Drug Action
Apremilast inhibits the activity of phosphodiesterase type-4 (PDE4) which results in suppression of pro-inflammatory mediator synthesis and promotes anti-inflammatory mediators.
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Drug reference
Apremilast inhibits the activity of phosphodiesterase type-4 (PDE4) which results in suppression of pro-inflammatory mediator synthesis and promotes anti-inflammatory mediators.
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Active psoriatic arthritis (in combination with disease- modifying antirheumatic drugs or alone) in patients who have had an inadequate response or who have been intolerant to a prior disease-modifying antirheumatic drug therapy | Moderate to severe chronic plaque psoriasis that has not responded to standard systemic Musculoskeletal system treatments or photochemotherapy, or when these treatments cannot be used because of intolerance or contra-indications ▶BY MOUTH ▶Adult: Initially 10 mg daily on day 1, then 10 mg twice daily on day 2, then 10 mg in the morning and 20 mg in the evening on day 3, then 20 mg twice daily on day 4, then 20 mg in the morning and 30 mg in the evening on day 5, then maintenance 30 mg twice daily, doses should be taken approximately 12 hours apart; review treatment if no response within 24 weeks of initiation
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Concomitant use of drugs likely to cause psychiatric symptoms. history of psychiatric illness. low body-weight—consider discontinuation if weight loss is unexplained or clinically significant
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NICE decisions ▶Apremilast for treating active psoriatic arthritis (February 2017) NICE TA433 Apremilast (Otezla ®), alone or in combination with disease-modifying antirheumatic drugs (DMARDs), is recommended as an option for treating active psoriatic arthritis in adults only if: . they have peripheral arthritis with 3 or more tender joints and 3 or more swollen joints, and . their disease has not responded to adequate trials of at least 2 standard DMARDs, given either alone or in combination, and . the manufacturer provides apremilast with the discount agreed in the patient access scheme. Musculoskeletal system Stop apremilast at 16 weeks if the psoriatic arthritis has not shown an adequate response using the Psoriatic Arthritis response Criteria, defined as an improvement in at least 2 of the 4 PsARC criteria (including joint tenderness or swelling score) with no worsening in any criteria. If the disease has a Psoriasis Area and Severity Index 75 response, a dermatologist should decide whether to continue treatment with apremilast after 16 weeks based on skin response. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta433 ▶Apremilast for treating moderate to severe plaque psoriasis (November 2016) NICE TA419 Apremilast (Otezla ®) is recommended as an option for treating chronic plaque psoriasis in adults whose disease has not responded to other systemic therapies, including ciclosporin, methotrexate and PUVA, or when these treatments are contra-indicated or not tolerated, only if: . the disease is severe, as defined by a total Psoriasis Area Severity Index (PASI) of 10 or more and a Dermatology Life Quality Index (DLQI) of more than 10, and . treatment is stopped if the psoriasis has not responded adequately at 16 weeks (defined as a 75% reduction in the PASI score (PASI 75) from when treatment started or a 50% reduction in the PASI score (PASI 50) and a 5- point reduction in DLQI from start of treatment), and . the manufacturer provides apremilast with the discount agreed in the patient access scheme. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/ta419 Scottish Medicines Consortium (SMC) decisions SMC No. 1053/15 The Scottish Medicines Consortium has advised (June 2015) that apremilast (Otezla ®) is accepted for restricted use within NHS Scotland for the treatment of active psoriatic arthritis in adults who have had an inadequate response with at least two prior Disease Modifying Antirheumatic Drug (DMARD) therapies or who are intolerant to such therapies. SMC No. 1052/15 The Scottish Medicines Consortium has advised (June 2015) that apremilast (Otezla ®) is accepted for use within NHS Scotland for the treatment of moderate to severe chronic plaque psoriasis in adults who failed to respond to or who have a contra-indication to, or are intolerant to other systemic therapy including ciclosporin, methotrexate or psoralen and ultraviolet-A light (PUVA).
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MHRA/CHM ADVICE (JANUARY 2017): APREMILAST (OTEZLA ®): RISK OF SUICIDAL THOUGHTS AND BEHAVIOUR A review of evidence from clinical trials and postmarketing cases has suggested a causal association between apremilast and suicidal thoughts and behaviour.
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→Appendix 1: apremilast
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▶Common or very common Appetite decreased. back pain. cough. depression. diarrhoea. fatigue. gastrointestinal discomfort. gastrointestinal disorders. headaches. increased risk of infection. insomnia. nausea. vomiting ▶Uncommon Gastrointestinal haemorrhage. rash. suicidal tendencies. weight decreased
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Exclude pregnancy before treatment and ensure effective contraception during treatment.
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Avoid—teratogenic in animal studies.
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Manufacturer advises avoid—present in milk in animal studies.
