Apremilast Avansor: Uses, Dosage & Side Effects
An oral PDE4 inhibitor for the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, and oral ulcers associated with Behçet's disease
Apremilast Avansor (apremilast) is a prescription oral medication belonging to the class of phosphodiesterase 4 (PDE4) inhibitors. It is approved for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy, active psoriatic arthritis in adults who have had an inadequate response or intolerance to prior disease-modifying antirheumatic drug (DMARD) therapy, and oral ulcers associated with Behçet's disease. By inhibiting PDE4, apremilast modulates the inflammatory response by increasing intracellular cyclic adenosine monophosphate (cAMP) levels, which reduces the production of pro-inflammatory cytokines while promoting anti-inflammatory mediators. It is taken orally as a 30 mg film-coated tablet twice daily after an initial dose titration period.
Quick Facts: Apremilast Avansor
Key Takeaways
- Apremilast Avansor is an oral PDE4 inhibitor approved for moderate to severe plaque psoriasis, active psoriatic arthritis, and oral ulcers associated with Behçet's disease, offering a targeted small-molecule alternative to injectable biologic therapies.
- Treatment begins with a 5-day dose titration schedule (starting at 10 mg once daily and increasing to the maintenance dose of 30 mg twice daily) to minimize gastrointestinal side effects such as diarrhea and nausea.
- Clinical trials (ESTEEM-1, ESTEEM-2, PALACE-1 through PALACE-3) demonstrated significant improvements in skin clearance (PASI-75) and joint symptoms (ACR20) compared with placebo, with benefits increasing over time.
- Apremilast does not require routine laboratory monitoring (no blood count or liver function tests needed), which is an advantage over many other systemic psoriasis and psoriatic arthritis treatments.
- The most common side effects are gastrointestinal (diarrhea, nausea, vomiting) and typically occur during the first two weeks of treatment, resolving within approximately four weeks of continued therapy.
What Is Apremilast Avansor and What Is It Used For?
Apremilast Avansor contains the active substance apremilast, a small-molecule oral inhibitor of the enzyme phosphodiesterase 4 (PDE4). PDE4 is the predominant phosphodiesterase enzyme found in inflammatory cells, including T cells, monocytes, macrophages, neutrophils, dendritic cells, and keratinocytes. This enzyme plays a critical role in regulating intracellular levels of cyclic adenosine monophosphate (cAMP), a key second messenger molecule that modulates the production of inflammatory mediators. By selectively inhibiting PDE4, apremilast raises intracellular cAMP levels, which in turn activates protein kinase A (PKA) and subsequently modulates the transcription of a broad range of genes involved in the inflammatory process.
The pharmacological consequence of PDE4 inhibition is a dual effect on the inflammatory cascade. On one hand, apremilast downregulates the production of pro-inflammatory cytokines and mediators, including tumor necrosis factor-alpha (TNF-α), interleukin-23 (IL-23), interleukin-17 (IL-17), interferon-gamma (IFN-γ), and inducible nitric oxide synthase (iNOS). On the other hand, it upregulates anti-inflammatory mediators such as interleukin-10 (IL-10). This modulation of the immune response differs fundamentally from the mechanism of action of biologic therapies, which target single specific cytokines or receptors. Instead, apremilast acts intracellularly to broadly rebalance the pro-inflammatory and anti-inflammatory cytokine milieu without causing the level of immunosuppression typically associated with traditional systemic therapies or biologics.
Apremilast Avansor is indicated for three distinct conditions, each of which involves dysregulated inflammatory pathways where PDE4-mediated signaling plays an important role:
- Moderate to severe plaque psoriasis: Apremilast is approved for adult patients with moderate to severe chronic plaque psoriasis who are candidates for phototherapy or systemic therapy. Plaque psoriasis is the most common form of psoriasis, affecting approximately 2–3% of the global population, and is characterized by raised, red, scaly patches (plaques) on the skin that are caused by accelerated keratinocyte proliferation and chronic inflammation driven by T cells and dendritic cells.
- Active psoriatic arthritis: Apremilast is approved for adult patients with active psoriatic arthritis who have had an inadequate response or intolerance to a prior disease-modifying antirheumatic drug (DMARD) therapy. Psoriatic arthritis is a chronic inflammatory joint disease that occurs in approximately 30% of patients with psoriasis and can cause progressive joint damage if inadequately treated.
