Adalimumab

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Pen-injector Kit, Subcutaneous [preservative free]:

Humira Pen: 40 mg/0.8 mL (1 ea); 40 mg/0.4 mL (1 ea) [contains polysorbate 80]

Humira Pen-CD/UC/HS Starter: 40 mg/0.8 mL (1 ea); 80 mg/0.8 mL (1 ea) [contains polysorbate 80]

Humira Pen-Ps/UV/Adol HS Start: 40 mg/0.8 mL (1 ea); 80 MG/0.8ML & 40MG/0.4ML (1 ea) [contains polysorbate 80]

Prefilled Syringe Kit, Subcutaneous [preservative free]:

Humira: 10 mg/0.2 mL (1 ea); 20 mg/0.4 mL (1 ea); 40 mg/0.8 mL (1 ea); 10 mg/0.1 mL (1 ea); 20 mg/0.2 mL (1 ea); 40 mg/0.4 mL (1 ea) [contains polysorbate 80]

Humira Pediatric Crohns Start: 40 mg/0.8 mL (1 ea); 80 mg/0.8 mL (1 ea); 80 MG/0.8ML & 40MG/0.4ML (1 ea) [contains polysorbate 80]

Pharmacology

Mechanism of Action

Adalimumab is a recombinant monoclonal antibody that binds to human tumor necrosis factor alpha (TNF-alpha), thereby interfering with binding to TNFα receptor sites and subsequent cytokine-driven inflammatory processes. Elevated TNF levels in the synovial fluid are involved in the pathologic pain and joint destruction in immune-mediated arthritis. Adalimumab decreases signs and symptoms of psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. It inhibits progression of structural damage of rheumatoid and psoriatic arthritis. Reduces signs and symptoms and maintains clinical remission in Crohn disease and ulcerative colitis; reduces epidermal thickness and inflammatory cell infiltration in plaque psoriasis.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 4.7 to 6 L; Synovial fluid concentrations: 31% to 96% of serum

Time to Peak

Serum: SubQ: 131 ± 56 hours

Half-Life Elimination

Terminal: ~2 weeks (range: 10 to 20 days)

Use in Specific Populations

Special Populations: Elderly

In patients with rheumatoid arthritis (RA), there was a trend toward lower clearance with increasing age in patients 40 to >75 years of age.

Use: Labeled Indications

Ankylosing spondylitis: Treatment (to reduce signs/symptoms) of active ankylosing spondylitis in adults.

Crohn disease: Treatment (to reduce signs/symptoms and to induce and maintain clinical remission) of active Crohn disease (moderate to severe) in adults and pediatric patients ≥6 years of age (Humira only) with an inadequate response to conventional therapy or who have lost response to or are intolerant to infliximab.

Hidradenitis suppurativa (Humira only): Treatment of moderate to severe hidradenitis suppurativa in adults and children ≥12 years of age.

Juvenile idiopathic arthritis: Treatment (to reduce signs/symptoms) of active polyarticular juvenile idiopathic arthritis (moderate to severe) in pediatric patients ≥2 years of age (Humira) or ≥4 years of age (Amjevita; Cyltezo); may be used alone or in combination with methotrexate.

Plaque psoriasis: Treatment of chronic plaque psoriasis (moderate to severe) in adults who are candidates for systemic therapy or phototherapy, and when other systemic therapies are less appropriate (with close monitoring and regular follow-up).

Psoriatic arthritis: Treatment (to reduce signs/symptoms, inhibit progression of structural damage, and improve physical function) of active psoriatic arthritis in adults; may be used alone or in combination with nonbiologic disease-modifying antirheumatic drugs (DMARDs).

Rheumatoid arthritis: Treatment (to reduce signs/symptoms, induce major clinical response, inhibit progression of structural damage, and improve physical function) of active rheumatoid arthritis (moderate to severe) in adults; may be used alone or in combination with methotrexate or other nonbiologic DMARDs.

