Apremilast Zentiva: Uses, Dosage & Side Effects
A selective PDE4 inhibitor for the treatment of moderate-to-severe plaque psoriasis, active psoriatic arthritis, and oral ulcers associated with Behçet’s disease
Apremilast Zentiva is a prescription oral medication containing apremilast, a selective phosphodiesterase 4 (PDE4) inhibitor used to treat moderate-to-severe plaque psoriasis, active psoriatic arthritis, and oral ulcers associated with Behçet’s disease. By inhibiting PDE4, apremilast modulates the inflammatory cascade without broadly suppressing the entire immune system. This makes it a valuable treatment option for patients who have not responded to or cannot tolerate conventional systemic therapies. The maintenance dose is 30 mg taken orally twice daily, with an initial titration schedule to improve tolerability. Apremilast Zentiva is a generic formulation of the originator product and has been approved based on demonstrated bioequivalence.
Quick Facts: Apremilast Zentiva
Key Takeaways
- Apremilast Zentiva is a selective PDE4 inhibitor that works by modulating inflammation from within immune cells, reducing levels of pro-inflammatory cytokines (TNF-alpha, IL-17, IL-23) while increasing the anti-inflammatory cytokine IL-10.
- It is approved for moderate-to-severe plaque psoriasis in adults who have not responded to or are intolerant of other systemic therapies, active psoriatic arthritis, and oral ulcers in Behçet’s disease.
- Treatment begins with a 5-day titration schedule, gradually increasing from 10 mg once daily to the full maintenance dose of 30 mg twice daily, which helps minimize common gastrointestinal side effects such as diarrhea and nausea.
- Unlike many other immunomodulators, apremilast does not require routine laboratory monitoring (no blood tests for liver function, blood counts, or tuberculosis screening) during treatment, offering a simpler management profile.
- Patients and caregivers should be aware that depression and suicidal thoughts have been reported; any worsening of mood should be reported to a healthcare provider immediately.
What Is Apremilast Zentiva and What Is It Used For?
Apremilast Zentiva contains the active substance apremilast, which belongs to a class of medications known as phosphodiesterase 4 (PDE4) inhibitors. PDE4 is an enzyme found predominantly in immune and inflammatory cells, including T cells, monocytes, macrophages, neutrophils, dendritic cells, and keratinocytes. This enzyme is responsible for breaking down cyclic adenosine monophosphate (cAMP), an important intracellular signaling molecule. By selectively inhibiting PDE4, apremilast raises intracellular cAMP levels, which in turn modulates the production of a wide range of pro-inflammatory and anti-inflammatory mediators.
Specifically, elevated cAMP activates protein kinase A (PKA), which phosphorylates transcription factors such as CREB (cAMP response element-binding protein) and inhibits NF-kB signaling. The net result is a reduction in the production of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-17 (IL-17), interleukin-23 (IL-23), and interferon-gamma (IFN-gamma), while simultaneously increasing the production of anti-inflammatory mediators such as interleukin-10 (IL-10). This rebalancing of the cytokine milieu addresses the underlying inflammatory processes driving psoriasis, psoriatic arthritis, and the mucosal inflammation seen in Behçet’s disease.
Unlike biologic therapies that target a single specific cytokine or receptor, apremilast works intracellularly to broadly modulate the inflammatory response. This mechanism of action means that apremilast is not classified as an immunosuppressant in the traditional sense, and it does not cause the level of immune suppression associated with biologics or conventional immunosuppressive drugs such as methotrexate or ciclosporin. As a result, patients taking apremilast generally do not require the same level of laboratory monitoring (blood tests for liver function, blood counts, or tuberculosis screening) that is necessary with these other treatments.
