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Apremilast: Drug information

Apremilast: Drug information
(For additional information see "Apremilast: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Otezla
Brand Names: Canada
  • APO-Apremilast;
  • AURO-Apremilast;
  • GLN-Apremilast;
  • JAMP-Apremilast;
  • MINT-Apremilast;
  • Otezla;
  • PMS-Apremilast;
  • SANDOZ Apremilast
Pharmacologic Category
  • Phosphodiesterase-4 Enzyme Inhibitor
Dosing: Adult
Behçet disease, psoriasis, or psoriatic arthritis

Behçet disease, psoriasis, or psoriatic arthritis: Oral: Initial: 10 mg in the morning on day 1. Titrate upward by additional 10 mg per day on days 2 to 5 as follows: Day 2: 10 mg twice daily; Day 3: 10 mg in the morning and 20 mg in the evening; Day 4: 20 mg twice daily; Day 5: 20 mg in the morning and 30 mg in the evening. Maintenance dose: 30 mg twice daily starting on day 6.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes.

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: Initial: 10 mg once daily in the morning on days 1 to 3; titrate using morning doses only (skip evening doses) to 20 mg once daily on days 4 and 5. Maintenance dose: 30 mg once daily in the morning starting on day 6.

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions (Significant): Considerations
GI effects

GI effects such as diarrhea, nausea, and vomiting, including severe cases, have been reported (Ref). GI effects typically resolve with continued treatment within ~4 weeks (Ref); however, dose reduction or discontinuation may be necessary for severe symptoms.

Mechanism: Related to pharmacologic action; phosphodiesterase 4 (PDE4) inhibition and increased cyclic adenosine monophosphate levels lead to activation of membrane chloride channels and subsequent fluid secretion into the gut, causing diarrhea. PDE4 inhibition and increased cyclic adenosine monophosphate levels may also contribute to both central and peripheral mechanisms that lead to nausea (Ref).

Onset: Intermediate; usually within the first 2 weeks of initiation (Ref).

Risk factors (for complications from severe GI effects):

• Patients ≥65 years

• Patients taking medications that may lead to volume depletion or hypotension

Neuropsychiatric effects

Neuropsychiatric effects (eg, anxiety, depression, mood changes, suicidal ideation, suicidal tendencies) have been reported rarely with apremilast (Ref). In one cohort study of patients with psoriasis, users of apremilast had similar rates of anxiety plus depression as users of other noncorticosteroid systemic psoriasis treatments; however, the rate of anxiety was higher (Ref).

Onset: Varied; occurred within 2 years after initiation (Ref).

Risk factors:

• History of bipolar disorder, depression, and/or emotional or physical abuse (Ref)

Weight loss

Over 52 weeks or longer, the mean weight loss with apremilast in the clinical trial population was ~1% (Ref). Over 156 weeks, the mean weight loss was 1.5% (Ref). Weight loss >5% has been reported in 12% to 14% of patients in the first 24 weeks (Ref). Over follow-up at 3 to 5 years, 20% to 22% of patients lost >5% body weight (Ref).

Mechanism: Related to pharmacologic action; phosphodiesterase 4 inhibition increases secretion of glucagon-like-peptide-1, which stimulates insulin secretion and inhibits glucagon secretion (Ref).

Onset: Varied; within 1 year (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%:

Endocrine & metabolic: Weight loss (>5% of body weight: 5%; 5% to 10% of body weight: 10% to 12%; ≥10% of body weight: 2%) (table 1)

Apremilast: Adverse Reaction: Weight Loss

Drug (Apremilast)

Placebo

Dose

Indication

Number of Patients (Apremilast)

Number of Patients (Placebo)

Comments

5%

4%

30 mg twice daily

Behçet disease

103

102

>5% of body weight

12%

5%

30 mg twice daily

Moderate to severe plaque psoriasis

784

382

5% to 10% of body weight

2%

1%

30 mg twice daily

Moderate to severe plaque psoriasis

784

382

≥10% of body weight

10%

3%

30 mg twice daily

Psoriatic arthritis

497

495

5% to 10% of body weight

Gastrointestinal: Diarrhea (8% to 41%; severe diarrhea: <1%) (table 2), nausea (7% to 22%; severe nausea: <1%) (table 3)

Apremilast: Adverse Reaction: Diarrhea

Drug (Apremilast)

Placebo

Dose

Indication

Number of Patients (Apremilast)

Number of Patients (Placebo)

Comments

41%

20%

30 mg twice daily

Behçet disease

104

103

Up to week 12

17%

6%

30 mg twice daily

Moderate to severe plaque psoriasis

920

506

Up to day 112

9%

1%

30 mg twice daily

Psoriatic arthritis

497

495

Day 1 to day 5

8%

2%

30 mg twice daily

Psoriatic arthritis

493

490

Day 6 to day 112

Apremilast: Adverse Reaction: Nausea

Drug (Apremilast)

Placebo

Dose

Indication

Number of Patients (Apremilast)

Number of Patients (Placebo)

