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Adalimumab

Class: Disease-modifying Antirheumatic Drugs
- DMARDs
ATC Class: L04AA17
VA Class: MS190
Chemical Name: Immunoglobulin G1, anti-(human tumor necrosis factor) (human monoclonal D2E7 heavy chain), disulfide with human monoclonal D2E7 light chain, dimer
CAS Number: 331731-18-1.
Brands: Humira

Medically reviewed by Drugs.com. Last updated on Jan 4, 2021.

Warning

    Serious Infections
  • Increased risk of serious infections involving various organ systems and sites that may require hospitalization or result in death; tuberculosis (frequently disseminated or extrapulmonary), invasive fungal infections (may be disseminated), bacterial (e.g., legionellosis, listeriosis) and viral infections, and other opportunistic infections reported. (See Infectious Complications under Cautions.)

  • Carefully consider risks and benefits prior to initiating adalimumab therapy in patients with chronic or recurring infections.

  • Evaluate patients for latent tuberculosis infection prior to and periodically during adalimumab therapy; if indicated, initiate appropriate antimycobacterial regimen prior to initiating adalimumab therapy.

  • Closely monitor patients for infection, including active tuberculosis in those with a negative tuberculin skin test, during and after treatment. Discontinue adalimumab if serious infection or sepsis occurs. Consider empiric antifungal therapy if serious systemic illness occurs in a patient at risk for invasive fungal infections.

    Malignancy
  • Lymphoma and other malignancies (some fatal) reported in children and adolescents receiving TNF blocking agents. (See Malignancies and Lymphoproliferative Disorders under Cautions.)

  • Aggressive, usually fatal hepatosplenic T-cell lymphoma reported mainly in adolescents and young adults with Crohn’s disease or ulcerative colitis receiving TNF blocking agents, including adalimumab. Most of the patients received a combination of immunosuppressive agents, including TNF blocking agents and thiopurine analogs (azathioprine or mercaptopurine).

Introduction

Biologic response modifier and disease-modifying antirheumatic drug (DMARD); a recombinant DNA-derived human immunoglobulin G1 (IgG1) monoclonal antibody specific for human tumor necrosis factor (TNF; TNF-α).

Uses for Adalimumab

Rheumatoid Arthritis in Adults

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 associated with the disease in adults with moderate to severe active rheumatoid arthritis. Use alone or in combination with methotrexate or other nonbiologic DMARDs.

Juvenile Arthritis

Management of the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in pediatric patients ≥2 years of age. Use with or without methotrexate.

Psoriatic Arthritis

Used to manage the signs and symptoms of psoriatic arthritis, to improve physical function, and to inhibit progression of structural damage associated with the disease in adults with active psoriatic arthritis. Use alone or in combination with other nonbiologic DMARDs.

Ankylosing Spondylitis

Management of the signs and symptoms of active ankylosing spondylitis.

Crohn’s Disease

Used to reduce signs and symptoms of Crohn’s disease and to induce and maintain clinical remission in adults with moderately to severely active disease who have had an inadequate response to conventional therapy. Also used to reduce signs and symptoms of the disease and to induce clinical remission in adults with moderately to severely active Crohn’s disease who have lost response to or are intolerant to infliximab.

Used to reduce signs and symptoms of Crohn’s disease and to induce and maintain clinical remission in pediatric patients ≥6 years of age with moderately to severely active disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, mercaptopurine, or methotrexate.

Ulcerative Colitis

Used to induce and sustain clinical remission in adults with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressive agents such as corticosteroids, azathioprine, or mercaptopurine.

Efficacy in patients who have lost response to or were intolerant to TNF blocking agents not established.

Plaque Psoriasis

Management of 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. Use only in patients who will be closely monitored and who will have regular follow-up visits with a clinician.

Uveitis

Management of noninfectious intermediate uveitis, posterior uveitis, and panuveitis in adults and pediatric patients ≥2 years of age.

