/ Adalimumab 17

Use. References. For the uses of adalimumab in children, and Uses and Administration 1. Nakamura et al. Clinical effects of actarit in rheumatoid arthritis: a recommended doses, see below. , a glycolic acid ester of indometacio, is an improvement of early disease activity mediated by reduction of serum concentrations of nitric oxide. Clin Exp Rheumato/ 2000; 18: 445-50. NSAID (p. 102.3). Its pharmacological activity is due to both Administration in children. Adalimumab is used in the acemetacin and its major metabolite, (p. 71.2). treatment of active polyarticular juvenile idiopathic Acemetacin is used in rheumatoid arthritis, osteoarthritis, ���F..�CI.��CI.�� ...... arthritis in children. In the UK, it is licensed for use in and low back pain, and for postoperative pain and PraprielaryPreparations (details are given in Volume B) those aged 2 years and older who have had an inadequate inflammation. Usual oral doses are 120 to 180mg daily in response to standard disease-modifying antirheumatic China: An Ji Xin ('�alil:)t; Kai divided doses. Acemetacin is eliminated by both hepatic and Single-ingredient Preparations. drugs (DMARDs). The dose in children aged 2 to 12 years Mai Si Jpn: Mover; Orcl. renal routes, although pharmacokinetics are not affected by is calculated according to body-surface and is given subcu­ moderate renal or hepatic impairment and appear to be (i!l'\i!I!i!!); taneously: 24mg/m2 up to a maximum dose of 20mg in unchanged in the elderly. those younger than 4 years of age and 40 mg in those References. Adalimumab !BAN, usAN, riNN! aged 4 to 12 years may be given every other week. Older 1. Jones RW, et al. Comparative pharmacokinetics of acemetacin in young children may receive 40 mg every other week regardless of subjects and elderly patients. Br J Clin Pharmacol l99I; 31: 543-5. body-surface area. licensed product information also 2. Hazleman B, Bernstein RM. Acemetacin in the long-term therapy of rheumatoid arthritis. Curr Med Res Opin 1993; 13: 119-26. recommends that it should be given with methotrexate, 3. Chou CT, Tsai YY. A double-blind, randomized, controlled parallel group although monotherapy may be used where treatment study evaluating the efficacy and safety of acemetacin for the with methotrexate is inappropriate. In the USA, adalimu­ management of osteoarthritis. lnt J Clin Pharmacal Res 2002; 22: 1--6. mab is licensed for use in children aged 4 to 17 years to 4. Leeb BF, et al. Behandlung der Gonarthrose: Wirksamkeit und Vertriiglichkeit von retardienem Acemetacin im Vergleich zu . reduce the signs and symptoms of moderately to severely Orthopade 2004; 33: 1032-41. active disease; the dose is calculated according to body­ weight and is given subcutaneously: those weighing 15 kg to less than 30 kg should be given 20 mg every other AdverseEffects, Treatment, and Precautions week, while heavier children may receive 40 mg every As for NSAIDs in general, p. 104.3. Uses and Administration other week. Adalimumab is a recombinant human monoclonal 1NF In the UK, adalimumab is also licensed for the treatment Interactions antibody that binds specifically to 1NF-a and blocks its of severe, active Crohn's disease in children aged 6 years interaction with endogenous cell-surface 1NF receptors. It and older who have had an inadequate response to For interactions associated with NSAIDs, see p. 107.3. also modulates biological responses that are induced or conventional therapy, or who have contra-indications for or regulated by 1NF. Elevated levels of 1NFhave been found in are intolerant of such treatments. The dose is given Pharmacokinetics the affected tissues and fluids of patients with rheumatoid subcutaneously, according to body-weight: those weighing arthritis (p. 18.1), axial spondyloarthritis, ankylosing less than 40 kg should be given an initial dose of 80 mg on Acemetacin is well absorbed after oral dosage. Its major spondylitis, and psoriatic arthritis (see