- Oral ulcers associated with Behçet's disease: Apremilast is approved for the treatment of oral ulcers associated with Behçet's disease, a rare, chronic, multisystem inflammatory disorder. This indication was granted by the FDA in 2019 based on the pivotal BCT-002 trial, making apremilast the first and, at the time of its approval, the only oral therapy specifically approved for this condition.
The efficacy of apremilast in plaque psoriasis was established in two pivotal phase III randomized, double-blind, placebo-controlled clinical trials: ESTEEM-1 and ESTEEM-2. In ESTEEM-1, which enrolled 844 patients, 33.1% of patients treated with apremilast 30 mg twice daily achieved a 75% or greater reduction in the Psoriasis Area and Severity Index (PASI-75) at week 16, compared with 5.3% of patients receiving placebo. In ESTEEM-2 (411 patients), 28.8% achieved PASI-75 at week 16 versus 5.8% with placebo. Both studies demonstrated that the clinical benefit continued to improve through week 32, with sustained responses observed in long-term extension studies of up to 5 years.
For psoriatic arthritis, efficacy was demonstrated in the PALACE-1, PALACE-2, and PALACE-3 trials. In PALACE-1 (504 patients), 38.1% of patients receiving apremilast 30 mg twice daily achieved an American College of Rheumatology 20% response (ACR20) at week 16, compared with 19.0% of patients receiving placebo. The treatment also showed improvements in physical function (as measured by the Health Assessment Questionnaire-Disability Index), enthesitis, dactylitis, and skin involvement. Long-term data from the PALACE trials demonstrated sustained efficacy over 5 years of treatment.
Apremilast was first approved by the FDA in March 2014 under the brand name Otezla and subsequently by the EMA in January 2015. Apremilast Avansor is a generic formulation containing the same active substance at the same strength (30 mg film-coated tablets), offering the same therapeutic profile as the originator product. The availability of generic formulations increases access to this important treatment option for patients with psoriasis, psoriatic arthritis, and Behçet's disease.
Apremilast offers several practical advantages over other systemic therapies for psoriasis and psoriatic arthritis: (1) it is taken orally rather than by injection, improving patient convenience and adherence; (2) it does not require routine laboratory monitoring (no blood counts, liver or kidney function tests); (3) it has no known requirement for tuberculosis screening before initiation; and (4) it has a relatively low risk of drug interactions. These characteristics make it a particularly useful option for patients who prefer oral treatment, have comorbidities that complicate the use of other systemics, or have contraindications to biologic therapies.
What Should You Know Before Taking Apremilast Avansor?
Contraindications
The primary contraindication to Apremilast Avansor is hypersensitivity (allergy) to apremilast or to any of the excipients. The excipients in the film-coated tablet include microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, and the film coating components (polyvinyl alcohol, titanium dioxide, macrogol, talc, and iron oxide red). Patients with known allergies to any of these substances should not take this medication.
Apremilast is also contraindicated during pregnancy. Animal reproductive toxicology studies have demonstrated embryotoxicity in mice at clinically relevant doses, including increased early resorptions, decreased fetal body weights, and skeletal variations. Due to the potential risk to the developing fetus, apremilast must not be used during pregnancy. Women of childbearing potential must use effective contraception to prevent pregnancy during treatment, and a pregnancy test should be performed before initiating therapy.
Warnings and Precautions
Apremilast has been associated with an increased risk of depression and, in rare cases, suicidal ideation and behavior. Patients and caregivers should be alert to the emergence or worsening of depression, suicidal thoughts, or other mood changes. If such symptoms occur, discontinue apremilast and contact a healthcare provider immediately. The risks and benefits of continuing treatment should be carefully assessed in patients with a history of psychiatric disorders.
Before starting Apremilast Avansor, discuss the following with your healthcare provider:
- Depression and psychiatric disorders: In clinical trials, depression was reported more frequently in patients receiving apremilast (1.0%) compared with placebo (0.8%). Cases of suicidal ideation and suicidal behavior, including completed suicides, have been observed in post-marketing experience. Patients with a pre-existing history of depression or suicidal ideation should be carefully evaluated before starting treatment. Patients and caregivers should be instructed to report any changes in mood, depression, or suicidal thoughts to their healthcare provider.
