PSORIASIX

The active ingredient in

OTEZLA/OTEZLA XR tablets is apremilast.

Apremilast drug substance is non-hygroscopic.

Apremilast drug substance is practically insoluble in water and slightly soluble in alcohol.

Apremilast is a phosphodiesterase 4 (PDE4) inhibitor.

Apremilast is known chemically as

N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide.

Its empirical formula is

C 22 H 24 N 2 O 7 S and the molecular weight is 460.5.

The chemical structure is

OTEZLA (apremilast) tablets are supplied in 10 mg, 20 mg, and 30 mg strengths for oral administration.

Each tablet contains apremilast as the active ingredient and the following inactive ingredients: croscarmellose sodium, iron oxide red, iron oxide yellow (20 and 30 mg only), iron oxide black (30 mg only), lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide.

XR (apremilast) extended-release tablets are supplied in a 75 mg strength for oral administration.

Each tablet contains apremilast as the active ingredient and the following inactive ingredients: cellulose acetate, colloidal silicon dioxide, ferrosoferric oxide, hydroxypropyl methylcellulose acetate succinate, hypromellose, iron oxide red, magnesium stearate, mannitol, microcrystalline cellulose, polyethylene glycol, polyethylene oxide, sodium chloride, titanium dioxide.

an inhibitor of phosphodiesterase 4 (PDE4), is indicated for the treatment of: Adult patients with: Active psoriatic arthritis Plaque psoriasis who are candidates for phototherapy or systemic therapy Oral ulcers associated with Behçet's Disease Pediatric patients 6 years of age and older with: Active psoriatic arthritis Moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy In the pediatric population, OTEZLA is indicated for patients weighing at least 20 kg, and OTEZLA XR is indicated for patients weighing at least 50 kg. 1.1 Psoriatic Arthritis OTEZLA is indicated for the treatment of adult patients and pediatric patients 6 years of age and older and weighing at least 20 kg with active psoriatic arthritis.

XR is indicated for the treatment of adult patients and pediatric patients 6 years of age and older and weighing at least 50 kg with active psoriatic arthritis. 1.2 Plaque Psoriasis OTEZLA/OTEZLA XR is indicated for the treatment of adult patients with plaque psoriasis who are candidates for phototherapy or systemic therapy.

OTEZLA is indicated for the treatment of 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.

XR is indicated for the treatment of pediatric patients 6 years of age and older and weighing at least 50 kg with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. 1.3 Oral Ulcers Associated with Behçet's Disease OTEZLA/OTEZLA XR is indicated for the treatment of adult patients with oral ulcers associated with Behçet's Disease.

Lactation History of psychiatric illness Female likely to be pregnant Severe renal impairment Psychiatric illness Elderly Subject at risk of psychiatric illness Low weight.

Apremilast is an oral small molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP).

PDE4 inhibition results in increased intracellular cAMP levels.

The specific mechanism(s) by which apremilast exerts its therapeutic action is not well defined. 12.2 Pharmacodynamics In clinical studies, apremilast decreased IL-17, IL-22 and TNF-alpha levels circulating in blood and reduced expression of these pro-inflammatory cytokine genes in skin.

The clinical implications of these pharmacodynamic responses remain unclear. 12.3 Pharmacokinetics Absorption OTEZLA when taken orally is absorbed with an absolute bioavailability of ~73%, with peak plasma concentrations (C max ) occurring at a median time (t max ) of ~2.5 hours.

Co-administration with food does not alter the extent of absorption of OTEZLA.

XR when taken orally is absorbed with peak plasma concentrations (C max ) occurring at a median time (t max ) of ~6 hours.

XR 75 mg administered once daily demonstrates comparable PK exposure (steady-state AUC and C max ) to OTEZLA 30 mg twice daily.

When administered with a high-fat meal, OTEZLA XR t max was delayed by 3 hours and C max and AUC were increased by ~28% compared to fasted conditions.

Therefore, OTEZLA XR may be taken without regard to meals.

Human plasma protein binding of apremilast is approximately 68%.