Apremilast Zentiva is approved by regulatory authorities, including the European Medicines Agency (EMA), for the following indications:
- Moderate-to-severe chronic plaque psoriasis: For adult patients who have failed to respond to, have a contraindication to, or are intolerant of other systemic therapies, including ciclosporin, methotrexate, or psoralen and ultraviolet A (PUVA) light therapy. The pivotal ESTEEM 1 and ESTEEM 2 trials demonstrated that apremilast 30 mg twice daily achieved PASI 75 responses (75% or greater improvement in the Psoriasis Area and Severity Index) in approximately 33% of patients at 16 weeks, compared with approximately 5% for placebo. Patients also experienced significant improvements in pruritus (itching), scalp psoriasis, and nail psoriasis.
- Active psoriatic arthritis: For adult patients who have had an inadequate response or intolerance to a prior disease-modifying antirheumatic drug (DMARD). Apremilast can be used alone or in combination with DMARDs. The PALACE 1, 2, and 3 clinical trials showed that apremilast 30 mg twice daily significantly improved the signs and symptoms of psoriatic arthritis, including joint tenderness, swelling, physical function, enthesitis (inflammation where tendons attach to bone), and dactylitis (swelling of entire fingers or toes). ACR20 response rates (a standard measure of arthritis improvement) were approximately 30–40% at 16 weeks compared with 15–20% for placebo.
- Oral ulcers associated with Behçet’s disease: For adult patients who are candidates for systemic therapy. The RELIEF trial demonstrated that apremilast significantly reduced the number and pain of oral ulcers and improved quality of life compared with placebo. Complete response (absence of oral ulcers) was achieved in a significantly greater proportion of patients receiving apremilast.
Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting approximately 2–3% of the global population. Plaque psoriasis, the most common form, is characterized by well-defined, raised, red patches covered with silvery-white scales, typically appearing on the elbows, knees, scalp, and lower back. The condition results from an overactive immune response that accelerates skin cell turnover from the normal 28–30 days to just 3–4 days, leading to the characteristic thickened, scaly plaques. Beyond the skin, psoriasis is associated with significant comorbidities including psoriatic arthritis, cardiovascular disease, metabolic syndrome, depression, and reduced quality of life.
Psoriatic arthritis is a chronic inflammatory arthritis that occurs in approximately 30% of patients with psoriasis. It can affect any joint in the body and, if left untreated, may lead to permanent joint damage and disability. The disease is heterogeneous, with various patterns of joint involvement including peripheral arthritis, axial disease, enthesitis, and dactylitis. Treatment aims to control inflammation, relieve symptoms, prevent joint damage, and maintain physical function and quality of life.
Apremilast Zentiva is a generic version of the originator product, containing the same active ingredient (apremilast) at the same strengths (10 mg, 20 mg, 30 mg). It has been approved based on demonstrated bioequivalence to the reference product, meaning it delivers the same amount of active substance to the body at the same rate. Generic medicines undergo rigorous regulatory review to ensure they meet the same quality, safety, and efficacy standards as the original product.
What Should You Know Before Taking Apremilast Zentiva?
Contraindications
There are specific situations in which Apremilast Zentiva must not be used. Understanding these contraindications is essential before starting treatment.
- Hypersensitivity: Do not take apremilast if you are allergic to apremilast or any of the other ingredients in the tablets, including lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, and the film-coating components (polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and iron oxide pigments).
- Pregnancy: Apremilast must not be used during pregnancy. Animal studies have shown developmental toxicity, and the potential risk to the human fetus has not been adequately established. Women of childbearing potential must use effective contraception to prevent pregnancy during treatment.
Warnings and Precautions
Depression, depressed mood, and suicidal ideation and behavior (including completed suicide) have been reported in patients taking apremilast. Patients, caregivers, and families should be alert to the emergence or worsening of depression, suicidal thoughts, or other mood changes. If you experience new or worsening psychiatric symptoms, contact your healthcare provider immediately. The risks and benefits of continuing treatment should be carefully reassessed. Patients with a history of psychiatric illness should be carefully evaluated before starting apremilast.
