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Adalimumab

Pronunciation: A-da-LIM-ue-mab
Class: Immunomodulator

Trade Names

Humira
- Injection, solution 20 mg per 0.4 mL
- Injection, solution 40 mg per 0.8 mL

Pharmacology

Blocks interaction of human tumor necrosis factor (TNF)–alpha with receptors and modulates biological responses induced or regulated by TNF.

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Pharmacokinetics

Absorption

C max is approximately 4.7 mcg/mL following a single 40 mg subcutaneous injection. T max is approximately 131 h. The average absolute bioavailability is 64%.

Distribution

V ss is 4.7 to 6 L.

Elimination

Mean terminal half-life is approximately 14 days. Systemic Cl is approximately 12 mL/h.

Special Populations

Renal Function Impairment

No pharmacokinetic data are available.

Hepatic Function Impairment

No pharmacokinetic data are available.

Elderly

In patients with rheumatoid arthritis (RA), there was a trend toward lower Cl with increasing age in patients 40 to older than 75 y.

Children

In children 4 to 17 y of age with juvenile idiopathic arthritis, mean steady-state trough serum adalimumab concentrations were 6.8 and 6.6 mcg/mL for children receiving adalimumab 20 or 40 mg, respectively, every other week as monotherapy.

Gender

No differences in pharmacokinetics were observed based on gender.

Indications and Usage

Reduce signs and symptoms, induce major clinical response, inhibit the progression of structural damage, and improve physical function in patients with moderate to severe active RA; reduce signs and symptoms, inhibit the progression of structural damage, and improve physical function in patients with active psoriatic arthritis; reduce signs and symptoms in adults with active ankylosing spondylitis; reduce signs and symptoms and induce and maintain clinical remission in adults with moderately to severely active Crohn disease; reduce signs and symptoms of moderate to severe active polyarticular juvenile idiopathic arthritis in patients 4 y and older; treatment of adults with moderate to severe chronic plaque psoriasis in patients who are candidates for systemic treatment or phototherapy when other systemic therapies are medically less appropriate.

Unlabeled Uses

Pyoderma gangrenosum.

Contraindications

None well documented.

Dosage and Administration

Ankylosing Spondylitis, Psoriatic Arthritis, RA
Adults

Subcutaneous 40 mg every other week. Patients with RA not receiving methotrexate concurrently may benefit from 40 mg every week.

Crohn Disease
Adults

Subcutaneous 160 mg on day 1 (given as four 40 mg injections in 1 day or as two 40 mg injections/day for 2 consecutive days), then 80 mg at week 2 (day 15) followed by a maintenance dosage of 40 mg every other week starting at week 4 (day 29).

Juvenile Idiopathic Arthritis
Children 4 to 17 y of age 15 kg to less than 30 kg

Subcutaneous 20 mg every other week.

30 kg or more

Subcutaneous 40 mg every other week.

Plaque Psoriasis
Adults

Subcutaneous 80 mg initially, followed by 40 mg every other week starting 1 week after the initial dose.

General Advice

  • For subcutaneous injection.
  • Aminosalicylates, corticosteroids, methotrexate, NSAIDs, analgesics, immunomodulatory agents (eg, 6-mercaptopurine, azathioprine), and/or other nonbiologic disease-modifying antirheumatic drugs may be continued during treatment.
  • The needle cover of the syringe contains dry rubber (latex) that should not be handled by persons sensitive to this substance.
  • Rotate injection sites (abdomen, thigh, upper arm). Give new injections at least 1 inch from old site and never into areas where the skin is tender, bruised, red, or hard.

Storage/Stability

Refrigerate between 36° and 46°F. Do not freeze. Store in original carton until time of administration. Protect from light. Discard unused portions of the drug remaining in the syringe.

Drug Interactions

Abatacept, tocilizumab

An increased rate of infection may occur. Concurrent therapy is not recommended. If coadministration occurs, closely monitor for signs of infection.

Anakinra

Do not use in combination; increased risk of serious infections and neutropenia.

Live vaccines

Do not give concurrently.

Methotrexate

Reduces apparent Cl of adalimumab; however, adjustments in the dose of either drug do not appear necessary.

Rituximab

A higher rate of serious infection has been observed in patients with RA treated with rituximab and subsequently receiving a TNF blocker (eg, adalimumab). There is insufficient information to provide recommendations for concurrent use of adalimumab and other biologic products.

Adverse Reactions

Cardiovascular

Hypertension (5%); arrhythmia, atrial fibrillation, chest pain, coronary artery disorder, heart arrest, hypertensive encephalopathy, leg thrombosis, MI, palpitation, pericardial effusion, pericarditis, syncope, tachycardia (less than 5%).

CNS

Headache (12%); confusion, paresthesia, subdural hematoma, tremor (less than 5%).

Dermatologic

Rash (12%); cellulitis, erysipelas, herpes zoster; cutaneous vasculitis, erythema multiforme, new or worsening psoriasis (all subtypes, including pustular and palmoplantar), Stevens-Johnson syndrome (postmarketing).

EENT

Cataract (less than 5%); pharyngitis, streptococcal pharyngitis.

GI

Nausea (9%); abdominal pain (7%); cholecystitis, cholelithiasis, esophagitis, gastroenteritis, GI hemorrhage, hepatic necrosis, vomiting (less than 5%); appendicitis; diverticulitis, large bowel perforations, pancreatitis (postmarketing).