Mean apparent volume of distribution (Vd) is 87 L. Metabolism Following oral administration in humans, apremilast is a major circulating component (45%) followed by inactive metabolite M12 (39%), a glucuronide conjugate of O-demethylated apremilast.

It is extensively metabolized in humans with up to 23 metabolites identified in plasma, urine and feces.

Apremilast is metabolized by both cytochrome (CYP) oxidative metabolism with subsequent glucuronidation and non-CYP mediated hydrolysis.

In vitro, CYP metabolism of apremilast is primarily mediated by CYP3A4, with minor contributions from CYP1A2 and CYP2A6.

The plasma clearance of apremilast is about 10 L/hr in healthy subjects, with a terminal elimination half-life of approximately 6-9 hours.

Following oral administration of radiolabeled apremilast, about 58% and 39% of the radioactivity is recovered in urine and feces, respectively, with about 3% and 7% of the radioactive dose recovered as apremilast in urine and feces, respectively.

Specific Populations Patients with Hepatic Impairment

The pharmacokinetics of apremilast is not affected by moderate or severe hepatic impairment.

The pharmacokinetics of apremilast is not affected by mild or moderate renal impairment.

In 8 adult subjects with severe renal impairment administered a single dose of 30 mg OTEZLA, the AUC and C max of apremilast increased by approximately 88% and 42%, respectively.

The effects of renal impairment have not been studied for OTEZLA XR.

A single oral dose of 30-mg apremilast was studied in young adults and elderly healthy subjects.

The apremilast exposure in elderly subjects (65 to 85 years of age) was about 13% higher in AUC and about 6% higher in C max than in young subjects (18 to 55 years of age) .

The pharmacokinetics of OTEZLA were evaluated in a clinical trial in pediatric subjects to 17 years of age with moderate to severe plaque psoriasis at the recommended pediatric dosage regimen.

Population pharmacokinetic analysis indicated that steady-state exposure (AUC and C max ) of OTEZLA in pediatric subjects receiving the pediatric maintenance dosage regimen (20 or 30 mg twice daily, based on body weight) was comparable to steady-state exposure in adult subjects at the 30 mg twice daily dosage.

In pharmacokinetic trials in healthy volunteers, the extent of exposure in females was about 31% higher and C max was about 8% higher than that in male subjects.

The pharmacokinetics of apremilast in Chinese and Japanese healthy male subjects is comparable to that in White healthy male subjects.

In addition, apremilast exposure is similar among White subjects (including Hispanic or Latino and not Hispanic or Latino subjects) and Black or African American subjects.

Drug Interactions In vitro data

Apremilast is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4 and not an inducer of CYP1A2, CYP2B6, CYP2C9, CYP2C19, or CYP3A4.

Apremilast is a substrate, but not an inhibitor of P-glycoprotein (P-gp) and is not a substrate or an inhibitor of organic anion transporter (OAT)1 and OAT3, organic cation transporter (OCT)2, organic anion transporting polypeptide (OATP)1B1 and OATP1B3, or breast cancer resistance protein (BCRP).

Drug interaction trials were performed with apremilast and CYP3A4 substrates (oral contraceptive containing ethinyl estradiol and norgestimate), CYP3A and P-gp inhibitor (ketoconazole), CYP450 inducer (rifampin) and frequently co-administered drug in this patient population (methotrexate).

No significant pharmacokinetic interactions were observed when 30-mg oral apremilast was administered with either oral contraceptive, ketoconazole, or methotrexate.

Co-administration of the

CYP450 inducer rifampin (600 mg once daily for 15 days) with a single oral dose of 30-mg apremilast resulted in reduction of apremilast AUC and C max by 72% and 43%, respectively.

Mechanism of action

Apremilast is a small, Oral taken molecule, phosphodiesterase 4 inhibitor (PDE4), which acts at the intracellular level to modulate a network of pro-inflammatory and anti-inflammatory mediators.

PDE4 is a specific cyclic adenosine monophosphate (CMP) cyclic phosphodiesterase, which is the predominant PDE in inflammatory cells.