Hidradenitis Suppurativa

Management of moderate to severe hidradenitis suppurativa in adults and pediatric patients ≥12 years of age.

Adalimumab Dosage and Administration

General

Concomitant Therapy

  • Methotrexate, other nonbiologic DMARDs, corticosteroids, NSAIAs, and/or analgesics may be continued in adults with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.

  • Methotrexate, corticosteroids, NSAIAs, and/or analgesics may be continued in pediatric patients with juvenile idiopathic arthritis.

  • Aminosalicylates and/or corticosteroids may be continued in adults with Crohn’s disease or ulcerative colitis. Azathioprine, mercaptopurine, or methotrexate may be continued, if necessary, in adults with Crohn’s disease. Azathioprine and mercaptopurine may be continued, if necessary, in adults with ulcerative colitis. (See Malignancies and Lymphoproliferative Disorders under Cautions.)

Administration

Sub-Q Injection

Available in prefilled syringes, prefilled injection pens, and vials; all are preservative free for single use only. Vials are for institutional use only; use promptly after withdrawing solution from vial. Various packaging configurations of the prefilled syringes and prefilled injection pens are available, including single- or multiple-strength starter packages.

Administer by sub-Q injection every other week or every week.

Adalimumab injection may sit at room temperature for 15–30 minutes prior to administration; do not remove the syringe needle cover or injection pen cap while the drug is warming to room temperature.

Administer sub-Q injections into anterior thighs or abdomen; do not make abdominal injections within 5.18 cm (2 inches) of the umbilicus. Rotate injection sites. Give new injections ≥2.54 cm (1 inch) from an old site; do not make injections into areas where the skin is tender, bruised, red, or hard, or into scars or stretch marks. Do not inject into psoriatic lesions.

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. The initial self-administered dose should be made under the supervision of a health-care professional.

Dosage

Pediatric Patients

Juvenile Arthritis
Sub-Q

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

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

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

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

Crohn’s 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). Start maintenance dosage of 20 mg once every other week on day 29 (2 weeks after the 40-mg dose).

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). Start maintenance dosage of 40 mg once every other week on day 29 (2 weeks after the 80-mg dose).

Uveitis
Sub-Q

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

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

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

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

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.

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). Start dosage of 40 mg once every week on day 29 (2 weeks after the 80-mg dose).

Adults

Rheumatoid Arthritis
Sub-Q

40 mg once every other week.

Patients not receiving methotrexate may obtain additional benefit from once weekly doses of 40 mg.

Psoriatic Arthritis
Sub-Q

40 mg once every other week.

Ankylosing Spondylitis
Sub-Q

40 mg once every other week.

Crohn’s 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). Start maintenance dosage of 40 mg once every other week on day 29 (2 weeks after the 80-mg dose).

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). Start maintenance dosage of 40 mg once every other week on day 29 (2 weeks after the 80-mg dose). If clinical remission is not achieved by 8 weeks (day 57), discontinue adalimumab.

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.

Uveitis
Sub-Q

80 mg on day 1, followed by 40 mg once every other week starting 1 week after the initial dose.

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). Start dosage of 40 mg once every week on day 29 (2 weeks after the 80-mg dose).

Prescribing Limits

Adults

Crohn’s Disease

Manufacturer states safety and efficacy of continuing adalimumab beyond 1 year have not been evaluated in clinical studies.

Plaque Psoriasis

Manufacturer states safety and efficacy of continuing adalimumab beyond 1 year have not been evaluated in clinical studies.

Cautions for Adalimumab

Contraindications

  • Known hypersensitivity to adalimumab or any ingredient in the formulation.

Warnings/Precautions

Warnings

Infectious Complications

Increased risk of serious infections involving various organ systems and sites that may require hospitalization or result in death. 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). Infections frequently are disseminated. (See Boxed Warning.)

Increased incidence of serious infections observed with concomitant use of a TNF blocking agent and anakinra or abatacept. (See Specific Drugs under Interactions.)

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.

Do not initiate adalimumab in patients with active infections, including localized infections. 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.

