Drug class: Tumor Necrosis Factor Inhibitors, Miscellaneous

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

Introduction

Tumor necrosis factor (TNF) inhibitor and biologic disease-modifying antirheumatic drug (DMARD); a recombinant DNA-derived human immunoglobulin G₁ (IgG₁) monoclonal antibody.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Adalimumab-aacf (Idacio), adalimumab-aaty (Yuflyma), adalimumab-adaz (Hyrimoz), adalimumab-adbm (Cyltezo), adalimumab-afzb (Abrilada), adalimumab-aqvh (Yusimry), adalimumab-atto (Amjevita), adalimumab-bwwd (Hadlima), adalimumab-fkjp (Hulio), and adalimumab-ryvk (Simlandi) are biosimilar to adalimumab (Humira).^{172 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

A biosimilar is a biological that is highly similar to an FDA-licensed reference biological with the exception of minor differences in clinically inactive components and for which there are no clinically meaningful differences in safety, purity, or potency.^{170 171} Biosimilars are approved through an abbreviated licensure pathway that establishes biosimilarity between proposed biological and reference biological but does not independently establish safety and effectiveness of the proposed biological.¹⁷¹ In order to be considered an interchangeable biosimilar, a biological product must meet additional requirements beyond demonstrating biosimilarity to its reference product.¹⁶⁹ Only adalimumab-afzb (Abrilada), adalimumab-adbm (Cyltezo), and adalimumab-ryvk (Simlandi) are designated as interchangeable with adalimumab (Humira) at this time.¹⁷²

In this monograph, unless otherwise stated, the term “adalimumab products” refers to adalimumab (the reference drug) and its biosimilars (adalimumab-aacf, adalimumab-aaty, adalimumab-adaz, adalimumab-adbm, adalimumab-afzb, adalimumab-aqvh, adalimumab-atto, adalimumab-bwwd, adalimumab-fkjp, adalimumab-ryvk).

Uses for Adalimumab

Several adalimumab biosimilars are available.^{2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Biosimilarity of these products has been demonstrated for the indications described in Table 1.^{172 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Originator adalimumab is labeled for use in adults and pediatric patients ≥5 years of age with UC; biosimilars are only labeled for use in adults with UC.

Originator adalimumab is labeled for use in adults and pediatric patients ≥12 years of age with HS; biosimilars are only labeled for use in adults with HS.

Originator adalimumab is labeled for use in adults and pediatric patients ≥2 years of age with UV; biosimilars are only labeled for use in adults with UV.

AS, ankylosing spondylitis; CD, Crohn disease; HS, hidradenitis suppurativa; JIA, juvenile idiopathic arthritis; Ps, plaque psoriasis; PsA, psoriatic arthritis; RA, rheumatoid arthritis; UC, ulcerative colitis ; UV, uveitis.

Rheumatoid Arthritis

Used to manage the signs and symptoms of rheumatoid arthritis, to induce a major clinical response, to improve physical function, and to inhibit progression of structural damage in adults with moderate to severe disease.^{1 3 9 11 12 13 55 56 57 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Use alone or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs).^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Disease-modifying treatments for rheumatoid arthritis include conventional DMARDs (e.g., hydroxychloroquine, leflunomide, methotrexate, sulfasalazine), biologic DMARDs (e.g., TNF blocking agents, abatacept, tocilizumab, sarilumab, rituximab), and/or targeted synthetic DMARDs (e.g., Janus kinase [JAK] inhibitors).²⁰⁰³

Guidelines generally support use of TNF blocking agents as add-on therapy to methotrexate in patients who do not meet treatment goals with methotrexate alone.²⁰⁰³

Specific agents for rheumatoid arthritis are selected according to current disease activity, prior therapies used, and presence of comorbidities.²⁰⁰³

Juvenile Idiopathic Arthritis

Used to manage signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in pediatric patients ≥2 years of age.^{1 20 39 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Use with or without methotrexate.^{1 20 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Drugs used to treat juvenile idiopathic arthritis include nonsteroidal antiinflammatory agents (NSAIAs), systemic and intra-articular corticosteroids, conventional DMARDs (e.g., methotrexate, sulfasalazine, hydroxychloroquine, leflunomide), and biologic DMARDs (e.g., TNF blocking agents, abatacept, tocilizumab, rituximab).²⁰¹³

Guidelines generally support use of TNF blocking agents, as add-on therapy in patients with moderate to high disease activity despite the use of methotrexate.²⁰¹³