- Body weight: Unexplained or clinically significant weight loss has been reported during treatment with apremilast. Body weight should be monitored regularly, particularly in patients who are underweight at baseline (body mass index less than 18.5 kg/m²). If clinically significant weight loss occurs, treatment should be reassessed and discontinuation considered if appropriate.
- Renal impairment: In patients with severe renal impairment (estimated glomerular filtration rate less than 30 mL/min/1.73 m² or creatinine clearance less than 30 mL/min), the dose of apremilast should be reduced to 30 mg once daily (instead of twice daily). No dose adjustment is needed for mild or moderate renal impairment. Renal function should be assessed before starting treatment.
- Lactose intolerance: Apremilast Avansor tablets contain lactose monohydrate. Patients with rare hereditary conditions of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medication.
- Severe hepatic impairment: Apremilast has not been studied in patients with severe hepatic impairment (Child-Pugh class C). Use in this population is not recommended due to insufficient data regarding safety and efficacy.
Pregnancy and Breastfeeding
Apremilast Avansor must not be used during pregnancy. Women of childbearing potential should use effective contraception during treatment and for at least 28 days after the last dose. If pregnancy is suspected, the medication should be discontinued immediately and the patient should contact her healthcare provider. There are no adequate data from the use of apremilast in pregnant women. Based on animal studies, apremilast is considered potentially harmful to the developing fetus, and the benefit of treatment does not outweigh the potential risk during pregnancy.
Apremilast has been detected in the milk of lactating mice. It is not known whether apremilast or its metabolites are excreted in human breast milk. A risk to the breastfed infant cannot be excluded. Apremilast should not be used during breastfeeding. The decision to either discontinue breastfeeding or discontinue apremilast therapy should be made in consultation with the treating physician, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.
Children and Adolescents
The safety and efficacy of apremilast have not been established in children and adolescents under 18 years of age for any of the approved indications. No data are available, and use in this age group is not recommended. Pediatric psoriasis and psoriatic arthritis require specialist assessment, and alternative treatment options should be considered for younger patients.
Elderly Patients
No dose adjustment is necessary for elderly patients based on age alone. However, elderly patients may be more susceptible to certain adverse effects, particularly gastrointestinal symptoms (diarrhea, nausea) and weight loss. In the clinical trial program, the safety profile of apremilast in patients aged 65 years and older was comparable to that in younger adults, though the number of elderly patients studied was limited. Renal function should be assessed, as age-related decline in kidney function may necessitate dose adjustment in patients with severe renal impairment.
Driving and Operating Machinery
Apremilast has no or negligible influence on the ability to drive and use machines. No studies on the effects of apremilast on driving ability have been performed. However, as with any medication, patients who experience adverse effects that could impair concentration or coordination should refrain from driving or operating machinery until the effects resolve.
How Does Apremilast Avansor Interact with Other Drugs?
Apremilast is extensively metabolized in the liver, primarily through oxidative metabolism mediated by cytochrome P450 (CYP) 3A4, with minor contributions from CYP1A2 and CYP2A6. The major circulating metabolite is the glucuronide conjugate of O-demethylated apremilast (M12), which is pharmacologically inactive. Understanding these metabolic pathways is important for predicting potential drug interactions.
Unlike many biologic therapies used in dermatology and rheumatology, apremilast has a relatively favorable drug interaction profile. It is not a potent inhibitor or inducer of CYP enzymes at therapeutic concentrations, and it has not been shown to significantly alter the pharmacokinetics of commonly co-administered medications. However, certain important interactions should be considered:
Major Interactions
| Interacting Drug | Effect | Clinical Recommendation |
|---|---|---|
| Rifampicin (Rifampin) | Strong CYP3A4 inducer; reduces apremilast exposure (AUC) by approximately 72% | Co-administration not recommended; loss of therapeutic efficacy expected |
| Carbamazepine | Strong CYP3A4 inducer; expected to significantly reduce apremilast exposure | Co-administration not recommended; consider alternative anticonvulsant |
| Phenytoin | Strong CYP3A4 inducer; expected to significantly reduce apremilast exposure | Co-administration not recommended; consider alternative anticonvulsant |
| Phenobarbital | Strong CYP3A4 inducer; expected to significantly reduce apremilast exposure | Co-administration not recommended; consider alternative |
| St. John's Wort (Hypericum perforatum) | Strong CYP3A4 inducer; may reduce apremilast efficacy | Avoid concomitant use |
Minor Interactions and No Significant Interactions
Formal drug interaction studies have demonstrated that apremilast does not significantly affect the pharmacokinetics of several commonly used medications:
- Methotrexate: No pharmacokinetic interaction was observed when apremilast was co-administered with methotrexate in patients with psoriatic arthritis. This is clinically important, as many patients with psoriatic arthritis take methotrexate as a concomitant DMARD.