Closely monitor patients during and after adalimumab therapy for signs or symptoms of infection (e.g., fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates, serious systemic illness including shock).

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

Evaluate all patients for active or latent tuberculosis and for risk factors for tuberculosis prior to and periodically during therapy. When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to adalimumab therapy. 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. Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.

Monitor all patients, including those with negative tuberculin skin tests, for active tuberculosis. 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.

Failure to recognize invasive fungal infections has led to delays in appropriate treatment. Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness. Whenever feasible, consult specialist in fungal infections when making decisions regarding initiation and duration of antifungal therapy.

When deciding whether to reinitiate TNF blocking agent therapy following resolution of an invasive fungal infection, reevaluate risks and benefits, particularly in patients who reside in regions where mycoses are endemic. Whenever feasible, consult specialist in fungal infections.

Malignancies and Lymphoproliferative Disorders

Lymphoma and other malignancies (some fatal) reported during postmarketing surveillance in children and adolescents receiving TNF blocking agents, particularly in those receiving other immunosuppressive agents (e.g., azathioprine, methotrexate) concomitantly. Malignancies included lymphomas (about 50% of the cases) (e.g., Hodgkin’s disease, non-Hodgkin’s lymphoma) and various other malignancies (e.g., leukemia, melanoma, solid organ cancers), including rare malignancies usually associated with immunosuppression and malignancies not usually observed in children and adolescents (e.g., leiomyosarcoma, hepatic malignancies, renal cell carcinoma). Median time to occurrence was 30 months (range: 1–84 months) after the initial TNF blocking agent dose. FDA has concluded that there is an increased risk of malignancy with TNF blocking agents in children and adolescents; however, the strength of the association is not fully characterized.

Hepatosplenic T-cell lymphoma (a rare, aggressive, usually fatal T-cell lymphoma) reported mainly in adolescents and young adults with Crohn’s disease or ulcerative colitis receiving TNF blocking agents and/or thiopurine analogs (mercaptopurine or azathioprine). Most of the patients received a combination of immunosuppressive agents, including TNF blocking agents and thiopurine analogs. Unclear whether occurrence is related to use of a TNF blocking agent or use of a TNF blocking agent in conjunction with other immunosuppressive agents.

In controlled studies, lymphoma was reported more frequently in patients receiving adalimumab or other TNF blocking agents than in control patients. Patients with Crohn’s disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, or other chronic inflammatory diseases, especially those with highly active disease and/or chronic exposure to immunosuppressive therapies, may be at increased risk of lymphoma, even in the absence of TNF blocking agent therapy; may be difficult to measure added risk of TNF blocking agents, azathioprine, and/or mercaptopurine.

Acute and chronic leukemias (some fatal) reported during postmarketing surveillance of TNF blocking agents in adults and pediatric patients, particularly in those receiving other immunosuppressive agents concomitantly. Leukemia (most commonly acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia) generally occurred during first 2 years of therapy. FDA has concluded that there is a possible association between TNF blocking agents and development of leukemia; interpretation of findings is complicated because patients with rheumatoid arthritis may be at increased risk for leukemia independent of any treatment with TNF blocking agents.

Other malignancies (e.g., breast, colorectal, lung, prostate, melanoma, nonmelanoma skin cancer) have occurred in patients receiving adalimumab.

In controlled studies of other TNF blocking agents in adults at increased risk of malignancies (e.g., patients with COPD and a history of heavy smoking, patients with Wegener’s granulomatosis receiving concomitant cyclophosphamide), a greater proportion of malignancies occurred in patients receiving the TNF blocking agent compared with control patients.

Some immune-related diseases (e.g., Crohn’s disease) have been shown to increase risk of cancer independent of treatment with TNF blocking agents, while for others (e.g., juvenile idiopathic arthritis) it is unknown whether there is an increased risk of cancer.