Specific agents for juvenile idiopathic arthritis treatment are selected according to presence of certain risk factors (e.g., positive anti-cyclic citrullinated peptide antibodies, positive rheumatoid factor, joint damage), level of disease activity, involvement of specific joints, presence of certain comorbidities (e.g., uveitis), and prior therapies.^{2013 2022}

Psoriatic Arthritis

Used to manage the signs and symptoms of active psoriatic arthritis, to improve physical function and to inhibit progression of structural damage in adults.^{1 14 15 58 59 60 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Use alone or in combination with other nonbiologic DMARDs.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Disease-modifying treatments for psoriatic arthritis include oral small molecules (OSMs; e.g., methotrexate, sulfasalazine, cyclosporine, leflunomide, apremilast), biologic DMARDs (e.g., TNF blocking agents, secukinumab, ixekizumab, ustekinumab, brodalumab, abatacept), and/or targeted synthetic DMARDs (e.g., tofacitinib).²⁰⁰⁵

Guidelines generally support use of TNF blocking agents as first-line treatment in patients with active psoriatic arthritis.²⁰⁰⁵

Recommendations for the use and selection of disease-modifying therapies in psoriatic arthritis vary based on the presence of certain disease characteristics (e.g., psoriatic spondylitis/axial disease, enthesitis) and comorbidities (e.g., inflammatory bowel disease, diabetes).²⁰⁰⁵

Ankylosing Spondylitis

Used to manage the signs and symptoms of active ankylosing spondylitis in adults.^{1 16 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Treatments for ankylosing spondylitis include NSAIAs, conventional DMARDs (e.g., methotrexate, sulfasalazine), biologic DMARDs (e.g., TNF blocking agents, secukinumab, ixekizumab), and/or targeted synthetic DMARDs (e.g., tofacitinib).²⁰⁰⁴

Guidelines generally support use of TNF blocking agents for treatment of ankylosing spondylitis in patients with active disease despite treatment with NSAIAs.²⁰⁰⁴

Recommendations for treatment selection in ankylosing spondylitis vary based on the presence of certain comorbidities (e.g., iritis, inflammatory bowel disease).²⁰⁰⁴

Crohn Disease

Used to treat moderately to severely active Crohn disease in adults and pediatric patients ≥6 years of age.^{1 61 62 63 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Guidelines generally support use of TNF blocking agents for use as induction and maintenance therapy in adults with moderate to severe Crohn disease.^{2000 2001} Specific treatments are selected according to the patient’s risk profile and disease severity.²⁰⁰⁰

Role of TNF blocking agents in pediatric Crohn disease is generally induction and maintenance therapy in patients who fail an adequate trial of steroids and exclusive enteral nutrition and/or immunomodulators, unless the patient has a complex perianal fistula at diagnosis.²⁰¹⁶

Has been used in a limited number of patients with fistulizing Crohn disease^{† [off-label]}.⁶⁴ Has been used to prevent recurrence of Crohn disease after surgical treatment^{† [off-label]}, but place in therapy for this use remains to be determined.^{63 65 66 67}

Ulcerative Colitis

Used to treat moderately to severely active ulcerative colitis in adults and pediatric patients ≥5 years of age.^{1 32 33 35 68} Biosimilar products labeled for use in adults with moderately to severely active ulcerative colitis only.^{2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Guidelines generally support first-line use of TNF blocking agents for induction and maintenance of remission in adults with moderate to severe ulcerative colitis.^{2019 2020} Specific treatments are selected according to disease severity, disease location/extent, disease prognosis, and previous therapies used.^{2018 2019 2020}

Role of TNF blocking agents in pediatric ulcerative colitis is generally in patients with moderate to severe disease who fail therapy with 5-aminosalicylates/azathioprine and/or who are unable to wean from corticosteroids on 5-aminosalicylate/azathioprine therapy.^{2015 2016}

Efficacy in patients who have lost response to or were intolerant to TNF blocking agents not established.^{1 33 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Plaque Psoriasis

Used to manage moderate to severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy and in whom other systemic therapies are medically less appropriate.^{1 26 46 69 70 71 2541 2542 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Use only in patients who will be closely monitored and who will have regular follow-up visits with a clinician.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Guidelines generally support use of TNF blocking agents in moderate to severe psoriasis, either as monotherapy or in combination with topical, oral, or phototherapy.^{2007 2009}