Ulcerative colitis: Treatment (to induce and sustain clinical remission) of active ulcerative colitis (moderate to severe) in adults who have had an inadequate response to conventional therapy (Note: Efficacy in patients that are intolerant to or no longer responsive to other TNF blockers has not been established).

Uveitis (Humira only): Treatment of non-infectious intermediate, posterior, and panuveitis in adults and children ≥2 years of age.

Use: Off Label

Crohn disease (management after surgical resection)byes

Data from a small prospective, randomized, controlled trial and a meta-analysis support the use of adalimumab in the management of Crohn disease after surgical resection and has demonstrated adalimumab lowers endoscopic and clinical recurrence rates Savarino 2013, Singh 2015.

Based on the American Gastroenterological Association Institute Guideline on the Management of Crohn’s Disease after Surgical Resection and American College of Gastroenterology Guidelines on the Management of Crohn’s Disease in Adults, adalimumab is an effective first-line agent for prophylactic therapy in patients who are at higher risk for clinical recurrence following surgical resection.

Crohn disease (perianal/fistulizing disease)byes

Data from a randomized, placebo-controlled phase III trial support the use of adalimumab in the treatment and maintenance of long-term healing of draining fistulas in patients with Crohn disease Colombel 2009.

Based on the American College of Gastroenterology Guideline for the Management of Crohn’s Disease in Adults, adalimumab may be effective and should be considered in the management of perianal fistulas in patients with Crohn disease ACG [Lichtenstein 2018].

Pyoderma gangrenosumc

Preliminary data suggest that adalimumab could be successful as an adjunct therapy or monotherapy for the treatment of severe pyoderma gangrenosum. Adalimumab has been shown to be beneficial in refractory pyoderma gangrenosum in cases in which infliximab and etanercept have failed. Controlled studies are needed to evaluate the efficacy and safety of adalimumab in order to fully determine its place in the treatment of pyoderma gangrenosum Fonder 2006, Heffernan 2007, Hubbard 2005, Jacob 2008.

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Known hypersensitivity to adalimumab or any component of the formulation; severe infection (eg, sepsis, tuberculosis, opportunistic infection); moderate-to-severe heart failure (NYHA class III/IV)

Dosage and Administration

Dosing: Adult

Note: Amjevita (adalimumab-atto) and Cyltezo (adalimumab-adbm) are approved as biosimilar agents to Humira. Approved uses may vary (consult product labeling).

Ankylosing spondylitis: SubQ: 40 mg every other week (may continue methotrexate, other nonbiologic DMARDS, corticosteroids, NSAIDs and/or analgesics).

Crohn disease: SubQ (may continue aminosalicylates and/or corticosteroids; if necessary, azathioprine or mercaptopurine may also be continued):

Initial: 160 mg (given on day 1 or split and given over 2 consecutive days), then 80 mg 2 weeks later (day 15).

Maintenance: 40 mg every other week beginning day 29. Note: Some patients may require 40 mg every week as maintenance therapy (Lichtenstein 2018).

Crohn disease management after surgical resection (off-label use): SubQ:

Initial: 160 mg (given on day 1), then 80 mg 2 weeks later (day 15) (Savarino 2013; Singh 2015). Note: Administer first infusion within 4 weeks after surgery in high-risk patients (Lichtenstein 2018).

Maintenance: 40 mg every 2 weeks (beginning day 29) (Savarino 2013; Singh 2015).

Crohn disease (perianal/fistulizing disease) (off-label use; Colombel 2009): SubQ:

Initial: 80 mg (given on day 1), then 40 mg 2 weeks later (day 15).

Maintenance: 40 mg every week or 40 mg every other week beginning day 29.

Hidradenitis suppurativa (Humira only): SubQ:

Initial: 160 mg (given on day 1 or split and given over 2 consecutive days), then 80 mg 2 weeks later (day 15).

Maintenance: 40 mg every week beginning day 29.

Plaque psoriasis: SubQ:

Initial: 80 mg as a single dose.