Inhibition of

PDE4 increases intracellular levels of cAMP, which in turn reduces the inflammatory response by modulating the expression of TNF-α, IL-23, IL-17 and other inflammatory cytokines.

Cyclic AMP also modulates levels of anti-inflammatory cytokines such as IL-10.

These pro-inflammatory and anti-inflammatory mediators have been involved in psoriasic rheumatism and psoriasis.

• Urticaria (Uncommon)
• Rash (Uncommon)
• Fatigue (Common)
• Hypersensitivity (Uncommon)
• Angioedema Weight (decrease) (Uncommon)
• Appetite decreased (Common)
• Rhinophyryngitis (Common)
• Suicidal ideation (Uncommon)
• Depression (Common)
• Anxiety (Uncommon)
• Insomnia (Common)
• Changing humor (Uncommon)
• Suicidal behaviour (Uncommon)
• Nausea (Very common)
• Common stools (Common)
• Diarrhoea (Very common)
• Gastroesophageal reflux (Common)
• Gastrointestinal haemorrhage (Uncommon)
• Vomiting (Common)
• Dyspepsia (Common)
• Upper abdominal pain (Common)
• Sleeping (Common)
• Headache (Very common)
• Stress headache (Common)
• Migraine (Common)
• Bronchitis (Common)
• Cough (Common)
• Upper respiratory tract infection (Very common).

is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation.

Known hypersensitivity to apremilast or to any of the excipients in the formulation.

To reduce the risk of gastrointestinal symptoms, titrate to recommended dosage as follows: Adults with Psoriatic Arthritis, Plaque Psoriasis, or Behçet's Disease See Table for the initial titration schedule.

Recommended maintenance dosage is

OTEZLA 30 mg twice daily or OTEZLA XR 75 mg once daily Pediatric Patients 6 Years of Age and Older and Weighing at Least 20 kg with Psoriatic Arthritis or Moderate to Severe Plaque Psoriasis See Table for the initial titration schedule For patients weighing 50 kg or more: Recommended maintenance dosage is OTEZLA 30 mg twice daily or OTEZLA XR 75 mg once daily For patients weighing 20 kg to less than 50 kg: Recommended maintenance dosage is OTEZLA 20 mg twice daily Dosage in Patients with Severe Renal Impairment: Adult Patients: For initial dosage titration, titrate using only morning schedule listed in Table and skip afternoon doses.

OTEZLA 30 mg once daily Pediatric Patients 6 Years of Age and Older and Weighing at Least 20 kg with Psoriatic Arthritis or Moderate to Severe Plaque Psoriasis: For initial dosage titration, titrate using only morning schedule for appropriate body weight category in Table and skip afternoon doses For patients weighing 50 kg or more: Recommended maintenance dosage is OTEZLA 30 mg once daily For patients weighing 20 kg to less than 50 kg: Recommended maintenance dosage is OTEZLA 20 mg once daily 2.1 Recommended Dosage in Adult and Pediatric Patients with Psoriatic Arthritis, Plaque Psoriasis, and Behçet's Disease Adult Patients with Psoriatic Arthritis, Plaque Psoriasis, or Behçet's Disease The recommended initial dosage titration from Day to Day is shown in Table 1.

Following the 5-day titration with OTEZLA, the recommended maintenance dosage is OTEZLA 30 mg twice daily or OTEZLA XR 75 mg once daily taken orally starting on Day 6.

This titration is intended to reduce the gastrointestinal symptoms associated with initial therapy.

Table 1.

Dosage Titration Schedule for Adult Patients with Psoriatic Arthritis, Plaque Psoriasis, or Behçet's Disease OTEZLA Dosage Titration OTEZLA tablets should be used for the initial titration regardless of whether OTEZLA or OTEZLA XR will be used for the maintenance dosage.