- Oral contraceptives: Apremilast did not affect the pharmacokinetics of ethinyl estradiol or norgestimate, confirming that it does not interfere with the efficacy of combined oral contraceptive pills.
- Ketoconazole: Co-administration with the strong CYP3A4 inhibitor ketoconazole increased apremilast exposure (AUC) by approximately 36%. This increase is not considered clinically significant, and no dose adjustment is needed.
- Topical therapies: Apremilast can be used in combination with topical psoriasis treatments (corticosteroids, vitamin D analogues, tar preparations) without dose adjustments.
- Phototherapy: Apremilast has been used in combination with UVB phototherapy in clinical practice without evidence of significant interaction or increased adverse effects.
Unlike many other systemic treatments for psoriasis and psoriatic arthritis (such as methotrexate, ciclosporin, and acitretin), apremilast does not require routine blood tests for monitoring liver function, complete blood counts, or lipid levels. This is a significant practical advantage for both patients and healthcare providers. However, monitoring body weight is recommended, particularly in patients who are underweight at baseline.
What Is the Correct Dosage of Apremilast Avansor?
Initial Dose Titration Schedule
To reduce the incidence of gastrointestinal adverse effects, apremilast treatment is initiated using a standardized 5-day dose titration schedule. This gradual dose escalation allows the body to adapt to the medication and significantly reduces the severity of initial nausea and diarrhea. Patients should be instructed to follow this titration schedule carefully:
| Day | Morning Dose | Evening Dose |
|---|---|---|
| Day 1 | 10 mg | — |
| Day 2 | 10 mg | 10 mg |
| Day 3 | 10 mg | 20 mg |
| Day 4 | 20 mg | 20 mg |
| Day 5 | 20 mg | 30 mg |
| Day 6 onwards | 30 mg | 30 mg |
Adults
Standard Adult Dosage
The recommended maintenance dose is 30 mg taken orally twice daily, approximately 12 hours apart (morning and evening). Tablets should be swallowed whole and can be taken with or without food. Do not crush, split, or chew the tablets, as the film coating is designed for optimal drug release and stability. If a dose is missed, take the next dose at the regularly scheduled time; do not take a double dose to make up for a missed one.
For all three approved indications (psoriasis, psoriatic arthritis, and Behçet's disease oral ulcers), the dose and titration schedule are identical. In the psoriasis trials, treatment response was assessed at week 16, and clinicians are advised to evaluate whether treatment is achieving the desired therapeutic response at approximately 24 weeks. If no improvement is observed after 24 weeks of treatment, the prescribing physician should reconsider the appropriateness of continued therapy.
Patients with Renal Impairment
Severe Renal Impairment (eGFR < 30 mL/min/1.73 m²)
The maintenance dose should be reduced to 30 mg once daily (instead of twice daily). The initial titration should use only the morning doses from the standard titration schedule (10 mg on Day 1, 10 mg on Day 2, 10 mg on Day 3, 20 mg on Day 4, 20 mg on Day 5, 30 mg from Day 6 onwards). No dose adjustment is needed for mild or moderate renal impairment.
Children
Apremilast is not approved for use in children and adolescents under 18 years of age. Safety and efficacy data in this population are not available, and no dosing recommendations can be made for pediatric patients.
Elderly
No dose adjustment is required for elderly patients based on age alone. However, as elderly patients are more likely to have reduced renal function, their estimated glomerular filtration rate (eGFR) should be assessed before starting treatment. If severe renal impairment is identified, the reduced dosing schedule (30 mg once daily) should be applied. Elderly patients should also be monitored for gastrointestinal side effects and weight loss.
