Phosphodiesterase-4 (PDE4) Inhibitor Pregnancy: Avoid — animal embryotoxicity; effective contraception required during treatment

Apremilast (Dermatology)

Brand names: Otezla

Adult dose

Dose: Titration week 1: 10 mg AM (D1), 10 mg BD (D2), 10 mg AM + 20 mg PM (D3), 20 mg BD (D4), 20 mg AM + 30 mg PM (D5), then 30 mg BD maintenance

Route: Oral

Frequency: Twice daily (after titration)

Max: 60 mg/day

Psoriasis (moderate-severe, inadequate response to phototherapy/DMARDs), Behçet's oral ulcers; titration schedule reduces GI side effects; take with or without food

Paediatric dose

Dose: Not established N/A/kg

Route: N/A

Frequency: N/A

Max: N/A

Not licensed in paediatrics

Dose adjustments

Renal

CrCl <30 mL/min: reduce to 30 mg once daily (no titration schedule required at reduced dose)

Hepatic

No dose adjustment required

Paediatric weight-based calculator

Patient weight (kg)

Not licensed in paediatrics

Clinical pearls

ESTEEM 1 and 2 trials: apremilast PASI 75 ~33% vs 6% placebo at week 16 — modest compared to biologics but important as oral agent without immunosuppression monitoring; positioned after conventional DMARDs but before or alongside biologics
MHRA depression/suicidal ideation warning: neuropsychiatric events reported — screen for depression before starting; monitor mood throughout; inform patients to report changes; apremilast may worsen pre-existing depression
Behçet's oral ulcers: RELIEF trial (NEJM 2019) — apremilast significantly reduced oral ulcer count vs placebo (0.5 vs 2.7 at week 12); first oral treatment with robust evidence for Behçet's recurrent aphthous ulcers; NICE TA781
Weight loss: modest mean reduction of 1-2 kg reported in trials — may be beneficial in overweight psoriasis patients or concerning if significant; monitor BMI
Dose titration is clinically important: starting at 10 mg and escalating over 5 days significantly reduces nausea/diarrhoea discontinuation; if drug stopped for >14 days, retitrate from start

Contraindications

Known hypersensitivity
Caution in patients with history of depression/suicidal ideation

Side effects

Nausea/diarrhoea (most common — self-limiting, improved by titration)
Headache
Upper respiratory tract infections
Nasopharyngitis
Depression/suicidal ideation (MHRA warning)
Weight loss

Interactions

Strong CYP3A4 inducers (rifampicin, carbamazepine) — significantly reduce apremilast levels; avoid combination
Avoid in patients on other PDE4 inhibitors (roflumilast)

Monitoring

Symptom response (PASI, DLQI)
Neuropsychiatric symptoms (depression screening)
Weight
No routine laboratory monitoring required — major advantage over DMARDs

Reference: BNFc; BNF 90; ESTEEM 1 & 2 trials (Papp et al. JAAD 2015); RELIEF trial (Hatemi et al. NEJM 2019); NICE TA785; MHRA SPC Otezla; NICE TA781 (Behçet's). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways