Apremilast Teva: Uses, Dosage & Side Effects

What Is Apremilast Teva and What Is It Used For?

Apremilast Teva contains the active substance apremilast, which belongs to a class of medications known as phosphodiesterase 4 (PDE4) inhibitors. PDE4 is an intracellular enzyme predominantly found 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), a critical intracellular signaling molecule that plays a central role in regulating inflammatory responses. When PDE4 is inhibited by apremilast, intracellular cAMP levels rise, which triggers a cascade of downstream effects that shift the balance of the immune system away from inflammation.

Specifically, elevated cAMP levels lead to the activation of protein kinase A (PKA), which phosphorylates various transcription factors. This results in the downregulation 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 upregulating anti-inflammatory mediators such as interleukin-10 (IL-10). This dual mechanism of action — suppressing pro-inflammatory signals while enhancing anti-inflammatory ones — provides a balanced immunomodulatory effect that differs fundamentally from the broad immunosuppression seen with older systemic therapies.

The unique intracellular mechanism of action of apremilast distinguishes it from biologic therapies that target specific extracellular cytokines or cell-surface receptors. Unlike TNF inhibitors (adalimumab, etanercept), IL-17 inhibitors (secukinumab, ixekizumab), or IL-23 inhibitors (guselkumab, risankizumab), apremilast works inside the cell to modulate multiple inflammatory pathways simultaneously. This broad but targeted approach means that apremilast affects the overall inflammatory milieu rather than blocking a single cytokine, which can be advantageous in conditions where multiple inflammatory pathways contribute to disease.

Apremilast Teva is approved by regulatory authorities including the European Medicines Agency (EMA) and is indicated for the following conditions:

• 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 cyclosporine, methotrexate, or psoralen plus ultraviolet A (PUVA) light therapy. In the pivotal ESTEEM 1 and ESTEEM 2 clinical trials, apremilast demonstrated significant improvements in Psoriasis Area and Severity Index (PASI) scores at week 16, with sustained efficacy through 52 weeks of treatment.
• Active psoriatic arthritis (PsA): Apremilast is used alone or in combination with disease-modifying antirheumatic drugs (DMARDs) in adult patients who have had an inadequate response to or are intolerant of a prior DMARD therapy. The PALACE clinical trial program (PALACE 1, 2, 3, and 4) demonstrated significant improvements in ACR20 response rates, physical function, and enthesitis and dactylitis scores at week 16.
• Oral ulcers associated with Behcet's disease: For adult patients who are candidates for systemic therapy. The BCT-002 study demonstrated significant reduction in the number and pain of oral ulcers, with rapid onset of effect. This represents an important treatment option for a condition with limited approved therapies.

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 raised, red patches covered with silvery-white scales, typically on the elbows, knees, scalp, and lower back. Psoriatic arthritis is an inflammatory joint disease that occurs in approximately 30% of psoriasis patients, causing joint pain, stiffness, swelling, and progressive joint damage. Behcet's disease is a rare systemic vasculitis characterized by recurrent painful oral ulcers, genital ulcers, and eye inflammation.

What Should You Know Before Taking Apremilast Teva?

Contraindications

Apremilast Teva must not be taken if you are allergic to apremilast or any of the other ingredients in the tablets. The most important absolute contraindication is pregnancy. Apremilast has been shown to cause developmental toxicity in animal studies, including increased post-implantation loss, reduced fetal weight, and delayed ossification. Women of childbearing potential must use effective contraception to prevent pregnancy during treatment.

Patients with known hypersensitivity to apremilast or to any of the excipients listed in the product composition should not take this medication. Although rare, serious hypersensitivity reactions including angioedema have been reported post-marketing. If such a reaction occurs, treatment should be discontinued immediately and appropriate medical care should be sought.

Warnings and Precautions

Several important warnings and precautions must be considered before and during treatment with apremilast:

• Psychiatric disorders: Apremilast has been associated with an increased risk of psychiatric adverse events including insomnia, depression, and in rare cases, suicidal ideation and behavior. Patients and their caregivers should be instructed to notify the prescribing physician of any changes in behavior or mood, new or worsening depression, or suicidal thoughts. The risks and benefits of continuing treatment should be carefully reassessed if such events occur. Patients with a history of psychiatric illness should be closely monitored.
• Body weight: Unexplained or clinically significant weight loss has been observed in patients treated with apremilast. In controlled clinical trials, approximately 10% of apremilast-treated patients experienced 5-10% weight loss compared with approximately 3.3% of placebo-treated patients. Approximately 1.5% of apremilast-treated patients experienced weight loss of 10% or more. Body weight should be monitored regularly, and if unexplained and clinically significant weight loss occurs, the patient should be evaluated and treatment discontinuation considered.
• Severe 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 the usual 30 mg twice daily. The initial titration schedule should also be modified, using only the morning doses during the titration period.
• Lactose intolerance: Apremilast Teva tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
• Gastrointestinal disorders: Patients with a history of severe gastrointestinal conditions should discuss the potential risks with their healthcare provider before starting treatment, as diarrhea, nausea, and vomiting are among the most common side effects.

Pregnancy and Breastfeeding

Apremilast is contraindicated during pregnancy. Animal reproductive studies have demonstrated adverse developmental effects at clinically relevant exposure levels, including embryo-fetal death, decreased fetal body weight, and delayed ossification in mice and monkeys at doses that were associated with maternal exposures below the clinical exposure at the recommended dose. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential must use effective contraception to prevent pregnancy during treatment and for at least 28 days after the last dose.

Pregnancy should be excluded before starting treatment. Healthcare providers are encouraged to advise women of childbearing potential to use a reliable method of contraception. If pregnancy occurs during treatment, the medication should be discontinued immediately and the patient should be referred to an obstetrician/gynecologist experienced in reproductive toxicology for further evaluation and counseling.

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 nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Breastfeeding is therefore not recommended during treatment with apremilast.

There are no data on the effects of apremilast on human fertility. In animal studies, apremilast had no adverse effects on fertility parameters in male or female mice at exposure levels that were multiples of the clinical dose. However, patients planning to become pregnant should discuss the timing of treatment cessation with their healthcare provider.

How Does Apremilast Teva Interact with Other Drugs?

Apremilast is extensively metabolized by cytochrome P450 enzymes, primarily CYP3A4, with minor contributions from CYP1A2 and CYP2A6. The metabolism of apremilast involves several pathways including oxidative metabolism followed by glucuronidation, hydrolysis, and non-enzymatic elimination. Understanding these metabolic pathways is essential for predicting and managing drug interactions.

Unlike many immunosuppressive and anti-inflammatory medications, apremilast has a relatively clean drug interaction profile. It does not significantly inhibit or induce major CYP450 enzymes at clinically relevant concentrations, which means it is unlikely to alter the metabolism of co-administered drugs that are substrates of these enzymes. This favorable pharmacokinetic characteristic makes apremilast suitable for use in combination with other medications commonly used by patients with psoriasis and psoriatic arthritis.

Major Interactions

The interaction with rifampicin is the most well-characterized and clinically important. In a pharmacokinetic study, co-administration of apremilast with rifampicin (a potent CYP3A4 inducer) resulted in a 72% decrease in apremilast area under the concentration-time curve (AUC) and a 43% decrease in peak plasma concentration (Cmax). This dramatic reduction in drug exposure would be expected to significantly reduce or eliminate the therapeutic effect of apremilast. For this reason, the concomitant use of apremilast with strong CYP3A4 inducers is not recommended and should be avoided whenever possible.

Minor Interactions

Co-administration with ketoconazole, a potent CYP3A4 inhibitor, increased apremilast exposure by approximately 36%. This modest increase is not considered clinically significant, and no dose adjustment is required when apremilast is co-administered with strong CYP3A4 inhibitors. Similarly, pharmacokinetic studies and clinical trial experience have shown no clinically meaningful interactions with methotrexate, oral contraceptives containing ethinylestradiol and norgestimate, or warfarin, making apremilast compatible with these commonly prescribed medications.

What Is the Correct Dosage of Apremilast Teva?

Adults

The recommended dose of Apremilast Teva for adults is 30 mg taken orally twice daily, approximately 12 hours apart (morning and evening). To reduce the gastrointestinal symptoms commonly experienced at the start of treatment, apremilast is initiated using a specific titration schedule over the first five days:

The tablets should be swallowed whole with water and can be taken with or without food. A starter pack containing the appropriate tablets for the titration period is typically provided for new patients. After completing the titration period, patients continue with the maintenance dose of 30 mg twice daily. There is no difference in the dosing regimen for psoriasis, psoriatic arthritis, or Behcet's disease oral ulcers — the same titration and maintenance dosing apply across all approved indications.

The therapeutic response to apremilast typically develops gradually. In psoriasis clinical trials, some patients showed improvement as early as week 2, but the primary assessment of efficacy was at week 16. For psoriatic arthritis, significant improvements in joint symptoms were demonstrated at week 16 in the PALACE studies. Patients should be informed that the full benefit of treatment may take several months to achieve. If no clinical response is observed after 24 weeks, treatment should be reconsidered.

Children

The safety and efficacy of apremilast in children and adolescents under 18 years of age have not been established. No data are available for this population, and therefore apremilast is not recommended for use in pediatric patients. Clinical trials in pediatric populations are ongoing, and future evidence may inform updated recommendations for younger patients.