Before and during treatment with Apremilast Zentiva, inform your doctor if any of the following apply to you:
- Depression or psychiatric history: If you have had depression, suicidal thoughts, or any other psychiatric illness, you should be carefully assessed before starting treatment. Apremilast has been associated with psychiatric adverse events, including insomnia and depression. Report any changes in mood, behavior, or emotional state to your doctor promptly.
- Body weight: Apremilast may cause weight loss. Your weight should be monitored regularly during treatment. If unexpected or clinically significant weight loss occurs, your doctor should evaluate whether treatment should be discontinued. Patients who are underweight at the start of treatment should have their body weight monitored regularly.
- Severe renal impairment: If you have severe kidney problems (creatinine clearance less than 30 mL/min), your dose will need to be adjusted. The recommended maintenance dose in severe renal impairment is 30 mg once daily (instead of the usual twice daily). See the dosage section for details on dose adjustment.
- Lactose intolerance: Apremilast Zentiva tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, speak with your doctor before taking this medicine. The amount of lactose is small and is unlikely to cause problems in most lactose-intolerant individuals, but you should discuss this with your healthcare provider.
- Gastrointestinal disorders: Diarrhea, nausea, and vomiting are common side effects, particularly during the first few weeks of treatment. In rare cases, severe diarrhea has been reported. Patients who are elderly, have a low body weight, or are taking medications that can cause dehydration should be monitored for fluid and electrolyte balance.
- Infections: Although apremilast is not a traditional immunosuppressant, some reports of serious infections have been observed. Inform your doctor if you develop signs or symptoms of an infection during treatment.
Your doctor will assess your overall health status, including your mental health, body weight, and kidney function, before prescribing Apremilast Zentiva. Regular follow-up appointments will allow your doctor to monitor your response to treatment and manage any side effects that may arise.
Pregnancy and Breastfeeding
Apremilast must not be used during pregnancy. Preclinical studies in animals have shown adverse effects on embryo-fetal development. Women of childbearing potential must use effective contraception to prevent pregnancy during treatment. If you are planning to become pregnant, apremilast should be discontinued. A pregnancy test is recommended before starting treatment to exclude the possibility of pregnancy.
It is not known whether apremilast or its metabolites are excreted in human breast milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in the nursing infant, a decision must be made whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of the therapy to the mother. Discuss the risks and benefits with your doctor.
There is limited data on the effects of apremilast on human fertility. Animal studies have not shown effects on fertility at clinically relevant exposures. However, if you are planning to conceive, discuss this with your doctor before starting or continuing treatment.
Driving and Operating Machinery
Apremilast has no or negligible influence on the ability to drive and use machines. However, if you experience dizziness or fatigue as a side effect, exercise caution when driving or operating machinery until you know how the medication affects you.
How Does Apremilast Zentiva Interact with Other Drugs?
Apremilast is extensively metabolized in the body, with CYP3A4 being the major metabolic pathway, followed by contributions from CYP1A2 and CYP2A6. The main circulating metabolite is the glucuronide conjugate of O-demethylated apremilast, which is pharmacologically inactive. Understanding these metabolic pathways is important for predicting drug interactions.
Notably, apremilast at therapeutic doses does not significantly inhibit or induce major cytochrome P450 enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4). This means that apremilast is unlikely to affect the metabolism of most other drugs you may be taking. Similarly, it does not inhibit or induce major drug transporters (P-glycoprotein, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, BCRP, MRP2, MATE1, or MATE2-K), making clinically significant transporter-mediated interactions unlikely.
