Apremilast Anabiosis
Phosphodiesterase 4 (PDE4) Inhibitor — Film-coated Tablet
Quick Facts About Apremilast Anabiosis
Key Takeaways About Apremilast Anabiosis
- Targeted immunomodulator: Apremilast works by inhibiting PDE4 inside immune cells, reducing inflammation without broadly suppressing the immune system like traditional immunosuppressants
- Gradual dose titration: Treatment starts with a 5-day titration schedule, beginning at 10 mg once daily and increasing to the maintenance dose of 30 mg twice daily to minimize gastrointestinal side effects
- No routine blood monitoring: Unlike methotrexate and many biologics, apremilast does not require regular blood tests to monitor liver function or blood cell counts
- GI side effects usually resolve: The most common side effects (diarrhea and nausea) typically occur in the first two weeks and resolve within four weeks of continued treatment
- Monitor for depression: Patients and caregivers should be aware of new or worsening depression, suicidal thoughts, or mood changes and report them immediately to a healthcare provider
What Is Apremilast Anabiosis and What Is It Used For?
Apremilast Anabiosis is an oral PDE4 inhibitor prescribed for moderate to severe plaque psoriasis, active psoriatic arthritis, and oral ulcers in Behçet's disease. It modulates the immune response by increasing intracellular cAMP levels, which reduces inflammation without broadly suppressing the immune system.
Apremilast belongs to a class of medications known as phosphodiesterase 4 (PDE4) inhibitors. PDE4 is the dominant phosphodiesterase enzyme expressed in inflammatory cells such as T cells, monocytes, macrophages, and neutrophils. By selectively inhibiting PDE4, apremilast increases intracellular levels of cyclic adenosine monophosphate (cAMP), which in turn modulates the production of various inflammatory mediators. This leads to a reduction in pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-23 (IL-23), interleukin-17 (IL-17), and interferon-gamma (IFN-γ), while simultaneously increasing anti-inflammatory mediators such as interleukin-10 (IL-10).
The European Medicines Agency (EMA) has approved apremilast for the treatment of moderate to severe chronic plaque psoriasis in adult patients who have failed to respond to, have a contraindication to, or are intolerant of other systemic therapy including ciclosporin, methotrexate, or psoralen and ultraviolet-A light (PUVA). Additionally, the U.S. Food and Drug Administration (FDA) has approved apremilast for the treatment of active psoriatic arthritis in adults who have had an inadequate response or intolerance to a prior disease-modifying antirheumatic drug (DMARD), and for the treatment of oral ulcers associated with Behçet's disease in adults.
Psoriasis is a chronic autoimmune condition that affects approximately 2–3% of the global population, characterized by raised, red, scaly patches on the skin that can be painful and itchy. Psoriatic arthritis is a chronic inflammatory arthritis that occurs in approximately 30% of people with psoriasis, causing joint pain, stiffness, and swelling that can lead to permanent joint damage if left untreated. Apremilast represents an important treatment option because it offers an oral alternative to injectable biologic therapies and carries a distinct safety profile that does not require routine laboratory monitoring.
Unlike biologic therapies such as TNF inhibitors or IL-17 inhibitors that target specific extracellular cytokines, apremilast works intracellularly by modulating multiple inflammatory pathways simultaneously. This mechanism of action means it does not carry the risk of injection site reactions, does not require screening for tuberculosis prior to initiation (though it is still advisable to follow local guidelines), and does not require regular blood monitoring for liver toxicity or blood count changes.
Mechanism of Action
The mechanism of action of apremilast is well characterized. PDE4 catalyzes the hydrolysis of cAMP to its inactive form, adenosine monophosphate (AMP). When PDE4 is inhibited by apremilast, cAMP accumulates inside the cell, activating protein kinase A (PKA). PKA then phosphorylates the transcription factor CREB (cAMP response element-binding protein), which promotes the expression of anti-inflammatory genes and suppresses the expression of pro-inflammatory genes. The net result is a rebalancing of the pro-inflammatory and anti-inflammatory mediator network, reducing the overactive immune response that drives psoriasis and psoriatic arthritis.
Clinical studies, including the pivotal ESTEEM 1 and ESTEEM 2 trials for psoriasis, and the PALACE 1–4 trials for psoriatic arthritis, have demonstrated that apremilast significantly reduces disease activity compared to placebo. In the ESTEEM trials, approximately 33% of patients achieved a 75% reduction in Psoriasis Area and Severity Index (PASI 75) at week 16, and responses were sustained through week 52 in those who continued treatment.