Maintenance: 40 mg every other week beginning 1 week after initial dose.

Psoriatic arthritis: SubQ: 40 mg every other week (may continue methotrexate, other nonbiologic DMARDS, corticosteroids, NSAIDs and/or analgesics).

Pyoderma gangrenosum (off-label use): SubQ: 40 to 80 mg every week or every other week (Fonder 2006; Heffernan 2007; Hubbard 2005; Jacob 2008). Additional data may be necessary to further define the role of adalimumab in the treatment of this condition.

Rheumatoid arthritis: SubQ: 40 mg every other week (may continue methotrexate, other nonbiologic DMARDS, corticosteroids, NSAIDs, and/or analgesics); patients not taking concomitant methotrexate may increase dose to 40 mg every week.

Ulcerative colitis: SubQ (may continue aminosalicylates and/or corticosteroids; if necessary, azathioprine, or mercaptopurine may also be continued):

Initial: 160 mg (given on day 1 or split and given over 2 consecutive days), then 80 mg 2 weeks later (day 15).

Maintenance: 40 mg every other week beginning day 29. Note: Only continue maintenance dose in patients demonstrating clinical remission by 8 weeks (day 57) of therapy.

Uveitis (Humira only): SubQ:

Initial: 80 mg as a single dose.

Maintenance: 40 mg every other week beginning 1 week after initial dose.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Amjevita (adalimumab-atto), Cyltezo (adalimumab-adbm), and Hyrimoz (adalimumab-adaz) are approved as biosimilar agents to Humira. Approved ages and uses may vary (consult product labeling).

Crohn disease; moderate to severe; refractory: Children ≥6 years and Adolescents:

17 kg to <40 kg: SubQ: Initial: 80 mg divided into 2 injections (40 mg each) on day 1, then 40 mg administered 2 weeks later (day 15); and then on day 29, begin maintenance dose: 20 mg every other week. Patients who continue to experience flares after 12 weeks of therapy may benefit from weekly dosing (Dubinsky 2016; Hyams 2012).

≥40 kg: SubQ: Initial: 160 mg divided into 4 injections (40 mg each, administered on one day or as 2 injections per day over 2 consecutive days), then 80 mg (divided into 2 injections [40 mg each] administered on one day) 2 weeks later (day 15); and then on day 29 begin maintenance dose: 40 mg every other week. Patients who continue to experience flares after 12 weeks of therapy may benefit from weekly dosing (Dubinsky 2016; Hyams 2012).

Hidradenitis suppurativa: Children ≥12 years and Adolescents: SubQ:

30 to <60 kg:

Initial: 80 mg on day 1, then 40 mg on day 8.

Maintenance: 40 mg every other week.

≥60 kg:

Initial: 160 mg (administered as full dose on day 1 or dose split and administered over 2 consecutive days), then 80 mg 2 weeks later (day 15).

Maintenance: 40 mg weekly beginning on day 29.

Juvenile idiopathic arthritis (JIA):

Fixed dosing:

Children 2 to 4 years:

10 kg to <15 kg: SubQ: 10 mg every other week.

15 to <30 kg: SubQ: 20 mg every other week.

Children ≥4 years and Adolescents:

15 kg to <30 kg: SubQ: 20 mg every other week.

≥30 kg: SubQ: 40 mg every other week.

Body surface area (BSA)-directed dosing: Note: Dosing based on trials performed with Humira product.

Children 2 to <4 years: SubQ: 24 mg/m²/dose every other week; maximum dose: 20 mg/dose (Humira Canadian product labeling 2018; Kingsbury 2014).

Children and Adolescents 4 to 17 years: SubQ: 24 mg/m²/dose every other week; maximum dose: 40 mg/dose (Burgos-Vargas 2015; Humira Canadian product labeling 2018; Lovell 2008).

