Adalimumab

( a y - da h - LIM -y ou -m ab )
CLASSIFICATION(S): Immunomodulator PREGNANCY CATEGORY: B Rx: Humira.

USES (1) Reduce signs and symptoms of rheumatoid arthritis, including major clinical response, inhibiting the progression of structural damage, and improving physical function in adults with moderate to severe rheumatoid arthritis. May be used alone or in combination with methotrexate or other disease-modifying antirheumatic drugs. (2) Treatment of adults with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy (when other systemic therapies are less appropriate). Give only to those who will be closely monitored and have regular follow-up visits with a health care provider. (3) Reduce signs and symptoms of active ankylosing spondylitis. (4) Reduce signs and symptoms and inducing and maintaining clinical remission in adults with moderate to severe active Crohns disease who have had an inadequate response to conventional therapy. Also, for those who have lost response to or are intolerant to infliximab. (5) Reduce signs and symptoms of moderate to severe active polyarticular juvenile idiopathic arthritis in clients 4 years of age and older. Can be used alone or in combination with methotrexate. (6) Reduce signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improvement in physical function in those with psoriatic arthritis. May be used alone or in combination with disease-modifying antirheumatic drugs. ACTION/KINETICS Action Tissue necrosis factor (TNF) is a naturally occurring cytokine involved in normal inflammatory and immune re-

sponses. TNF plays an important role in the pathologic inflammation and joint destruction in rheumatoid arthritis. Adalimumab binds specifically to TNFalpha and blocks its interaction with p55 and p75 cell surface TNF receptors. This results in a rapid decrease in levels of the acute phase reactants of inflammation and erythrocyte sedimentation rate and serum cytokines. Pharmacokinetics Maximum serum levels: 131 hr following a single SC injection of 40 mg. Absolute bioavailability is 64%. Adults, mean steady-state trough levels: About 5 mcg/mL (without methotrexate) or 8-9 mcg/mL (with methotrexate) after 40 mg every other week. Children, mean steady-state trough levels: 6.8 mcg/mL (without methotrexate) or 10.9 mcg/mL (with methotrexate) after 20 mg every other week in those 1 less than 30 kg. t /2, terminal: 2 weeks. Clearance is lower in clients 40 to 75 years of age and older. Methotrexate reduces adalimumab apparent clearance. CONTRAINDICATIONS Hypersensitivity to adalimumab or components of the product. Administration of live vaccines. Use in active infections, including chronic or localized infections. Lactation. SPECIAL CONCERNS Tuberculosis (frequently disseminated or extrapulmonary at clinical presentation), invasive fungal infections, and other opportunistic infections have been seen in clients receiving adalimumab. Some of these infections have been fatal. Antituberculosis treatment of clients with latent tuberculosis reduces the risk of reactivation in those receiving adalimumab. However, active tuberculosis has developed in clients receiving adalimumab whose screening for latent tuberculosis was negative. Evaluate clients for tuberculosis risk factors and test for latent tuberculosis infection prior to therapy with adalimumab. Monitor clients receiving adalimumab for signs and symptoms of active tuberculosis, including those who tested negative for latent tuberculosis inIV = Intravenous

