Apremilast STADA: Uses, Dosage & Side Effects

What Is Apremilast STADA and What Is It Used For?

Apremilast STADA Arzneimittel AG contains the active substance apremilast, a small-molecule inhibitor of phosphodiesterase 4 (PDE4). PDE4 is an intracellular enzyme that is the predominant phosphodiesterase in inflammatory cells, including T cells, monocytes, macrophages, neutrophils, dendritic cells, and keratinocytes. By selectively inhibiting PDE4, apremilast increases intracellular levels of cyclic adenosine monophosphate (cAMP), which in turn activates protein kinase A (PKA) and other downstream effectors. This signaling cascade leads to a broad modulation of the inflammatory response: pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), interleukin-17 (IL-17), interleukin-23 (IL-23), and interferon-gamma (IFN-gamma) are downregulated, while anti-inflammatory mediators such as interleukin-10 (IL-10) are upregulated.

This dual mechanism of reducing pro-inflammatory signals while enhancing anti-inflammatory signals makes apremilast fundamentally different from traditional immunosuppressants. Rather than broadly suppressing the immune system, apremilast fine-tunes the balance of inflammatory mediators. This targeted approach contributes to a favorable safety profile: unlike methotrexate, cyclosporine, or biologic agents, apremilast does not require routine blood monitoring for organ toxicity, and it is not associated with the increased risk of serious infections or malignancies seen with some other systemic therapies.

Apremilast is approved by the European Medicines Agency (EMA) and regulatory authorities worldwide for three distinct indications. The first is 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 cyclosporine, methotrexate, or psoralen plus ultraviolet A (PUVA). Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting approximately 2-3% of the global population, characterized by raised, red, scaly plaques that can cause significant physical discomfort, psychological distress, and reduced quality of life.

The second approved indication is active psoriatic arthritis in adult patients, either alone or in combination with disease-modifying antirheumatic drugs (DMARDs), who have had an inadequate response or have been intolerant to a prior DMARD therapy. Psoriatic arthritis is a chronic inflammatory joint disease that occurs in up to 30% of patients with psoriasis and can cause joint pain, stiffness, swelling, and progressive joint damage if left untreated. The PALACE clinical trial program (PALACE 1, 2, 3, and 4) demonstrated that apremilast significantly improves signs and symptoms of psoriatic arthritis, including joint tenderness, swelling, physical function, and patient-reported outcomes.

The third approved indication is oral ulcers associated with Behcet's disease in adult patients who are candidates for systemic therapy. Behcet's disease is a chronic, relapsing, multisystem inflammatory disorder characterized by recurrent painful oral ulcers, genital ulcers, and eye inflammation. The BCT-002 (RELIEF) trial demonstrated that apremilast significantly reduced the number and pain of oral ulcers in patients with Behcet's disease, representing an important treatment advance for this difficult-to-manage condition.

This particular formulation, manufactured by STADA Arzneimittel AG, is a generic version of apremilast that contains the same active ingredient in the same strengths (10 mg, 20 mg, and 30 mg film-coated tablets) as the originator product. Generic medications must demonstrate bioequivalence to the reference product, meaning they deliver the same amount of active ingredient to the bloodstream at the same rate. Patients can expect the same therapeutic effect and safety profile from this generic formulation.

What Should You Know Before Taking Apremilast STADA?

Before beginning treatment with apremilast, it is essential that your prescribing physician has a complete picture of your medical history, current medications, and any relevant conditions. Apremilast has specific contraindications, warnings, and precautions that must be considered to ensure safe and effective treatment. Your doctor will evaluate whether apremilast is the right choice for your particular situation and will discuss the potential benefits and risks with you.

Contraindications

Apremilast must not be used if you have a known hypersensitivity (allergic reaction) to apremilast or to any of the excipients (inactive ingredients) in the tablets. Signs of hypersensitivity may include rash, swelling, difficulty breathing, or anaphylaxis. If you experience any symptoms suggestive of a serious allergic reaction, stop taking the medication immediately and seek emergency medical attention.

Apremilast is contraindicated during pregnancy. Animal studies have shown reproductive toxicity, including increased embryo-fetal loss and reduced fetal weight. Women of childbearing potential must use effective contraception during treatment. A pregnancy test is recommended before starting treatment, and women should not become pregnant during therapy or for at least 48 hours after the last dose. If pregnancy occurs during treatment, the medication must be discontinued immediately and the patient should be referred to an obstetrician or physician experienced in reproductive toxicology for further evaluation and counseling.

Warnings and Precautions

Psychiatric disorders: Depression and depressed mood have been reported in clinical trials and post-marketing experience with apremilast. In some cases, suicidal ideation and suicidal behavior, including completed suicide, have been reported. The causal relationship between apremilast and these psychiatric events has not been fully established, as patients with psoriasis and psoriatic arthritis already have a higher baseline rate of depression and psychiatric comorbidities. Nevertheless, patients and caregivers should be instructed to report any new or worsening symptoms of depression, mood changes, or suicidal thoughts to the prescribing physician promptly. If new or worsening psychiatric symptoms develop, or if suicidal ideation or behavior is identified, treatment with apremilast should be reassessed. It may be appropriate to discontinue the medication if the risks outweigh the benefits.

Body weight: Weight loss has been observed in patients treated with apremilast. In clinical trials, approximately 10% of patients experienced weight loss of 5-10% from baseline, and about 2% experienced weight loss exceeding 10%. Body weight should be monitored regularly during treatment, and unexplained or clinically significant weight loss should be evaluated. In underweight patients at baseline, body weight should be monitored particularly carefully, and discontinuation of treatment should be considered if clinically significant weight loss occurs.

Renal impairment: In patients with severe renal impairment (creatinine clearance less than 30 mL/min), the dose of apremilast should be reduced to 30 mg once daily (instead of twice daily). During the initial dose titration, only the morning doses should be administered using the standard titration schedule. No dose adjustment is needed for mild or moderate renal impairment.

Lactose intolerance: Apremilast tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medication.

Gastrointestinal disorders: Severe diarrhea, nausea, and vomiting have been reported with apremilast use. Most gastrointestinal adverse events occur within the first 2 weeks of treatment and typically resolve within 4 weeks. In patients aged 65 years and older, the incidence of gastrointestinal adverse events, particularly diarrhea, may be higher. Patients experiencing severe diarrhea or vomiting should be monitored for adequate hydration and electrolyte balance.

Pregnancy and Breastfeeding

As noted above, apremilast is contraindicated during pregnancy due to evidence of reproductive toxicity in animal studies. Pre-clinical studies in mice showed increased post-implantation losses at doses equivalent to clinical exposure, and studies in monkeys showed apremilast-related fetal losses at exposures approximately 2.1 times the clinical exposure. There are no adequate data from the use of apremilast in pregnant women. Women of childbearing potential must use an effective method of contraception to prevent pregnancy during treatment.

It is not known whether apremilast or its metabolites are excreted in human breast milk. A risk to newborns or infants cannot be excluded, and a decision must be made whether to discontinue breastfeeding or to discontinue apremilast therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother. This decision should be made in consultation with a healthcare provider who can help weigh the individual risks and benefits.

Apremilast has no effect on male fertility based on animal studies. However, the effects on human fertility have not been formally studied. There is no requirement for men to use contraception during treatment.

How Does Apremilast STADA Interact with Other Drugs?

Apremilast is primarily metabolized by cytochrome P450 3A4 (CYP3A4), with minor contributions from CYP1A2 and CYP2A6. This metabolic pathway means that drugs that strongly induce or inhibit CYP3A4 can potentially alter the plasma levels of apremilast. However, apremilast itself does not significantly inhibit or induce CYP enzymes at clinically relevant concentrations, meaning it is unlikely to affect the levels of other medications metabolized by these enzymes. This is a notable advantage compared to some other immunomodulatory agents.

In clinical pharmacology studies, co-administration of apremilast with the strong CYP3A4 inducer rifampicin resulted in an approximately 72% reduction in the area under the curve (AUC) and a 43% reduction in peak plasma concentration (Cmax) of apremilast. This dramatic reduction in exposure would be expected to significantly reduce the therapeutic efficacy of apremilast. Therefore, co-administration of apremilast with strong CYP3A4 inducers is not recommended.