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Dose adjustments Reduce dose if eGFR less than 30 mL/minute/1.73 m2; consult product literature for initial dose titration.
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▶Manufacturer advises monitor body-weight regularly in patients underweight at the start of treatment. ▶Manufacturer advises monitor for psychiatric symptoms (including depression, suicidal ideation and behaviour)— discontinue treatment if new or worsening psychiatric symptoms are identified.
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There can be variation in the licensing of different medicines containing the same drug. Tablet CAUTIONARY AND ADVISORY LABELS 25 ▶Otezla (Celgene Ltd) Apremilast 10 mg Otezla 10mg tablets | 4 tablet P s Apremilast 20 mg Otezla 20mg tablets | 4 tablet P s Apremilast 30 mg Otezla 30mg tablets | 56 tablet P £550.00 DT = £550.00 Hyperuricaemia and gout Gout Overview It is important to distinguish drugs used for the treatment of acute attacks of gout from those used in the long-term control of the disease. The latter exacerbate and prolong the acute manifestations if started during an attack. The management of gout in adolescents requires specialist supervision. Acute attacks of gout Acute attacks of gout are usually treated with high doses of NSAIDs such as diclofenac sodium p. 1198, diclofenac potassium p. 1197, etoricoxib p. 1201, indometacin p. 1206, ketoprofen p. 1207, naproxen p. 1211 or sulindac p. 1213. Colchicine p. 1183 is an alternative in patients in whom NSAIDs are contra-indicated. Aspirin p. 130 is not indicated in gout. Allopurinol p. 1183, febuxostat p. 1184, and uricosurics are not effective in treating an acute attack and may prolong it indefinitely if started during the acute episode. The use of colchicine is limited by the development of toxicity at higher doses, but it is of value in patients with heart failure since, unlike NSAIDs, it does not induce fluid retention; moreover, it can be given to patients receiving anticoagulants. Oral or parenteral corticosteroids are an effective alternative in those who cannot tolerate NSAIDs or who are resistant to other treatments. Intra-articular injection of a corticosteroid can be used in acute monoarticular gout [unlicensed indication]. A corticosteroid by intramuscular injection can be effective in podagra. Canakinumab p. 889, a recombinant monoclonal antibody, can be used for the symptomatic treatment of frequent gouty arthritis attacks (at least 3 in the previous 12 months). It is licensed for use in patients whose condition has not responded adequately to treatment with NSAIDs or colchicine, or who are intolerant of them. Long-term control of gout Frequent recurrence of acute attacks of gout, the presence of tophi, or signs of chronic gouty arthritis may call for the initiation of long-term (‘interval’) treatment. For long-term control of gout the formation of uric acid from purines may be reduced with the xanthine-oxidase inhibitors allopurinol or febuxostat alternatively the uricosuric drug sulfinpyrazone may be used to increase the excretion of uric acid in the urine. Treatment should be continued indefinitely to prevent further attacks of gout by correcting the hyperuricaemia. These drugs should never be started during an acute attack; they are usually started 1–2 weeks after the attack has settled. The initiation of treatment may precipitate an acute attack, and therefore an anti- inflammatory analgesic or colchicine should be used as a prophylactic and continued for at least one month after the hyperuricaemia has been corrected. However, if an acute attack develops during treatment, then the treatment should continue at the same dosage and the acute attack treated in its own right. Allopurinol is widely used and is especially useful in patients with renal impairment or urate stones when uricosuric drugs cannot be used; it is not indicated for the treatment of asymptomatic hyperuricaemia. It can cause rashes. Febuxostat is licensed for the treatment of chronic hyperuricaemia where urate deposition has already occurred; it is not indicated for patients in whom the rate of urate formation is greatly increased, such as in malignant disease or in Lesch-Nyhan syndrome. Sulfinpyrazone can be used instead of allopurinol or in conjunction with it in cases that are resistant to treatment. Benzbromarone (available from ‘special-order’ manufacturers or specialist importing companies) is a uricosuric drug that can be used in patients with mild renal impairment. Crystallisation of urate in the urine can occur with the uricosuric drugs and it is important to ensure an adequate urine output especially in the first few weeks of treatment. As an additional precaution the urine may be rendered alkaline. Aspirin and other salicylates antagonise the uricosuric drugs; they do not antagonise allopurinol but are nevertheless not indicated in gout. Other drugs used for Hyperuricaemia and gout Naproxen with esomeprazole, p. 1212 ALKALOIDS › PLANT ALKALOIDS
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Manufacturer advises patients and carers should be instructed to notify the prescriber of any changes in behaviour or mood, and of any suicidal ideation.
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Initially 10 mg daily on day 1, then 10 mg twice
First-line fragment. Read the complete Indications and Dose section above.
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