Recommendations for use and selection of psoriasis therapies vary based on patient age, disease characteristics (e.g., severity, location, presence of psoriatic arthritis), and comorbidities (e.g., inflammatory bowel disease).^{2007 2008 2009 2010 2011 2012}

Hidradenitis Suppurativa

Used to manage moderate to severe hidradenitis suppurativa in adults and pediatric patients ≥12 years of age.^{1 43 73 74} Biosimilar products labeled for use in adults with moderate to severe hidradenitis suppurativa only.^{2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Current guidelines recommend adalimumab to improve disease severity and quality of life in patients with moderate to severe hidradenitis suppurativa.²⁰²³

Uveitis

Management of noninfectious intermediate uveitis, posterior uveitis, and panuveitis in adults and pediatric patients ≥2 years of age.^{1 47 48 49 50 72} Biosimilar products labeled for use in adults with noninfectious intermediate uveitis, posterior uveitis, and panuveitis only.^{2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Recommendations from an international expert panel support use of adalimumab in patients with noninfectious uveitis whose disease is inadequately controlled by corticosteroids and nonbiologic immunomodulatory therapies.²⁰²¹

Adalimumab Dosage and Administration

General

Pretreatment Screening

• Evaluate all patients for active and inactive tuberculosis prior to initiating therapy.¹

• Screen at-risk patients for hepatitis B virus (HBV) infection before initiating therapy.¹

• Do not initiate therapy in patients with an active infection, including clinically important localized infections.¹

• Examine all patients for the presence of nonmelanoma skin cancer, particularly those with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of psoralen and ultraviolet A radiation (PUVA) treatment.¹

Patient Monitoring

• Monitor patients closely for signs or symptoms of infection during and after treatment; monitor for possible development of tuberculosis in patients who tested negative for latent tuberculosis prior to initiating therapy.¹

• Perform periodic dermatologic evaluations in all patients, particularly those with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment.¹

• Evaluate and monitor chronic carriers of HBV during treatment and for up to several months following treatment.¹

Dispensing and Administration Precautions

• To avoid medication errors, the Institute for Safe Medication Practices (ISMP) recommends that prescribers communicate both the brand and generic names for adalimumab on the prescription order form.⁷⁷

• Of the available adalimumab biosimilars, only adalimumab-afzb (Abrilada), adalimumab-adbm (Cyltezo), and adalimumab-ryvk (Simlandi) are designated as interchangeable with adalimumab (Humira).¹⁷²

Other General Considerations

• Methotrexate, other nonbiologic DMARDs, corticosteroids, NSAIAs, and/or analgesics may be continued in adults receiving adalimumab for the management of rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

• Methotrexate, corticosteroids, NSAIAs, and/or analgesics may be continued in pediatric patients receiving adalimumab for the management of juvenile idiopathic arthritis.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

• Aminosalicylates and/or corticosteroids may be continued in adults receiving adalimumab for the treatment of Crohn disease or ulcerative colitis.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Azathioprine, mercaptopurine, or methotrexate may be continued, if necessary, in adults receiving adalimumab for the treatment of Crohn disease.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Azathioprine and mercaptopurine may be continued, if necessary, in adults receiving adalimumab for the treatment of ulcerative colitis.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Administration

Sub-Q Injection

Administer by sub-Q injection.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Adalimumab, adalimumab-aacf, adalimumab-adaz, adalimumab-adbm, adalimumab-afzb, and adalimumab-fkjp commercially available in single-use prefilled syringes and single-use prefilled injection pens.^{1 2501 2502 2504 2505 2506}

Adalimumab-aaty, adalimumab-atto, and adalimumab-bwwd commercially available in single-use prefilled syringes and single-use prefilled autoinjectors.^{2500 2503 2507}

Adalimumab-aqvh commercially available as a single-use prefilled injection pen.²⁵⁰⁸

Adalimumab-ryvk commercially available as a single-dose autoinjector.²⁵⁴⁰

Various packaging configurations (e.g., starter packs) may be available; contact individual product manufacturers for more information.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Some adalimumab products not available in presentations suitable for pediatric use, even if product is labeled for pediatric use; consult specific product information and manufacturer websites for details.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Adalimumab products contain no preservatives; discard any unused portions of solution.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Adalimumab products may sit outside of refrigeration for 15–30 minutes prior to administration to allow liquid to reach room temperature; do not remove cap or cover while the drug is warming to room temperature.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Administer sub-Q injections into anterior thighs or abdomen; do not administer abdominal injections within 5.18 cm (2 inches) of the umbilicus.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Rotate injection sites.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Administer new injections ≥2.54 cm (1 inch) from an old site; avoid injections into areas where the skin is tender, bruised, red, or hard, or into scars or stretch marks.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Do not inject into psoriatic lesions.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Intended for use under the guidance and supervision of a clinician, but may be self-administered if the clinician determines that the patient and/or their caregiver is competent to safely administer the drug after appropriate training and with medical follow-up as necessary.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Dosage

