APREMILAST

Treatment with apremilast should be initiated by specialists experienced in the diagnosis and treatment of psoriasis, psoriatic arthritis or Behçet’s disease. Posology The recommended dose of apremilast is 30 mg taken orally twice daily.

An initial titration schedule is required as shown below in Table 1.

Table 1:

Dose titration schedule Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 & thereafter AM AM PM AM PM AM PM AM PM AM PM 10 mg 10 mg 10 mg 10 mg 20 mg 20 mg 20 mg 20 mg 30 mg 30 mg 30 mg No re-titration is required after initial titration. The recommended twice daily apremilast dose should be taken approximately 12 hours apart (morning and evening), with no food restrictions.

If patients miss a dose, the next dose should be taken as soon as possible. If it is close to the time for their next dose, the missed dose should not be taken and the next dose should be taken at the regular time. During pivotal trials the greatest improvement was observed within the first 24 weeks of treatment for PsA and PSOR and within the first 12 weeks of treatment for BD.

If a patient shows no evidence of therapeutic benefit after this time period, treatment should be reconsidered. The patient's response to treatment should be evaluated on a regular basis. 2). Patients with renal impairment No dose adjustment is needed in patients with mild and moderate renal impairment.

The dose of apremilast should be reduced to 30 mg once daily in patients with severe renal impairment (creatinine clearance of less than 30 mL per minute estimated by the Cockcroft-Gault equation). 2). 2). Paediatric population The safety and efficacy of apremilast in children aged 0 to 17 years have not been established.

No data are available. Method of administration Apremilast is for oral use. The film-coated tablets should be swallowed whole and can be taken either with or without food.

9%). 2%) and are mostly mild to moderate in severity. 7%) and are mostly mild to moderate in severity. The gastrointestinal adverse reactions generally occurred within the first 2 weeks of treatment and usually resolved within 4 weeks.

3). Tabulated list of adverse reactions The adverse reactions observed in patients treated with apremilast are listed below by system organ class (SOC) and frequency for all adverse reactions. Within each SOC and frequency grouping, adverse reactions are presented in order of decreasing seriousness.

The adverse drug reactions were determined based on data from the apremilast clinical development programme and post-marketing experience. The frequencies of adverse drug reactions are those reported in the apremilast arms of the four Phase III studies in PsA (n = 1,945) or the two Phase III studies in PSOR (n = 1,184), and in the phase III study in BD (n = 207).

The highest frequency from either data pool is represented in Table 2). Frequencies are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); not known (cannot be estimated from the available data).

Table 2:

Summary of adverse reactions in psoriatic arthritis (PsA), psoriasis (PSOR) and Behçet’s disease (BD) System Organ Class Frequency Adverse reaction Very common Upper respiratory tract infectiona Bronchitis Infections and infestations Common Nasopharyngitis* Immune system disorders Uncommon Hypersensitivity Metabolism and nutrition disorders Common Decreased appetite* InsomniaCommon Depression Psychiatric disorders Uncommon Suicidal ideation and behaviour Very common Headache*, a Migraine* Nervous system disorders Common Tension headache* Respiratory, thoracic, and mediastinal disorders Common Cough Diarrhoea*Very Common Nausea* Vomiting* Dyspepsia Frequent bowel movements Upper abdominal pain* Common Gastroesophageal reflux disease Gastrointestinal disorders Uncommon Gastrointestinal haemorrhage RashUncommon Urticaria Skin and subcutaneous tissue disorders Not known Angioedema Musculoskeletal and connective tissue disorders Common Back pain* General disorders and administration site conditions Common Fatigue Investigations Uncommon Weight decrease *At least one of these adverse reactions was reported as serious a Frequency reported as common in PSA and PSOR Description of selected adverse reactions Psychiatric disorders In clinical studies and post-marketing experience, uncommon cases of suicidal ideation and behaviour, were reported, while completed suicide was reported post- marketing.

Diarrhoea, nausea, and vomiting There have been post-marketing reports of severe diarrhoea, nausea, and vomiting associated with the use of apremilast. Most events occurred within the first few weeks of treatment. In some cases, patients were hospitalised.

Patients 65 years of age or older may be at a higher risk of complications. If patients develop severe diarrhoea, nausea, or vomiting, discontinuation of treatment with apremilast may be necessary. Psychiatric disorders Apremilast is associated with an increased risk of psychiatric disorders such as insomnia and depression.

8). The risks and benefits of starting or continuing treatment with apremilast should be carefully assessed if patients report previous or existing psychiatric symptoms or if concomitant treatment with other medicinal products likely to cause psychiatric events is intended.

Patients and caregivers should be instructed to notify the prescriber of any changes in behaviour or mood and of any suicidal ideation. If patients suffered from new or worsening psychiatric symptoms, or suicidal ideation or suicidal attempt is identified, it is recommended to discontinue treatment with apremilast.

2). Underweight patients Patients who are underweight at the start of treatment should have their body weight monitored regularly. In the event of unexplained and clinically significant weight loss, these patients should be evaluated by a medical practitioner and discontinuation of treatment should be considered.

Lactose content Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per film-coated tablet, that is to say essentially ‘sodium-free’.

1. 6).