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Apremilast is what I offer when someone wants a pill, no injections and no standing lab appointments. It is milder than the biologics, and I say so plainly — for thick plaques expect clear improvement, not clear skin. It does better with itch, scalp psoriasis and the mouth ulcers of Behcet's disease. Three things I raise at every visit are loose stools and nausea early on, weight loss that is not always welcome, and mood, because depression is on the label.
— Dr. Schwarz, Board Certified Dermatologist
Key Facts
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| Also called | Otezla |
| Drug class | PDE4 inhibitor, taken by mouth |
| Taken as | Tablet, twice a day |
| Typical course | Ongoing for as long as it helps |
| Time to work | Itch within a few weeks, skin judged at 16 weeks |
| Routine blood monitoring | None required |
| Prescription only | Yes |
What It Is
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Apremilast is a small tablet taken twice a day for inflammatory disease. It was approved in 2014 for psoriatic arthritis and for plaque psoriasis in people who are candidates for phototherapy or systemic treatment, in 2019 for the mouth ulcers of Behcet's disease, and in 2021 for milder psoriasis. It is unusual. It works on the whole body rather than one patch of skin, but it is not an immunosuppressant the way biologics and methotrexate are. It does not raise the risk of serious infection, needs no tuberculosis or hepatitis screening, and has no blood test schedule. That combination is what it is chosen for: stronger than creams, taken by mouth, no needles, no lab visits.
How It Works
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Apremilast blocks an enzyme called phosphodiesterase 4, or PDE4, inside inflammatory cells. PDE4 breaks down a signaling molecule called cyclic AMP, so blocking it lets cyclic AMP build up, and cells with more of it make less of the inflammatory messengers that drive psoriasis — TNF, interleukin-17 and interleukin-23 — and more of the calming ones such as interleukin-10.
That is a broad, gentle turn of the dial rather than the complete blockade a biologic achieves, which explains the rest of the drug: moderate effectiveness, a good safety record, no infection screening, no laboratory abnormality to monitor.
The same enzyme sits in the gut lining and the brain, the likeliest explanation for early diarrhea and nausea and for the mood changes a small number of people report.
Here is where Apremilast (Otezla) acts in the skin, and what the others do instead.
About Apremilast (Otezla)
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Skin basics
Apremilast (Otezla) works on the immune signal throughout the body, not just where the rash is. That is what makes it powerful in widespread disease, and why it needs monitoring. A pill that blocks PDE4, which lowers several signals at once. Milder than the injections, and no lab monitoring.
Apremilast (Otezla) arrives from the inside, carried to the skin by the blood, rather than crossing the barrier from outside. That is why it works everywhere at once, and why it needs monitoring.
In a plaque, skin cells travel from the bottom of the epidermis to the surface in four to six days instead of a month, and pile up as scale. This slows them back down, so the plaque thins.
The outer film of dead cells and oil. It holds water in and keeps irritants out, and it is thinner than a sheet of paper. Almost every dry, itchy, stinging skin problem starts here.
The outer layer, and the only one anything in a jar reaches. It renews itself constantly: a cell made at the bottom takes about a month to reach the surface and flake off. Most of what a skincare product does, it does here.
The living layer underneath, holding the blood vessels, the nerves and the collagen. It is where lasting change happens and it is hard to reach: most of what is sold for the skin never gets this far.
What It Treats
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Not the Best For
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Forms
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There is one form:
Starter pack:
Roflumilast cream:
Strengths
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The dose is fixed, not worked out from body weight. The smaller strengths exist only to climb to the full dose gently.
Dose
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Nothing about the dose depends on weight or on how severe your disease is. It is built up gradually only to give your stomach time to settle.
How to Take It
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When to take it: Twice a day, roughly 12 hours apart, with or without food — food helps some people with nausea. Swallow the tablets whole; do not crush, split or chew them.
If you miss a dose: Take it as soon as you remember, unless the next dose is close, in which case skip it. Never take two at once. If you have stopped for more than a few days, ask before restarting; the full dose brings the stomach side effects straight back, so the starter pack is usually repeated.
What to Expect
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Side Effects
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Almost all of it is stomach upset and headache in the first two weeks, and it fades. The step-up starter pack exists to make that stretch manageable.
Common — expected, and they settle
- Diarrhea and nausea Worst in the first two weeks, then settles.
- Headache Same pattern. Early, then better.
- Weight loss A few pounds for some people.
- Colds and sore throats A little more often than usual.
Tell your doctor — worth a call, not an emergency
- Diarrhea that does not settle Especially if you are losing weight with it.
- Weight loss you did not want Your doctor may weigh you at visits.
- Low mood or new anxiety Uncommon, but reported.
Stop and get care
- Thoughts of harming yourself Get help the same day.
- Severe diarrhea with dehydration Dizzy, dark urine, or unable to keep fluids down.
What to Avoid
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- St John's wort It clears apremilast from the body fast enough that the drug may stop working. The most common over-the-counter culprit.
- Crushing, splitting or chewing the tablets They are made to be swallowed whole, and breaking them changes how the drug is released.
- Restarting at the full dose after a break The stomach side effects come back at full force. Repeat the gradual build-up instead.
- Doubling up after a missed dose It causes nausea and diarrhea and gains nothing.
