Apremilast

Abstract

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The September 2014 monograph topics are tedizolid phosphate, ceritinib, omega-3-carboxylic acids, umeclidinium bromide inhalation powder, and siltuximab. The DUE/MUE is on avoidance of insulin use errors.

Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases

“…Apremilast showed obvious effects on innate immunity and cellular immunity, especially the release of inflammatory mediators with a wide therapeutic index in ferret lung neutrophilia model, when compared with its gastrointestinal effects (Schafer et al, 2014 ). After great efforts, apremilast (brand name Otezla, Figure 3B ) was approved in 2014 for treatment in adults who suffered from active PsA and moderate-to-severe plaque psoriasis (Cada et al, 2014 ; Varada et al, 2014 ; Chiricozzi et al, 2016 ). A pharmacokinetic study found that apremilast is absorbed well from the gut with independence of food intake and is mainly metabolized by CYP450 3A4, with minor contributions from CYP1A2 and CYP2A6, to about 23 metabolites clarified in plasma, urine, and feces (Bianchi et al, 2016 ).…”

“…A pharmacokinetic study found that apremilast is absorbed well from the gut with independence of food intake and is mainly metabolized by CYP450 3A4, with minor contributions from CYP1A2 and CYP2A6, to about 23 metabolites clarified in plasma, urine, and feces (Bianchi et al, 2016 ). Apremilast exposure is unexpectedly reduced when coadministered with CYP450 inducers, such as rifampin, phenobarbital, carbamazepine, and phenytoin, which may result in the loss of therapeutic efficacy (Cada et al, 2014 ).…”

“…Unlike other topical treatments, apremilast shows wider applications and systemic impacts. However, some other adverse effects, including headache (5.9%), abdominal pain (2%), depression (1%), weight loss (10%), nausea (8.9%), diarrhea (7.7%), vomiting (3.2%), nasopharyngitis (2.6%), and upper respiratory tract infections (3.9%), were nonnegligible (Cada et al, 2014 ; Gooderham and Papp, 2015 ). To some extent, treatment with apremilast is related to an increased potential in depression or depression mood in the clinical trials.…”

“…To some extent, treatment with apremilast is related to an increased potential in depression or depression mood in the clinical trials. In the period of treatment, unwanted, or clinically significant weight loss should be evaluated without any delay and then discontinuation of apremilast therapy should be considered (Cada et al, 2014 ). Nausea and diarrhea that appeared in the first 2 weeks of apremilast treatment were predominantly light-to-mild, and the incidence rates of malignancies, additional severe infections, and major cardiac events were comparable with those in the placebo group.…”

Drug safety evaluation of apremilast for treating psoriatic arthritis

“…In vitro CYP metabolism of apremilast is primarily mediated by CYP3A4. Thus, the use of apremilast in conjunction with CYP450 enzyme inducers such as rifampin, phenobarbital, carbamazepine and phenytoin is not recommended [1][2][3][4]. The pharmacokinetic profile of apremilast is not affected by moderate or severe hepatic impairment.…”