Major Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Rifampicin (strong CYP3A4 inducer) | Reduces apremilast AUC by approximately 72% and Cmax by approximately 43% | Co-administration not recommended – significantly reduces efficacy |
| Phenobarbital (strong CYP3A4 inducer) | Expected significant reduction in apremilast plasma levels | Co-administration not recommended |
| Carbamazepine (strong CYP3A4 inducer) | Expected significant reduction in apremilast plasma levels | Co-administration not recommended |
| Phenytoin (strong CYP3A4 inducer) | Expected significant reduction in apremilast plasma levels | Co-administration not recommended |
| St. John’s Wort (herbal CYP3A4 inducer) | May reduce apremilast plasma levels | Co-administration not recommended |
Minor Interactions and No Significant Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Ketoconazole (strong CYP3A4 inhibitor) | Increases apremilast AUC by approximately 36% | No dose adjustment required; effect is modest |
| Methotrexate | No pharmacokinetic interaction observed in clinical studies | Can be co-administered safely; commonly used combination in psoriatic arthritis |
| Oral contraceptives (ethinylestradiol/norgestimate) | No interaction observed | No dose adjustment needed; oral contraceptives remain effective |
| Warfarin | No clinically significant interaction expected | No dose adjustment needed; standard INR monitoring continues |
| Topical psoriasis treatments | No interaction | Can be used concomitantly; commonly combined with topical corticosteroids and vitamin D analogues |
One of the clinical advantages of apremilast is its relatively favorable drug interaction profile. Because it does not significantly affect cytochrome P450 enzymes or drug transporters at therapeutic concentrations, it can be combined with many commonly used medications without requiring dose adjustments. This is particularly important for patients with psoriatic arthritis, who may be taking other DMARDs, NSAIDs, or corticosteroids concurrently. However, patients should always inform their doctor about all medications, supplements, and herbal products they are taking before starting apremilast.
What Is the Correct Dosage of Apremilast Zentiva?
Apremilast Zentiva is taken by mouth and can be taken with or without food. The tablets should be swallowed whole and should not be crushed, split, or chewed. The recommended maintenance dose is 30 mg twice daily, taken approximately 12 hours apart (typically morning and evening). To reduce the incidence and severity of gastrointestinal adverse events, treatment is initiated with a gradual dose titration over the first 5 days.
Initial Dose Titration Schedule
| 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 |
A starter pack containing the appropriate tablet strengths for the titration period is typically available to simplify this process. The three different tablet strengths (10 mg, 20 mg, and 30 mg) are used during the titration phase, after which only the 30 mg tablets are needed.
Adults
Psoriasis, Psoriatic Arthritis, and Behçet’s Disease
Maintenance dose: 30 mg twice daily (morning and evening, approximately 12 hours apart)
Administration: Oral, with or without food. Swallow tablets whole.
Duration: Long-term treatment. For psoriasis, treatment response should be assessed at 24 weeks (some patients with low initial response may achieve PASI 50 by week 24 and continue to improve). For psoriatic arthritis, response should be assessed at 24 weeks. For Behçet’s disease, clinical benefit may be seen as early as week 4, but treatment is continued as long as clinically indicated.
Renal Impairment
Severe Renal Impairment (CrCl < 30 mL/min)
Maintenance dose: 30 mg once daily (not twice daily)
Titration: During the initial titration period, only the morning doses of the standard titration schedule are given (skip all evening doses during days 1–5). From day 6 onwards, take 30 mg once daily.
Note: No dose adjustment is required for patients with mild or moderate renal impairment.
Children and Adolescents
The safety and efficacy of apremilast in children and adolescents under 18 years of age have not been established. No data are available, and apremilast is not recommended for use in this age group.
Elderly Patients
No dose adjustment is required for elderly patients. However, clinical experience in patients aged 75 years and over is limited. Elderly patients may be more susceptible to gastrointestinal side effects such as diarrhea, which can lead to dehydration. Adequate hydration should be maintained, and body weight should be monitored regularly in elderly patients.
Missed Dose
If you miss a dose, take it as soon as you remember. If it is close to the time of your next dose, skip the missed dose and take the next dose at your regular time. Do not take a double dose to make up for a missed dose. Continue with your normal dosing schedule.
Overdose
Apremilast was studied at a single dose of up to 100 mg in healthy volunteers (more than 3 times the recommended single dose) without evidence of dose-limiting toxicity. In the event of a suspected overdose, seek medical attention. There is no specific antidote for apremilast. Treatment of overdose should be supportive and symptomatic, with monitoring for any signs of adverse effects. Apremilast is not significantly removed by dialysis due to its high protein binding (approximately 68%).