OTEZLA/OTEZLA XR Maintenance Dosage Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 & thereafter AM AM PM AM PM AM PM AM PM BID = twice daily; QD = once daily 10 mg 10 mg 10 mg 10 mg 20 mg 20 mg 20 mg 20 mg 30 mg OTEZLA 30 mg BID OR OTEZLA XR 75 mg QD Pediatric Patients 6 Years of Age and Older and Weighing at Least 20 kg with Psoriatic Arthritis Moderate to Severe Plaque Psoriasis The recommended dosage for pediatric patients 6 years of age and older and weighing at least 20 kg with psoriatic arthritis or moderate to severe plaque psoriasis is based on body weight.

Following the appropriate initial titration schedule shown in Table 2, the recommended maintenance dosage is: For pediatric patients who weigh at least 50 kg: OTEZLA 30 mg twice daily or OTEZLA XR 75 mg once daily taken orally For pediatric patients who weigh from 20 kg to less than 50 kg: OTEZLA 20 mg twice daily taken orally The initial titration is intended to reduce the gastrointestinal symptoms associated with initial therapy.

Table 2.

Patients 6 Years of Age and Older and Weighing at Least 20 kg with Psoriatic Arthritis or Moderate to Severe Plaque Psoriasis OTEZLA Dosage Titration OTEZLA tablets should be used for the initial titration regardless of whether OTEZLA or OTEZLA XR will be used for the maintenance dosage.

OTEZLA/OTEZLA XR Maintenance Dosage Body Weight Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 & thereafter AM AM PM AM PM AM PM AM PM BID = twice daily; QD = once daily 50 kg or more 10 mg 10 mg 10 mg 10 mg 20 mg 20 mg 20 mg 20 mg 30 mg OTEZLA 30 mg BID OR OTEZLA XR 75 mg QD 20 kg to less than 50 kg 10 mg 10 mg 10 mg 10 mg 20 mg 20 mg 20 mg 20 mg 20 mg OTEZLA 20 mg BID 2.2 Switching Between OTEZLA and OTEZLA XR Patients treated with OTEZLA 30 mg twice daily may be switched to OTEZLA XR 75 mg once daily the day following the last dose of OTEZLA 30 mg. Patients treated with OTEZLA XR 75 mg once daily may be switched to OTEZLA 30 mg twice daily the day following the last dose of OTEZLA XR 75 mg. 2.3 Dosage Adjustment in Adult and Pediatric Patients with Severe Renal Impairment Adult Patients with Psoriatic Arthritis, Plaque Psoriasis, or Behçet's Disease For initial dosage titration in adult patients with severe renal impairment (creatinine clearance [CLcr] of less than 30 mL per minute estimated by the Cockcroft–Gault equation), titrate OTEZLA using only the AM schedule listed in Table and skip the PM doses.

The recommended maintenance dosage in this group is OTEZLA 30 mg once daily.

XR is not recommended for adult patients with severe renal impairment; the appropriate dosage for these patients has not been determined.

Patients 6 Years of Age and Older and Weighing at Least 20 kg with Psoriatic Arthritis or Moderate to Severe Plaque Psoriasis For initial dosage titration in pediatric patients 6 years of age and older and weighing at least 20 kg with psoriatic arthritis or moderate to severe plaque psoriasis and severe renal impairment (CLcr of less than 30 mL per minute estimated by the Cockcroft–Gault equation), titrate OTEZLA using only the AM schedule listed in Table for the appropriate body weight category and skip the PM doses.

The recommended maintenance dosage is

For pediatric patients who weigh at least 50 kg: OTEZLA 30 mg once daily taken orally For pediatric patients who weigh 20 kg to less than 50 kg: OTEZLA 20 mg once daily taken orally OTEZLA XR is not recommended for pediatric patients with severe renal impairment; the appropriate dosage for these patients has not been determined. 2.4 Important Administration Instructions Administer OTEZLA/OTEZLA XR with or without food.

Swallow tablets whole.

Do not crush, split, or chew.

is available as diamond-shaped, film-coated tablets in the following dosage strengths: 10 mg pink tablet engraved with "APR" on one side and "10" on the other side; 20 mg brown tablet engraved with "APR" on one side and "20" on the other side; 30 mg beige tablet engraved with "APR" on one side and "30" on the other side.