Ulcerative colitis; moderate to severe, refractory: Limited data available: Children and Adolescents: SubQ: Initial: 100 mg/m² (maximum dose: 160 mg/dose), then 50 mg/m² (maximum dose: 80 mg/dose) 2 weeks later; then on day 29, begin maintenance therapy: 25 mg/m² every other week (maximum dose: 40 mg/dose) (Turner 2012). Note: Trials performed with Humira product.

Uveitis (noninfectious intermediate, posterior, and panuveitis):

Fixed dosing: Children ≥2 years and Adolescents:

10 kg to <15 kg: SubQ: 10 mg every other week.

15 to <30 kg: SubQ: 20 mg every other week.

≥30 kg: SubQ: 40 mg every other week.

BSA-directed dosing: Children ≥4 years and Adolescents: SubQ: 24 or 40 mg/m² every 2 weeks; maximum dose 40 mg/dose (Gallagher 2007; Simonini 2011). Dosing based on one prospective trial comparing 24 mg/m²/dose every 2 weeks of adalimumab (n=16, ages 6 to 12 years) to infliximab (n=17, ages 5 to 13 years) and on a retrospective trial of biologic response modifiers, including five patients who received adalimumab at 40 mg/m²/dose every 2 weeks. Note: Trials performed with Humira product.

Administration

SubQ: For SubQ injection at separate sites in the thigh or lower abdomen (avoiding areas within 2 inches of navel); rotate injection sites. May leave at room temperature for ~15 to 30 minutes prior to use; do not remove cap or cover while allowing product to reach room temperature. Do not use if solution is discolored or contains particulate matter. Do not administer to skin which is red, tender, bruised, hard, or that has scars, stretch marks, or psoriasis plaques. Needle cap of the prefilled syringe or needle cover for the adalimumab pen may contain latex. Prefilled pens and syringes are available for use by patients and the full amount of the syringe should be injected (self-administration); the vial is intended for institutional use only. Vials do not contain a preservative; discard unused portion. Citrate-free formulations may be associated with less pain on injection.

Storage

Store at 2°C to 8°C (36°F to 46°F) in original container to protect from light; do not freeze. Do not use if frozen even if it has been thawed. Do not store in extreme heat or cold. If needed, may be stored at room temperature up to a maximum of 25°C (77°F) for up to 14 days; discard if not used within 14 days.

Drug Interactions

Abatacept: Anti-TNF Agents may enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported. Avoid combination

Anakinra: Anti-TNF Agents may enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported. Avoid combination

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Belimumab: May enhance the immunosuppressive effect of Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Avoid combination

Biologic Disease-Modifying Antirheumatic Drugs (DMARDs): May enhance the immunosuppressive effect of other Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Avoid combination

Canakinumab: Anti-TNF Agents may enhance the adverse/toxic effect of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased. Avoid combination

Certolizumab Pegol: Anti-TNF Agents may enhance the immunosuppressive effect of Certolizumab Pegol. Avoid combination

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

CycloSPORINE (Systemic): Adalimumab may decrease the serum concentration of CycloSPORINE (Systemic). Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Rilonacept: Anti-TNF Agents may enhance the adverse/toxic effect of Rilonacept. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Theophylline Derivatives: Adalimumab may decrease the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

Thiopurine Analogs: Anti-TNF Agents may enhance the adverse/toxic effect of Thiopurine Analogs. Specifically, the risk for T-cell non-Hodgkin's lymphoma (including hepatosplenic T-cell lymphoma) may be increased. Monitor therapy

Tocilizumab: May enhance the immunosuppressive effect of Anti-TNF Agents. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Vedolizumab: Anti-TNF Agents may enhance the adverse/toxic effect of Vedolizumab. Avoid combination

Warfarin: Adalimumab may decrease the serum concentration of Warfarin. Monitor therapy

Adverse Reactions

>10%:

Central nervous system: Headache (12%)

Dermatologic: Skin rash (6% to 12%)

Hematologic & oncologic: Positive ANA titer (12%)

Immunologic: Antibody development (3% to 26%)

