Drug information of Apremilast

Apremilast


Apremilast is a phosphodiesterase 4 (PDE4) inhibitor used to treat various types of symptoms resulting from certain inflammatory autoimmune diseases.

Mechanism of effect

The full mechanism of action of this drug is not fully established, however, it is known that apremilast is an inhibitor of phosphodiesterase 4 (PDE4), which mediates the activity of cyclic adenosine monophosphate (cAMP), a second messenger. The inhibition of PDE4 by apremilast leads to increased intracellular cAMP levels. An increase in cAMP results in the suppression of inflammation by decreasing the expression of TNF-α, IL-17, IL-23, and other inflammatory mediators. The above inflammatory mediators have been implicated in various psoriatic conditions as well as Behcet's disease, leading to their undesirable inflammatory symptoms such as mouth ulcers, skin lesions, and arthritis. Apremilast administration leads to a cascade which eventually decreases the levels of the above mediators, relieving inflammatory symptoms.

Pharmacodynamic

Apremilast reduces but does not completely inhibit various inflammatory cytokines such as IL-1α, IL-6, IL-8, IL-10 MCP-1, MIP-1β, MMP-3, and TNF-α, relieving the symptoms of psoriasis and Behcet's disease, which are caused by an increase in these inflammatory mediators. This drug has also been proven to be effective in relieving the pain associated with oral ulcers in Behcet's disease.

Apremilast may cause unwanted weight loss and worsen depression, leading to suicidal thoughts or actions.

Pharmacokinetics

Absolute bioavailability: 73%

Peak plasma time: 2.5 hr

Coadministration with food does not alter absorption

Protein bound: 68%

Vd: 87 L

Metabolism

Apremilast is a major circulating component (45%) followed by inactive metabolite M12 (39%), a glucuronide conjugate of O-demethylated apremilast

Metabolized by both CYP oxidative metabolism with subsequent glucuronidation and non-CYP mediated hydrolysis

In vitro CYP metabolism primarily by CYP3A4, with minor contribution from CYP1A2 and CYP2A6

Half-life: 6-9 hr

Clearance: 10 L/hr

Excretion: 58% urine; 39% feces

Drug indications

Psoriasis , psoriatic arthritis

Dosage

Adult

Active Psoriatic Arthritis

Day 1: 10 mg in AM

Day 2: 10 mg AM and PM

Day 3: 10 mg AM and 20 mg PM

Day 4: 20 mg AM and PM

Day 5: 20 mg AM and 30 mg PM

Day 6 and thereafter: 30 mg PO BID

Psoriasis

Indicated for moderate-to-severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy

Day 1: 10 mg in AM

Day 2: 10 mg AM and PM

Day 3: 10 mg AM and 20 mg PM

Day 4: 20 mg AM and PM

Day 5: 20 mg AM and 30 mg PM

Day 6 and thereafter: 30 mg PO BID

Oral Ulcers associated with Behςet Disease

Day 1: 10 mg in AM

Day 2: 10 mg AM and PM

Day 3: 10 mg AM and 20 mg PM

Day 4: 20 mg AM and PM

Day 5: 20 mg AM and 30 mg PM

Day 6 and thereafter: 30 mg PO BID

Pediatric

Safety and efficacy not established

Alerts

Associated with an increase in adverse reactions of depression; before using, evaluate patient for history of depression and/or suicidal thoughts or behavior

Weight decrease of 5-10% of body weight reported in 10-12% of patients

Severe GI adverse effects

  • Severe diarrhea, nausea, and vomiting reported; mostly occurred within the first few weeks of treatment
  • In some cases, patients were hospitalized
  • Patients aged ≥65 yr and patients taking medications that cause volume depletion or hypotension may be at a higher risk of these complications; monitor those who are more susceptible to complications of diarrhea or vomiting
  • Quick improvement observed with dosage reduction or discontinuation; consider dose reduction or suspension if patients develop severe diarrhea, nausea, or vomiting

Drug interaction overview

  • Coadministration with strong CYP inducers (eg, rifampin, carbamazepine, phenobarbital phenytoin) may occur and result in a loss of efficacy of apremilast; therefore, coadministration is not recommended

Points of recommendation

  • Tell all of your health care providers that you take apremilast. This includes your doctors, nurses, pharmacists, and dentists.
  • This medicine may cause weight loss. You will need to have your weight checked while taking apremilast. Talk with your doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using apremilast while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • Take with or without food.
  • Swallow whole. Do not chew, break, or crush.
  • To gain the most benefit, do not miss doses.
  • Keep taking apremilast as you have been told by your doctor or other health care provider, even if you feel well.
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Pregnancy level

Group c - Not adequate studies in pregnant women


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