Tablets are supplied in the strengths and package configurations listed in Table 14.

Table 14.

OTEZLA Package Configurations Package configuration Tablet strength NDC number Configurations for 30 mg BID Dosage 28-day treatment initiation pack 55-tablet blister pack including tablets for titration and maintenance dosage: 4 tablets (10 mg each), 4 tablets (20 mg each), and 47 tablets (30 mg each) 55513-369-55 60-count bottle 30 mg 55513-137-60 Configurations for 20 mg BID Dosage 28-day treatment initiation pack 55-tablet blister pack including tablets for titration and maintenance dosage: 4 tablets (10 mg each) and 51 tablets (20 mg each) 55513-508-55 60-count bottle 20 mg 55513-497-60 OTEZLA XR is available as 75 mg round, biconvex, pink, film-coated extended-release tablets with "APR 75" printed in black on one side and a hole or indentation on either side of the tablet, which may or may not be visible.

Tablets are supplied in the strengths and package configurations listed in Table 15.

Table 15.

OTEZLA XR Package Configurations Package configuration Tablet strength NDC number 28-day treatment initiation pack 41-tablet blister titration pack including tablets for titration and maintenance dosage: OTEZLA: 4 tablets (10 mg each), 4 tablets (20 mg each), and 19 tablets (30 mg each) and OTEZLA XR: 14 tablets (75 mg each) 55513-516-41 Bottles of 30 OTEZLA XR: 30 tablets (75 mg each) 55513-519-30 Storage and Handling Store OTEZLA tablets below 30°C (86°F).

XR tablets between 20°C and 25°C (68°F and 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) .

OTEZLA tablets below 30°C (86°F).

XR tablets between 20°C and 25°C (68°F and 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) .

Risk Summary Available data with

OTEZLA use in pregnant women have not identified a drug-associated risk of major birth defects or adverse maternal or fetal outcomes.

In animal embryo-fetal development studies, the administration of apremilast to pregnant cynomolgus monkeys during organogenesis resulted in dose-related increases in abortion/embryo-fetal death at dose exposures approximately 2-times the maximum recommended human therapeutic dose (MRHD) and no adverse effect at an exposure of 1.4-times the MRHD.

When apremilast was administered to pregnant mice during organogenesis, there were no apremilast-induced malformations up to exposures 4-times the MRHD.

Based on findings from animal reproduction studies, OTEZLA/OTEZLA XR may increase the risk for fetal loss.

Advise pregnant women of the potential risk of fetal loss.

The background risk of major birth defects and miscarriage for the indicated populations 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% to 4% and 15% to 20%, respectively.

Data Human Data A pregnancy registry conducted by the Organization of Teratology Information Specialists (OTIS) in the United States and Canada assessed the risk of major birth defects in liveborn infants of women with psoriatic arthritis, psoriasis, or Behçet's Disease exposed to apremilast in the first trimester.

The study compared pregnant women treated with apremilast (n = 15) with disease matched pregnant women who were not exposed to apremilast (n = 106).

In the apremilast-exposed cohort, there were no reports of liveborn infants with major birth defects nor miscarriages.

One stillbirth was reported in the apremilast exposed cohort.

These data are limited by the small sample size of apremilast-exposed pregnancies.

In an embryo-fetal developmental study, pregnant cynomolgus monkeys were administered apremilast at doses of 20, 50, 200, or 1000 mg/kg/day during the period of organogenesis (gestation Days [GD] 20 through 50).

There was a dose -related increase in spontaneous abortions, with most abortions occurring during Weeks to 4 of dosing in the first trimester, at doses approximately 2-times the MRHD and greater (on an area under the curve [AUC] basis at doses ≥ 50 mg/kg/day).

No abortifacient effects were observed at a dose approximately 1.4-times the MRHD (on an AUC basis at a dose of 20 mg/kg/day).

Although there was no evidence for a teratogenic effect at doses of 20 mg/kg/day and greater when examined at Day 100, aborted fetuses were not examined.