Infection: Infection (children and adolescents: 45%)

Local: Injection site reaction (5% to 20%)

Neuromuscular & skeletal: Increased creatine phosphokinase (15%)

Respiratory: Upper respiratory tract infection (17%), sinusitis (11%)

1% to 10%:

Cardiovascular: Hypertension (5%), atrial fibrillation (<5%), cardiac arrhythmia (<5%), chest pain (<5%), coronary artery disease (<5%), deep vein thrombosis (<5%), hypertensive encephalopathy (<5%), myocardial infarction (<5%), palpitations (<5%), pericardial effusion (<5%), pericarditis (<5%), peripheral edema (<5%), subdural hematoma (<5%), syncope (<5%), tachycardia (<5%)

Central nervous system: Confusion (<5%), myasthenia (<5%), paresthesia (<5%), torso pain (<5%)

Dermatologic: Cellulitis, erysipelas

Endocrine & metabolic: Hyperlipidemia (7%), hypercholesterolemia (6%), dehydration (<5%), ketosis (<5%), menstrual disease (<5%), parathyroid disease (<5%)

Gastrointestinal: Nausea (9%), abdominal pain (7%), cholecystitis (<5%), cholelithiasis (<5%), esophagitis (<5%), gastrointestinal hemorrhage (<5%), vomiting (<5%), diverticulitis of the gastrointestinal tract

Genitourinary: Urinary tract infection (≤8%), hematuria (5%), cystitis (<5%), pelvic pain (<5%)

Hematologic & oncologic: Adenoma (<5%), agranulocytosis (<5%), paraproteinemia (<5%), polycythemia (<5%), carcinoma (including breast, gastrointestinal, skin, urogenital), malignant lymphoma, malignant melanoma

Hepatic: Increased serum alkaline phosphatase (5%), hepatic necrosis (<5%)

Hypersensitivity: Hypersensitivity reaction (children 5% to 6%; adults 1%)

Infection: Serious infection (4%), herpes simplex infection (≤4%), herpes zoster infection (≤4%), sepsis

Neuromuscular & skeletal: Back pain (6%), arthritis (<5%), arthropathy (<5%), bone disease (<5%), bone fracture (<5%), limb pain (<5%), muscle cramps (<5%), myasthenia (<5%), osteonecrosis (<5%), septic arthritis (<5%), synovitis (<5%), tendon disease (<5%), tremor (<5%), arthralgia (3%; plaque psoriasis)

Ophthalmic: Cataract (<5%)

Renal: Nephrolithiasis (<5%), pyelonephritis

Respiratory: Flu-like symptoms (7%), asthma (<5%), bronchospasm (<5%), dyspnea (<5%), pleural effusion (<5%), respiratory depression (<5%), pharyngitis (juvenile idiopathic arthritis: ≤4%), pneumonia (≤4%), tuberculosis (including reactivation of latent infection; disseminated, miliary, lymphatic, peritoneal, and pulmonary)

Miscellaneous: Accidental injury (10%), abnormal healing (<5%), postoperative complication (infection)

