OTEZLA INDICATIONS AND IMPORTANT SAFETY INFORMATION
OTEZLA (apremilast) 10 mg, 20 mg and 30 mg film coated-tablets.
Refer to the Summary of Product Characteristics (SmPC) before prescribing.
Name of medicine: OTEZLA.
Active ingredients: apremilast.
List of excipients: Microcrystalline cellulose, Lactose monohydrate, Croscarmellose sodium, Magnesium stearate, Polyvinyl alcohol, Titanium dioxide (E171), Macrogol 3350, Talc, Iron oxide red (E172). The 20mg tablets also contain iron oxide yellow (E172). The 30mg tablets also contain iron oxide yellow (E172) and iron oxide black (E172).
Available dosage form: Film-coated tablets.
Authorised Indication(s): 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. Psoriasis: OTEZLA is indicated for the treatment of moderate to severe chronic plaque psoriasis 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).
Dosage regimens and routes of administration: Treatment with OTEZLA should be initiated by specialists experienced in the diagnosis and treatment of psoriasis or psoriatic arthritis. The recommended dose of OTEZLA is 30 mg twice daily taken orally, morning and evening, approximately 12 hours apart, with no food restrictions. An initial titration schedule is required as shown below in Table 1. No re-titration is required after initial titration.
Table 1. Dose titration schedule
|Day 1||Day 2||Day 3||Day 4||Day 5||Day 6 & thereafter|
|10 mg||10 mg||10 mg||10 mg||20 mg||20 mg||20 mg||20 mg||30 mg||30 mg||30 mg|
|Day 1||10 mg||—|
|Day 2||10 mg||10 mg|
|Day 3||10 mg||20 mg|
|Day 4||20 mg||20 mg|
|Day 5||20 mg||30 mg|
|Day 6 & thereafter||30 mg||30 mg|
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. If a patient shows no evidence of therapeutic benefit after 24 weeks, treatment should be reconsidered. The patient’s response to treatment should be evaluated on a regular basis. Clinical experience beyond 52 weeks is not available.
Reference to special groups of patients: Paediatric population. The safety and efficacy of apremilast in children aged 0 to 17 years have not been established. No data are available. Elderly patients: No dose adjustment is required for this patient population. 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). For initial dose titration in this group, it is recommended that OTEZLA be titrated using only the AM schedule listed in Table 1 and the PM doses be skipped. Patients with hepatic impairment: No dose adjustment is necessary for patients with hepatic impairment.
Contraindications: Hypersensitivity to the active substance(s) or to any of the excipients. Pregnancy.
Warnings: Patients with rare hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. There have been post-marketing reports of severe diarrhoea, nausea, and vomiting associated with the use of OTEZLA. 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. Instances of suicidal ideation andbehaviour, including suicide, have been observed in patients with or without history of depression. The risks and benefits of starting or continuing treatment with apremilast should be carefully assessed if patients report previous or existing psychiatricsymptoms 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.OTEZLAshould be dose reduced to 30mg once daily in patients with severe renalimpairment. 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.
Clinically significant interactions: 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 lossof 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. In clinical studies, apremilast has been administered concomitantly with topical therapy (including corticosteroids, coal tar shampoo and saliycyilic acid scalp preparations) and UVB phototherapy. There was no clinically meaningful drug-drug interaction between ketoconazole and apremilast. Apremilast can be co-administered with a potent CYP3A4 inhibitor such as ketoconazole. There was no pharmacokinetic drug-drug interaction between apremilast and methotrexate in psoriatic arthritis patients. Apremilast can be co-administered with methotrexate. There was no pharmacokinetic drug-drug interaction between apremilast and oral contraceptives containing ethinyl estradiol and norgestimate. Apremilast can be co-administered with oral contraceptives.
Additional information: Pregnancy should be excluded before treatment can beinitiated. Women of childbearing potential should use an effective method of contraception to prevent pregnancy during treatment. Apremilast should not be used during breast-feeding.
Reported side effects: The most commonly reported adverse reactions in PhaseIII clinical studies have been gastrointestinal disorders including diarrhoea and nausea. These adverse reactions generally occurred within the first 2weeks of treatment and usually resolved within 4weeks. The other most commonly reported adverse reactions included upper respiratory tract infections, headache, and tension headache. Prescribers should consult the summary of product characteristics in relation to other side-effects.
Storage conditions: Do not store above 30ºC.
Classification: Medicinal product subject to restricted medical prescription.
Marketing Authorisation Numbers: EU/1/14/981/001, EU/1/14/981/002, and EU/1/14/981/003.
Marketing Authorisation Holder: Amgen Europe B.V. Minervum 7061, 4817 ZK Breda, The Netherlands.
Internal ID of the printed material: GLII-APR170008.
Date of last revision: 09 November 2017.
*Data on File, Amgen Inc.