Apremilast

With the cause of plaque psoriasis and the related psoriatic arthritis still remaining elusive, there is still a great need for medications such as Apremilast that can help to contain the symptoms that appear on a person's skin or within the joints as inflammation occurs.

Overview

Also known under its brand name Otezla, the oral medication far surpasses the efficacy of many of the past solutions that were often toxic and of a very limited usefulness. It is able to target the enzyme PDE4 (phosphodiesterase 4), and that is its primary means of action against the aforementioned skin conditions and also possibly against various other inflammatory diseases that are related to the immune system. Use against Behcet's disease (BD) has also been looked into, and the drug seemed to be useful against oral ulcers in those afflicted.

The United States Food and Drug Administration (FDA) first approved apremilast in the year 2014 because of its perceived effectiveness against psoriasis and psoriatic arthritis. It is in the same category as methotrexate as far as its ability to alleviate some of the abnormal skin patches that appear on patients with those diseases. Celgene is the company who is responsible for Otezla (apremilast), and in the United States it is marketed as a prescription drug that does require access to a specialty pharmacy network that will deliver the medication right to the door of a patient's home each month. Other countries, such as Austria, do allow it to be received at all normal retail pharmacies throughout the region. This drug is usually given to patients with psoriasis that has responded to other phototherapy or systemic treatment regimens already. In the United States, the average cost for an entire year of the drug is about $22,500, and this can mostly be covered by insurance plans if the patient does have one to utilize.

With the skin condition affecting about two to four percent of the population, it still draws a great deal of research due to its complexity and mystery. It is thought that both genetic factors and environmental factors are the most likely culprits in causing what can often be a rough and uncomfortable disease. The plaques on the skin are often painful, and those who have endured for some years will often manifest the linked arthritis after some time. About one-third of psoriasis patients will eventually have psoriatic arthritis as well. However, as the first selective PDE4 inhibitor, apremilast is helping a plethora of people to deal with their psoriasis and/or PsA in a new way and through individualized treatment plans.

Research so far seems to indicate that apremilast helps to increase cyclic adenosine monophosphate (cAMP) levels because of the way that it inhibits the enzyme that breaks it down. The end result is a reduction in a number of different pro-inflammatory factor expressions, and the patient suffering from plaque psoriasis or the related PsA is then able to live a more normal lifestyle that is not hampered as much by the symptoms that come with it.

Treated Conditions

  • Plaque psoriasis
  • Psoriatic arthritis (PsA)
  • Other chronic inflammatory diseases

Type of Medicine

  • Diamond-shaped 10mg pink tablet with engraved "APR" on obverse and "10" on reverse
  • Diamond-shaped 20mg brown tablet with engraved "APR" on obverse and "20" on reverse
  • Diamond-shaped 30mg beige tablet with engraved "APR" on obverse and "30" on reverse
  • tablets in a generic form

Side Effects

Some of the more common side effects associated with apremilast are nausea, vomiting, and diarrhea. These can be severe in some cases, and they are more likely to manifest in a severe form during the titration period that is often used in order to reach the appropriate dose in people who are just starting to use the drug. These side effects are also more likely to appear in the geriatric population or when used in combination with other systemic drugs for the treatment of psoriasis.

There are also some other side effects that are fairly common in those using apremilast, and these include upper respiratory tract infections, headache, back pain, fatigue, and nasopharyngitis. However, most of these instances are only of mild to moderate severity. Depression and mood changes have been seen during some of the trials, with users noticing increased levels of depression and this was sometimes accompanied by suicidal thoughts and behavior. It is important to talk with the prescribing physician if there is already a history of depression, and further discussion is especially relevant if these feelings seem to be exacerbated by the medication. Also during the trials, some patients did experience weight loss that was affiliated with the drug. The average loss was between 5 and 10 percent with a segment consisting of about 10% of the study participants experiencing this change. If any of these side effects are noticed, then it is important to discuss with the healthcare professional in order to determine whether it is appropriate to continue taking the drug or to transition away from apremilast.