Spondyloarthropa­ day 1, followed by 40 mg 2 weeks later (day 15). After a metabolite is indometacio (p. 71.2) which, after repeated thies, p. 18.1), plaque psoriasis (below), and Crohn's disease further 2 weeks (day 29), a maintenance dose of 20 mg doses, is present at higher concentrations than those of and ulcerative colitis (see Inflammatory Bowel Disease, every other week may be started. There is a high risk of acemetacin. Acemetacio is bound to plasma proteins to a below). Adalimumab is described as a biological disease­ adverse effects associated with the above induction dose, slightly lesser extent than indometacio. It is eliminated via modifying antirheumatic drug (DMARD). consequently, in those who do not require a more rapid both the liver and the kidneys. Adalimumab is used in the treatment of moderate to response to therapy, licensed product information advises r ti severe, active rheumatoid arthritis and active and that a lower dose of 40 mg may be given initially, followed �-�J>.CI. c:J <>,��...... progressive psoriatic arthritis. In the UK, it is licensed for by 20 mg 2 weeks later; thereafter, usual maintenance doses ProprielaryPreparations (details are given in Volume B) use in patients who have had an inadequate response to may be given. Patients who have an insufficient response standard DMARDs, although in severe progressive rheu­ may benefit from increasing the maintenance dose to 20 mg Austria: Rheutrop; China: Ran­ Single-ingredient Preparations. matoid arthritis it may be used in patients not previously every week. Heavier children may be given the usual adult tU!lil ({It'll:); Shun Song {JI�f$); Cz.: Rantudilt; Ger.: Acemeta· treated with methotrexate; in the USA, it is licensed for use dose (see above) for this indication. doct; Rantudil; Gr.: Gamespir; Rantudal; Hung.: Rantudil; Jp n: Rantudil; Malaysia: Acemet; Mex. : Rantudil; Philipp.: Rantu­ in early disease. Adalimumab is also used in the treatment of dilt; Pol.: Rantudil; Port.: Rantudil; Switz.: Tilur; Turk.: Rantu­ active ankylosing spondylitis: UK licensed product Hidradenitis suppurativa. For mention of adalimumab dil; UK: Emflex; Venez. : Pranex. information recommends that it should ortly be used in having been used in the treatment of hidradenitis suppur­ patients with severe disease who have had an inadequate ativa, see under Infliximab, p. 75.1. Multi-ingredientPreparations. Arg.: Rucaten Forte; Rucaten Pre­ response to conventional treatment; however, in the USA it dnisolona; Thai.: Aceo. may be used in early disease. In the UK, it is also used in the lnRammatory bowel disease. Adalimumab is used in the treatment of severe axial spondyloarthritis without management of inflammatory bowel disease (p. 1811.3) radiographic evidence of ankylosing spondylitis in patients such as Crohn's disease and ulcerative colitis. 1"9 It has also Acetanilide who have had an inadequate response to, or are intolerant been tried in children.10·12 of, NSAIDs. For all the above indications, it is given by 1. Plosker GL, Lyseng-Williamson Adalimumab: in Crohn's disease. KA. BioDruos 2007; 125-32. subcutaneous injection in a dose of 40 mg every other week. ll: In the treatment of rheumatoid arthritis, UK licensed 2. NICE. Inflixim.ab (review) and adalimumab for the treatment of Crohn's disease (includes a review of NICE technology appraisal guidance 40): product information recommends that adalimumab should Technology Appraisal Guidance 187 (issued May 2010). Available at: be given with methotrexate, although monotherapy may be http: //www . nice.org. uk/nicemedia/live 12985/485 52/485 52.pdf I used where treatment with methotrexate would be (accessed 19/10/IO) inappropriate. When used as monotherapy in rheumatoid 3. Huang ML, et al. Efficacy and safety of adalimumab in Crohn's disease: meta-analysis of placebo-controlled trials. J Dis Dis 201 1; 12: 165-72. Pharmacopoeias. In Fr. arthritis, some patients may benefit from increasing the dose 4. Guidi