
with active psoriatic arthritis.
PATIENT
COUNSELING INFORMATION
Additions
and/or revisions underlined:
.
. .
Infections
Inform
patients that SOTYKTU may lower the ability of their immune system to fight
infections and to contact their healthcare provider immediately if they develop
any signs or symptoms of infection [see
Warnings and Precautions (5.2)].
Inform
patients that herpes infections, including serious infections, may occur
with use of SOTYKTU [see Warnings and
Precautions (5.2)].
.
. .
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