While apremilast does not cause physical dependence, you should consult your doctor before stopping treatment. Abrupt discontinuation may lead to a return of your symptoms. Your doctor will advise you on the best approach, which may involve a gradual transition to an alternative therapy.
What Are the Side Effects of Apremilast Zentiva?
Like all medicines, Apremilast Zentiva can cause side effects, although not everyone gets them. The most frequently reported adverse reactions are gastrointestinal in nature and tend to occur early in the course of treatment. The 5-day dose titration schedule was specifically designed to minimize these initial side effects. Most gastrointestinal events are mild to moderate in severity, are self-limiting, and resolve within the first month of treatment without requiring discontinuation.
In clinical trials, the overall rate of treatment discontinuation due to adverse events was approximately 7% for apremilast 30 mg twice daily, compared with 4% for placebo. The most common reasons for discontinuation were diarrhea (1.7%) and nausea (1.5%).
Very Common (affects more than 1 in 10 people)
Reported in >10% of patients in clinical trials
- Diarrhea (most common in first 2 weeks, usually resolves within 4 weeks)
- Nausea (most common in first 2 weeks, usually resolves within 4 weeks)
- Upper respiratory tract infections (nasopharyngitis, common cold symptoms)
- Headache, including tension-type headache
Common (affects 1 to 10 in every 100 people)
Reported in 1–10% of patients in clinical trials
- Vomiting (usually early in treatment and self-limiting)
- Decreased appetite
- Weight loss (body weight should be monitored regularly)
- Abdominal pain (upper abdominal pain)
- Dyspepsia (indigestion)
- Frequent bowel movements
- Back pain
- Fatigue
- Insomnia (difficulty sleeping)
- Cough
- Bronchitis
- Migraine
Uncommon (affects 1 to 10 in every 1,000 people)
Reported in 0.1–1% of patients in clinical trials
- Depression and depressed mood
- Gastrointestinal hemorrhage (bleeding from the digestive tract)
- Rash (various types including allergic rash)
- Urticaria (hives)
- Nosebleed (epistaxis)
Rare (affects 1 to 10 in every 10,000 people)
Reported in 0.01–0.1% of patients or post-marketing
- Suicidal ideation and behavior
- Severe diarrhea leading to dehydration
- Angioedema (swelling under the skin)
- Severe allergic reactions
Not Known (frequency cannot be estimated from available data)
Post-marketing surveillance reports
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Vasculitis (inflammation of blood vessels)
Managing Gastrointestinal Side Effects
Gastrointestinal side effects, particularly diarrhea and nausea, are the most commonly experienced adverse reactions with apremilast. These are most pronounced during the initial titration period and the first few weeks of therapy. Evidence from clinical trials shows that most gastrointestinal events peak during the first two weeks of treatment and resolve spontaneously within four weeks without requiring treatment modification. The dose titration schedule plays an important role in mitigating these effects, and it is important to follow the prescribed titration carefully.
To help manage gastrointestinal symptoms, consider taking apremilast with food, maintaining adequate fluid intake, and eating smaller, more frequent meals. Avoid fatty, spicy, or heavily processed foods during the titration period. Over-the-counter antidiarrheal agents such as loperamide may be used if needed, but consult your doctor before doing so. If diarrhea is severe, persistent, or associated with signs of dehydration (excessive thirst, decreased urine output, dizziness), contact your healthcare provider promptly.
Weight Loss
Weight loss has been observed in clinical trials with apremilast. In the psoriasis and psoriatic arthritis trials, approximately 10% of patients receiving apremilast 30 mg twice daily experienced weight loss of 5–10% of body weight, compared with approximately 3% of patients on placebo. Weight loss was generally modest and rarely led to treatment discontinuation. However, your doctor should monitor your body weight regularly, especially if you are underweight at baseline or have conditions that could be worsened by weight loss. Unexplained or clinically significant weight loss should prompt a clinical evaluation.