Missed Dose
If you forget to take a dose of Apremilast Avansor, take it as soon as you remember, unless it is almost time for your next scheduled dose. In that case, skip the missed dose and take your next dose at the regular time. Do not take two doses at the same time or a double dose to compensate for a forgotten dose. To help remember, it may be useful to take the medication at the same times each day, such as with breakfast and dinner.
Overdose
Apremilast has been studied at doses up to 100 mg daily (50 mg twice daily) without additional safety concerns beyond those observed at the 30 mg twice daily dose. In the event of an overdose, no specific antidote exists. Treatment should be supportive and symptomatic. Contact your local poison control center or emergency medical services if you suspect an overdose. The most likely symptoms of overdose would be gastrointestinal in nature (severe nausea, vomiting, diarrhea) and headache. Hemodialysis is not expected to be effective in removing apremilast from the body due to its extensive protein binding (approximately 68%).
Always take Apremilast Avansor exactly as prescribed by your doctor. Do not increase the dose on your own, even if you feel that the medication is not working quickly enough. The therapeutic benefit may take several weeks to become apparent. If you have concerns about your treatment, discuss them with your healthcare provider before making any changes.
What Are the Side Effects of Apremilast Avansor?
Like all medicines, Apremilast Avansor can cause side effects, although not everybody gets them. The adverse reaction profile of apremilast has been well characterized through extensive clinical trial data involving more than 4,000 patients across multiple indications, as well as through ongoing post-marketing surveillance since its initial approval in 2014. The side effects are categorized below by frequency according to the standard convention used in regulatory documents:
Very Common (may affect more than 1 in 10 people)
- Diarrhea (approximately 15–17% of patients; usually mild to moderate and self-limiting within the first 4 weeks)
- Nausea (approximately 14–17% of patients; most pronounced during the first 2 weeks, usually resolves with continued treatment)
Common (may affect up to 1 in 10 people)
- Upper respiratory tract infections (bronchitis, nasopharyngitis)
- Headache and tension headache
- Vomiting (most common during the first 2 weeks)
- Abdominal pain (upper abdominal pain)
- Back pain
- Dyspepsia (indigestion)
- Decreased appetite
- Frequent bowel movements
- Fatigue
- Insomnia
- Cough
- Weight loss
- Migraine
Uncommon (may affect up to 1 in 100 people)
- Depression
- Allergic reactions (rash, urticaria)
- Gastrointestinal hemorrhage
- Suicidal ideation
Rare (may affect up to 1 in 1,000 people)
- Severe allergic reactions (angioedema)
- Suicidal behavior (observed in post-marketing surveillance)
The gastrointestinal side effects of apremilast deserve special attention, as they are the most common reason for treatment discontinuation. In clinical trials, approximately 1.5–2.0% of patients discontinued treatment due to diarrhea, and approximately 1.0–1.5% discontinued due to nausea. It is important to understand that these side effects are usually self-limiting: in the majority of patients, diarrhea and nausea begin within the first two weeks of treatment and resolve by week 4 without requiring dose reduction or discontinuation. The 5-day dose titration schedule was specifically designed to mitigate the onset and severity of these gastrointestinal effects. Patients should be counseled about this expected time course to improve adherence.
Weight loss is another important side effect that warrants monitoring. In clinical trials, approximately 10% of patients experienced weight loss of 5–10% of their baseline body weight, while approximately 2% experienced weight loss exceeding 10%. This effect may be related to the gastrointestinal side effects (reduced appetite, nausea, diarrhea) or may represent a direct pharmacological effect of PDE4 inhibition on metabolic pathways. Body weight should be monitored regularly, and unexplained or clinically significant weight loss should prompt reassessment of treatment.
The psychiatric adverse effects of apremilast are of particular clinical significance. While depression was reported in approximately 1.0% of patients in clinical trials (compared with 0.8% on placebo), post-marketing surveillance has identified cases of suicidal ideation, suicidal behavior, and completed suicides. A causal relationship has not been definitively established, and the background rate of depression in patients with psoriasis is higher than in the general population. Nevertheless, patients should be screened for depression and suicidal risk before starting treatment, and both patients and caregivers should be educated about recognizing the signs and symptoms of depression.