L, et al. Update on the management of inflammatory bowel to 40 mg every week. In the UK, NICE recommends that disease: specific role of adalimumab. Clin Exp Gastroenterol 2011; 4: 163- adalimumab be stopped if there is no adequate response 72. Profile after 6 months for the treatment of rheumatoid arthritis, 5. Wasan SK, Kane SV. Adalimumab for the treatment of inflammatory bowel disease. Expert Gastroenterol Hepato/ 2011; 5: 679-84. Rev Acetanilide, a para-aminophenol derivative related to and after 12 weeks for psoriatic arthritis or ankylosing 6. Reinisch W, et al. Adalimumab for induction of clinical remission in (p. 115.1), has and spondylitis. moderately to severely active ulcerative colitis: results of a randomised controlled Gut 20l l; 60: 780-7. properties. It was replaced by safer . Adalimumab is used in the treatment of moderate to trial. severe, active Crohn's disease and ulcerative colitis 7. Sandborn WJ, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. unresponsive to conventional treatment; it may also be used Gastroenterolo9Y 2012; 142: 257-65.e1-3. r . �-��I:'CI. c:l��<>,��...... in patients with Crohn's disease who have relapsed while 8. Burness CB, Keating GM. Adalimumab: a review of its use in the (details are given in Volume B) Praprielary Preparations taking infliximab. For both these indications, patients may treatment of patients with ulcerative colitis. BioDruos 2013; 27: 247-62. 9. Panacdone R, et al. Adalimumab maintains remission of Crohn's disease Fr.: Neth.: be given an initial dose of 160 mg subcutaneously on day 1 HomoeopalhicPreparations. Neurocynesinet; Neuro­ after up to 4 years of treatment: data from CHARM and ADHERE. cynesinet. (given as four 40-mg injections in one day or two 40-mg Aliment Pharmacal Ther2013; 38: 1236-47. injections daily for 2 consecutive days), followed by 80 mg 10. Viola F, et al. Efficacy of adalimumab in moderate-to-severe pediatric two weeks later (day 15). After a further two weeks (day Crohn's disease. Am J Gastroentero/ 2009; 104: 2566-71. 29), a maintenance dose of 40 mg every other week may be 11. Russell RK, et al. A British Society of Paediatric Gastroenterology, Actarit (r!NNJ Hepatology and Nutrition survey of the effectiveness and safety of started. There is a high risk of adverse effects associated with adalimumab in children with inflammatory bowel disease. Aliment the above induction dose, consequently, in those with Pharmacal Ther 20l l; 33: 946-53. Crohn's disease who do not require a more rapid response to 12. Hyams JS, et al. Safety and efficacy of adalimumab for moderate to 143: therapy, UK licensed product information advises that a severe Crohn's disease in children. GastroenteroloBY 2012; 365-74. e2. lower dose of 80 mg may be given initially, followed by 40 mg 2 weeks later; thereafter, usual maintenance doses Psoriasis. Adalimumab is used in the treatment of plaque may be given. A clinical response is usually seen within 8 or psoriasis1·7 (p. 1688.1). 12 weeks of starting treatment for ulcerative colitis or I. NICE. Adalimumab for the treatment of adults with psoriasis: Profile Crohn's disease, respectively; for both indications, those Technology Appraisal Guidance 146 (issued June 2008). Available at: Actarit is reported to be a disease-modifying antirheumatic patients who relapse while on adalimumab may benefit http://www.nice.org.uk/nicemedia/pdf/TA146Guidance.pdf (accessed drug. It has been given in the treatment of rheumatoid from increasing the maintenance dose to 40 mg every week. 25/07/08) arthritis in a usual oral dose of 100 mg three times daily. In the treatment of moderate to severe chronic plaque 2. Papoutsaki M. et al. Adalimumab for the treatment of severe psoriasis psoriasis in patients unresponsive to, or intolerant of, and psoriatic arthritis. Expert Opin Bioi Ther 2008; 8: 363-70. 