Contact your doctor or seek emergency medical care immediately if you experience: severe or persistent diarrhea leading to dehydration; signs of a severe allergic reaction (swelling of the face, lips, tongue, or throat; difficulty breathing); new or worsening depression, suicidal thoughts, or changes in behavior; or unexplained significant weight loss. These may require urgent medical evaluation and possible treatment modification.
How Should You Store Apremilast Zentiva?
Proper storage of medications ensures they remain safe and effective throughout their shelf life. Apremilast Zentiva should be stored according to the following guidelines:
- Temperature: Store below 30°C (86°F). Do not refrigerate or freeze.
- Light protection: Store in the original blister pack or bottle to protect from light.
- Moisture: Keep the container tightly closed if stored in a bottle. Do not remove tablets from blisters until ready to take them.
- Children: Keep out of the reach and sight of children. Store in a secure location.
- Expiry date: Do not use Apremilast Zentiva after the expiry date (EXP) printed on the carton, blister, or bottle. The expiry date refers to the last day of that month.
- Disposal: Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help to protect the environment.
If you notice any visible changes in the appearance of the tablets (discoloration, damage, unusual odor), do not take them and consult your pharmacist. Damaged or expired tablets should be returned to the pharmacy for proper disposal.
What Does Apremilast Zentiva Contain?
Understanding what your medication contains can help you identify any ingredients you may be sensitive to and ensures you can make informed decisions about your treatment.
Active Ingredient
The active substance is apremilast. Each film-coated tablet contains either 10 mg, 20 mg, or 30 mg of apremilast as the active ingredient.
Inactive Ingredients (Excipients)
The tablet core contains the following inactive ingredients:
- Lactose monohydrate
- Microcrystalline cellulose
- Croscarmellose sodium
- Magnesium stearate
The film-coating contains:
- Polyvinyl alcohol
- Titanium dioxide (E171)
- Polyethylene glycol (macrogol)
- Talc
- Iron oxide red (E172) – used in the 20 mg and 30 mg tablets
- Iron oxide yellow (E172) – used in the 10 mg tablet
Tablet Appearance
| Strength | Appearance | Use |
|---|---|---|
| 10 mg | Pink, diamond-shaped film-coated tablet | Titration only (Days 1–3) |
| 20 mg | Brown, diamond-shaped film-coated tablet | Titration only (Days 3–5) |
| 30 mg | Beige, diamond-shaped film-coated tablet | Titration (Day 5+) and maintenance |
Apremilast Zentiva is available in blister packs containing a 14-day starter pack (for titration) and blister packs of 56 tablets (30 mg) for ongoing maintenance treatment. Not all pack sizes may be marketed in every country.
Frequently Asked Questions
Apremilast Zentiva is used to treat three conditions: moderate-to-severe plaque psoriasis in adults who have not responded to, have a contraindication to, or are intolerant of other systemic therapies; active psoriatic arthritis in adults who have had an inadequate response or intolerance to prior disease-modifying therapy; and oral ulcers associated with Behçet’s disease in adults who are candidates for systemic therapy. It works by selectively inhibiting the PDE4 enzyme, which modulates inflammation.
Clinical improvement typically begins within the first 2–4 weeks of treatment, but the full therapeutic effect is usually assessed at 16–24 weeks. For psoriasis, some patients with low initial response at week 16 may continue to improve up to week 24 and beyond. For psoriatic arthritis, the response is evaluated at approximately 24 weeks. For Behçet’s disease oral ulcers, improvement in the number and pain of ulcers can be seen as early as week 4. Your doctor will assess your response to determine whether continued treatment is appropriate.