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

Consider risks and benefits of TNF blocking agents, including adalimumab, 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. Carefully consider risks and benefits of these agents, especially in adolescents and young adults and especially in the treatment of Crohn’s disease or ulcerative colitis.

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.

Sensitivity Reactions

Hypersensitivity Reactions

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

Latex Sensitivity

In certain packaging configurations (injection pen containing 40 mg in 0.8 mL; prefilled syringes containing 40 mg in 0.8 mL, 20 mg in 0.4 mL, or 10 mg in 0.2 mL), the needle cover may contain dry natural rubber (latex) and should not be handled by individuals sensitive to latex.

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]). Use of multiple immunosuppressive agents may contribute to HBV reactivation.

Screen at-risk patients prior to initiation of therapy. Evaluate and monitor HBV carriers before, during, and for up to several months after therapy. Safety and efficacy of antiviral therapy for prevention of HBV reactivation not established. Discontinue adalimumab and initiate appropriate treatment (e.g., antiviral therapy) if HBV reactivation occurs. Not known whether adalimumab can be readministered once control of a reactivated HBV infection is achieved; caution advised in this situation.

Nervous System Effects

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.

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

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

Hematologic Effects

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

Cardiovascular Effects

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

Immunologic Reactions and Antibody Formation

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

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

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

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.

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

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.

Immunization

Patients may receive inactivated vaccines. Avoid live vaccines (e.g., measles virus vaccine live, mumps virus vaccine live, rubella virus vaccine live, smallpox vaccine, typhoid vaccine live oral, varicella virus vaccine live, yellow fever vaccine). (See Interactions.)

Psoriasis

New-onset psoriasis, including pustular and palmoplantar psoriasis, and exacerbation of existing psoriasis reported with TNF blocking agents, including adalimumab. Most patients experienced improvement following discontinuance of the TNF blocking agent.

Consider possibility of and monitor for manifestations (e.g., new rash) of new or worsening psoriasis, particularly pustular and palmoplantar psoriasis.

Hepatic Effects

Severe hepatic reactions, including acute liver failure, reported in patients receiving TNF blocking agents. Serum ALT elevations of ≥3 times the ULN observed in patients receiving adalimumab; causal relationship not clear because many patients received concomitant therapy with drugs known to increase liver enzyme concentrations (e.g., methotrexate, NSAIAs).

Specific Populations

Pregnancy

Available studies do not reliably establish an association between adalimumab and major birth defects. A prospective, controlled, observational, pregnancy registry cohort study indicated that 10% of adalimumab-exposed women (8.7% of those with rheumatoid arthritis, 10.5% of those with Crohn’s disease) delivered a live-born infant with a major birth defect, compared with 7.5% of disease-matched women not exposed to the drug (6.8% of those with rheumatoid arthritis, 9.4% of those with Crohn’s disease); however, no pattern of major birth defects was observed, and differences in the cohorts may have affected the observed occurrence rates. Methodologic limitations (e.g., small sample size, voluntary nature of the study, nonrandomized design) preclude definitive conclusions regarding risk of major birth defects.

No fetal harm or malformations observed in animal studies.

Data suggest increased disease activity in women 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).

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

In utero exposure to adalimumab may affect immune response of infants. 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.

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. However, effects of local GI tract exposure are unknown. No reports of adverse effects on breast-fed infants or effects on milk production.

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.

Pediatric Use

Safety and efficacy for uses other than polyarticular juvenile idiopathic arthritis, Crohn’s disease, and noninfectious uveitis not established in pediatric patients. Clinical trials in adults support use for management of hidradenitis suppurativa in adolescents.

Use for management of polyarticular juvenile idiopathic arthritis in pediatric patients ≥2 years of age supported by a safety and efficacy study in pediatric patients 4–17 years of age and a safety study in children 2 to <4 years of age; adverse effects generally similar to those observed in adults. Safety and efficacy for this indication not established in pediatric patients <2 years of age or weighing <10 kg.