C = see color insert

H = Herbal

E = sound alike drug

ADALIMUMAB
sia, subdural hematoma, tremor. CV: Hypertension, arrhythmia, atrial fibrillation, CV disorder, chest pain, CHF (new onset or worsening), coronary artery disorder, MI, cardiac arrest, hypertensive encephalopathy, palpitation, pericardial effusion, pericarditis, syncope, tachycardia, vascular disorder, leg thrombosis, cutaneous vasculitis. Hematologic: Agranulocytosis including aplastic anemia, granulocytopenia, leukopenia, lymphoma-like reaction, pancytopenia, polycythemia, thrombocytopenia. GU: UTI, hematuria, pyelonephritis, cystitis, kidney calculus, menstrual disorder, ketosis. Dermatologic: Erysipelas, cellulitis, herpes zoster, cutaneous vasculitis, erythema multiforme. Musculoskeletal: Arthritis, bone disorder, bone fracture (not spontaneous), bone necrosis, joint disorder, muscle cramps, myasthenia, pyogenic (septic) arthritis, synovitis, tendon disorder. Miscellaneous: Accidental injury, back pain, dehydration, abnormal healing, peripheral edema, pain in extremities, pelvic pain, thorax pain, parathyroid disorder, cataract, paraproteinemia. Side effects observed in children, 4-17 years of age with juvenile idiopathic arthritis: Neutropenia, streptococcal pharyngitis, increased aminotransferases (ALT, AST), herpes zoster, myositis, metrorrhagia, appendicitis, herpes simplex, pneumonia, UTI, granuloma annulare, hypersensitivity reactions, mild to moderate increased creatine phosphokinase. LABORATORY TEST CONSIDERATIONS Alkaline phosphatase. Hypercholesterolemia, hyperlipidemia, hematuria. OD OVERDOSE MANAGEMENT Treatment: In case of overdose, monitor for signs and symptoms of side effects. Begin appropriate symptomatic treatment immediately. DRUG INTERACTIONS Anakinra / Coadministration with anakinra increased risk of serious infections, neutropenia, pancytopenia (including aplastic anemia) and hypersensitivity reactions (including anaphylaxis) Immunosuppressants / Possible develW = Available in Canada

fection. Use with caution in the elderly, in those with pre-existing or recentonset CNS demyelinating disorders, in those with active infections or a history of recurrent infection, in underlying conditions that may predispose to infections, or in those who have resided in regions where tuberculosis and histoplasmosis are endemic. Simultaneous use with other TNF-blocking drugs is discouraged. Safety and efficacy have not been determined in children other than for juvenile idiopathic arthritis. The frequency of serious infection and malignancy is higher for those 65 years of age and older; use with caution in this population. SIDE EFFECTS Most Common Injection site reactions (erythema and/or itching, hemorrhage, pain, swelling), headache, sinusitis, URTI, rash, nausea, UTI. Body as a whole: Serious infections (including opportunistic infections) and sepsis, especially in those also receiving immunosuppressants. Fever, lymphomas, adenoma, flu syndrome, immunosuppression, tuberculosis (miliary, lymphatic, peritoneal, pulmonary), lupuslike syndrome (due to development of autoantibodies), prosthetic and postsurgical infections. Cancers, including breast, skin, GI, urogenital, colon-rectum, uterine-cervical, prostate, melanoma, gallbladder-bile ducts. Reactivation of hepatitis B virus. New onset or exacerbation of demyelinating disease. Hypersensitivity: Rash, anaphylaxis, fixed and/or nonspecific drug reaction, urticaria, angioneurotic edema. Injection site: Erythema, itching, hemorrhage, pain, swelling, clinical flare reaction, rash. GI: N&V, abdominal pain, cholecystitis, cholelithiasis, esophagitis, gastroenteritis, GI disorder, diverticulitis, GI hemorrhage, hepatic necrosis. Respiratory: Pneumonia, URTI, bronchitis, sinusitis, flu syndrome, asthma, bronchospasm, dyspnea, lung disorder, decreased lung function, pleural effusion, interstitial lung disease (including pulmonary fibrosis). CNS: Confusion, headache, multiple sclerosis, parestheBold Italic = life threatening side effect

