Apremilast: Indication, Dosage, Side Effect, Precaution

Generic Medicine Info Patient Medicine Information

This information is not country-specific. Please refer to the Malaysia prescribing information.

Generic Medicine Info

Indications and Dosage

Oral
Psoriatic arthritis

Adult: As monotherapy or in combination with disease-modifying antirheumatic drugs (DMARDs) in patients with active cases who have had an inadequate response or who have been intolerant to previous DMARD therapy: Initial titration schedule: Day 1: 10 mg in the morning. Day 2: 10 mg bid. Day 3: 10 mg in the morning then 20 mg in the evening. Day 4: 20 mg bid. Day 5: 20 mg in the morning then 30 mg in the evening. Day 6 and thereafter (recommended maintenance): 30 mg bid (approx 12 hours apart).

Oral
Plaque psoriasis

Adult: For the treatment of moderate to severe chronic cases in patients who are intolerant to, failed to respond to or who have a contraindication to other systemic therapy or phototherapy: Initial titration schedule: Day 1: 10 mg in the morning. Day 2: 10 mg bid. Day 3: 10 mg in the morning then 20 mg in the evening. Day 4: 20 mg bid. Day 5: 20 mg in the morning then 30 mg in the evening. Day 6 and thereafter (recommended maintenance): 30 mg bid (approx 12 hours apart).

Oral
Oral ulcers associated with Behcet’s disease

Adult: In patients who are candidates for systemic therapy: Initial titration schedule: Day 1: 10 mg in the morning. Day 2: 10 mg bid. Day 3: 10 mg in the morning then 20 mg in the evening. Day 4: 20 mg bid. Day 5: 20 mg in the morning then 30 mg in the evening. Day 6 and thereafter (recommended maintenance): 30 mg bid (approx 12 hours apart).

Renal Impairment

CrCl (mL/min)	Dosage
<30	Initially, 10 mg once daily in the morning on days 1-3, then titrate (using only the morning doses; skip the evening doses) to 20 mg once daily on days 4-5. Maintenance: 30 mg once daily in the morning beginning on day 6.

Contraindications

Pregnancy and lactation.

Special Precautions

Patient with history of depression and/or suicidal thoughts or behaviour. Patient receiving drugs that may cause volume depletion or hypotension. Underweight patient. Severe renal impairment. Elderly. Concomitant use with strong CYP3A4 inducers is not recommended.

Adverse Reactions

Significant: Severe diarrhoea, nausea, vomiting; neuropsychiatric effects (e.g. mood changes, suicidal ideation and behaviour, depression); unexplained or clinically significant weight loss.
Gastrointestinal disorders: Dyspepsia, upper abdominal pain, GERD, gastrointestinal haemorrhage.
General disorders and administration site conditions: Fatigue.
Metabolism and nutrition disorders: Decreased appetite.
Musculoskeletal and connective tissue disorders: Back pain.
Nervous system disorders: Headache (including tension headache), migraine.
Psychiatric disorders: Insomnia.
Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infection, cough, bronchitis, nasopharyngitis.
Skin and subcutaneous tissue disorders: Rash, urticaria.

Monitoring Parameters

Verify pregnancy status in women of childbearing potential before treatment initiation. Monitor weight (regularly during treatment) and renal function. Observe for emergence or worsening of suicidal thoughts, depression, or other mood changes.

Drug Interactions

Decreased plasma concentration with strong CYP3A4 inducers (e.g. rifampicin, phenobarbital, carbamazepine, phenytoin).

Food Interaction

Decreased exposure with St. John's wort.

Action

Description:
Mechanism of Action: Apremilast, a cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase type-4 (PDE-4) inhibitor, exhibits its effect intracellularly to regulate a network of pro-inflammatory and anti-inflammatory mediators. The inhibition of PDE-4 increases intracellular cAMP levels, which in turn downregulates the inflammatory response by modulating the expression of tumour necrosis factor-α (TNF-α), interleukin (IL)-23, IL-17, and other inflammatory cytokines, and promotes the production of anti-inflammatory mediators, such as IL-10.
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract. Bioavailability: Approx 73%. Time to peak plasma concentration: Approx 2.5 hours.
Distribution: Volume of distribution: 87 L. Plasma protein binding: Approx 68%.
Metabolism: Extensively metabolised in the liver by non-CYP and CYP-mediated pathways, mainly by the CYP3A4 isoenzyme, including CYP1A2 and CYP2A6 isoenzymes (minor pathways).
Excretion: Via urine (58%; 3% as unchanged drug); faeces (39%; 7% as unchanged drug). Elimination half-life: Approx 6-9 hours.

Chemical Structure

Storage

Store below 30°C.

MIMS Class

Immunosuppressants / Psoriasis, Seborrhea & Ichthyosis Preparations

ATC Classification

L04AA32 - apremilast ; Belongs to the class of selective immunosuppressive agents. Used to induce immunosuppression.

References

Amgen (New Zealand) Limited. Otezla 30 mg Tablets; Otezla Titration Pack 10 mg, 20 mg, 30 mg data sheet 19 October 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 06/01/2022.

Anon. Apremilast. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/01/2022.

Buckingham R (ed). Apremilast. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/01/2022.

Joint Formulary Committee. Apremilast. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/01/2022.

Otezla 10 mg, 20 mg, 30 mg Film-Coated Tablets (Amgen). European Medicines Agency [online]. Accessed 06/01/2022.

Otezla Tablet, Film Coated (Celgene Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/01/2022.

Otezla Tablets (Amgen Biopharmaceuticals Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 21/01/2022.

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