Use for management of Crohn’s disease in pediatric patients ≥6 years of age supported by adequate, well-controlled studies in adults and a randomized, double-blind, clinical study of 2 adalimumab dosages in 192 pediatric patients 6–17 years of age. Safety and efficacy for this indication not established in pediatric patients <6 years of age.

Use for management of noninfectious uveitis in pediatric patients ≥2 years of age supported by adequate, well-controlled studies in adults and a randomized controlled study in 90 pediatric patients. Safety and efficacy for this indication not established in pediatric patients <2 years of age.

Use for management of hidradenitis suppurativa in adolescents ≥12 years of age supported by adequate, well-controlled studies in adults. Similarity of the disease course allows extrapolation of data from adults to adolescents. Population pharmacokinetic modeling and simulation data suggest exposure resulting from weight-based dosing in adolescents is generally similar to exposure in adults. Safety and efficacy for this indication not established in pediatric patients <12 years of age.

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

Malignancies, some fatal, reported in children and adolescents who received TNF blocking agents, including adalimumab. (See Malignancies and Lymphoproliferative Disorders under Cautions.)

Neonates and infants exposed to adalimumab in utero may have impaired immune responses. Adalimumab crosses the placenta; clinical importance of elevated concentrations in infants is unknown. Consider risks and benefits of administering live vaccines to infants exposed to adalimumab in utero; safety of live vaccines in these infants is unknown.

Geriatric Use

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

The incidence of serious infection and malignancy in adalimumab-treated patients >65 years of age is higher than the incidence in younger adults. The overall incidence of infection and malignancy is higher in the geriatric population in general than in younger adults; use with caution.

Common Adverse Effects

Adults: Infection (e.g., upper respiratory tract infection, sinusitis), injection site reactions, headache, rash.

Pediatric patients 4–17 years of age: Infection, injection site pain, injection site reaction, hypersensitivity reaction (e.g., localized allergic sensitivity reaction, rash), increased CPK concentration. Similar safety profile observed in children 2 to <4 years of age.

Interactions for Adalimumab

Administered concomitantly with aminosalicylates, methotrexate, other DMARDs, corticosteroids, other immunomodulatory agents (e.g., azathioprine, mercaptopurine), and/or NSAIAs in clinical studies. (See Concomitant Therapy under Dosage and Administration.)

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.

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.

Biologic Antirheumatic Agents

For abatacept, anakinra, rituximab, and tocilizumab, see Specific Drugs under Interactions. For other biologic agents used in the management of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, noninfectious uveitis, or hidradenitis suppurativa, manufacturer states data regarding concomitant use with adalimumab are insufficient.

Concomitant use of adalimumab and other biologic DMARDs not recommended.

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase the risk of infection.

Vaccines

Patients may receive inactivated vaccines.

Avoid live vaccines. (See also Pediatric Use under Cautions.) No data available on secondary transmission of infection by live vaccines in adalimumab-treated patients.

Specific Drugs

Drug

Interaction

Comments

Abatacept

Increased incidence of infection and serious infection, without additional clinical benefit, reported with abatacept and TNF blocking agents in rheumatoid arthritis

Concomitant use not recommended

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection

Anakinra

Increased incidence of serious infections and neutropenia, without additional clinical benefit, reported with anakinra and etanercept (another TNF blocking agent) in rheumatoid arthritis

Concomitant use not recommended

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection

Cyclosporine

Possible effect on cyclosporine metabolism; 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

Monitor therapeutic effect and concentrations of cyclosporine following initiation or discontinuance of adalimumab; adjust dosage as needed

Influenza virus vaccine inactivated

Antibody titers in adalimumab-treated rheumatoid arthritis patients were protective, albeit lower than in placebo-treated patients

Methotrexate

Decreased adalimumab clearance

Dosage adjustment not necessary

Natalizumab

Increased risk of progressive multifocal leukoencephalopathy (PML) or other serious infections

Avoid concomitant use in the management of Crohn’s disease

Pneumococcal polysaccharide vaccine

No difference in antibody response between adalimumab- and placebo-treated rheumatoid arthritis patients