Elderly

No dose adjustment is required for elderly patients. In clinical trials, patients aged 65 years and older who received apremilast showed similar safety and efficacy profiles to younger adults. However, greater sensitivity of some older individuals to the drug cannot be ruled out, and elderly patients should be monitored with particular attention to weight loss and psychiatric symptoms. The pharmacokinetics of apremilast are not significantly affected by advancing age.

Severe Renal Impairment

Missed Dose

If a dose of apremilast is missed, it should be taken as soon as possible. However, if it is nearly time for the next scheduled dose, the missed dose should be skipped and the next dose taken at the usual time. Patients should not take a double dose to make up for a missed dose. The twice-daily dosing schedule should be resumed as normal, with approximately 12 hours between doses. Occasional missed doses are unlikely to significantly affect the overall therapeutic response.

Overdose

There is limited clinical experience with apremilast overdose. In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse reactions, and appropriate supportive treatment should be given. Because apremilast is highly protein-bound (approximately 68%), dialysis is unlikely to be an effective method of drug removal. There is no specific antidote for apremilast overdose. In a pharmacokinetic study, a single dose of 50 mg was administered without significant safety concerns. Patients who accidentally take more than their prescribed dose should contact their healthcare provider or poison control center immediately.

What Are the Side Effects of Apremilast Teva?

Like all medicines, apremilast can cause side effects, although not everybody gets them. The side effect profile of apremilast has been well characterized through extensive clinical trials involving over 4,000 patients across the psoriasis (ESTEEM), psoriatic arthritis (PALACE), and Behcet's disease (BCT-002) programs, as well as through post-marketing surveillance data collected since the drug's initial approval.

The gastrointestinal side effects are the most frequently reported and typically represent an adaptation response as the body adjusts to the medication. The initial dose titration schedule over five days was specifically designed to minimize these effects. Clinical experience has shown that most gastrointestinal symptoms peak during the first two weeks and resolve spontaneously within the first month of treatment. If patients experience persistent or severe gastrointestinal symptoms beyond this period, they should consult their healthcare provider.

The following side effect categories use standard medical frequency classifications:

In long-term extension studies lasting up to five years, the overall safety profile of apremilast remained consistent with that observed in the controlled clinical trial periods. No new safety signals emerged with prolonged use, and the incidence of serious infections, malignancies, and major adverse cardiovascular events was not increased compared with the general population of patients with psoriasis or psoriatic arthritis. This reassuring long-term safety profile is an important consideration for a medication used to treat chronic conditions requiring prolonged therapy.

Weight monitoring is recommended for all patients receiving apremilast. In controlled clinical trials, approximately 10% of patients experienced a body weight decrease of 5-10%, and approximately 1.5% experienced a decrease of 10% or more. The mechanism of weight loss is not fully understood but may relate to reduced appetite and gastrointestinal effects. Underweight patients should be monitored particularly closely, and discontinuation should be considered if clinically significant weight loss occurs.

How Should You Store Apremilast Teva?

Proper storage of medications is essential to maintain their efficacy and safety. Apremilast Teva film-coated tablets should be stored in their original packaging (blister pack or bottle) to protect them from light and moisture. The medication should be stored at temperatures below 30°C (86°F). Do not freeze the tablets. Keep the medication out of the reach and sight of children to prevent accidental ingestion.

Do not use Apremilast Teva after the expiry date which is stated on the carton and the blister/bottle after “EXP”. The expiry date refers to the last day of that month. When dispensed in a blister starter pack, each individual blister strip is labeled with the day of the titration schedule to help patients follow the correct dosing regimen.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment and prevent accidental exposure to unused medication. If tablets appear discolored, damaged, or have an unusual odor, they should not be taken and should be returned to the pharmacy for proper disposal.

What Does Apremilast Teva Contain?

The active substance in Apremilast Teva is apremilast. The tablets are available in three strengths to accommodate the initial dose titration schedule and the maintenance dose:

• 10 mg film-coated tablets: Each tablet contains 10 mg of apremilast. These are pink, diamond-shaped tablets used during the initial titration period (Days 1-3).
• 20 mg film-coated tablets: Each tablet contains 20 mg of apremilast. These are brown, diamond-shaped tablets used during the titration period (Days 3-5).
• 30 mg film-coated tablets: Each tablet contains 30 mg of apremilast. These are beige, diamond-shaped tablets used as the maintenance dose from Day 6 onwards.

The inactive excipients (non-active ingredients) in the tablet core typically include:

• Lactose monohydrate
• Microcrystalline cellulose
• Croscarmellose sodium
• Magnesium stearate

The film coating contains hypromellose, titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172), and triacetin. The specific coloring agents vary between the different tablet strengths to allow easy visual identification. Patients with known allergies to any of these excipients should inform their healthcare provider before starting treatment. As noted in the warnings section, patients with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medication due to the presence of lactose.