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 ?
The results showed statistically significant reductions in oral ulcers with apremilast 30 mg twice daily versus placebo through week 12.
Celgene Corporation announced that data from a randomized, placebo-controlled, multi-center, phase II clinical trial of apremilast in patients with active ulcerative colitis who had failed at least one conventional therapy but were naive to biologic therapy were presented in an oral session today at the 13th Congress of ECCO in Vienna.
Phototherapy, topical steroids, and apremilast (Otezla) did the trick.
Contract award notice: Pnsp 34/2017 lenalidomide, Paclitaxel / albumin, Apremilast and azacitidine
Near term products also included Trazodone which is used for anti-depression, and Apremilast which is used for Psoriasis and Psoriatic Arthritis.
In addition, some new classes of drugs have been approved for PsA treatment, including ustekinumab (Stelara), apremilast (Otezla), both of which target inflammation, and an anti-TNF blocker, certolizumab (Cimzia).
Treatments for more advanced psoriasis include narrow-band ultraviolet B (UVB) light, psoralen with ultraviolet A (UVA) light retinoids (isotretinoin [Accutane, Claravis], acitretin [Soriatane]), methotrexate (particularly for arthritis), cyclosporine (Neoral, Sandimmune), infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), apremilast (Otezla), and secukinumab (Cosentyx).
The other topical medication, OPA-15406 (also known as MM36), and the systemic PDE-4 inhibitor apremilast (currently approved for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis) are being investigated as AD therapies that target the PDE-4 pathways.
Experts say Otezla, also known as apremilast, works by targeting a protein (PDE4) that controls inflammation of the skin.
Apremilast may be an effective treatment for Lichen planus, but double-blinded controlled trials are lacking.
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.
Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis.