Dosing & Uses
Dosage Forms & Strengths
tablet
- 10mg
- 20mg
- 30mg
Psoriatic Arthritis
Indicated for active psoriatic arthritis
Day 1: 10 mg PO in AM
Day 2: 10 mg PO AM and PM
Day 3: 10 mg PO AM and 20 PO mg PM
Day 4: 20 mg PO AM and PM
Day 5: 20 mg PO AM and 30 PO mg PM
Day 6 and thereafter: 30 PO mg BID
Plaque Psoriasis
Indicated for any severity of plaque psoriasis in adults who are candidates for phototherapy or systemic therapy
Day 1: 10 mg PO in AM
Day 2: 10 mg PO AM and PM
Day 3: 10 mg PO AM and 20 PO mg PM
Day 4: 20 mg PO AM and PM
Day 5: 20 mg PO AM and 30 mg PO PM
Day 6 and thereafter: 30 mg PO BID
Oral Ulcers associated with Behςet Disease
Indicated for oral ulcers associated with Behςet disease
Day 1: 10 mg PO in AM
Day 2: 10 mg PO AM and PM
Day 3: 10 mg PO AM and 20 mg PO PM
Day 4: 20 mg PO AM and PM
Day 5: 20 mg PO AM and 30 mg PO PM
Day 6 and thereafter: 30 mg PO BID
Dosage Modifications
Hepatic impairment: No dosage adjustment required
Renal impairment
- Mild-to-moderate (CrCl ≥30): No dosage adjustment required
- Severe (CrCl <30 mL/min)
- Reduce dose to 30 mg PO qDay
- For initial dosage titration, titrate using only the AM schedule listed above and skip the PM doses
Safety and efficacy not established
Ulcerative Colitis (Orphan)
Orphan designation for treatment of pediatric patients with ulcerative colitis
Sponsor
- Celgene Corporation; 86 Morris Avenue Summit, New Jersey 07901
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (29)
- abametapir
abametapir will increase the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
- apalutamide
apalutamide will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- bosentan
bosentan will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- carbamazepine
carbamazepine will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- dabrafenib
dabrafenib will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- dexamethasone
dexamethasone will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- efavirenz
efavirenz will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- enzalutamide
enzalutamide will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- etravirine
etravirine will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- fexinidazole
fexinidazole will increase the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- fosphenytoin
fosphenytoin will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- idelalisib
idelalisib will increase the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
- ivosidenib
ivosidenib will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- lonafarnib
lonafarnib will increase the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- lopinavir
lopinavir will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
- mitotane
mitotane will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- nafcillin
nafcillin will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- nevirapine
nevirapine will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- oxcarbazepine
oxcarbazepine will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- pentobarbital
pentobarbital will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- phenobarbital
phenobarbital will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- phenytoin
phenytoin will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- primidone
primidone will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- rifabutin
rifabutin will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- rifampin
rifampin will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- rifapentine
rifapentine will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong CYP inducers results in a significant decrease of systemic exposure of apremilast, which may result in loss of efficacy
- secobarbital
secobarbital will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- voxelotor
voxelotor will increase the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
Monitor Closely (13)
- amobarbital
amobarbital will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- belzutifan
belzutifan will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
- cenobamate
cenobamate will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- elagolix
elagolix will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
- encorafenib
encorafenib, apremilast. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- fedratinib
fedratinib will increase the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- istradefylline
istradefylline will increase the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
- lenacapavir
lenacapavir will increase the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- lorlatinib
lorlatinib will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rucaparib
rucaparib will increase the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- stiripentol
stiripentol, apremilast. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
- tazemetostat
tazemetostat will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
Minor (6)
- acetazolamide
acetazolamide will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- levoketoconazole
levoketoconazole will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ribociclib
ribociclib will decrease the level or effect of apremilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
>10% (Psoriasis and Psoriatic Arthritis)