Pediatric Patients

Juvenile Idiopathic Arthritis

Sub-Q

Pediatric patients ≥2 years of age weighing 10 to <15 kg: 10 mg once every other week.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Pediatric patients ≥2 years of age weighing 15 to <30 kg: 20 mg once every other week.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Pediatric patients ≥2 years of age weighing ≥30 kg: 40 mg once every other week.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Not studied for this use in patients <2 years of age or weighing <10 kg.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Crohn Disease

Sub-Q

Pediatric patients ≥6 years of age weighing 17 to <40 kg: 80 mg on day 1, followed by 40 mg once 2 weeks later (on day 15).^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Start maintenance dosage of 20 mg once every other week on day 29 (2 weeks after the 40-mg dose).^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Pediatric patients ≥6 years of age weighing ≥40 kg: 160 mg on day 1 (given in one day or divided over 2 consecutive days), followed by 80 mg once 2 weeks later (on day 15).^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Start maintenance dosage of 40 mg once every other week on day 29 (2 weeks after the 80-mg dose).^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Ulcerative Colitis

Sub-Q

Pediatric patients ≥5 years of age weighing 20 to <40 kg: 80 mg on day 1, followed by 40 mg once on day 8 (1 week after the 80-mg dose) and 40 mg once on day 15 (1 week after the first 40-mg dose).¹ Start maintenance dosage of 40 mg once every other week or 20 mg once every week on day 29 (2 weeks after the second 40-mg dose).¹

Pediatric patients ≥5 years of age weighing ≥40 kg: 160 mg on day 1 (given in one day or divided over 2 consecutive days), followed by 80 mg once on day 8 (1 week after the 160-mg dose) and 80 mg once on day 15 (1 week after the first 80-mg dose).¹ Start maintenance dosage of 80 mg once every other week or 40 mg once every week on day 29 (2 weeks after the second 80-mg dose).¹

Recommended pediatric dosage should be continued in patients who turn 18 years of age and who are well-controlled on their adalimumab regimen.¹

Biosimilars not labeled for use in pediatric patients with ulcerative colitis.^{2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Hidradenitis Suppurativa

Sub-Q

Adolescents ≥12 years of age weighing 30 to <60 kg: 80 mg on day 1, followed by 40 mg once on day 8, then 40 mg once every other week.¹

Adolescents ≥12 years of age weighing ≥60 kg: 160 mg on day 1 (given in one day or divided over 2 consecutive days), followed by 80 mg once 2 weeks later (on day 15).¹ Start dosage of 40 mg once every week or 80 mg once every other week on day 29 (2 weeks after the 80-mg dose).¹

Biosimilars not labeled for use in pediatric patients with hidradenitis suppurativa.^{2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Uveitis

Sub-Q

Pediatric patients ≥2 years of age weighing 10 to <15 kg: 10 mg once every other week.¹

Pediatric patients ≥2 years of age weighing 15 to <30 kg: 20 mg once every other week.¹

Pediatric patients ≥2 years of age weighing ≥30 kg: 40 mg once every other week.¹

Not been studied for this use in patients <2 years of age or weighing <10 kg.¹

Biosimilars not labeled for use in pediatric patients with uveitis.^{2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Adults

Rheumatoid Arthritis

Sub-Q

40 mg once every other week.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Patients not receiving methotrexate may obtain additional benefit from 40 mg once every week or 80 mg once every other week.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Psoriatic Arthritis

Sub-Q

40 mg once every other week.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Ankylosing Spondylitis

Sub-Q

40 mg once every other week.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Crohn Disease

Sub-Q

160 mg once on day 1 (given in one day or divided over 2 consecutive days), followed by 80 mg once 2 weeks later (on day 15).^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Start maintenance dosage of 40 mg once every other week on day 29 (2 weeks after the 80-mg dose).^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Ulcerative Colitis

Sub-Q

160 mg on day 1 (given in one day or divided over 2 consecutive days), followed by 80 mg once 2 weeks later (on day 15).^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Start maintenance dosage of 40 mg once every other week on day 29 (2 weeks after the 80-mg dose).^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} If clinical remission is not achieved by 8 weeks (day 57), discontinue adalimumab.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Plaque Psoriasis