<1%, postmarketing, and/or case reports: Abscess (limb, perianal), alopecia, anal fissure, anaphylactoid shock, anaphylaxis, anemia, angioedema, aplastic anemia, appendicitis, asthenia, bacterial infection, basal cell carcinoma, blepharitis, bronchitis, cardiac failure, cerebrovascular accident, cervical dysplasia, circulatory shock, clonus, cytopenia, dermal ulcer, diarrhea, diplopia, endometrial hyperplasia, eosinophilia, erythema multiforme, fever, fixed drug eruption, fulminant necrotizing fasciitis, fungal infection, Guillain-Barré syndrome, hepatic failure, hepatitis B (reactivation), hepatosplenic T-cell lymphomas (children, adolescents, and young adults), hepatotoxicity (idiosyncratic) (Chalasani 2014), histoplasmosis, hyperreflexia, hypersensitivity angiitis, increased serum transaminases, interstitial pulmonary disease (including pulmonary fibrosis), intestinal obstruction, intestinal perforation, leukemia, leukopenia, lichenoid eruption, liver metastases, lupus-like syndrome, lymphadenopathy, lymphocytosis, malignant neoplasm of ovary, meningitis (viral), Merkel cell carcinoma, multiple sclerosis, musculoskeletal chest pain, mycobacterium avium complex, myositis (children and adolescents), neutropenia, nocturia, optic neuritis, pancreatitis, pancytopenia, protozoal infection, psoriasis (including new onset, palmoplantar, pustular, or exacerbation), pulmonary embolism, respiratory failure, sarcoidosis, septic shock, skin granuloma (annulare; children and adolescents), Stevens-Johnson syndrome, streptococcal pharyngitis (children and adolescents), supraventricular cardiac arrhythmia, swelling of eye, systemic lupus erythematosus, testicular neoplasm, thrombocytopenia, urticaria, vascular disease, vasculitis (systemic), viral infection

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: May rarely cause hypersensitivity, anaphylaxis, anaphylactoid reactions, or angioneurotic edema; medications for the treatment of hypersensitivity reactions should be available for immediate use.
• Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop.
• Demyelinating disease: Rare cases of new-onset or exacerbation of demyelinating disorders (eg, multiple sclerosis, optic neuritis, peripheral demyelinating disease, including Guillain-Barré syndrome) have been reported; there is a known association between intermediate uveitis and central demyelinating disorders. Consider discontinuing use in patients who develop peripheral or central nervous system demyelinating disorders during treatment. Use with caution in patients with preexisting or recent onset central or peripheral nervous system demyelinating disorders.
• Heart failure: Worsening and new-onset heart failure (HF) has been reported with adalimumab and other TNF blockers. Use with caution in patients with HF or decreased left ventricular function. In a scientific statement from the American Heart Association, TNF blockers have been determined to be agents that may either cause direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).
• Hematologic disorders: Rare cases of pancytopenia and aplastic anemia have been reported with TNF-blockers. Patients must be advised to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias; discontinue if significant hematologic abnormalities are confirmed. Use with caution in patients with a history of significant hematologic abnormalities.
• Hepatitis B: Rare reactivation of hepatitis B (HBV) has occurred in chronic carriers of the virus, usually in patients receiving concomitant immunosuppressants (some have been fatal); evaluate for HBV prior to initiation in all patients. Monitor during and for several months following discontinuation of treatment in HBV carriers; interrupt therapy if reactivation occurs and treat appropriately with antiviral therapy; if resumption of therapy is deemed necessary, exercise caution and monitor patient closely.
• Infections: [US Boxed Warning]: Patients receiving adalimumab are at increased risk for serious infections which may result in hospitalization and/or fatality; infections usually developed in patients receiving concomitant immunosuppressive agents (eg, methotrexate, corticosteroids) and may present as disseminated (rather than local) disease. Active tuberculosis (including reactivation of latent tuberculosis), invasive fungal (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis) and bacterial, viral or other opportunistic infections (including legionellosis and listeriosis) have been reported. Monitor closely for signs/symptoms of infection during and after treatment. Discontinue for serious infection or sepsis. Consider risks versus benefits prior to initiating therapy in patients with chronic or recurrent infection. Consider empiric antifungal therapy in patients who are at risk for invasive fungal infections who develop severe systemic illness. Caution should be exercised when considering use in the elderly, patients with a history of an opportunistic infection, patients taking concomitant immunosuppressants (eg, corticosteroids, methotrexate), or in patients with conditions that predispose them to infections (eg, advanced or poorly controlled diabetes) or residence/travel in areas of endemic tuberculosis or mycoses (blastomycosis, coccidioidomycosis, histoplasmosis), or with latent infections. Do not initiate adalimumab in patients with an active infection, including clinically important localized infection. Patients who develop a new infection while undergoing treatment should be monitored closely.
• Malignancy: [US Boxed Warning]: Lymphoma and other malignancies (some fatal) have been reported in children and adolescents receiving TNF-blocking agents, including adalimumab. Half of the malignancies reported in children and adolescents were lymphomas (Hodgkin and non-Hodgkin) while other cases varied and included rare malignancies usually associated with immunosuppression and malignancies not typically observed in this population. Most patients were receiving concomitant immunosuppressants. [US Boxed Warning]: Hepatosplenic T-cell lymphoma (HSTCL), a rare T-cell lymphoma, has been reported (some fatal) primarily in patients with Crohn disease or ulcerative colitis treated with adalimumab and who received concomitant azathioprine or mercaptopurine; reports occurred predominantly in adolescent and young adult males. The impact of adalimumab on the development and course of malignancy is not fully defined. Compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis alone has been previously associated with an increased rate of lymphoma and leukemia. A higher incidence of nonmelanoma skin cancers was noted in adalimumab-treated patients (0.7/100 patient years), when compared to the control group (0.2/100 patient years).
• Tuberculosis: [US Boxed Warnings]: Active tuberculosis (disseminated or extrapulmonary), including reactivation of latent tuberculosis, has been reported in patients receiving adalimumab. Evaluate patients for tuberculosis risk factors and latent tuberculosis infection (with a skin test) prior to and during therapy. Treatment for latent tuberculosis should be initiated before use. Patients with initial negative tuberculin skin tests should receive continued monitoring for tuberculosis during and after treatment. Consider antituberculosis treatment if an adequate course of treatment cannot be confirmed in patients with a history of latent or active tuberculosis or with risk factors despite negative skin test. Some patients who tested negative prior to therapy have developed active infection; tests for latent tuberculosis infection may be falsely negative while on adalimumab therapy. Use with caution in patients who have traveled to or resided in regions where tuberculosis is endemic. Monitor for signs and symptoms of tuberculosis in all patients.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Infection and malignancy has been reported at a higher incidence; use caution in elderly patients.
• Pediatric: Malignancies have been reported among children and adolescents.
• Surgery patients: Limited experience with patients undergoing surgical procedures while on therapy; consider long half-life with planned procedures. Monitor closely for infection.

