apremilast

apremilast

(a-pre-mil-ast),

Otezla

(trade name)

Classification

Therapeutic: antirheumatics
Pharmacologic: temporary class
Pregnancy Category: C

Indications

Treatment of active psoriatic arthritis.

Action

Acts as an inhibitor of phosphodiesterase type 4 (PDE4). Inhibition of PDE4 results in ↑ intracellular levels of cyclic adenosine monophosphate (cAMP).

Therapeutic effects

Decreased severity of psoriatic arthritis with improved joint function.

Pharmacokinetics

Absorption: 73 % absorbed following oral administration.
Distribution: Unknown.
Metabolism and Excretion: Extensively metabolized (mostly by CYP3A4); metabolites are not pharmacologically active. Excreted in urine (58%) and feces (39%) as inactive metabolites; 3% excreted unchanged in urine, 7% in feces.
Half-life: 6–9 hr.

Time/action profile (blood levels†)

ROUTEONSETPEAKDURATION
POunknown2.5 hr 12–24 hr
† Improvement in joint symptoms make take up to 4 mos.

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Concurrent use of P450 enzyme inducers.
Use Cautiously in: History of depression or suicidal ideation; Severe renal impairment (dose reduction required for CCr <30 mL/min); Obstetric: Use during pregnancy only if potential benefits justify potential fetal risks; Lactation: Use caution if breastfeeding; Pediatric: Safe and effective use in children <18 yr has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • depression
  • headache

Gastrointestinal

  • diarrhea
  • nausea
  • upper abdominal pain
  • vomiting

Metabolic

  • weight loss

Interactions

Drug-Drug interaction

Concurrent use of P450 enzyme inducers including carbamazepine, phenobarbital, phenytoin and rifampin may ↓ blood levels and effectiveness; concurrent use should be avoided.

Route/Dosage

Oral (Adults ) Day 1—10 mg in the morning; day 2—10 mg in the morning and 10 mg in the evening; day 3—10 mg in the morning and 20 mg in the evening; day 4—20 mg in the morning and 20 mg in the evening; day 5—20 mg in the morning and 30 mg in the evening; day 6 and thereafter—30 mg in the morning and 30 mg in the evening.

Renal Impairment

Oral (Adults CCr <30 mL/min) Days 1–3—10 in the morning; days 4–5—20 mg in the morning; day 6 and thereafter—30 mg in the morning.

Availability

Tablets: 10 mg, 20 mg, 30 mg

Nursing implications

Nursing assessment

  • Assess pain and range of motion before and periodically during therapy.
  • Monitor mental status for signs and symptoms of depression (orientation, mood behavior) frequently. Assess for suicidal tendencies, especially during early therapy.
  • Obtain weight and BMI initially and periodically during treatment. If clinically significant weight loss occurs, evaluate weight loss and consider discontinuation of therapy.

Potential Nursing Diagnoses

Chronic pain (Indications)
Impaired skin integrity (Indications)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Follow titration guidelines when beginning therapy to minimize GI side effects.
  • Oral: Administer without regard for meals. Swallow tablet whole; do not crush, break, or chew.

Patient/Family Teaching

  • Instruct patient to take apremilast as directed.
  • Advise patient, family and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care professional immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior occur.
  • Inform patient of need to monitor weight regularly. Notify health care professional if unexplained or clinically significant weight loss occurs.
  • Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • Improvement in pain and function in patients with psoriatic arthritis.
References in periodicals archive ?
Drugs profile mention in this report includes : adalimumab biosimilar, apremilast, BI-655066, certolizumab pegol biosimilar, COVA-322, DNX-114, DNX-514, etanercept biosimilar, golimumab, IBI-303, IBPM-004AM, IBPM-005IX, infliximab biobetter, INV-17, secukinumab, thalidomide, tofacitinib, VTP-43742.
Updated recommendations from GRAPPA include new data regarding ustekinumab, apremilast, and secukinumab, as well as data on comorbidities (J Rheumatol.
The drugs for autoimmune diseases are tocilizumab (Actemra), leflunomide (Arava), teriflunomide (Aubagio), certolizumab pegol (Cimzia), etanercept (Enbrel), adalimumab (Humira), abatacept (Orencia), apremilast (Otezla), ustekinumab (Stelara), tofacitinib (Xeljanz), infliximab (Remicade), and methotrexate.
In the past year, a new advanced oral systemic was approved for use with PsA: apremilast is a phosphodiesterase 4 (PDE4) inhibitor that modulates mRNA expression and blocks the synthesis of TNF-a, IL-23 and several pro-inflammatory chemokines.
Apremilast is an oral PDE4 inhibitor that modulates cyclic AMP metabolism and in inflammatory cells results in decreased production of pro-inflammatory mediators, such as TNF, IL17, and IL23, and increased production of anti-inflammatory mediators, such as IL10.
The Street, in our view, has never paid much attention to apremilast given the relatively early stage of the program and efficacy data that was not overwhelming," said Geoff Meacham, an analyst at J.
In addition, patients on apremilast also achieved a statistically significant benefit over placebo in the major secondary endpoint, Static Physician Global Assessment (sPGA).
The three drugs in the immunologic pharmaceutical class are apremilast (Otezla), metreleptin (Myalept), and vedolizumab (Entyvio).
An Indirect Comparison and Cost Per Responder Analysis of Adalimumab, Methotrexate (MTX) and Apremilast in the Treatment of MTX-naive Psoriatic Arthritis (PsA) Patients , Abstract 1555, Monday, November 17, 8:30 a.
myeloma treatment Revlimid and phase III data for apremilast in
57) Apremilast, an oral phosphodiesterase-4 inhibitor that suppresses multiple pro-inflammatory mediators and cytokines, was tested in a 12-week trial and showed modest efficacy (ACR20, 43.
Net product sales growth between 2013 and 2017 is expected to be 19% (CAGR%), 13% for the existing business, 15% including ABRAXANE pancreatic cancer and 19% including apremilast