Sub-Q

80 mg on day 1, followed by 40 mg once every other week (maintenance dosage) starting 1 week after the initial dose.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Hidradenitis Suppurativa

Sub-Q

160 mg on day 1 (given in one day or divided over 2 consecutive days), followed by 80 mg once 2 weeks later (on day 15).^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Start dosage of 40 mg once every week or 80 mg once every other week on day 29 (2 weeks after the 80-mg dose).^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Uveitis

Sub-Q

80 mg on day 1, followed by 40 mg once every other week starting 1 week after the initial dose.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Special Populations

Hepatic Impairment

No dosage recommendations at this time.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Renal Impairment

No dosage recommendations at this time.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Geriatric Patients

No dosage recommendations at this time.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Cautions for Adalimumab

Contraindications

• None.¹

Warnings/Precautions

Warnings

Serious Infections

Increased risk of serious infections involving various organ systems and sites that may require hospitalization or result in death.^{1 23} Opportunistic infections caused by bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens (e.g., aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, tuberculosis) reported, particularly in patients receiving concomitant therapy with immunosuppressive agents (e.g., methotrexate, corticosteroids).^{1 23} Infections frequently are disseminated.¹ (See Boxed Warning.)

Increased incidence of serious infections observed with concomitant use of a TNF blocking agent and anakinra or abatacept.¹ Use of adalimumab in combination with other biologic DMARDs, including abatacept and anakinra, not recommended.¹

Patients >65 years of age, with comorbid conditions, and/or receiving concomitant therapy with immunosuppressive agents (e.g., corticosteroids, methotrexate) may be at increased risk of infection.^{1 23}

Do not initiate adalimumab in patients with active infections, including localized infections.¹ Consider potential risks and benefits of the drug prior to initiating therapy in patients with a history of chronic, recurring, or opportunistic infections; patients with underlying conditions that may predispose them to infections; and patients who have been exposed to tuberculosis or who have resided or traveled in regions where tuberculosis or mycoses such as histoplasmosis, coccidioidomycosis, and blastomycosis are endemic.^{1 23}

Closely monitor patients during and after adalimumab therapy for signs or symptoms of infection, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis prior to initiating therapy.^{1 23}

If new infection occurs during therapy, perform thorough diagnostic evaluation (appropriate for immunocompromised patient), initiate appropriate anti-infective therapy, and closely monitor patient.¹ Discontinue adalimumab if serious infection or sepsis develops.¹

Evaluate all patients for active or latent tuberculosis and for risk factors for tuberculosis prior to and periodically during therapy.^{1 23} When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to adalimumab therapy.¹ Also consider antimycobacterial therapy prior to adalimumab therapy for individuals with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed and for individuals with a negative tuberculin skin test who have risk factors for tuberculosis.¹ Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.¹

Monitor all patients, including those with negative tuberculin skin tests, for active tuberculosis.¹ Strongly consider tuberculosis in patients who develop new infections while receiving adalimumab, especially if they previously have traveled to countries where tuberculosis is highly prevalent or have been in close contact with an individual with active tuberculosis.¹

Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.^{1 23} Whenever feasible, consider consulting a specialist in invasive fungal infections.¹

Malignancies

Cases of lymphoma and other malignancies (some fatal) reported in children, adolescents, and adults receiving TNF blocking agents; most patients received other immunosuppressive agents concomitantly.¹ Malignancies included lymphomas and various other malignancies (e.g., leukemia, melanoma, solid organ cancers).¹ (See Boxed Warning.)

Consider possibility of and monitor for occurrence of malignancies during and following treatment with TNF blocking agents.²⁴

Consider risks and benefits of TNF blocking agents prior to initiating therapy in patients with a known malignancy (other than successfully treated nonmelanoma skin cancer) or when deciding whether to continue therapy in patients who develop a malignancy.¹ Carefully consider risks and benefits of these agents, especially in adolescents and young adults and especially in the treatment of Crohn disease or ulcerative colitis.^{1 24}

Examine all patients, but particularly those with a history of prior prolonged immunosuppressive therapy or a history of psoralen and UVA light (PUVA) therapy, for nonmelanoma skin cancer before and during adalimumab therapy.¹