Genitourinary

UTI (8%); hematuria (5%); cystitis, kidney calculus, menstrual disorder (less than 5%); metrorrhagia, pyelonephritis.

Hematologic

Agranulocytosis, polycythemia (less than 5%); neutropenia.

Lab Tests

Mild to moderate increase in CPK (15%); abnormal laboratory test (8%); hyperlipidemia (7%); hypercholesterolemia (6%); increased alkaline phosphatase (5%); elevated ALT (4%); increased aminotransferases.

Local

Injection-site reactions (20%); injection-site pain (19%).

Metabolic

Abnormal healing, dehydration, ketosis, paraproteinemia, peripheral edema (less than 5%).

Musculoskeletal

Back pain (6%); arthralgia (3%); arthritis, bone disorder, bone fracture, bone necrosis, joint disorder, muscle cramps, myasthenia, pain in extremity, pyogenic arthritis, synovitis, tendon disorder (less than 5%); myositis, septic arthritis.

Respiratory

Upper respiratory tract infection (17%); sinusitis (11%); asthma, bronchospasm, decreased lung function, dyspnea, pleural effusion (less than 5%); pneumonia; interstitial lung disease, including pulmonary fibrosis (postmarketing).

Miscellaneous

Development of positive titers antinuclear antibody titers (12%); flu syndrome (7%); hypersensitivity reactions (6%); low-titer antibodies to adalimumab (5%); adenoma, parathyroid disorder, pelvic pain, surgery, thorax pain (less than 5%); granuloma annulare, herpes simplex, malignancies, opportunistic infections, prosthetic and postsurgical infection, reactivated tuberculosis (TB); systemic vasculitis (postmarketing).

Precautions

Warnings

Serious infection

Patients are at an increased risk of developing serious infections that may lead to hospitalization or death. Most patients were taking concomitant immunosuppressive agents (eg, corticosteroids, methotrexate). Discontinue adalimumab if a patient develops a serious infection or sepsis. Reported infections include active TB (including reactivation of latent TB), invasive fungal infections (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis), and bacterial, viral, or other infections caused by opportunistic pathogens. Carefully consider the risks and benefits of treatment with adalimumab prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with adalimumab, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Malignancy

Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with TNF blockers, including adalimumab. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including adalimumab. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases has occurred in patients with Crohn disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.


Monitor

Closely monitor patients who develop a new infection during treatment, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy. Monitor patients with heart failure carefully. Evaluate patients at risk of hepatitis B virus (HBV) infection for prior evidence of HBV infection prior to initiating TNF blocker therapy. Closely monitor patients who are carriers of HBV and require treatment with TNF-blocking agents for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of treatment.


Pregnancy

Category B .

Lactation

Undetermined.

Children

Juvenile idiopathic arthritis

Safety and efficacy not established in children younger than 4 y; there are limited data in treating children who weigh less than 15 kg.

Other indications

Safety and efficacy not established.

Elderly

Because of a higher incidence of infections and malignancies in elderly patients, use with caution.

Hypersensitivity

Anaphylaxis and angioedema have been rarely reported.

Autoimmunity

May result in formation of autoantibodies and, rarely, in the development of a lupus-like syndrome.

Heart failure

Worsening of CHF and new-onset CHF have occurred. Use with caution.

Hematologic events

Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF-blocking agents. Adverse reactions of the hematologic system, including medically significant cytopenia (eg, leukopenia, thrombocytopenia), have been reported infrequently with adalimumab.

Hepatitis B

Risk of reactivation of HBV may be increased in chronic carriers of this virus. Use with caution in known HBV carriers.

Immunizations

If possible, bring juvenile idiopathic arthritis patients up to date with all immunizations prior to initiating therapy. Do not administer live vaccines concurrently with adalimumab.

Neurologic events

Rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease, including multiple sclerosis, and peripheral demyelinating disease, including Guillain-Barré syndrome, have occurred. Exercise caution in considering the use of adalimumab in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.

Overdosage

Symptoms

Doses of up to 10 mg/kg have been administered without evidence of toxicity.

Patient Information

  • Advise patient or caregiver to review the Medication Guide before starting therapy and with each refill.
  • Inform patients that adalimumab may lower the ability of their immune system to fight infections. Instruct patients of the importance of contacting their health care provider if they develop any symptoms of infection, including TB, invasive fungal infections, and reactivation of HBV infections.
  • Advise patients to report any signs of new or worsening medical conditions, such as congestive heart disease, neurological disease, autoimmune disorders, or cytopenias. Advise patients to report any symptoms suggestive of a cytopenia, such as bruising, bleeding, or persistent fever.
  • Counsel patients about the risk of malignancies while receiving adalimumab.
  • Advise patients to seek immediate medical attention if they experience any symptoms of severe allergic reactions. Advise latex-sensitive patients that the needle cap of the prefilled syringe contains latex.
  • Perform the first injection under the supervision of a qualified health care provider. If a patient or caregiver is to administer adalimumab, instruct them in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of adalimumab. Instruct patients or caregivers on proper syringe and needle disposal, and caution them against reuse of these items.

Copyright © 2009 Wolters Kluwer Health.

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