Diarrhea (7.7-17%)
Nausea (7.4-17%)
>10% (Behςet Disease)
Diarrhea (41.3%)
Nausea (19.2%)
Headache (14.4%)
Upper respiratory tract infection (11.5%)
1-10% (Behςet Disease)
Upper abdominal pain (8.7%)
Vomiting (8.7%)
Back pain (7.7%)
Viral upper respiratory tract infection (6.7%)
Arthralgia (5.8%)
1-10% (Psoriasis and Psoriatic Arthritis)
Upper respiratory tract infection (0.6-9%)
Tension headache (8%)
Headache (4.8-6%)
Vomiting (0.8-4%)
Fatigue (3%)
Dyspepsia (3%)
Decreased appetite (3%)
Insomnia (2%)
Back pain (2%)
Migraine (2%)
Frequent bowel movements (2%)
Depression (1%)
Bronchitis (1%)
Tooth abscess (1%)
Folliculitis (1%)
Frequency Not Defined (Psoriasis and Psoriatic Arthritis)
Immune system disorders: Hypersensitivity
Investigations: Weight decrease
Gastrointestinal disorders: Frequent bowel movement, gastroesophageal reflux disease, dyspepsia
Metabolism and nutrition disorders: Decreased appetite
Nervous system disorders: Migraine
Respiratory, thoracic, and mediastinal disorders: Cough
Skin and SC tissue disorders: Rash
Warnings
Contraindications
Hypersensitivity to apremilast or to any of the excipients in the formulation
Cautions
Hypersensitivity reactions, including angioedema and anaphylaxis, reported; with known hypersensitivity to apremilast; if signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue and institute appropriate therapy
Associated with an increase in adverse reactions of depression; before using, evaluate patient for history of depression and/or suicidal thoughts or behavior
Weight decrease of 5-10% of body weight reported in 10-12% of patients
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
Severe GI adverse effects
- Severe diarrhea, nausea, and vomiting reported; mostly occurred within the first few weeks of treatment
- In some cases, patients were hospitalized
- Patients aged ≥65 yr and patients taking medications that cause volume depletion or hypotension may be at a higher risk of these complications; monitor those who are more susceptible to complications of diarrhea or vomiting
- Quick improvement observed with dosage reduction or discontinuation; consider dose reduction or suspension if patients develop severe diarrhea, nausea, or vomiting
Drug interaction overview
- Coadministration with strong CYP inducers (eg, rifampin, carbamazepine, phenobarbital phenytoin) may occur and result in a loss of efficacy of apremilast; therefore, coadministration is not recommended
Pregnancy & Lactation
Pregnancy
Available pharmacovigilance data use in pregnant women have not established a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes, but data are extremely limited
Based on findings from animal reproduction studies, may increase the risk for fetal loss
Pregnancy exposure registry
- Registry monitors pregnancy outcomes in women exposed to apremilast during pregnancyRegistry information can be obtained by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/otezla
Animal data
- 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 6 of gestation through Day 20 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)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)
- Apremilast distributed across the placenta into the fetal compartment in mice and monkeys
- Advise pregnant women of the potential risk of fetal lossConsider pregnancy planning and prevention for females of reproductive potential
Lactation
There are no data on the presence of apremilast in human milk, the effects on the breastfed infant, or the effects on milk production
Detected in the milk of lactating mice
Consider developmental and health benefits of breastfeeding along with the mother’s clinical need and any potential adverse effects on the breastfed infant or from the underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Oral small molecule inhibitor of phosphodiesterase-4 specific for cAMP, resulting in increased intracellular cAMP levels
The specific mechanism by which apremilast exerts it therapeutic action in psoriatic arthritis is not well defined
Absorption
Absolute bioavailability: 73%
Peak plasma time: 2.5 hr
Coadministration with food does not alter absorption
Distribution
Protein bound: 68%
Vd: 87 L
Metabolism
Apremilast is a major circulating component (45%) followed by inactive metabolite M12 (39%), a glucuronide conjugate of O-demethylated apremilast
Metabolized by both CYP oxidative metabolism with subsequent glucuronidation and non-CYP mediated hydrolysis
In vitro CYP metabolism primarily by CYP3A4, with minor contribution from CYP1A2 and CYP2A6
Elimination
Half-life: 6-9 hr
Clearance: 10 L/hr
Excretion: 58% urine; 39% feces
Administration
Oral Administration
To reduce risk of GI symptoms associated with initial therapy, titrate to recommended dose (30 mg PO BID) according to the dosage schedules listed above
Can be administered without regard to meals
Swallow tablet whole; do not crush, split, or chew
Storage
Store below 30ºC (86ºF)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Otezla Starter oral - | 10 mg (4)-20 mg (4)-30 mg(19) tablet |  | |
| Otezla Starter oral - | 10 mg (4)-20 mg (4)-30 mg (47) tablet |  | |
| Otezla Starter oral - | 10 mg (4)-20 mg (4)-30 mg (47) tablet |  | |
| Otezla oral - | 30 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
Formulary
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