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis, angioedema, and other allergic reactions (e.g., allergic rash, anaphylactoid reactions, fixed drug reaction, nonspecified drug reaction, urticaria) observed.¹ If serious allergic reaction or anaphylaxis occurs, immediately discontinue adalimumab and initiate appropriate therapy.¹

Latex Sensitivity

Needle covers of certain packaging configurations of reference product adalimumab (injection pen and prefilled syringes containing 40 mg in 0.8 mL) may contain dry natural rubber (latex) and should not be handled by individuals sensitive to latex.¹

Needle caps of adalimumab-adbm (Cyltezo) injection pens and prefilled syringes also contain natural rubber latex.²⁵⁰²

Other Warnings/Precautions

HBV Reactivation

Increased risk of reactivation of HBV infection in patients who are chronic carriers of the virus (i.e., hepatitis B surface antigen-positive [HBsAg-positive]).¹ Use of multiple immunosuppressive agents may contribute to HBV reactivation.¹

Screen at-risk patients prior to initiation of therapy.¹ Evaluate and monitor HBV carriers before, during, and for up to several months after therapy.¹ Safety and efficacy of antiviral therapy for prevention of HBV reactivation not established.¹

Discontinue adalimumab and initiate appropriate treatment (e.g., antiviral therapy) if HBV reactivation occurs.¹ Not known whether adalimumab can be readministered once control of a reactivated HBV infection is achieved; caution advised in this situation.¹

Neurologic Reactions

New onset or exacerbation of central or peripheral nervous system demyelinating disorders (e.g., multiple sclerosis, optic neuritis, Guillain-Barré syndrome) reported rarely in patients receiving adalimumab or other TNF blocking agents.¹

Exercise caution when considering adalimumab therapy in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.¹ Consider discontinuing adalimumab if any such disorders develop during therapy.¹

Intermediate uveitis is known to be associated with central demyelinating disorders.¹

Hematological Reactions

Possible pancytopenia (including aplastic anemia), leukopenia, or thrombocytopenia.¹ Consider discontinuance in patients with confirmed hematologic abnormalities.¹

Heart Failure

Worsening heart failure and new-onset heart failure reported in patients receiving adalimumab or other TNF blocking agents.¹ Use with caution and carefully monitor patients with heart failure.¹

Autoimmunity

Possible formation of autoimmune antibodies.¹ Lupus-like syndrome reported.¹ If manifestations suggestive of lupus-like syndrome develop, discontinue adalimumab.¹

Immunogenicity

Antibodies to adalimumab may develop.¹ Long-term immunogenicity remains to be determined.¹

In adults with rheumatoid arthritis, incidence of antibodies to adalimumab is lower in patients receiving adalimumab with methotrexate compared with those receiving adalimumab monotherapy.¹ Incidence also may be lower with weekly compared with every-other-week monotherapy.¹ In patients receiving every-other-week monotherapy, clinical response achieved in fewer antibody-positive patients than antibody-negative patients.¹

In pediatric patients with juvenile idiopathic arthritis, incidence of antibodies to adalimumab is lower in those receiving adalimumab with methotrexate compared with those receiving adalimumab monotherapy.^{1 20}

In adults with noninfectious uveitis, no association observed between antibody development and adalimumab safety or efficacy.¹

In pediatric patients with ulcerative colitis, development of antibodies to adalimumab associated with reduced serum adalimumab concentrations; no association between antibody development and adalimumab safety observed.¹ Association between antibody development and efficacy not assessed.¹

In patients with hidradenitis suppurativa, development of antibodies to adalimumab associated with reduced serum adalimumab concentrations (magnitude of reduction generally greater with increasing antibody titers); no apparent association between antibody development and adalimumab safety.¹

Immunization

Patients may receive inactivated vaccines.¹ No data available on secondary transmission of infection by live vaccines in adalimumab-treated patients.¹ Avoid live vaccines.¹

When considering adalimumab for pediatric patients, review vaccination status of child and administer all age-appropriate vaccines included in current immunization guidelines.¹

In utero exposure to adalimumab may affect immune response of infants.¹ Consider risks and benefits of administering live vaccines to infants exposed to the drug in utero; safety of live vaccines in such infants is unknown.¹

Specific Populations

Pregnancy

Available studies do not reliably establish an association between adalimumab and major birth defects.¹ In a pregnancy registry cohort study, a higher incidence of major birth defects observed in females exposed to adalimumab; however, methodologic limitations preclude definitive conclusions.^{1 38}