Unlike many other systemic treatments for psoriasis and psoriatic arthritis (such as methotrexate, ciclosporin, or biologic therapies), apremilast does not require routine laboratory monitoring, including blood tests for liver function, blood counts, or tuberculosis screening. This is one of the advantages of apremilast compared with other systemic therapies. However, your doctor may still recommend occasional check-ups to monitor your weight, kidney function (if relevant), and overall health. Regular follow-up appointments are important to assess treatment response and manage any side effects.
Yes, apremilast can generally be combined with topical psoriasis treatments such as corticosteroid creams, vitamin D analogues, and moisturizers. In psoriatic arthritis, it can be used together with methotrexate and other DMARDs. However, the combination of apremilast with biologic therapies has not been studied and is generally not recommended. It is important to avoid strong CYP3A4 inducers (rifampicin, phenobarbital, carbamazepine, phenytoin, St. John’s Wort) as they can significantly reduce apremilast levels. Always discuss all your medications with your doctor.
Apremilast Zentiva contains the same active ingredient (apremilast) as the originator product Otezla and is available in the same strengths (10 mg, 20 mg, 30 mg). It is a generic formulation that has been approved by regulatory authorities based on demonstrated bioequivalence, meaning it delivers the same amount of active substance to the body at the same rate as the reference product. Generic medicines meet the same quality, safety, and efficacy standards as the original product. Your doctor or pharmacist can advise you on switching between the branded and generic versions.
Diarrhea is the most common side effect of apremilast and is most likely to occur during the first two weeks of treatment. In most cases, it is mild to moderate and resolves on its own within four weeks. To manage diarrhea, stay well hydrated, eat smaller and more frequent meals, and avoid fatty or spicy foods. Over-the-counter antidiarrheal agents may help, but consult your doctor before using them. If diarrhea is severe, persistent, or accompanied by signs of dehydration (dizziness, dry mouth, decreased urination), contact your healthcare provider. Do not stop the medication without medical advice, as the gastrointestinal symptoms usually improve with continued use.
References
- European Medicines Agency (EMA). Apremilast – Summary of Product Characteristics. Last updated 2025. Available at: www.ema.europa.eu
- U.S. Food and Drug Administration (FDA). Otezla (apremilast) Prescribing Information. Revised 2024. Available at: www.fda.gov
- Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (ESTEEM 1). J Am Acad Dermatol. 2015;73(1):37-49. doi:10.1016/j.jaad.2015.03.049
- Paul C, Cather J, Goff K, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (ESTEEM 2). J Am Acad Dermatol. 2015;73(1):37-49.
- Cutolo M, Myerson GE, Fleischmann RM, et al. A phase III, randomized, controlled trial of apremilast in patients with psoriatic arthritis: Results of the PALACE 2 trial. J Rheumatol. 2016;43(9):1724-1734.
- Edwards CJ, Blanco FJ, Crowley J, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: A phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis. 2016;75(6):1065-1073.
- Hatemi G, Mahr A, Ishigatsubo Y, et al. Trial of apremilast for oral ulcers in Behçet’s syndrome (RELIEF). N Engl J Med. 2019;381(20):1918-1928. doi:10.1056/NEJMoa1816594
- Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with nonbiologic systemic therapies. J Am Acad Dermatol. 2024;90(4):891-924.
- 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.
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd List, 2023. Geneva: WHO; 2023.
Editorial Team
This article has been written and reviewed by licensed medical professionals specializing in dermatology, rheumatology, and clinical pharmacology. All content follows international guidelines and the GRADE evidence framework.
Medical Content Team
Specialist physicians in dermatology and rheumatology with clinical and academic experience in the treatment of immune-mediated inflammatory diseases
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Independent panel reviewing all content according to EMA, FDA, AAD-NPF, and EULAR guidelines with conflict-of-interest disclosure
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Clinical pharmacologists specializing in immunomodulatory therapies, drug interactions, and therapeutic drug monitoring
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Last medical review: | Evidence level: 1A (systematic reviews and meta-analyses of RCTs) | Guideline adherence: EMA SmPC, FDA Label, AAD-NPF, EULAR