What Should You Know Before Taking Apremilast Anabiosis?
Before starting Apremilast Anabiosis, inform your healthcare provider about any history of depression or suicidal thoughts, kidney problems, current pregnancy or plans to become pregnant, and all medications you are taking. Dose adjustment is required for severe renal impairment (creatinine clearance below 30 mL/min).
It is essential to have a thorough discussion with your prescribing physician before beginning treatment with Apremilast Anabiosis. While this medication has a favorable safety profile compared to many systemic treatments for psoriasis and psoriatic arthritis, there are several important factors that must be considered to ensure safe and effective use.
Contraindications
Apremilast Anabiosis is contraindicated in patients who have a known hypersensitivity to apremilast or any of the excipients contained in the formulation. Allergic reactions, while rare, can include angioedema and anaphylaxis. If you have previously experienced an allergic reaction to apremilast in any formulation, you must not take this medication.
Additionally, apremilast is contraindicated during pregnancy. Animal studies have shown evidence of embryotoxicity at doses that are clinically relevant. Women of childbearing potential must use effective contraception during treatment and for at least 28 days after discontinuation. A pregnancy test should be performed before starting treatment.
Warnings and Precautions
Depression and suicidal ideation: During clinical trials, a small number of patients reported depression, suicidal ideation, and suicidal behavior. While the overall incidence was low, patients and their caregivers should be alert to any new or worsening symptoms of depression, changes in mood, or suicidal thoughts. Treatment should be carefully re-evaluated if patients experience such symptoms. Apremilast should be used with caution in patients with a history of psychiatric disorders, and the risks and benefits should be carefully weighed.
If you or someone close to you notices new or worsening depression, suicidal thoughts, anxiety, or other significant mood changes after starting Apremilast Anabiosis, contact your healthcare provider immediately. Do not stop taking the medication abruptly without medical advice, but seek urgent evaluation.
Body weight monitoring: Unexplained or clinically significant weight loss has been observed in some patients treated with apremilast. Body weight should be monitored regularly, and if unexplained clinically significant weight loss occurs, treatment should be re-evaluated. In clinical trials, approximately 10% of patients experienced weight loss of 5–10% of body weight, and about 2% lost more than 10% of body weight.
Severe renal impairment: In patients with severe renal impairment (creatinine clearance less than 30 mL/min as estimated by the Cockcroft-Gault equation), the dose of apremilast should be reduced to 30 mg once daily instead of twice daily. The initial titration schedule should also be modified, using only the morning doses. No dose adjustment is required for mild or moderate renal impairment.
Lactose intolerance: Apremilast Anabiosis film-coated tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
Pregnancy and Breastfeeding
Apremilast Anabiosis must not be used during pregnancy. Animal reproductive studies have demonstrated adverse developmental effects including embryo lethality, reduced fetal weight, and delayed ossification at clinically relevant exposures. Women of childbearing potential must use effective contraception during treatment and for at least 28 days after discontinuing apremilast. If pregnancy occurs during treatment, the medication should be discontinued immediately, and the patient should be referred to an obstetrician experienced in reproductive toxicology.
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 serious adverse reactions in nursing infants, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother. The EMA recommends that breastfeeding is avoided during treatment with apremilast.
How Does Apremilast Anabiosis Interact with Other Drugs?
Apremilast has relatively few drug interactions compared to other immunomodulatory therapies. The most clinically significant interaction is with strong CYP3A4 enzyme inducers (such as rifampicin, phenobarbital, carbamazepine, and phenytoin) which can significantly reduce apremilast blood levels and decrease its effectiveness. St. John's Wort should also be avoided.
Apremilast is metabolized through multiple pathways, including cytochrome P450 (CYP) oxidative metabolism (primarily CYP3A4, with minor contributions from CYP1A2 and CYP2A6) and non-CYP-mediated hydrolysis. Because of this multiple-pathway metabolism, inhibition of a single CYP enzyme is unlikely to produce a clinically meaningful drug interaction. This distinguishes apremilast from many other systemic therapies where single-pathway metabolism creates vulnerability to drug interactions.