No fetal harm or malformations observed in animal studies.¹

Data suggest increased disease activity in females with rheumatoid arthritis or inflammatory bowel disease is associated with increased risk of adverse pregnancy outcomes (e.g., preterm delivery, low birth weight, small size for gestational age at birth).^{1 38}

As pregnancy progresses, monoclonal antibodies are increasingly transported across the placenta.¹ Adalimumab is actively transferred across the placenta during the third trimester of pregnancy.¹ Some data suggest adalimumab may be detectable in serum of infants exposed to the drug in utero for ≥3 months following birth.¹

In utero exposure to adalimumab may affect immune response of infants.¹ Consider risks and benefits of administering live vaccines to infants exposed to the drug in utero; safety of live vaccines in such infants is unknown.¹

Lactation

Distributes into human milk in small amounts (0.1–1% of maternal serum concentrations); systemic exposure in nursing infants is likely to be low because drug is degraded in GI tract.^{1 34} However, effects of local GI tract exposure are unknown.¹ No reports of adverse effects on breast-fed infants or effects on milk production.^{1 34}

Consider developmental and health benefits of breast-feeding along with the mother's clinical need for adalimumab and any potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition.¹

Pediatric Use

Safety and efficacy for uses other than polyarticular juvenile idiopathic arthritis, Crohn disease, ulcerative colitis, and noninfectious uveitis not established in pediatric patients.¹ Clinical trials in adults support use for management of hidradenitis suppurativa in adolescents.¹ For marketing exclusivity reasons, adalimumab biosimilars are not labeled for use in pediatric patients with ulcerative colitis, hidradenitis suppurativa, or noninfectious uveitis.^{2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Review vaccination status of the child and administer all age-appropriate vaccines, if possible, prior to initiation of adalimumab.¹

Geriatric Use

In geriatric patients with rheumatoid arthritis, no substantial differences in efficacy relative to younger adults.¹

The incidence of serious infection and malignancy in adalimumab-treated patients >65 years of age is higher than the incidence in younger adults.¹ The overall incidence of infection and malignancy is higher in the geriatric population than in younger adults; consider risks and benefits of adalimumab in geriatric patients and closely monitor for development of infection or malignancy.¹

Hepatic Impairment

No pharmacokinetic data available.¹

Renal Impairment

No pharmacokinetic data available.¹

Common Adverse Effects

Common adverse effects (≥10%) include infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, rash.¹

Drug Interactions

Administered concomitantly with aminosalicylates, methotrexate, other DMARDs, corticosteroids, other immunomodulatory agents (e.g., azathioprine, mercaptopurine), and/or NSAIAs in clinical studies.¹

Drugs Metabolized by Hepatic Microsomal Enzymes

Because increased levels of TNF during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF activity by adalimumab may normalize formation of CYP enzymes.¹

Drugs metabolized by CYP isoenzymes that have a low therapeutic index: Monitor therapeutic effect and/or serum concentrations following initiation or discontinuance of adalimumab; adjust dosage as needed.¹

Biologic Antirheumatic Agents

For other biologic agents used in the management of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn disease, ulcerative colitis, plaque psoriasis, noninfectious uveitis, or hidradenitis suppurativa, manufacturer states data regarding concomitant use with adalimumab are insufficient.¹

Concomitant use of adalimumab and other biologic DMARDs not recommended.¹

Vaccines

Patients may receive inactivated vaccines.¹

Avoid live vaccines.¹ No data available on secondary transmission of infection by live vaccines in adalimumab-treated patients.¹

Specific Drugs

Adalimumab Pharmacokinetics

Absorption

Bioavailability

Bioavailability is approximately 64%.¹ Peak serum concentrations achieved in 131 hours.¹

Distribution

Extent

Distributed into synovial fluid.¹

Distributed into human milk in small amounts.^{1 34} Crosses placenta.¹

Elimination

Metabolism

Metabolic fate undetermined.¹

Elimination Route

Unknown.¹

Half-life

2 weeks (range: 10–20 days).¹

Special Populations

In patients with adalimumab antibodies, clearance of adalimumab is higher.¹

Clearance of adalimumab is lower with increasing age in patients 40 to >75 years of age.¹

Stability

Storage

Parenteral

Injection

2–8°C.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Do not freeze; do not use solutions that have been frozen.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540} Protect from light; store in original carton until time of administration.^{1 2500 2501 2502 2503 2504 2505 2506 2507 2508 2540}