3. Traczewski P, Rudnicka L. Adalimumab in dermatology. Br J Clin Adverse effects. A photosensitivity reaction developed in conventional systemic therapy including phototherapy, the Pharmacol 2008; 66: 618-25. a 52-year-old woman one month after starting actarit and recommended initial dose of adalimumab is 80 mg 4. Croom KF, McCormack PL. Adalimumab: in plaque psoriasis. Am J Clin doxycycline.' Photopatch tests for both drugs were only subcutaneously; this may be followed by a maintenance Dermatol 2009; 10: 43-50. 5. Iaconi A, et al. Psoriasis and its treatment with adalimumab. Expert Opin dose of 40 mg subcutaneously on alternateweeks, starting 1 positive for the patches containing actarit. Biol 2010; 10: 133-52. Ther 1. Kawada A, et al. Photosensitivity due to actarit. ContactDermatitis 1997; week after the initial dose. A clinical response is usually seen 6. Leonardi C, et al. Efficacy, safety and medication cost implications of 36: 175-6. within 16 weeks of starting treatment. adalimumab 40 mg weekly dosing in patients with psoriasis with

The symbol t denotes a preparation no longer actively marketed 18

suboptimal response to 40 mg every other week dosing: results from an References. surgical procedures. It may be given by continuous open-label study. Br J Dermatol 2012: 167: 658-67. 1. Burmester GR, et al. Adalimumab: long-term safety in 23 458 patients intravenous infusion in ventilated patients. 7. Saraceno R, et al. Adalimumab in the treatment of plaque-type psoriasis from global clinical trials in rheumatoid arthritis, juvenile idiopathic and psoriatic arthritis. Expert Opin Biol Ther 201 3; 13: 1325-34. arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's The dosage of used depends on whether the disease. Ann Rheum Dis 2012. Available at: doi: l0.1l36/annrheumdis- patient has spontaneous respiration or assisted ventilation 20l l-20I244 and on the expected duration of anaesthesia. Doses are Rheumatoid arthritis. Some references1·9 to the use of adjusted according to the needs of the patient. Children may adalimumab in rheumatoid arthritis 13.2) and juvenile Porphyria. The Drug Database for Acute Porphyria, com­ require higher or more frequent doses than adults, whereas idiopathic arthritis (p. 12.1). (P- piled by the Norwegian Porphyria Centre (NAPOS) and the elderly or debilitated patients may require lower or less I. Navarra-Sarabia F, et al. Adalimumab for treating rheumatoid arthritis. the Porphyria Centre Sweden, dassifies adalimumab as frequent doses. Obese patients may require doses based on Available in The Cochrane Database of Systematic Reviews; Issue 3. possibly porphyrinogenic; it should be used only when no their ideal (lean) body-weight. Chichester: John Wiley; 2005 (accessed 13/06/08). 2. CvetkoviC RS, Scott LJ. Adalimumab: a review of its use in adult patients safer alternative is available and precautions should be When used as an adjunct in the maintenance of with rheumatoid arthritis. BioDrugs 2006; 20: 293-311. considered in vulnerable patients.1 general anaesthesia the initial licensed dose in the UK is as 3. Chen Y-F, et al. NHS Health Technology Assessment Programme. A l. The Drug Database for Acute Porphyria. Available at: http;//www. follows: systematic review of the effectiveness of adalimumab, etanercept and drugs-porphyria.org (accessed 15/ll/11) in patients with spontaneous respiration, up to 500 micr­ infliximab for the treatment of rheumatoid arthritis in adults and an • economic evaluation of their cost-effectiveness (issued November ograms may be given slowly over about 30 seconds with 2006}. Available at: http://www.hta.ac.uk/fullmono/mon1042.pdf Interactions supplementary doses of 250 micrograms (accessed 31110/08) ventiLated patients may be given 30 to 50 micrograms/kg 4. Mease PJ. Adalimumab in the treatment of arthritis. Ther Clin RiskManag • As for Infliximab, p. 77.3. with supplements of 15 micrograms/kg. When given by 2007; 3: 133-48. Methotrexate is reported to reduce the clearance of 5. NICE. Adalimmnab, ctanercept and infliximab for the treatment of infusion to ventilated