In an embryo-fetal development study in mice, apremilast was administered at doses of 250, 500, or 750 mg/kg/day to dams during organogenesis (GD 6 through 15).

In a combined fertility and embryo-fetal development study in mice, apremilast was administered at doses of 10, 20, 40, or 80 mg/kg/day starting 15 days before cohabitation and continuing through GD 15.

No teratogenic findings attributed to apremilast were observed in either study; however, there was an increase in post-implantation loss at doses corresponding to a systemic exposure of approximately 2-times the MRHD and greater (≥ 20 mg/kg/day).

At doses of ≥ 20 mg/kg/day skeletal variations included incomplete ossification sites of tarsals, skull, sternebra, and vertebrae.

No effects were observed at a dose approximately 1.3-times the MRHD (10 mg/kg/day).

Apremilast distributed across the placenta into the fetal compartment in mice and monkeys.

In a pre and postnatal study in mice, apremilast was administered to pregnant female mice at doses of 10, 80, or 300 mg/kg/day from Day of gestation through Day of lactation, with weaning on Day 21.

Dystocia, reduced viability, and reduced birth weights occurred at doses corresponding to ≥ 4-times the MRHD (on an AUC basis at doses ≥ 80 mg/kg/day).

No adverse effects occurred at a dose 1.3-times the MRHD (10 mg/kg/day).

There was no evidence for functional impairment of physical development, behavior, learning ability, immune competence, or fertility in the offspring at doses up to 7.5-times the MRHD (on an AUC basis at a dose of 300 mg/kg/day).

OTEZLA 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 years of age and older with moderate to severe plaque psoriasis.

Weight loss in

OTEZLA-treated pediatric subjects was comparable to weight loss observed in adults.

Closely monitor growth (height and weight) in pediatric patients treated with OTEZLA.

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 The safety and effectiveness of OTEZLA have been established for pediatric patients 6 years of age and older and weighing at least 20 kg with psoriatic arthritis.

OTEZLA in these patients is supported by evidence from adequate and well controlled trials of OTEZLA in adults with psoriatic arthritis, pharmacokinetic data from adult patients with psoriatic arthritis, adult patients with psoriasis, and pediatric patients with psoriasis, and safety data from a clinical trial in 245 pediatric patients 6 years of age and older with psoriasis.

Steady-state exposure of

OTEZLA in pediatric patients with psoriatic arthritis is estimated to be comparable to adults with psoriatic arthritis and pediatric patients with psoriasis.

Closely monitor growth (height and weight) in OTEZLA-treated pediatric patients.

OTEZLA have not been established in pediatric patients below the age of 6 years or weighing less than 20 kg with psoriatic arthritis.

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.

OTEZLA XR Plaque Psoriasis and Psoriatic Arthritis The safety and effectiveness of OTEZLA XR have been established for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis in pediatric patients 6 years of age and older and weighing at least 50 kg. Use of OTEZLA XR in these patients is supported by pharmacokinetic data from healthy adults demonstrating comparable PK exposure between OTEZLA XR 75 mg once daily and OTEZLA 30 mg twice daily, which is the recommended OTEZLA dosage for pediatric patients weighing at least 50 kg.

Closely monitor growth (height and weight) in pediatric patients treated with OTEZLA XR.

The safety and effectiveness of OTEZLA

XR have not been established in pediatric patients below the age of 6 years or weighing less than 50 kg with moderate to severe plaque psoriasis or psoriatic arthritis.

Behçet's Disease The safety and effectiveness of OTEZLA XR have not been established in pediatric patients with oral ulcers associated with Behçet's Disease.

Of the 1493 patients who enrolled in Trials PsA-1, PsA-2, and PsA-3, a total of 146 (9.8%) psoriatic arthritis patients were 65 years of age and older, including 19 (1.3%) patients 75 years and older.

No overall differences were observed in the safety profile of geriatric patients ≥ 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 total of 108 (8.6%) plaque psoriasis patients were 65 years of age and older, including 9 (0.7%) patients who were 75 years of age and older.

No overall differences were observed in the safety or effectiveness in geriatric patients ≥ 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.