Dosage

The dosage of the apremilast drug, especially the Otezla variant, will generally need to be determined through feedback, and a titration period will help those who are just starting to reach the desired level. This usually lasts about one week with the beginning stages using a 10mg dose and working upwards until 30mg twice per day is achieved. The purpose of this gradual increase is to avoid most of the gastrointestinal symptoms and side effects (such as gastroesophageal reflux disease, dyspepsia, or frequent bowel movement) that are known to occur if a person's system is shocked by the introduction of too much of the drug at one time. Lower doses are better suited for those with existing renal problems so that the body can handle the drug accurately. The doctor will be able to outline the specific regimen that should be followed. If any doses are missed, then they can be taken as soon as possible unless it is already about time for the next subsequent dose. In that case, simply take the next one and do not double up. According to the manufacturer's guidelines, apremilast tablets should not be split, crushed, or chewed before taking. However, if there is a need, a number of similar immediate-release tablets are able to be split, crushed, or chewed, and so it is usually at the prescribing physician's discretion as to whether one of these actions can be taken.

Drug Interactions

One of the primary interactions that has been seen with apremilast occurs when taken concurrently with strong P450 enzyme inducers whereby the efficacy of the drug is reduced in such cases. Some of the P450 enzyme inducers that are known to lessen apremilast's benefits are St. John's Wort, rifampicin, phenobarbital, carbamazepine, and phenytoin. In terms of pharmacokinetics, the AUC and CMAX of the drug were significantly reduced in trials where both drugs were administered, and as such, it is not recommended to take these drugs at the same time as apremilast due to this loss of effectiveness. The agent methotrexate was also looked into, and there does not appear to be any reaction to this drug that is also often used as a means of treatment for those with psoriasis or psoriatic arthritis.

Warnings

There have been studies conducted where monkeys and mice have encountered pregnancy problems such as miscarriage when they were administered very high doses of the drug apremilast. For this reason, the drug is contraindicated in pregnant women in Europe. However, in the United States, it is allowable in some instances as long as the recommending physician determines that the benefit outweighs the potential risks that might manifest. Likewise, nursing mothers should also be careful about using the drug since no thorough studies have been completed in order to determine its presence in human milk.

A dose adjustment (lowering the daily intake) is recommended for those who have severe renal impairment because of the fact that the 30mg twice daily regimen is likely too much for that segment of the population. Also, the treatment plan should be customized and monitored more closely in the geriatric population as well as in children due to the potential for them to respond quite differently to the medicine. Of course, anyone with a known allergy to apremilast, or any of the ingredients in the tablets, should not take the drug due to likely complications.

Storage

It is necessary to store the tablets at a temperature of 30 degrees Celsius (86 degrees Fahrenheit) or below, and they should be kept in closed containers to avoid exposure to moisture and light.

Summary

Inflammation of the skin is the primary symptom in those with plaque psoriasis that accounts for the majority of the cases of the disease. Just like the disease, the exact method of action is not fully understood in apremilast, but the class of enzymes known as phosphodiesterase 4 (PDE4) is thought to be responsible for this process of inflammation. Apremilast is able to limit much of the activity of this enzyme due to its select inhibition, and this then limits the inflammatory molecule production. When this inflammation occurs around the joints of a patient and the surrounding connective tissue, this is known as psoriatic arthritis (PsA), and apremilast can be useful in reducing the swelling and pain that come along with that disorder.

The tablets are taken orally, brand name Otezla, and the patient will undergo a titration period in order to allow their body time to adjust to the dose that will ultimately be achieved. There are some side effects that have been seen in a number of people, but these are generally only of mild to moderate severity and include things like nausea, diarrhea, and vomiting primarily. Worse symptoms might include increased depression or suicidal thoughts or a significant weight loss effect. The drug has been approved since 2014 for use in the United States. There has not been noted any significant drug interactions with apremilast except for the possibility of reduced efficacy when given along with cytochrome P450 enzyme inducers.

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Last Reviewed:
December 22, 2017
Last Updated:
December 22, 2017
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