Apremilast

FDA Drug Information • Also known as: Otezla

Brand Names: Otezla
Dosage Form: POWDER
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION 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. OTEZLA 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. Chemical Structure

What Is Apremilast Used For?

1 INDICATIONS AND USAGE OTEZLA/OTEZLA XR, an inhibitor of phosphodiesterase 4 (PDE4), is indicated for the treatment of: Adult patients with: Active psoriatic arthritis ( 1.1 ) Plaque psoriasis who are candidates for phototherapy or systemic therapy ( 1.2 ) Oral ulcers associated with Behçet's Disease ( 1.3 ) Pediatric patients 6 years of age and older with: Active psoriatic arthritis ( 1.1 ) Moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy ( 1.2 ) 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. OTEZLA 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. OTEZLA 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.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION 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 1 for the initial titration schedule. Recommended maintenance dosage is OTEZLA 30 mg twice daily or OTEZLA XR 75 mg once daily ( 2.1 ) 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 2 for the initial titration schedule ( 2.1 ) For patients weighing 50 kg or more : Recommended maintenance dosage is OTEZLA 30 mg twice daily or OTEZLA XR 75 mg once daily ( 2.1 ) For patients weighing 20 kg to less than 50 kg : Recommended maintenance dosage is OTEZLA 20 mg twice daily ( 2.1 ) Dosage in Patients with Severe Renal Impairment : Adult Patients : For initial dosage titration, titrate using only morning schedule listed in Table 1 and skip afternoon doses. Recommended maintenance dosage is OTEZLA 30 mg once daily ( 2.3 ) 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 2 and skip afternoon doses ( 2.3 ) For patients weighing 50 kg or more: Recommended maintenance dosage is OTEZLA 30 mg once daily ( 2.3 ) For patients weighing 20 kg to less than 50 kg: Recommended maintenance dosage is OTEZLA 20 mg once daily ( 2.3 ) 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 1 to Day 5 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Warnings and Precautions (5.1) ] Diarrhea, Nausea, and Vomiting [see Warnings and Precautions (5.2) ] Depression [see Warnings and Precautions (5.3) ] Weight Decrease [see Warnings and Precautions (5.4) ] Drug Interactions [see Warnings and Precautions (5.5) ] Psoriatic Arthritis : The most common adverse reactions (≥ 5%) are diarrhea, nausea, and headache ( 6.1 ) Plaque Psoriasis : The most common adverse reactions (≥ 5%) are diarrhea, nausea, upper respiratory tract infection, and headache, including tension headache ( 6.1 ) Behçet's Disease : The most common adverse reactions (≥ 10%) are diarrhea, nausea, headache, and upper respiratory tract infection ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Psoriatic Arthritis Clinical Trials OTEZLA was evaluated in three multicenter, randomized, double-blind, placebo-controlled trials (PsA-1, PsA-2, and PsA-3) of similar design in adult subjects with active psoriatic arthritis [see Clinical Studies (14.1) ] . Across the three trials, there were 1493 subjects randomized equally to placebo, OTEZLA 20 mg twice daily or OTEZLA 30 mg twice daily. Titration was used over the first 5 days [see Dosage and Administration (2.1) ] . Placebo subjects whose tender and swollen joint counts had not improved by at least 20% were re-randomized 1:1 in a blinded fashion to either OTEZLA 20 mg twice daily or 30 mg twice daily at week 16 while OTEZLA subjects remained on their initial treatment. Subjects ranged in age from 18 to 83 years, with an overall median age of 51 years. The majority of the most common adverse reactions presented in Table 3 occurred within the first 2 weeks of treatment and tended to resolve over time with continued dosing. Diarrhea, headache, and nausea were the most commonly reported adverse reactions. The most common adverse reactions leading to discontinuation for subjects taking OTEZLA were nausea (1.8%), diarrhea (1.8%), and headache (1.2%). The proportion of subjects with psoriatic arthritis who discontinued treatment due to any adverse reaction was 4.6% for subjects taking OTEZLA 30 mg twice daily and 1.2% for placebo-treated subjects. Table 3. Adverse Reactions Reported in ≥ 2% of Adult Subjects with Active Psoriatic Arthritis on OTEZLA 30 mg Twice Daily and ≥ 1% than That Observed in Subjects on Placebo up to Day 112 (Week 16) Placebo OTEZLA 30 mg BID BID = twice daily. Adverse Reactions Day 1 to 5 (N = 495) n (%) n (%) indicates number of subjects and percent. Day 6 to Day 112 (N = 490) n (%) Day 1 to 5 (N = 497) n (%) Day 6 to Day 112 (N = 493) n (%) Diarrhea Of the reported gastrointestinal adverse reactions, 1 subject experienced a serious adverse reaction of nausea and vomiting in OTEZLA 30 mg twice daily; 1 subject treated with OTEZLA 20 mg twice daily experienced a serious adverse reaction of diarrhea; 1 subject treated with OTEZLA 30 mg twice daily experienced a serious adverse reaction of headache. 6 (1.2) 8 (1.6) 46 (9.3) 38 (7.7) Nausea 7 (1.4) 15 (3.1) 37 (7.4) 44 (8.9) Headache 9 (1.8) 11 (2.2) 24 (4.8) 29 (5.9) Upper respiratory tract infection Of the reported adverse drug reactions none were serious. 3 (0.6) 9 (1.8) 3 (0.6) 19 (3.9) Vomiting 2 (0.4) 2 (0.4) 4 (0.8) 16 (3.2) Nasopharyngitis 1 (0.2) 8 (1.6) 1 (0.2) 13 (2.6) Abdominal pain upper 0 (0.0) 1 (0.2) 3 (0.6) 10 (2.0) Moderate to Severe Plaque Psoriasis Clinical Trials Adverse Reactions from Clinical Trials in Adults The safety of OTEZLA was assessed in 1426 subjects in three...

Drug Interactions

7 DRUG INTERACTIONS 7.1 Strong CYP450 Inducers Co-administration with strong CYP450 inducers (such as rifampin) decreases apremilast exposure and may result in loss of efficacy of OTEZLA/OTEZLA XR [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3) ] .

Contraindications

4 CONTRAINDICATIONS OTEZLA/OTEZLA XR is contraindicated in patients with a known hypersensitivity to apremilast or to any of the excipients in the formulation [see Warnings and Precautions (5.1) , see Adverse Reactions (6.1) ] . Known hypersensitivity to apremilast or to any of the excipients in the formulation ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy 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 (see Data ) . 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 (see Data ) . 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. Animal Data In an...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING OTEZLA 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). Store OTEZLA 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) [see USP Controlled Room...

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.