Dosage form specific issues:

• Latex: The packaging (needle cover of prefilled syringe and autoinjector) may contain latex.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Immunizations: Patients should be brought up to date with all immunizations before initiating therapy; live vaccines should not be given concurrently. There are no data available concerning the effects of therapy on vaccination or secondary transmission of live vaccines in patients receiving therapy.

Monitoring Parameters

Monitor improvement of symptoms and physical function assessments. Latent TB screening prior to initiating and during therapy; signs/symptoms of active infection, including tuberculosis (prior to, during, and following therapy); CBC with differential; signs/symptoms/worsening of heart failure; HBV screening prior to initiating (all patients), HBV carriers (during and for several months following therapy); signs and symptoms of hypersensitivity reaction; symptoms of lupus-like syndrome; signs/symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss), including periodic skin examination. The American Gastroenterological Association suggests reactive therapeutic drug monitoring to guide treatment changes in adult patients treated with adalimumab for active inflammatory bowel disease (Feuerstein 2017).

Pregnancy

Pregnancy Considerations

Adalimumab crosses the placenta.

Adalimumab is a humanized monoclonal antibody (IgG₁). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Following administration to pregnant patients with inflammatory bowel disease, cord blood and newborn serum concentrations of adalimumab are greater than maternal serum at delivery (Julsgaard 2016; Mahadevan 2013). The mean time to adalimumab clearance was 4 months (range: 2.9 to 5 months) in a study in 36 infants exposed in utero. The estimated mean half-life of adalimumab in these infants was 26 days (Julsgaard 2016). One case report notes adalimumab was detectable in the infant serum for 19 months following in utero exposure (Labetoulle 2018).