- Ignoring steady weight loss Losing weight without trying is a known effect, not a coincidence. Report it rather than waiting for the next appointment.
- Nothing to avoid with food or sun No food restriction, no alcohol restriction, no sun sensitivity.
Monitoring
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The absence of blood tests is why many people choose this drug. No baseline blood count, no liver panel, no tuberculosis test, no hepatitis screen, nothing repeated. Kidney function is checked once before starting, because severe impairment halves the dose.
What replaces it is clinical monitoring, which is not lighter, only different. Weight comes first. Weight loss is common and can be substantial, with some people losing five to ten percent of their body weight. If you wanted that, it is welcome. If you are older, frail or already underweight, it is a reason to reconsider, and unexplained loss should prompt a review.
Mood is second. Depression, low mood and, rarely, suicidal thoughts have been reported and appear on the label. The risk is low, but new or worsening depression should be reported promptly, and a history of depression belongs on the record before you start.
Diarrhea and nausea are third. They usually settle within the first few weeks, but severe or persistent diarrhea is not something to push through. In older adults, and in anyone on a water tablet or a blood pressure medicine, it has caused dehydration and kidney injury.
The one scheduled checkpoint is the 16-week review of skin or joints. If nothing meaningful has changed, continuing is not useful.
If You Stop
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No taper, no withdrawal, no rebound flare. Apremilast can be stopped outright. Psoriasis returns gradually over weeks to a few months, and psoriatic arthritis follows the same pattern. Side effects clear fast. Diarrhea, nausea and headache settle within days, and weight generally comes back over the following months. Restarting works. Most people get the same response as before, though the five-day build-up is repeated so the stomach side effects do not arrive all at once.
Cost
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Apremilast is expensive, priced far closer to the biologics than to older oral drugs such as methotrexate or acitretin. So insurers commonly ask that cheaper options be tried first, and prior authorization is usual. The manufacturer runs a copay assistance program, which typically helps people with commercial insurance and is not available on government plans. What it saves is indirect: no injection supplies, no screening tests, no repeated laboratory work. That does not close the gap with a generic tablet, but it is part of the comparison.
Ask Your Doctor
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How It Compares
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Myths
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- "It is a biologic." It is not. Biologics are injected antibodies that block one specific inflammatory messenger. Apremilast is a small molecule in a tablet that turns down several at once. That is why it is milder and needs no screening.
- "No blood tests means no side effects." It means there is no laboratory abnormality to watch for. The side effects you do get are ones you feel — diarrhea, nausea, headache, weight loss and, in a small number of people, low mood.
- "The diarrhea never goes away." For most people it stays inside the first two to four weeks and then settles, which is what the starter pack is for. Diarrhea past the first month, or severe diarrhea, means being reviewed rather than tolerated.
- "It will clear my psoriasis." For most people with thick plaques it improves the skin rather than clearing it. Roughly one in three reached a seventy-five percent improvement at 16 weeks. Knowing that in advance is the difference between a useful drug and a disappointing one.
Questions Patients Ask
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Do I really need no blood tests?
Correct. No monitoring schedule, no tuberculosis screen, no repeated bloodwork. Kidney function is checked once before starting, because severe impairment halves the dose.
Will the diarrhea stop?
For most people it is worst in the first two weeks and settles within a month, which is what the five-day starter pack softens. Diarrhea that is severe or lasts past a month is a reason to be reviewed.
Will I lose weight?
Some people do, and some of them lose five to ten percent of their body weight. It happens gradually, so weigh yourself every few weeks rather than judging by how clothes fit.
How does it compare with the injections?
Less effective for thick plaques — about one in three reached a seventy-five percent improvement at 16 weeks, where biologics reach much higher figures. What it offers is a tablet, no needles, no screening, no monitoring.
Can it affect my mood?
Low mood and depression are uncommon but on the label, and rare reports of suicidal thoughts exist. Report any new or worsening low mood promptly.
How long until I know whether it is working?
About 16 weeks for the skin, up to 24 weeks for joints. If nothing meaningful has changed, continuing is not worthwhile.
References
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- Nast A, Smith C, Spuls PI, et al. EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 1: treatment and monitoring recommendations. Journal of the European Academy of Dermatology and Venereology : JEADV. 2020. — Journal of the European Academy of Dermatology and Venereology : JEADV, 2020
- Menter A, Gelfand JM, Connor C, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies. Journal of the American Academy of Dermatology. 2020. — Journal of the American Academy of Dermatology, 2020
- Sbidian E, Chaimani A, Guelimi R, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. The Cochrane database of systematic reviews. 2025. — The Cochrane database of systematic reviews, 2025
- Kerschbaumer A, Smolen JS, Ferreira RJO, et al. Efficacy and safety of pharmacological treatment of psoriatic arthritis: a systematic literature research informing the 2023 update of the EULAR recommendations for the management of psoriatic arthritis. Annals of the rheumatic diseases. 2024. — Annals of the rheumatic diseases, 2024
- Hatemi G, Ramiro S, Ozguler Y, et al. EULAR recommendations for the management of Behçet's syndrome: 2025 update. Annals of the rheumatic diseases. 2026. — Annals of the rheumatic diseases, 2026