Co-administration with the strong CYP3A4 inhibitor ketoconazole resulted in a modest 36% increase in the AUC of apremilast. No dose adjustment is required when apremilast is used with CYP3A4 inhibitors. Apremilast can be safely used with commonly prescribed medications including methotrexate, oral contraceptives, and most over-the-counter medications.

Major Interactions

Minor Interactions

It is always important to inform your doctor and pharmacist about all medications you are taking, including prescription medicines, over-the-counter drugs, vitamins, and herbal supplements. Even though apremilast has relatively few interactions, your healthcare team needs a complete medication list to ensure your safety and to avoid any unexpected interactions.

What Is the Correct Dosage of Apremilast STADA?

The recommended dosing regimen for apremilast follows a specific initial titration schedule designed to minimize the gastrointestinal side effects that are most common during the early phase of treatment. This gradual dose escalation allows the body to adjust to the medication and significantly reduces the incidence and severity of nausea, diarrhea, and vomiting. It is critically important that patients follow this titration schedule exactly as prescribed and do not skip ahead to the full dose.

Adults

From Day 6 onwards, the recommended maintenance dose is 30 mg taken twice daily, approximately 12 hours apart (morning and evening). The tablets can be taken with or without food. Each dose should be swallowed whole with water and should not be crushed, split, or chewed. A starter pack is usually provided that contains the correct tablets for the first 2 weeks of treatment, clearly labeled by day and time of day to simplify the titration process.

Children

Apremilast is not recommended for use in children and adolescents under 18 years of age because the safety and efficacy in this population have not been established. There are currently no adequate clinical trial data available to support a dosage recommendation in pediatric patients. If a clinician is considering treatment for a younger patient with severe psoriasis or psoriatic arthritis, alternative approved therapies should be explored first.

Elderly

No dose adjustment is required for elderly patients based on age alone. However, clinical experience with apremilast in patients aged 75 years and over is limited. Elderly patients may be more susceptible to gastrointestinal side effects, particularly diarrhea, and should be monitored closely during the first weeks of treatment. Adequate hydration should be maintained, especially in older patients who may be more vulnerable to dehydration from diarrhea or vomiting. Renal function should be assessed before starting treatment, as age-related decline in renal function may necessitate dose adjustment in those with severe renal impairment.

Missed Dose

If a dose of apremilast is missed, it should be taken as soon as the patient remembers, unless it is nearly time for the next scheduled dose. In that case, the missed dose should be skipped and the next dose taken at the regular time. Patients should not take a double dose to make up for a forgotten dose. The medication works best when taken consistently at approximately the same times each day, maintaining approximately 12-hour intervals between the morning and evening doses.

Overdose

Apremilast was studied in healthy volunteers at a daily dose of up to 100 mg (50 mg twice daily) for 4.5 days with no evidence of dose-limiting toxicities. In the event of an overdose, patients should be monitored for signs and symptoms of adverse effects and appropriate symptomatic treatment should be given. There is no specific antidote for apremilast overdose. Due to its moderate protein binding (approximately 68%), hemodialysis is unlikely to be effective in removing apremilast from the body. Contact a poison control center or seek immediate medical attention if overdose is suspected.

What Are the Side Effects of Apremilast STADA?

Like all medicines, apremilast can cause side effects, although not everybody gets them. The overall safety profile of apremilast has been well characterized through extensive clinical trials involving more than 4,000 patients and ongoing post-marketing surveillance. The most frequently reported adverse reactions are gastrointestinal in nature and tend to occur during the initial weeks of treatment. Understanding the frequency and nature of potential side effects can help patients and healthcare providers make informed treatment decisions and know when to seek medical attention.

The side effects listed below are categorized by frequency according to the standard medical convention: very common (affects more than 1 in 10 people), common (affects 1 in 10 to 1 in 100 people), uncommon (affects 1 in 100 to 1 in 1,000 people), and rare (affects fewer than 1 in 1,000 people). This classification helps put the relative likelihood of each side effect into perspective.