Adalimumab, adalimumab-adbm, adalimumab-aqvh, adalimumab-atto, adalimumab-bwwd, adalimumab-fkjp, and adalimumab-ryvk: If necessary (e.g., during travel), may store at room temperature up to 25°C, protected from light, for a period of up to 14 days; discard if not used within 14 days.^{1 2500 2502 2503 2504 2508 2540}

Adalimumab-aacf: If necessary (e.g., during travel), may store at room temperature up to 25°C, protected from light, for a period of up to 28 days; discard if not used within 28 days.²⁵⁰⁶

Adalimumab-afzb: If necessary (e.g., during travel), may store at room temperature up to 30°C, protected from light, for a period of up to 30 days; discard if not used within 30 days.²⁵⁰¹

Adalimumab-aaty: If necessary (e.g., during travel), may be stored at room temperature up to 25°C, protected from light, for a period of up to 31 days; discard if not used within 31 days.²⁵⁰⁷

Adalimumab-adaz: If necessary (e.g., during travel), the 10 mg/0.2 mL prefilled syringe, 20 mg/0.4 mL prefilled syringe, 40 mg/0.8 mL prefilled syringe, and 40 mg/0.8 mL prefilled pen may be stored at room temperature up to 25°C, protected from light, for a period of up to 21 days (discard if not used within 21 days); the 10 mg/0.1 mL prefilled syringe, 20 mg/0.2 mL prefilled syringe, 40 mg/0.4 mL prefilled syringe, 80 mg/0.8 mL prefilled syringe, 40 mg/0.4 mL prefilled pen, and 80 mg/0.8 mL prefilled pen may be stored at room temperature up to 25°C, protected from light, for a period of up to 14 days (discard if not used within 14 days).²⁵⁰⁵

Actions

• Potent antagonist of TNF biologic activity.^{1 3 8}

• Has high specificity and affinity for TNF (TNF-α); does not bind to or inactivate lymphotoxin α (TNF-β).^{1 3 8} Prevents the binding of TNF to cell surface TNF receptors, thereby blocking the biologic activity of TNF.^{1 3 8}

• Produced by recombinant DNA technology in a mammalian cell expression system; purified by a process that includes specific viral inactivation and removal steps.¹

Advice to Patients

• Advise patients to read the manufacturer’s patient information (medication guide) prior to initiation of therapy and each time the prescription is refilled.^{1 23 24}

• Instruct patients and/or caregivers regarding proper dosage and administration of adalimumab, including the use of aseptic technique, and proper disposal of needles, syringes, and used pens if it is determined that the patient and/or caregiver is competent to safely administer the drug.¹

• Advise patients that if a dose is missed, the missed dose should be administered as soon as it is remembered and then the regular dosing schedule should be resumed.¹

• Increased susceptibility to infection.¹ Advise patients to seek immediate medical attention if signs and symptoms suggestive of infection (e.g., fever; fatigue; cough; warm, red, or painful skin; sores on the body; muscle aches; diarrhea; stomach pain; shortness of breath; weight loss; burning on urination; urinary frequency) develop.¹

• Risk of lymphoma, including hepatosplenic T-cell lymphoma, leukemia, or other malignancies with use of TNF blocking agents.^{1 24} Counsel patients about the risk of malignancy with adalimumab.¹ Advise patients to inform clinicians if signs and symptoms of malignancies (e.g., unexplained weight loss; fatigue; abdominal pain; persistent fever; night sweats; easy bruising or bleeding; swollen lymph nodes in the neck, underarm, or groin; hepatomegaly or splenomegaly) occur.²⁴

• Advise patients to inform clinicians of any new or worsening medical conditions (e.g., neurologic conditions, heart failure, autoimmune disorders, psoriasis, cytopenias).¹ Advise patients to report symptoms suggestive of cytopenias (e.g., bruising, bleeding, persistent fever).¹

• Advise patients to alert their clinician if allergy to latex exists.^{1 2502} Advise latex-sensitive patients that the needle cover or cap included in adalimumab-adbm (Cyltezo) and certain packaging configurations of reference product adalimumab (injection pens and prefilled syringes containing 40 mg in 0.8 mL) may contain natural rubber latex.^{1 2502}

• Advise patients to promptly contact a clinician if manifestations of an allergic reaction (e.g., urticaria, facial swelling, difficulty breathing) occur.¹

• Advise patients to take the drug as prescribed and to not discontinue therapy without first consulting with a clinician.²⁴

• Advise females to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or any history of cancer, tuberculosis, HBV infection, or other chronic or recurring infections.^{1 23}

• Inform patients of other important precautionary information.¹

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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