Otezla · 4.3 Contraindications · 1

HOS-097004 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile The most commonly reported adverse reactions with apremilast in adults with PsA and PSOR are gastrointestinal (GI) disorders including diarrhoea (15.7%) and nausea (13.9%). The other most commonly reported adverse reactions include upper respiratory tract infections (8.4%), headache (7.9%), and tension headache (7.2%) and are mostly mild to moderate in severity. The most commonly reported adverse drug reactions with apremilast in adults with BD are diarrhoea (41.3%), nausea (19.2%), headache (14.4%), upper respiratory tract infection (11.5%), upper abdominal pain (8.7%), vomiting (8.7%) and back pain (7.7%) 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. Hypersensitivity reactions are uncommonly observed (see section 4.3). Tabulated list of adverse reactions The adverse reactions observed in adult 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 in adult patients. 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 3. 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 3. 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 Infections and Bronchitis infestations Common Nasopharyngitis* Immune system Uncommon Hypersensitivity disorders Metabolism and Common Decreased appetite* nutrition disorders

Auszug; vollständigen Abschnitt im Original lesen.

HOS-097000 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1. Pregnancy (see section 4.6).

HOS-096999 · has-indication-information · PDF-Seite 3

Psoriatic arthritis Otezla, alone or in combination with Disease Modifying Antirheumatic Drugs (DMARDs), is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior DMARD therapy (see section 5.1). Psoriasis Otezla is indicated for the treatment of moderate to severe chronic plaque psoriasis (PSOR) in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or psoralen and ultraviolet-A light (PUVA). Paediatric psoriasis Otezla is indicated for the treatment of moderate to severe plaque psoriasis in children and adolescents from the age of 6 years and weighing at least 20 kg who are candidates for systemic therapy. Behçet’s disease Otezla is indicated for the treatment of adult patients with oral ulcers associated with Behçet’s disease (BD) who are candidates for systemic therapy.

HOS-097002 · has-interaction-information · PDF-Seite 6

Co-administration of strong cytochrome P450 3A4 (CYP3A4) enzyme inducer, rifampicin, resulted in a reduction of systemic exposure of apremilast, which may result in a loss of efficacy of apremilast. Therefore, the use of strong CYP3A4 enzyme inducers (e.g. rifampicin, phenobarbital, carbamazepine, phenytoin and St. John’s Wort) with apremilast is not recommended. Co-administration of apremilast with multiple doses of rifampicin resulted in a decrease in apremilast area-under-the-concentration time curve (AUC) and maximum serum concentration (Cmax) by approximately 72% and 43%, respectively. Apremilast exposure is decreased when administered concomitantly with strong inducers of CYP3A4 (e.g. rifampicin) and may result in reduced clinical response. In clinical studies, apremilast has been administered concomitantly with topical therapy (including corticosteroids, coal tar shampoo and salicylic acid scalp preparations) and UVB phototherapy. There was no clinically meaningful interaction between ketoconazole and apremilast. Apremilast can be co-administered with a potent CYP3A4 inhibitor such as ketoconazole. There was no pharmacokinetic interaction between apremilast and methotrexate in psoriatic arthritis patients. Apremilast can be co-administered with methotrexate. There was no pharmacokinetic interaction between apremilast and oral contraceptives containing ethinyl estradiol and norgestimate. Apremilast can be co-administered with oral contraceptives.

HOS-097003 · has-pregnancy-information · PDF-Seite 6

Women of childbearing potential Pregnancy should be excluded before treatment can be initiated. Women of childbearing potential should use an effective method of contraception to prevent pregnancy during treatment. Pregnancy There are limited data about the use of apremilast in pregnant women. Apremilast is contraindicated during pregnancy (see section 4.3). Effects of apremilast on pregnancy included embryofoetal loss in mice and monkeys, and reduced foetal weights and delayed ossification in mice at doses higher than the currently recommended highest human dose. No such effects were observed when exposure in animals was at 1.3-fold the clinical exposure (see section 5.3). Breast-feeding Apremilast was detected in milk of lactating mice (see section 5.3). It is not known whether apremilast, or its metabolites, are excreted in human milk. A risk to the breastfed infant cannot be excluded, therefore apremilast should not be used during breast-feeding. Fertility No fertility data is available in humans. In animal studies in mice, no adverse effects on fertility were observed in males at exposure levels 3-fold clinical exposure and in females at exposure levels 1-fold clinical exposure. For pre-clinical fertility data, see section 5.3. 6

HOS-097001 · has-warning-information · PDF-Seite 5

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, anxiety, altered mood, and depression. Instances of suicidal ideation and behaviour, including suicide, have been observed in patients with or without history of depression (see section 4.8). 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. Severe renal impairment The Otezla dose should be reduced to 30 mg once daily in adult patients with severe renal impairment (see sections 4.2 and 5.2). In paediatric patients 6 years of age and older with severe renal impairment, the dose should be reduced to 30 mg once daily for paediatric patients who weigh at least 50 kg, and to 20 mg once daily for paediatric patients who weigh 20 kg to less than 50 kg (see sections 4.2 and 5.2). Underweight patients Patients who are underweight and paediatric patients who have a borderline to low body mass index 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. 5 Lactose content Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption should not take this medicinal product.