Major Interactions
The most significant drug interaction is with strong CYP3A4 enzyme inducers. Co-administration with rifampicin, a potent CYP3A4 inducer, was shown to reduce apremilast exposure (area under the curve, AUC) by approximately 72% in a pharmacokinetic study. This reduction is clinically meaningful and would likely result in loss of therapeutic efficacy. Therefore, the following strong CYP3A4 inducers should be avoided or used with extreme caution during apremilast treatment:
| Interacting Drug | Interaction Type | Effect | Clinical Recommendation |
|---|---|---|---|
| Rifampicin | Strong CYP3A4 inducer | Reduces apremilast AUC by ~72% | Avoid co-administration |
| Phenobarbital | Strong CYP3A4 inducer | Significantly reduces apremilast levels | Avoid co-administration |
| Carbamazepine | Strong CYP3A4 inducer | Significantly reduces apremilast levels | Avoid co-administration |
| Phenytoin | Strong CYP3A4 inducer | Significantly reduces apremilast levels | Avoid co-administration |
| St. John's Wort | Herbal CYP3A4 inducer | May reduce apremilast levels | Avoid co-administration |
Minor Interactions
Apremilast has been studied in combination with several commonly used medications and no clinically significant interactions were found. Co-administration with ketoconazole (a strong CYP3A4 inhibitor) increased apremilast AUC by approximately 36%, which was not considered clinically significant and does not require dose adjustment. Similarly, no dose adjustments are needed when apremilast is used alongside methotrexate, oral contraceptives, or warfarin.
In clinical trials, apremilast was administered concomitantly with low doses of methotrexate, oral corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) in patients with psoriatic arthritis without evidence of altered pharmacokinetics or increased adverse events. This flexibility in combination therapy is one of the advantages of apremilast over some other treatment options.
What Is the Correct Dosage of Apremilast Anabiosis?
The maintenance dose of Apremilast Anabiosis is 30 mg taken orally twice daily, approximately 12 hours apart. Treatment begins with a 5-day dose titration schedule to reduce the risk of gastrointestinal side effects. The tablets can be taken with or without food.
Apremilast treatment follows a carefully designed titration schedule during the first five days to minimize the incidence and severity of gastrointestinal adverse effects, particularly diarrhea and nausea. After the titration phase, the maintenance dose is 30 mg twice daily. Clinical evidence from the ESTEEM and PALACE trial programs consistently supports this dosing regimen for both psoriasis and psoriatic arthritis indications.
Initial 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 |
Adults
Standard Adult Dosage
After completing the 5-day titration, the recommended maintenance dose is 30 mg taken orally twice daily, approximately 12 hours apart. Tablets may be taken with or without food. Swallow the tablets whole; do not crush, split, or chew them. If a significant response is not observed within 24 weeks of treatment, the decision to continue should be carefully reconsidered.
Children
Pediatric Use
The safety and efficacy of Apremilast Anabiosis in children and adolescents under 18 years of age have not been established. There are no data available from controlled clinical trials in pediatric populations. Therefore, apremilast is not recommended for use in patients under 18 years of age.
Elderly
Elderly Patients (65 years and older)
No dose adjustment is required for elderly patients based on age alone. However, clinical experience in patients aged 75 years and older is limited. Elderly patients may be more susceptible to certain adverse effects, particularly gastrointestinal events and weight loss, and should be monitored accordingly. Renal function should be assessed before starting treatment, as age-related decline in kidney function may necessitate dose adjustment.
Severe Renal Impairment
Dose Adjustment for Renal Impairment
In patients with severe renal impairment (creatinine clearance < 30 mL/min), the dose should be reduced to 30 mg once daily. During the initial titration period, only the morning doses of the titration schedule should be administered. No dose adjustment is required for mild or moderate renal impairment. No dose adjustment is required for hepatic impairment.
Missed Dose
If a dose is missed, it should be taken as soon as the patient remembers. However, if it is close to the time of the next scheduled dose, the missed dose should be skipped, and the next dose should be taken at the regular time. A double dose should not be taken to compensate for a missed dose. Patients should be encouraged to take apremilast at consistent times each day to maintain stable plasma drug levels.
Overdose
There is limited clinical experience with overdose of apremilast. In a pharmacokinetic study, a healthy volunteer received a single dose of 50 mg with no adverse effects reported. In the event of overdose, it is recommended that the patient be monitored for signs and symptoms of adverse effects and appropriate symptomatic treatment be initiated. There is no specific antidote for apremilast. Due to its high protein binding (~68%), hemodialysis is unlikely to significantly enhance drug elimination.
