Apremilast

Question 1

What is Apremilast?

Answer 1

A PD4 (phosphodiesterase 4) inhibitor

Works intracellularly to reduce the production of pro-inflammatory mediators and increase those that are anti-inflammatory

Downregulation of pro-inflammatory cytokines:

↓ TNF-α

↓ IL-17, IL-23

↑ IL-10 (anti-inflammatory)

Question 2

Dosage of apremilast

Answer 2

30mg BD

Rapid uptitration to reduce GI side effects, starting at 10mg a day and increased 10mg every day:
○ Day 1: 10mg mane
○ Day 2: 10mg mane + 10mg nocte
○ Day 3: 10mg mane + 20mg nocte
○ Day 4: 20mg mane + 20mg nocte
○ Day 5: 20mg mane + 30mg nocte
○ Day 6: 30mg mane + 30mg nocte

Question 3

Adverse effects of Apremilast?

Answer 3

• Nausea + diarrhoea (most evidence in first 15 days, gradually resolve)
  
  • Headache
  • Nasopharyngitis/URTIs
  • Depression/suicidal ideation 1%
  • Loss of 5-10% body weight in 10% patients
  • Arthralgias
  • Decreased appetite
  • Hypersensitivity reaction
  • Rebound psoriasis on cessation

Question 4

PBS criteria for Apremilast?

Answer 4

• Severe CPP
  • Must have failed MTX 10mg weekly for 6 weeks OR must have contraindication to MTX OR have demonstrated toxicity to MTX, AND
  • Significant impairment of QoL, AND
  • Must not be undergoing PBS-subsidised treatment for psoriasis with biologic agent or cyclosporin
  • Must be treated by a dermatologist
  • Must be 18 years or older

Note: effective for PsA, but not PBS listed

Question 5

Contraindications for Apremilast?

Answer 5

Hypersensitivity

Relative:
○ Depression or suicidal ideation history, instruct patients to monitor mood
○ Pregnancy, may cause increase in pregnancy loss, but can use if risks outweigh benefits, category B3
○ Lactation: unknown if secreted in breast milk
○ Co-administration with potent CYP450 inducers (rifampicin, phenobarbital, carbamazepine, phenytoin, may diminish apremilast levels)

Question 6

Pregnancy category of Apremilast?

Answer 6

Pregnancy, may cause increase in pregnancy loss, but can use if risks outweigh benefits, category B3

Question 7

Pre Treatment Investigations for apremilast

Answer 7

Question 8

Monitoring Ix for apremilast

Answer 8

Not required

Question 9

T/F
- apremilast is pregnancy category C
- has a half life of 24 hours
- requires dose adjustment in hepatic failure
- requires dose adjustment in renal failure
- is not recommended in breastfeeding

Answer 9

F - B3
F - 6 - 9 hours
F
T - half dose (30mg OD)
T

Question 10

Regarding apremilast
- is useful for PsA
- is excreted in the urine only
- is contraindicated in patients with major depression

Answer 10

T
F - faeces and urine
T