Comments

19%

11%

30 mg twice daily

Behçet disease

104

103

Up to week 12

17%

7%

30 mg twice daily

Moderate to severe plaque psoriasis

920

506

Up to day 112

9%

3%

30 mg twice daily

Psoriatic arthritis

493

490

Day 6 to day 112

7%

1%

30 mg twice daily

Psoriatic arthritis

497

495

Day 1 to day 5

Nervous system: Headache (5% to 14%)

Respiratory: Upper respiratory tract infection (4% to 12%; viral upper respiratory tract infection: 7%)

1% to 10%:

Dermatologic: Folliculitis (1%)

Gastrointestinal: Abdominal pain (4%; upper abdominal pain: ≤9%), decreased appetite (3%), dyspepsia (3%), frequent bowel movements (2%), tooth abscess (1%), vomiting (0.8% to 9%; severe vomiting: <1%) (table 4)

Apremilast: Adverse Reaction: Vomiting

Drug (Apremilast)

Placebo

Dose

Indication

Number of Patients (Apremilast)

Number of Patients (Placebo)

Comments

9%

2%

30 mg twice daily

Behçet disease

104

103

Up to week 12

4%

2%

30 mg twice daily

Moderate to severe plaque psoriasis

920

506

Up to day 112

3%

0.4%

30 mg twice daily

Psoriatic arthritis

493

490

Day 6 to day 112

0.8%

0.4%

30 mg twice daily

Psoriatic arthritis

497

495

Day 1 to day 5

Nervous system: Depressed mood (≤1%), depression (≤1%; severe depression: <1%) (table 5), fatigue (3%), insomnia (2%), migraine (2%), tension headache (8%)

Apremilast: Adverse Reaction: Depression

Drug (Apremilast)

Placebo

Indication

Number of Patients (Apremilast)

Number of Patients (Placebo)

Comments

1%

1%

Behçet disease

104

103

Described as depression or depressed mood

1%

0.4%

Moderate to severe plaque psoriasis

920

506

N/A

Severe depression: 0.1%

0%

Moderate to severe plaque psoriasis

1,308

506

N/A

1%

0.8%

Psoriatic arthritis

998

495

Described as depression or depressed mood

Severe depression: 0.2%

0%

Psoriatic arthritis

1,441

495

Described as depression or depressed mood

Neuromuscular & skeletal: Arthralgia (6%), back pain (2% to 8%)

Respiratory: Bronchitis (1%), nasopharyngitis (3%), sinus headache (1%)

<1%:

Dermatologic: Exacerbation of psoriasis (rebound following discontinuation)

Nervous system: Suicidal ideation (table 6), suicidal tendencies (table 7)

Apremilast: Adverse Reaction: Suicidal Ideation

Drug (Apremilast)

Placebo

Indication

Number of Patients (Apremilast)

Number of Patients (Placebo)

Comments

0.2%

0%

Psoriatic arthritis

1,441

495

Described as suicidal ideation and behavior

Apremilast: Adverse Reaction: Suicidal Tendencies

Drug (Apremilast)

Placebo

Indication

Number of Patients (Apremilast)

Number of Patients (Placebo)

Comments

0.1%

0.2%

Moderate to severe plaque psoriasis

1,308

506

N/A

0.2%

0%

Psoriatic arthritis

1,441

495

Described as suicidal ideation and behavior

Frequency not defined:

Dermatologic: Skin rash

Gastrointestinal: Gastroesophageal reflux disease

Hypersensitivity: Hypersensitivity reaction

Respiratory: Cough

Postmarketing:

Hypersensitivity: Anaphylaxis, angioedema

Nervous system: Anxiety (Vasilakis-Scaramozza 2020)

Contraindications

Hypersensitivity to apremilast or any component of the formulation.

Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; breastfeeding.

Warnings/Precautions

Disease-related concerns:

• Renal impairment: Use with caution in renal impairment. Systemic exposure is increased in patients with severe renal impairment (CrCl <30 mL/minute); dosage reduction is recommended.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Otezla: 30 mg

Tablet Therapy Pack, Oral:

Otezla: 10 & 20 & 30 mg (55 ea)

Generic Equivalent Available: US

No

Pricing: US

Tablet Therapy Pack (Otezla Oral)

10 & 20 & 30 mg (per each): $105.39

Tablets (Otezla Oral)

30 mg (per each): $96.61

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Otezla: 30 mg

Generic: 30 mg

Tablet Therapy Pack, Oral:

Otezla: 10 & 20 & 30 mg (27 ea)

Generic: 10 & 20 & 30 mg (27 ea)

Administration: Adult

Oral: Administer without regard to food. Do not crush, chew, or split tablets.

Use: Labeled Indications

Behçet disease: Treatment of oral ulcers associated with Behçet disease.

Psoriasis: Treatment of patients with plaque psoriasis who are candidates for phototherapy or systemic therapy.

Psoriatic arthritis: Treatment of patients with active psoriatic arthritis.

Metabolism/Transport Effects

Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

COVID-19 Vaccines: Apremilast may diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding apremilast for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. These guidelines consider apremilast to be an immunomodulatory or immunosuppressive medication. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Apremilast. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Apremilast. Risk X: Avoid combination

Riociguat: Apremilast may enhance the hypotensive effect of Riociguat. Management: Riociguat is contraindicated with nonselective phosphodiesterase (PDE) inhibitors and PDE type 5 inhibitors. Other types of PDE inhibitors are not contraindicated, but caution is advised and patients should be monitored for hypotension. Risk C: Monitor therapy

Reproductive Considerations

Based on data from animal reproduction studies, in utero exposure to apremilast may cause an increase in pregnancy loss. According to the manufacturer, pregnancy planning and prevention should be considered for patients who could become pregnant.

Recommendations for use of apremilast to treat rheumatic and musculoskeletal diseases in patients planning to become pregnant or patients who are planning to father a child are not available due to lack of data (ACR [Sammaritano 2020]).

Pregnancy Considerations

Based on data from animal reproduction studies, in utero exposure to apremilast may cause an increase in pregnancy loss.

Recommendations for use of apremilast in pregnant patients with rheumatic and musculoskeletal diseases are not available due to lack of data. Placental transfer may be expected based on molecular weight (ACR [Sammaritano 2020]).

Breastfeeding Considerations

It is not known if apremilast is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Recommendations for use of apremilast in breastfeeding patients with rheumatic and musculoskeletal diseases are not available due to lack of data. Transfer into breast milk may be expected based on molecular weight (ACR [Sammaritano 2020]).

Monitoring Parameters

Monitor weight regularly during therapy; renal function; signs or symptoms of mood changes, depression, or suicidal thoughts; diarrhea or vomiting, especially patients more susceptible to complications of diarrhea (eg, older patients, patients taking medications that may lead to volume depletion or hypotension).

Mechanism of Action

Apremilast inhibits phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP) which results in increased intracellular cAMP levels and regulation of numerous inflammatory mediators (eg, decreased expression of nitric oxide synthase, TNF-α, and interleukin [IL]-23, as well as increased IL-10) (Schafer, 2012).

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Well absorbed

Distribution: Vd: 87 L

Protein binding: ~68%

Metabolism: Hepatic, primarily via CYP3A4: minor pathways include CYP1A2 and CYP2A6

Bioavailability: ~73%

Half-life elimination: ~6 to 9 hours

Time to peak: ~2.5 hours

Excretion: Urine (58%; 3% unchanged drug); feces (39%; 7% unchanged drug)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: The AUC and Cmax of apremilast increased by ~88% and 42%, respectively, in patients with severe renal impairment.

Older adult: The apremilast exposure in elderly subjects (65 to 85 years of age) was about 13% higher in AUC and about 6% higher in Cmax than in younger subjects (18 to 55 years of age).

Sex: The extent of exposure in females was about 31% higher and Cmax was about 8% higher than that in male subjects.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (BD) Bangladesh: Aprima | Arsenor;
  • (BR) Brazil: Otezla;
  • (CO) Colombia: Otezla;
  • (EC) Ecuador: Apremax;
  • (HR) Croatia: Otezla;
  • (KE) Kenya: Aprezo;
  • (MX) Mexico: Otezla;
  • (QA) Qatar: Otezla | Otezla Titration Pack;
  • (RU) Russian Federation: Otezla;
  • (ZA) South Africa: Otezla
  1. Crowley J, Thaçi D, Joly P, et al. Long-term safety and tolerability of apremilast in patients with psoriasis: Pooled safety analysis for ≥156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2). J Am Acad Dermatol. 2017;77(2):310-317.e1. doi:10.1016/j.jaad.2017.01.052 [PubMed 28416342]
  2. Kavanaugh A, Gladman DD, Edwards CJ, et al. Long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a PALACE 1-3 pooled analysis. Arthritis Res Ther. 2019;21(1):118. doi:10.1186/s13075-019-1901-3 [PubMed 31077258]
  3. Mease PJ, Gladman DD, Gomez-Reino JJ, et al. Long-term safety and tolerability of apremilast versus placebo in psoriatic arthritis: A pooled safety analysis of three phase III, randomized, controlled trials. ACR Open Rheumatol. 2020;2(8):459-470. doi:10.1002/acr2.11156 [PubMed 32710493]
  4. Otezla (apremilast) [prescribing information]. Thousand Oaks, CA: Amgen Inc; December 2021.
  5. Otezla (apremilast) [product monograph]. Mississauga, Ontario, Canada: Amgen Canada Inc; August 2020.
  6. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020;72(4):529‐556. doi:10.1002/art.41191 [PubMed 32090480]
  7. Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83(12):1583-1590. doi:10.1016/j.bcp.2012.01.001 [PubMed 22257911]
  8. Vasilakis-Scaramozza C, Persson R, Hagberg KW, Jick S. The risk of treated anxiety and treated depression among patients with psoriasis and psoriatic arthritis treated with apremilast compared to biologics, DMARDs and corticosteroids: A cohort study in the United States MarketScan database. J Eur Acad Dermatol Venereol. 2020;34(8):1755-1763. doi:10.1111/jdv.16231 [PubMed 31981426]
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