Action and Spectrum

Actions and Spectrum:   

apremilast is an oral medication that is used to treat inflammatory conditions such as psoriasis and psoriatic arthritis. Its mechanism of action involves inhibiting an enzyme called phosphodiesterase 4 (PDE4), which plays a role in the inflammation response. By inhibiting PDE4, apremilast reduces the production of pro-inflammatory cytokines, leading to a decrease in inflammation. 

The spectrum of apremilast’s action is primarily focused on the treatment of psoriasis and psoriatic arthritis, although it has also shown some efficacy in treating other inflammatory conditions such as Behcet’s disease and oral ulcers associated with recurrent aphthous stomatitis. apremilast has not been shown to be effective in treating other types of arthritis or autoimmune diseases. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% (psoriasis and psoriatic arithritis) 

Adults 

Nausea (7.4-17%) 

Diarrhea (7.7-17%) 

>10% (Behςet Disease)  

Headache (14.4%) 

Upper respiratory tract infection (11.5%) 

Diarrhea (41.3%) 

Nausea (19.2%) 

1-10% (Behςet Disease) 

Back pain (7.7%) 

Viral upper respiratory tract infection (6.7%) 

Arthralgia (5.8%) 

Upper abdominal pain (8.7%) 

Vomiting (8.7%) 

1-10% (Psoriasis and Psoriatic Arthritis) 

Dyspepsia (3%) 

Decreased appetite (3%) 

Insomnia (2%) 

Back pain (2%) 

Migraine (2%) 

Frequent bowel movements (2%) 

Upper respiratory tract infection (0.6-9%) 

Tension headache (8%) 

Headache (4.8-6%) 

Frequency Not Defined (Psoriasis and Psoriatic Arthritis) 

Nervous system disorders: Migraine 

Respiratory, thoracic, and mediastinal disorders: Cough 

Gastrointestinal disorders: Frequent bowel movement, gastroesophageal reflux disease, dyspepsia 

Metabolism and nutrition disorders: Decreased appetite 

Black Box Warning

Black Box Warning:  

The black box warning of apremilast is related to the potential for serious psychiatric events, including depression, suicidal ideation, and suicidal behavior. Patients should be monitored for the emergence or worsening of these symptoms while taking apremilast.

Healthcare providers should carefully evaluate the risks and benefits of apremilast in patients with a history of depression or suicidal thoughts or behavior before prescribing it.

If any of these symptoms occur, apremilast should be discontinued immediately, and appropriate treatment should be initiated. apremilast should also be used with caution in patients with a history of depression, suicidal thoughts or behavior, or other psychiatric disorders. 

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: apremilast is contraindicated in patients with a known hypersensitivity to apremilast or any of its components. 

Pregnancy: apremilast has been shown to cause harm to the developing fetus and should not be used during pregnancy. Women of childbearing age should use effective contraception while taking apremilast and for at least 3 days after stopping treatment.  

Breastfeeding: It is unknown whether apremilast is excreted in human milk, and breastfeeding should be avoided during treatment.  

Severe renal impairment: apremilast should not be used in patients with severe renal impairment (creatinine clearance less than 30 mL/min) because its safety and efficacy have not been established in these patients.  

Severe hepatic impairment: apremilast should not be used in patients with severe hepatic impairment because its safety and efficacy have not been established in these patients.  

Immunodeficiency: apremilast has immunosuppressive properties and may increase the risk of infection. It should be used with caution in patients with a history of immunodeficiency, including HIV infection. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

apremilast is a medication that is used to treat psoriasis and psoriatic arthritis. It works by inhibiting an enzyme called phosphodiesterase 4 (PDE4), which is involved in the inflammation process. By inhibiting PDE4, apremilast reduces inflammation and improves symptoms. 

Pharmacodynamics: 

The pharmacodynamics mechanism of apremilast involves inhibiting the enzyme PDE4, increasing cAMP levels, and modulating cytokine production to reduce inflammation and improve symptoms of psoriasis and psoriatic arthritis. 

MOA:  

apremilast works by inhibiting the enzyme PDE4, which is involved in the inflammation process. PDE4 breaks down cyclic adenosine monophosphate (cAMP), a molecule that helps regulate immune responses. By inhibiting PDE4, apremilast increases levels of cAMP, which in turn reduces inflammation and improves symptoms of psoriasis and psoriatic arthritis.  

Pharmacokinetics: 

Absorption: 

After oral administration, apremilast is rapidly absorbed in the gastrointestinal tract, with a bioavailability of approximately 73%. The maximal plasma concentration is achieved within 1.5 to 2.5 hours following administration. 

Distribution: 

apremilast is a phosphodiesterase 4 (PDE4) inhibitor that is primarily distributed in the body following oral administration. 

Metabolism: 

apremilast undergoes biotransformation in the liver, mainly by hydrolysis to its active metabolite, M12. The activity of cytochrome P450 enzymes in the liver does not play a significant role in apremilast metabolism. 

Excretion and elimination:  

The elimination half-life of apremilast is approximately 6 to 9 hours, and its steady-state is reached within 4 days of once-daily dosing.

Adminstartion

Administration:  

apremilast is taken orally in tablet form. The tablets come in various strengths, including 10 mg, 20 mg, and 30 mg. 

The recommended starting dose for most patients is 30 mg once daily, taken with or without food.  

Depending on how well the patient tolerates the medication and how effective it is in treating their condition, the dose may be increased to a maximum of 30 mg twice daily.  

If a dose is missed, it should be taken as soon as possible, but if it is almost time for the next dose, the missed dose should be skipped and the regular dosing schedule should be resumed. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: apremilast 

Why do we use apremilast?  

apremilast is a medication that is used to treat certain inflammatory conditions such as psoriasis, psoriatic arthritis, and oral ulcers associated with Behcet’s disease. It works by inhibiting an enzyme called phosphodiesterase 4 (PDE4), which is involved in the regulation of inflammation in the body. 

By inhibiting PDE4, apremilast can reduce the production of pro-inflammatory cytokines, which are molecules that play a role in the development and progression of inflammatory diseases. This can help to alleviate symptoms such as redness, swelling, and pain. 

apremilast is often used as an alternative to traditional treatments such as corticosteroids or immunosuppressive agents, which can have significant side effects. It is generally well-tolerated, with common side effects including nausea, diarrhea, and headache.  

Overall, the use of apremilast can help to improve the quality of life for individuals with inflammatory conditions by reducing inflammation and associated symptoms.