Contact your doctor immediately if you experience: new or worsening feelings of depression, sadness, or hopelessness; thoughts of suicide or self-harm; severe or persistent diarrhea (more than 6 loose stools per day for more than 2 days); signs of severe allergic reaction such as facial swelling, difficulty breathing, or widespread rash; or unexplained significant weight loss. These symptoms may require discontinuation of treatment or additional medical assessment.
How Should You Store Apremilast Avansor?
Proper storage of Apremilast Avansor is essential to ensure that the medication retains its full potency and safety throughout its shelf life. Film-coated tablets are sensitive to environmental conditions, and improper storage may affect the stability of the active ingredient or the integrity of the film coating.
Follow these storage guidelines carefully:
- Temperature: Store below 30°C (86°F). Do not freeze the tablets. Avoid exposing the medication to extreme temperatures or temperature fluctuations, such as leaving it in a car during hot weather or near a window exposed to direct sunlight.
- Packaging: Keep the tablets in the original blister packaging until you are ready to take them. The blister pack provides protection against moisture and light. Do not transfer tablets to a pill organizer or other container for extended periods.
- Light: Protect from direct sunlight and strong artificial light. The film coating contains components that may degrade upon prolonged light exposure.
- Moisture: Store in a dry place. Do not store in the bathroom or kitchen, where humidity levels are typically elevated.
- Children: Keep out of the sight and reach of children. The tablets should be stored in a secure location, as accidental ingestion by children could cause adverse effects.
- Expiry date: Do not use Apremilast Avansor after the expiry date stated on the blister pack and carton. The expiry date refers to the last day of that month.
Do not dispose of unused or expired medications via wastewater or household waste. Return any unused medication to your pharmacist for proper disposal in accordance with local regulations. This helps protect the environment from potential contamination.
What Does Apremilast Avansor Contain?
Understanding the complete composition of Apremilast Avansor is important for patients who have known allergies or intolerances to specific pharmaceutical excipients. The full composition of each film-coated tablet is detailed below:
Active Ingredient
Each film-coated tablet contains 30 mg of apremilast. Apremilast (chemical name: N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide) is a white to pale yellow powder with a molecular weight of 460.5 g/mol. It is practically insoluble in water, slightly soluble in ethanol, and soluble in acetone. The S-enantiomer is the pharmacologically active form.
Inactive Ingredients (Excipients)
Tablet core: Microcrystalline cellulose (bulking agent), lactose monohydrate (filler), croscarmellose sodium (disintegrant), and magnesium stearate (lubricant). These excipients are commonly used in pharmaceutical tablet manufacturing and are generally well tolerated.
Film coating: Polyvinyl alcohol (partially hydrolyzed), titanium dioxide (E171, opacifier), macrogol/polyethylene glycol (plasticizer), talc (anti-adherent), and iron oxide red (E172, colorant). The film coating provides protection of the tablet core from moisture and light, facilitates swallowing, and gives the tablet its characteristic appearance.
This medication contains lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, or if you have hereditary galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption, contact your doctor before taking this medicine. The amount of lactose per tablet is small, but patients with severe lactose intolerance should discuss this with their healthcare provider.
Frequently Asked Questions About Apremilast Avansor
Apremilast Avansor and Otezla both contain the same active ingredient, apremilast, at the same strength (30 mg). Otezla is the original brand-name product developed by Celgene (now part of Amgen), while Apremilast Avansor is a generic formulation. Generic medications must demonstrate bioequivalence to the originator product, meaning they deliver the same amount of active drug to the bloodstream at the same rate. The therapeutic effects, side effect profile, and clinical outcomes are expected to be the same. The main differences may be in the inactive ingredients (excipients), packaging, and cost, with generic formulations typically being more affordable.
There are no specific contraindications regarding alcohol consumption with apremilast. No formal drug interaction studies have been conducted with alcohol. However, both alcohol and apremilast can cause gastrointestinal symptoms (nausea, diarrhea), and consuming alcohol may worsen these effects, particularly during the early weeks of treatment. Additionally, alcohol can contribute to depression, which is a potential side effect of apremilast. Moderate alcohol consumption is generally considered acceptable, but patients should discuss their individual situation with their healthcare provider, especially if they have a history of depression or liver problems.