= black box warning

ADALIMUMAB
opment of malignancies and/or infections Methotrexate / Adalimumab clearance after single and multiple dosing; dosage adjustment may be needed HOW SUPPLIED Injection Solution: 20 mg/0.4 mL, 40 mg/ 0.8 mL. DOSAGE SC Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis. Adults: 40 mg every other week SC. Clients not taking methotrexate concomitantly may benefit more by increasing the dosing frequency to 40 mg every week. Methotrexate, glucocorticoids, salicylates, NSAIDs, analgesics, or other disease-modifying antirheumatic drugs may be continued during adalimumab therapy. Crohns disease. Adults, initial: 160 mg on day 1 (given as 4 injections in 1 day or as 2 injections per day for 2 consecutive days) followed by 80 mg 2 weeks later (i.e., day 15). Two weeks later (i.e., day 29) begin a maintenance dose of 40 mg every other week. Aminosalicylates, corticosteroids and/or immunomodulatory drugs (e.g., 6-mercaptopurine, azathioprine) maybe continued during adalimumab therapy. Use of adalimumab for Crohns disease has not been studied beyond 1 year. Plaque psoriasis. Adults, initial: 80 mg; then, 40 mg every other week starting 1 week after the initial dose. Use in moderate to severe chronic plaque psoriasis beyond 1 year has not been evaluated. Juvenile idiopathic arthritis. Children, 4-17 years, 15 kg (33 lbs) to <30 kg (66 lbs): 20 mg every other week (use 20 mg prefilled syringe); 30 kg (66 lbs) or greater: 40 mg every other week (use adalimumab pen or 40 mg prefilled syringe). Methotrexate, corticosteroids, salicylates, NSAIDs, or analgesics may be continued during adalimumab treatment. Limited data are available for use in children weighing less than 15 kg.

NURSING CONSIDERATIONS
ADMINISTRATION/STORAGE 1. During treatment, methotrexate, glucocorticoids, salicylates, NSAIDs, analgesics, and other antirheumatic drugs may be continued. 2. Syringe needle cover is made of latex; if sensitive to latex do not handle the product. 3. Discard unused portions remaining in the vial/syringe; no preservative in product. 4. Refrigerate at 28C (3646F). Do not freeze. 5. Protect vial/prefilled syringe from exposure to light. Store in original carton until administered. ASSESSMENT 1. Note reasons for therapy, joints affected, presenting symptoms, other agents trialed/failed. 2. Assess carefully for evidence of chronic/local infections. Look for latent tuberculosis infection with a tuberculin skin test. Begin treatment of latent TB prior to adalimumab therapy. Discontinue if a serious infection develops. 3. Use cautiously in elderly and those with pre-existing or recent-onset CNS demylinating disorders, recurrent infections or those who have resided in regions endemic with TB or histoplasmosis. 4. Observe client perform first injection after instruction. CLIENT/FAMILY TEACHING 1. Used to preserve joint structure and stability. Methotrexate, glucocorticoids, salicylates, NSAIDs, analgesics, and other prescribed antirheumatic drugs may be continued during treatment. 2. May self-administer drug after proper training in injection technique. Review procedures for storage (refrigerate in original container), reconstitution, inspection, withdraw, administration, site rotation, and disposal of syringes. Use the prefilled syringes or pen to inject the full amount in the syringe (0.8 mL) which provides the full 40 mg dose. When using the pediatric prefilled syringe (clients 15 to <30 kg), inject the
IV = Intravenous

C = see color insert

H = Herbal

E = sound alike drug

ADALIMUMAB
7. Serious infections including TB (tuberculosis) and infections caused by viruses, fungi, or bacteria may occur with this therapy; may be fatal. 8. Avoid immunizations with live vaccines. 9. Review risks of therapy related to lymphoma, and some types of cancer. Report bumps/open sores that do not heal or lupus-like reactions (chest discomfort/pain that does not go away, SOB, joint pain, rash on your cheeks or arms that gets worse in the sun. 10. If sensitive to latex do not handle the needle cover of the syringe. Keep all F/U to evaluate response to therapy and for any adverse SE. OUTCOMES/EVALUATE Joint pain/swelling; delayed structural damage with RA

full amount in the syringe (0.4 mL) which provides the full 20 mg dose. 3. Always rotate sites for self-injection which include the thigh, abdomen, or upper arm. Give new injections at least one inch from the old site and never into areas where the skin is tender, bruised, red, or hard. 4. May experience rash, pain, or swelling at injection site. A cool moist compress should relieve. If no relief or S&S worsen, report. 5. Any evidence of dizziness, infection, numbness or tingling, weakness of legs or vision problems as well as facial swelling, chest pain, increased cough, fever, SOB, flu-like symptoms, rash, or joint pains require medical evaluation. 6. Drug may make one more likely to get infections or make any infection that you may have worse.

Bold Italic = life threatening side effect

= black box warning

W = Available in Canada