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Apremilast

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Apremilast
File:Apremilast.svg
Systematic (IUPAC) name
N-{2-[(1S)-1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide
Clinical data
Trade names Otezla
  • US: C (Risk not ruled out)
Pharmacokinetic data
Bioavailability 73%[1]
Protein binding 68%[1]
Metabolism Hepatic (CYP3A4, with minor contributions from CYP2A6, CYP1A2)[1]
Half-life 6-9 hours[1]
Excretion Urine (58%), faeces (39%)[1]
Identifiers
608141-41-9
L04AA32
PubChem CID 11561674
ChemSpider 9736448
ChEBI CHEBI:78540
ChEMBL CHEMBL514800
Chemical data
Formula C22H24N2O7S
460.500 g/mol

Apremilast (brand name Otezla[2]) is an orally available small molecule inhibitor of phosphodiesterase 4 (PDE4). Apremilast specifically inhibits PDE4 and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells.[3] It has anti-inflammatory activity.

Medical use

Apremilast was approved by the USFDA in March 2014 for treatment of adults with active psoriatic arthritis.[4] Apremilast is the first oral agent that is FDA-approved for the treatment of psoriatic arthritis and offers the convenience of oral dosing compared to treatment with biopharmaceuticals.[5] In September 2014, the USFDA approved Otezla (apremilast) for the treatment of moderate to severe plaque psoriasis.[6] It is also being tested for its efficacy in treating other chronic inflammatory diseases such as ankylosing spondylitis, Behcet's disease,[7] and rheumatoid arthritis.Celgene reported seven kinds of crystal form A,B,C,D,E,F and G and thought the crystal form B was the most thermodynamically stable anhydrous form.However,Utopharm company reported another more thermodynamically stable anhydrous form II than the crystal form B,.[8]

Adverse effects

Common mild to moderate adverse effects associated with apremilast include:[9]

Warning/Precautions

Depression: Worsening depression, suicidal thoughts, and other mood changes may occur with apremilast. Risks and benefits of therapy must be carefully evaluated by a health professional before apremilast is prescribed in patients with a history of depression and/or suicidal thoughts.[10]

Weight loss: Weight loss has been associated with apremilast and should be frequently monitored during treatment. Reports from clinical studies indicated a 5-10% decrease in body weight in 10% of patients taking Otezla (compared to 3.3% of patients taking placebo).[10]

Drug interactions

Concurrent use of strong cytochrome P450 enzyme inducers has been shown to decrease exposure of apremilast and can result in reduced or loss of efficacy of apremilast. It is not recommended to use simultaneously with strong P450 enzyme inducers, including:[10]

  • Rifampin
  • Phenobarbital
  • Carbamazepine
  • Phenytoin
  • St. John's Wort (drug-herb interaction)[11]

Accessibility

Otezla is available in the U.S., but is dispensed only through a network of specialty pharmacies.[6] The estimated wholesale price is $22,500 for a year of treatment.[5]

See also

References

  1. ^ a b c d e "Otezla (aprelimast) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 28 March 2014. 
  2. ^ "Celgene Corporation Announces 2014 Financial Outlook and Preliminary 2013 Results" (Press release). Celgene Corporation. 13 January 2014. Retrieved 2014-01-21. 
  3. ^ Apremilast
  4. ^ FDA approves Otezla to treat psoriatic arthritis
  5. ^ a b Apremilast for the Treatment of Psoriatic Arthritis American College of Rheumatology (14 June 2014). Retrieved 29 October 2014.
  6. ^ a b "Oral Otezla (apremilast) Approved by the U.S. Food and Drug Administration for the Treatment of Patients with Moderate to Severe Plaque Psoriasis" (Press release). Celgene Corporation. 23 September 2014. Retrieved 29 October 2014.
  7. ^ http://www.nejm.org/doi/full/10.1056/NEJMoa1408684#t=articleBackground
  8. ^ http://www.utopharm.com/youchuo_en/news_sub.aspx?id=61
  9. ^ Mease, PJ; Armstrong, AW (25 February 2014). "Managing Patients with Psoriatic Disease: The Diagnosis and Pharmacologic Treatment of Psoriatic Arthritis in Patients with Psoriasis". Drugs 74 (4): 423–41. PMID 24566842. doi:10.1007/s40265-014-0191-y. 
  10. ^ a b c "Otezla (Prescribing Information)". Celgene Corporation, Summit, NJ; March 2014. Retrieved 29 October 2014.
  11. ^ "OTEZLA® Product Monograph" (PDF). Celgene Canada. Celgene Corporation. Retrieved 3 April 2015.