Apremilast differs from biologic treatments in several important ways. First, it is a small molecule taken orally as a tablet, whereas biologics are large proteins administered by injection or infusion. Second, apremilast works intracellularly by inhibiting the PDE4 enzyme, which broadly modulates the inflammatory response, rather than targeting a single specific cytokine (such as TNF-alpha, IL-17, or IL-23). Third, apremilast does not require routine laboratory monitoring, tuberculosis screening, or hepatitis B/C testing before initiation. Fourth, in clinical trials, the efficacy of apremilast in psoriasis (PASI-75 response rates of 29–33%) is generally lower than that of newer biologic therapies (which achieve PASI-75 rates of 60–90%), making it more suitable for patients with moderate disease, those who prefer oral therapy, or those with contraindications to biologics.
Mild to moderate diarrhea is common when starting apremilast and usually improves within 2 to 4 weeks. To manage it, stay well hydrated by drinking plenty of water and clear fluids, avoid spicy, fatty, or high-fiber foods during the initial weeks, and eat smaller, more frequent meals. Over-the-counter antidiarrheal medications such as loperamide may be used if needed. However, if you experience severe diarrhea (more than 6 loose stools per day), diarrhea lasting more than 2 to 3 days without improvement, signs of dehydration (excessive thirst, dry mouth, dark urine, dizziness), or bloody stools, contact your doctor immediately. In some cases, it may be necessary to temporarily reduce the dose or discontinue treatment.
Yes, apremilast can be used in combination with methotrexate. In fact, in the PALACE clinical trials for psoriatic arthritis, a significant proportion of patients were receiving concomitant methotrexate, and no pharmacokinetic interactions were observed between the two drugs. The combination was well tolerated, and the safety profile was consistent with that of each drug used alone. However, both medications can cause gastrointestinal side effects, so patients using both should be monitored for increased gastrointestinal symptoms. The decision to use combination therapy should be made by the treating rheumatologist or dermatologist based on individual patient factors and disease severity.
Apremilast modulates the immune system rather than suppressing it in the way that many biologics or traditional immunosuppressants do. It works by rebalancing the production of pro-inflammatory and anti-inflammatory cytokines through PDE4 inhibition, rather than blocking a specific immune pathway entirely. In clinical trials, apremilast was not associated with increased rates of serious infections, opportunistic infections, or malignancies compared with placebo. It does not require tuberculosis screening, hepatitis testing, or regular blood monitoring. However, as with any medication that affects immune function, patients should be vigilant for signs of infection and report any unusual symptoms to their healthcare provider.
References
- European Medicines Agency (EMA). Otezla (apremilast) — Summary of Product Characteristics. Last updated 2025. Available from: EMA — Otezla.
- U.S. Food and Drug Administration (FDA). Otezla (apremilast) — Prescribing Information. Revised 2024. Available from: FDA — Otezla Label.
- Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73(1):37–49. doi:10.1016/j.jaad.2015.03.049.
- Paul C, Cather J, Gooderham M, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). Br J Dermatol. 2015;173(6):1387–1399. doi:10.1111/bjd.14164.
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- Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics and oral systemics. J Am Acad Dermatol. 2019;80(4):1029–1072. doi:10.1016/j.jaad.2018.11.057.
- Gossec L, Baraliakos X, Kerschbaumer A, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update. Ann Rheum Dis. 2024;83(6):706–719. doi:10.1136/ard-2024-225531.
- Smith CH, Yiu ZZN, Bale T, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2020. Br J Dermatol. 2020;183(4):628–637. doi:10.1111/bjd.19039.
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Editorial Team
Medical Content
iMedic Medical Editorial Team — Specialists in Dermatology, Rheumatology and Clinical Pharmacology
Medical Review
iMedic Medical Review Board — Independent review according to EMA, FDA, AAD, and EULAR guidelines
Evidence Framework
GRADE (Grading of Recommendations Assessment, Development and Evaluation) — Level 1A evidence from systematic reviews and RCTs
Sources
EMA SmPC, FDA Label, AAD-NPF Guidelines, EULAR Recommendations, BAD Guidelines, Cochrane Reviews
Last medical review: . This article was written, reviewed and fact-checked by licensed physicians specializing in dermatology, rheumatology and clinical pharmacology. All medical claims are supported by peer-reviewed evidence at Evidence Level 1A. For our complete editorial process and quality standards, see our Editorial Standards.