What Are the Side Effects of Apremilast Anabiosis?
The most common side effects of Apremilast Anabiosis are gastrointestinal (diarrhea and nausea), which typically occur during the first two weeks of treatment and usually resolve within four weeks. Other common side effects include upper respiratory tract infections, headache, and decreased appetite. Serious side effects are rare but include depression and significant weight loss.
The safety profile of apremilast has been extensively evaluated in clinical trials involving more than 4,000 patients treated for up to 5 years. Overall, the most frequently reported adverse reactions are gastrointestinal in nature and tend to occur early in the course of treatment, particularly during the first two weeks. The dose titration schedule described above was specifically designed to reduce the incidence of these gastrointestinal effects. The following frequency categories are based on data from pooled clinical trials.
Very Common (affects more than 1 in 10 patients)
Frequency: >10%
- Diarrhea (typically resolves within 4 weeks)
- Nausea (most common in first 2 weeks)
Common (affects 1 to 10 in 100 patients)
Frequency: 1–10%
- Upper respiratory tract infections
- Headache and tension headache
- Decreased appetite
- Vomiting
- Abdominal pain (upper)
- Dyspepsia (indigestion)
- Frequent bowel movements
- Back pain
- Fatigue
- Weight loss
- Migraine
- Cough
- Nasopharyngitis (common cold)
Uncommon (affects 1 to 10 in 1,000 patients)
Frequency: 0.1–1%
- Gastrointestinal hemorrhage
- Rash
- Urticaria (hives)
- Depression
- Suicidal ideation
Rare (affects less than 1 in 1,000 patients)
Frequency: <0.1%
- Angioedema (severe swelling)
- Severe allergic reactions
- Suicidal behavior (completed suicide)
Long-term safety data from open-label extension studies of up to 5 years have shown that the adverse effect profile remains consistent over time, with no new safety signals emerging. The incidence of serious infections was not increased compared to placebo, and there was no increased risk of malignancy observed. This safety profile is an important distinguishing feature of apremilast compared to some biologic therapies and conventional immunosuppressants.
Seek immediate medical attention if you experience severe allergic reactions (difficulty breathing, swelling of face, lips, tongue, or throat), signs of depression or suicidal thoughts, unexplained and significant weight loss, severe or persistent diarrhea, or signs of dehydration. If you experience any unusual or concerning symptoms, contact your healthcare provider promptly.
How Should You Store Apremilast Anabiosis?
Store Apremilast Anabiosis below 30°C (86°F) in its original packaging to protect from light and moisture. Do not use after the expiry date printed on the blister and carton. Keep out of sight and reach of children.
Proper storage of medication is essential to maintain its safety and efficacy throughout its shelf life. Apremilast Anabiosis film-coated tablets should be stored in their original blister packaging until the time of use. The packaging has been specifically designed to protect the tablets from environmental factors that could affect their stability.
The recommended storage conditions are as follows:
- Temperature: Store below 30°C (86°F). Do not refrigerate or freeze.
- Light: Keep in the original blister packaging to protect from light.
- Moisture: Protect from moisture. Do not remove tablets from the blister until ready to take them.
- Children: Keep out of sight and reach of children.
- Expiry date: Do not use this medicine after the expiry date stated on the blister and carton. The expiry date refers to the last day of that month.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist about how to throw away medicines you no longer use. These measures will help protect the environment. If you notice any visible changes to the appearance of the tablets (discoloration, crumbling, unusual odor), do not take them and consult your pharmacist.
What Does Apremilast Anabiosis Contain?
Each Apremilast Anabiosis film-coated tablet contains apremilast as the active substance, available in strengths of 10 mg, 20 mg, and 30 mg. The tablets also contain several inactive excipients including lactose monohydrate, microcrystalline cellulose, and other standard pharmaceutical ingredients.
Understanding the composition of your medication is important, particularly if you have known allergies or intolerances to specific pharmaceutical ingredients. Below is a comprehensive breakdown of the active and inactive ingredients in Apremilast Anabiosis film-coated tablets.
Active Ingredient
The active substance is apremilast. Each tablet contains either 10 mg, 20 mg, or 30 mg of apremilast, depending on the strength prescribed. Apremilast is a small molecule with the molecular formula C22H24N2O7S and a molecular weight of 460.5 g/mol.
Inactive Ingredients (Excipients)
The tablet core typically contains the following excipients:
- Lactose monohydrate — a common tablet filler (important for patients with lactose intolerance)
- Microcrystalline cellulose — provides structure and aids disintegration
- Croscarmellose sodium — a disintegrant that helps the tablet break down in the gastrointestinal tract
- Magnesium stearate — a lubricant used in tablet manufacturing
The film coating typically contains:
- Polyvinyl alcohol
- Titanium dioxide (E171) — provides white color
- Macrogol (polyethylene glycol)
- Talc
- Iron oxide red (E172) — used in some tablet strengths for color differentiation
- Iron oxide yellow (E172) — used in some tablet strengths for color differentiation
The different tablet strengths are typically distinguished by color and/or markings to help prevent dosing errors. The 10 mg tablets are usually pink, the 20 mg tablets are brown, and the 30 mg tablets are beige. Always verify the tablet appearance matches what your pharmacist has described when you receive a new prescription or refill.
Frequently Asked Questions About Apremilast Anabiosis
Apremilast Anabiosis is used to treat three conditions: moderate to severe plaque psoriasis in adults who have not responded to or cannot tolerate other systemic therapies; active psoriatic arthritis in adults who have had an inadequate response to DMARDs; and oral ulcers associated with Behçet's disease. It works by inhibiting the PDE4 enzyme, which helps reduce the inflammation that drives these conditions.
Some patients may notice initial improvement within 2 to 4 weeks after reaching the full maintenance dose. However, the maximum therapeutic benefit for psoriasis is typically observed after 16 to 24 weeks of continuous treatment. For psoriatic arthritis, joint symptoms may improve within the first few weeks, while the full effect on joint inflammation usually develops over several months. Your doctor should evaluate your response at around 24 weeks to determine whether to continue treatment.
There is no specific contraindication for alcohol use with apremilast, and no clinically significant pharmacokinetic interaction has been demonstrated. However, alcohol can worsen gastrointestinal side effects such as nausea and diarrhea, which are already common with apremilast, especially during the initial weeks of treatment. Additionally, alcohol may have negative effects on psoriasis itself. It is advisable to limit alcohol consumption and discuss this with your healthcare provider.
Apremilast is classified as an immunomodulator, not a traditional immunosuppressant. It works by modifying the immune response rather than broadly suppressing it. Unlike drugs such as ciclosporin, methotrexate, or biologic TNF inhibitors, apremilast has not been associated with increased rates of serious infections, opportunistic infections, or malignancies in clinical trials. This is one of the reasons it does not require routine laboratory monitoring during treatment.
Diarrhea is one of the most common side effects and typically occurs during the first two weeks of treatment. In most cases, it is mild to moderate and resolves within four weeks without intervention. Stay well hydrated and eat small, frequent meals. If diarrhea is severe, persistent, or accompanied by signs of dehydration (excessive thirst, dry mouth, dark urine, dizziness), contact your healthcare provider. The dose titration schedule is designed to minimize this effect, so it is important to follow it carefully.
The concurrent use of apremilast with biologic therapies has not been extensively studied in controlled clinical trials. While some real-world evidence suggests potential benefit of combining apremilast with certain biologics, this is not currently a standard recommendation. The decision to combine therapies should be made on an individual basis by a dermatologist or rheumatologist experienced in managing these conditions. Apremilast has been safely combined with methotrexate, low-dose corticosteroids, and NSAIDs in clinical trials.
References
All medical information is based on peer-reviewed research and international clinical guidelines.
- European Medicines Agency (EMA). Otezla (apremilast) – Summary of Product Characteristics. Last updated 2024. Available at: www.ema.europa.eu
- 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, 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
- Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor (PALACE 1). Ann Rheum Dis. 2014;73(6):1020-1026. doi:10.1136/annrheumdis-2013-205056
- Hatemi G, Mahr A, Ishigatsubo Y, et al. Trial of Apremilast for Oral Ulcers in Behçet's Syndrome. N Engl J Med. 2019;381(20):1918-1928. doi:10.1056/NEJMoa1816594
- National Institute for Health and Care Excellence (NICE). Apremilast for treating moderate to severe plaque psoriasis. Technology Appraisal Guidance [TA419]. Updated 2024.
- Gossec L, Baraliakos X, Kerschbaumer A, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis. 2020;79(6):700-712. doi:10.1136/annrheumdis-2020-217159
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List. 2023.
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