patients there is an initial loading adalimumab by up to 44% but licensed product information rheumatoid Mthritis (includes a review of technology appraisal guidance dose of 50 to 100 micrograms/kg given as a bolus or by 36): Technology Appraisal Guidance 130 (issued October 2007). for the latter states that dosage adjustment for either drug infusion over I 0 minutes, followed by infusion at a rate Available at: http: //www .nicc.org. uk/nicemedia/pdfiTAl3 0guidance. does not appear to be necessary. of 0.5 to I microgram/kg per minute pdf (accessed 03/ll/08) 6. Lovell DJ, et a!. Pediatric Rheumatology Collaborative Study Group. Typical doses that have been used in the USA are as follows: Pediatric Rheumatology International Trials Organisation. Ada!imumab Pharmacokinetics • for short surgical procedures of less than hour in patients with or without methotrexate in juvenile rheumatoid arthritis. N Eng! J with spontaneous respiration or assisted1 ventilation, the Med 2008; 359: 810-20. Adalimumab is reported to have linear pharmacokinetics at dose is 8 to 20 micrograms/kg; this may be followed by 7. NICE. Adalimumab, etanercept, infliximab, rituximab and abatacept for usual dosages. After subcutaneous injection peak concen­ supplementary doses of 3 to 5 micrograms/kg every 5 to the treatment of rheumatoid arthritis after the failure of a TNF inhibitor trations are reached in about 3 to 8 days and bioavailability (part review of NICE technology appraisal guidance 36 and review of 20 minutes or an infusion of 0.5 to 1 microgram/kg per is estimated to be 64%. The mean terminal half-life is about NICE technology appraisal guidance 126 and 141}: Technology minute. Alternatively patients with assisted or controlled Appraisal Guidance 195 (issued August 2010). Available at: http:// 2 weeks. Adalimumab crosses the placenta and is distributed ventilation may be given an initial dose of 20 to www.nice.org.uk/nicemedia/live/13108/50413/'50413. pdf (accessed into breast milk. 04111110) 50 micrograms/kg, followed by supplementary doses of 5 8. Wiens A, et al. Meta-analysis of the eflicacy and safety of adalimumab, References. to 15 micrograms/kg every 5 to 20 minutes etanercept, and infliximab for the treatment of rheumatoid arthritis. l. Nestorov I. of tumor necrosis factor in general surgical procedures in patients with assisted or Pharmacotherapy 2010; 30: 339-'53. antagonists. 74 (suppl): 13-18. • controlled ventilation, an initial dose of 50 to 9. Poddubnyy D, Rudwaleit M. Efficacy and safety of adalimumab treatment in patients with rheumatoid arthritis, ankylosing spondylitis P ?.ns 75 micrograms/kg may be followed by an infusion of and psoriatic arthritis. Expert Opin Drug Safety 20ll; 10: 655-73. P.r.� �-r�_ti 0.5 to 3 micrograms/kg per minute. If alfentanil has been ProprietaryPreparations (details are given in Volume B) given in anaesthetic doses (see below) for the induction of anaesthesia, infusion rates may need to be reduced by Spondyloarthropathies. References1-13 to the use of adali­ Single-ingredient Preparations. Arg. : Humira; Austral.: Humira; 30 to 50% during the first hour of maintenance mumab in ankylosing spondylitis, axial spondyloarthritis, Austria: Belg. : Braz. : Canad.: Humira; Humira; Humira; Maintenance infusions of alfentanil should be stopped 10 to and psoriatic arthritis (p. 14.3). Humira; Chile: Humira; China: Humira (1��5-f-); Cz.: Humira; 30 minutes before the anticipated end of surgery. 1. Simpson D, Scott LJ. Adalimumab: in psoriatic arthritis. Drugs 2006; 66: Denm.: Humira; Fin.: Humira; Fr.: Humira; Ger.: Humira; Gr.: The dose for the induction of anaesthesia in patients 1487-96. Humira; Trudexa; Hong Kong: Humira; Hung.: Humira; Irl. : 2. McLeod C, et a!. NHS Health Technology Assessment Programme. Humira; Israel: Humira; Ital. : Humira; Jpn: Humira; Malaysia: with assisted ventilation undergoing procedures of at least Ada!imum

All cross-references refer to entries in Volume A