The gastrointestinal side effects of apremilast deserve special discussion because they are the most common reason patients may consider discontinuing treatment. In clinical trials, diarrhea and nausea each occurred in approximately 15-17% of patients taking apremilast, compared with 6-8% of patients taking placebo. Importantly, these symptoms were typically mild to moderate in severity, occurred primarily during the first two weeks of treatment, and resolved within the first four weeks in most patients. The dose titration schedule is specifically designed to minimize these effects by allowing the gastrointestinal tract to adjust gradually.

Weight loss during apremilast treatment is generally mild and stabilizes over time. In controlled clinical trials, the mean weight change from baseline was approximately -1.5 to -2.0 kg at 52 weeks. However, in a small percentage of patients, weight loss can be more pronounced. Patients who are already underweight or who experience unexplained or significant weight loss should be monitored closely, and discontinuation should be considered if clinically warranted.

Depression and psychiatric adverse events are of particular clinical importance. While the overall incidence of depression in apremilast-treated patients was similar to placebo in controlled trials, post-marketing reports have included cases of suicidal ideation and completed suicide. It is important to note that psoriasis and psoriatic arthritis are themselves associated with an increased risk of depression and psychological distress. All patients should be counseled about the potential for mood changes and instructed to report any new or worsening psychiatric symptoms promptly.

How Should You Store Apremilast STADA?

Proper storage of medications is essential to maintain their efficacy, safety, and quality throughout their shelf life. Apremilast film-coated tablets should be stored at temperatures below 30°C (86°F). There is no need for refrigeration. The tablets should be kept in the original blister pack or bottle to protect them from moisture and light. Exposure to excessive heat, humidity, or direct sunlight may degrade the active ingredient and reduce the effectiveness of the medication.

As with all medicines, apremilast must be kept out of the reach and sight of children. The starter pack with its titration schedule may be particularly attractive to young children, so extra care should be taken with storage during the initial treatment period. If child-resistant packaging is provided, ensure that it is properly resealed after each use.

Do not use apremilast after the expiry date (EXP) stated on the blister, bottle, or outer carton. The expiry date refers to the last day of that month. Do not dispose of medications through wastewater or household waste. Ask your pharmacist about safe disposal methods for medicines you no longer use or that have expired. Proper disposal helps protect the environment and prevents accidental ingestion by others.

When traveling with apremilast, keep the tablets in their original packaging with the pharmacy label visible. This is important for security screening and for identification in case of a medical emergency. If traveling to hot climates, take precautions to keep the medication within the recommended temperature range, such as using an insulated travel bag. Avoid leaving medication in a car or in direct sunlight, as temperatures can quickly exceed safe storage limits.

What Does Apremilast STADA Contain?

Each Apremilast STADA tablet contains the active substance apremilast in one of three strengths: 10 mg, 20 mg, or 30 mg. The 10 mg and 20 mg tablets are typically used only during the initial 5-day dose titration period, while the 30 mg tablet is the strength used for ongoing maintenance treatment. All three strengths are provided in the starter pack to facilitate the titration schedule.

The tablets also contain inactive ingredients (excipients) that are necessary for the manufacturing process, stability, and proper release of the active ingredient. The typical excipients found in apremilast film-coated tablets include:

• Tablet core: Lactose monohydrate, microcrystalline cellulose, croscarmellose sodium (as a disintegrant to help the tablet break apart), and magnesium stearate (as a lubricant for the manufacturing process).
• Film coating: The coating typically contains polyvinyl alcohol, titanium dioxide (E171), macrogol (polyethylene glycol), talc, and iron oxide pigments for coloring. The film coating helps protect the tablet from moisture, makes it easier to swallow, and provides the distinctive appearance that differentiates each strength.

The different tablet strengths are typically distinguished by their color and shape: the 10 mg tablet is pink and diamond-shaped, the 20 mg tablet is brown and diamond-shaped, and the 30 mg tablet is beige and diamond-shaped. These visual differences help patients and healthcare professionals easily identify the correct strength, which is particularly important during the dose titration phase when multiple strengths are used on the same day.

Patients with known intolerances to any of the listed excipients should discuss this with their doctor or pharmacist before starting treatment. Of particular note, the tablets contain lactose, and patients with rare hereditary conditions affecting lactose metabolism (galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption) should not take this medication. The sodium content of the tablets is negligible and is not a concern for patients on sodium-restricted diets.