Outcome data from a pregnancy registry are available. Included were women with rheumatoid arthritis treated with adalimumab at least during the first trimester (n=74), women with RA not treated with adalimumab (n=80), and healthy pregnant women without RA (n=219). The incidence of major birth defects was not significantly different between the treatment groups. No pattern of specific defects was noted. There were no adverse pregnancy outcomes associated with therapy (Burmester 2017). Information related to this class of medications is emerging, but based on available data, tumor necrosis factor alpha (TNFα) blocking agents are considered to have low to moderate risk when used in pregnancy (ACOG 776 2019).

The risk of immunosuppression may be increased following third trimester maternal use of TNFα blocking agents; the fetus, neonate/infant should be considered immunosuppressed for 1 to 3 months following in utero exposure (AAD-NPF [Menter 2019]). Vaccination with live vaccines (eg, rotavirus vaccine) should be avoided for the first 6 months of life if exposure to a biologic agent occurs during the third trimester of pregnancy (eg, >27 weeks' gestation) (Mahadevan 2019).

Maternal adalimumab serum concentrations were found to remain stable during pregnancy in a study of nine women with Crohn disease (Seow 2017).

Inflammatory bowel disease is associated with adverse pregnancy outcomes including an increased risk of miscarriage, premature delivery, delivery of a low birth weight infant, and poor maternal weight gain. Management of maternal disease should be optimized prior to pregnancy. Treatment decreases disease flares, disease activity, and the incidence of adverse pregnancy outcomes (Mahadevan 2019).

Use of immune modulating therapies in pregnancy should be individualized to optimize maternal disease and pregnancy outcomes (ACOG 776 2019). The American Academy of Dermatology considers TNFα blocking agents for the treatment of psoriasis to be compatible with pregnancy (AAD-NPF [Menter 2019]). When treatment for inflammatory bowel disease is needed in pregnant women, appropriate biologic therapy can be continued without interruption. Serum levels should be evaluated prior to conception and optimized to avoid subtherapeutic concentrations or high levels which may increase placental transfer. Dosing can be adjusted so delivery occurs at the lowest serum concentration. For adalimumab, the final injection can be given 2 to 3 weeks prior to the estimated date of delivery (1 to 2 weeks if weekly dosing), then continued 48 hours postpartum (Mahadevan 2019).

The American Academy of Dermatology considers TNF blocking agents for the treatment of psoriasis to be compatible for use in male patients planning to father a child (AAD-NPF [Menter 2019]). Women with psoriasis planning a pregnancy may continue treatment with adalimumab. Women with well-controlled psoriasis who wish to avoid fetal exposure can consider discontinuing adalimumab 10 weeks prior to attempting pregnancy (Rademaker 2018). Treatment algorithms are available for use of biologics in female patients with Crohn disease who are planning a pregnancy (Weizman 2019).

Data collection to monitor pregnancy and infant outcomes following exposure to adalimumab is ongoing. Women exposed to adalimumab during pregnancy for the treatment of an autoimmune disease (eg, inflammatory bowel disease) may contact the OTIS Autoimmune Diseases Study at 877-311-8972.

Patient Education

What is this drug used for?

• It is used to treat some types of arthritis.
• It is used to treat Crohn's disease.
• It is used to treat ankylosing spondylitis.
• It is used to treat plaque psoriasis.
• It is used to treat ulcerative colitis.
• It is used to treat a skin problem called hidradenitis suppurativa.
• It is used to treat uveitis.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Common cold symptoms
• Abdominal pain
• Nausea
• Back pain
• Injection site irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain
• Lupus like rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs
• Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out
• Aplastic anemia like fever, sore throat, mouth sores, infections, bruising, or purple skin splotches
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin
• Severe headache
• Burning or numbness feeling
• Severe dizziness
• Passing out
• Seizures
• Vision changes
• Extremity weakness
• Excessive weight loss
• Night sweats
• Persistent fever
• Swollen glands
• Skin growth
• Skin changes
• Mole changes
• Pale skin
• Skin eczema
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.