Rituximab

Increased risk of serious infection reported in patients who received rituximab and subsequently received a TNF blocking agent

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection

Theophylline

Possible effect on theophylline metabolism; 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

Monitor therapeutic effect and serum concentrations of theophylline following initiation or discontinuance of adalimumab; adjust dosage as needed

TNF blocking agents

Concomitant use not recommended

Tocilizumab

Concomitant use not studied; possibility of increased immunosuppression and increased risk of infection

Avoid concomitant use

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection

Warfarin

Possible effect on warfarin metabolism; 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

Monitor therapeutic effect of warfarin following initiation or discontinuance of adalimumab; adjust dosage as needed

Adalimumab Pharmacokinetics

Absorption

Bioavailability

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

Distribution

Extent

Distributed into synovial fluid.

Distributed into milk in small amounts. Crosses placenta.

Elimination

Metabolism

Metabolic fate undetermined.

Elimination Route

Unknown.

Half-life

2 weeks (range: 10–20 days).

Special Populations

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

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

Stability

Storage

Parenteral

Injection

2–8°C. Do not freeze; do not use solutions that have been frozen. Protect from light; store in original carton until time of administration.

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.

Actions

  • Potent antagonist of TNF biologic activity.

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

  • An immunoglobulin G1 (IgG1) made by phage display technology with amino acid sequences from the human germline; does not contain nonhuman components or artificially fused human peptide sequences. Indistinguishable in structure and function from naturally occurring human IgG.

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

Advice to Patients

  • Importance of patients reading the manufacturer’s patient information (medication guide) prior to initiation of therapy and each time the prescription is refilled.

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

  • 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.

  • Increased susceptibility to infection. Importance of seeking 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.

  • Risk of lymphoma, including hepatosplenic T-cell lymphoma, leukemia, or other malignancies with use of TNF blocking agents. Importance of informing patients and caregivers about the increased risk of cancer development in children, adolescents, and young adults, taking into account the clinical utility of TNF blocking agents, the relative risks and benefits of these and other immunosuppressive drugs, and the risks associated with untreated disease. Importance of promptly informing 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.

  • Importance of informing clinician of any new or worsening medical conditions (e.g., neurologic conditions [e.g., demyelinating disorders], heart failure, autoimmune disorders [e.g., lupus-like syndrome], psoriasis, cytopenias).

  • Importance of alerting clinician if allergy to latex exists. Advise latex-sensitive patients that the needle cover included in certain packaging configurations of adalimumab (injection pen containing 40 mg in 0.8 mL; prefilled syringes containing 40 mg in 0.8 mL, 20 mg in 0.4 mL, or 10 mg in 0.2 mL) may contain natural rubber latex.

  • Importance of promptly contacting a clinician if manifestations of an allergic reaction (e.g., urticaria, facial swelling, difficulty breathing) occur.

  • Importance of taking the drug as prescribed and of not altering or discontinuing therapy without first consulting with a clinician.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing 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.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

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.

Adalimumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

10 mg/0.1 mL

Humira (available as disposable prefilled syringes with alcohol swabs)

AbbVie

10 mg/0.2 mL

Humira (available as disposable prefilled syringes with alcohol swabs)

AbbVie

20 mg/0.2 mL

Humira (available as disposable prefilled syringes with alcohol swabs)

AbbVie

20 mg/0.4 mL

Humira (available as disposable prefilled syringes with alcohol swabs)

AbbVie

40 mg/0.4 mL

Humira (available as disposable prefilled syringes and prefilled injection pens with alcohol swabs)

AbbVie

40 mg/0.8 mL

Humira (available as disposable prefilled syringes and prefilled injection pens with alcohol swabs, and as single-use vials)

AbbVie

80 mg/0.8 mL

Humira (available as disposable prefilled syringes and prefilled injection pens with alcohol swabs)

AbbVie

AHFS DI Essentials™. © Copyright 2021, Selected Revisions January 4, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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